haemodynamic disorders , thromboembolism and shock by dr nadeem (rmc)

HAEMODYNAMIC HAEMODYNAMIC DISORDERS, DISORDERS,

THROMBOEMBOLISTHROMBOEMBOLISM M

AND AND SHOCKSHOCK

HAEMODYNAMIC HAEMODYNAMIC CHANGESCHANGES

The health and well- being of cells and tissues The health and well- being of cells and tissues depends upon:depends upon:1. An intact blood circulation to deliver oxygen 1. An intact blood circulation to deliver oxygen 2. Normal fluid homeostasis2. Normal fluid homeostasis

The abnormalities in blood supply or fluid balance The abnormalities in blood supply or fluid balance leads to different disorders like:leads to different disorders like: (i) Edema(i) Edema (ii) Vascular Congestion(ii) Vascular Congestion (iii) Hemorrhage(iii) Hemorrhage

(iv) Thrombosis(iv) Thrombosis (v) Embolism(v) Embolism

(vi) Infarction(vi) Infarction (vii) Shock(vii) Shock

Thrombosis, embolism and Thrombosis, embolism and Infarction underlie three most Infarction underlie three most impotent causes of morbidity and impotent causes of morbidity and mortality in Western societymortality in Western society

For example:For example: -Myocardial Infarction-Myocardial Infarction - Cerbrovascular accident- Cerbrovascular accident - Stroke - Stroke

HYPEREMIA HYPEREMIA AND AND

CONGESTIONCONGESTION

HYPEREMIA AND HYPEREMIA AND CONGESTIONCONGESTION

The term hyperemia and congestion indicate The term hyperemia and congestion indicate a a local increased volume of blood in a local increased volume of blood in a particular tissueparticular tissue

HYPEREMIAHYPEREMIA It is an It is an Active ProcessActive Process resulting from resulting from

increased tissue inflow because of arteriolar dilation, increased tissue inflow because of arteriolar dilation, as in skeletal muscle during exercise, or at sites in as in skeletal muscle during exercise, or at sites in inflammation.inflammation. The effected tissue is redder because of the The effected tissue is redder because of the engorgement with oxygenated bloodengorgement with oxygenated blood

CONGESTIONCONGESTIONIt is a It is a Passive ProcessPassive Process resulting from resulting from

impaired outflow from a tissue. It may occur impaired outflow from a tissue. It may occur systemically or locally.systemically or locally.

Systemic Congestion:Systemic Congestion: As in cardiac failure As in cardiac failure Local Congestion:Local Congestion: As in isolated venous obstruction As in isolated venous obstruction

In congestion tissue has a blue red In congestion tissue has a blue red colour colour ((CyanosisCyanosis)) particularly as worsening particularly as worsening congestion leads to accumulation of deoxygenated congestion leads to accumulation of deoxygenated hemoglobin in the affected tissues.hemoglobin in the affected tissues.

Congestion of capillary beds is closely related Congestion of capillary beds is closely related to the development of edema, so that congestion to the development of edema, so that congestion and edema commonly occur togetherand edema commonly occur together

HYPEREMIAHYPEREMIA CONGESTIONCONGESTIONActive processActive process Passive processPassive processResults from Results from increased tissue in- increased tissue inflow due to arteriolar flow due to arteriolar dilatationdilatation

Results from impaired Results from impaired out flow from a tissueout flow from a tissue

Effected tissue is red Effected tissue is red because of the because of the engorgement with engorgement with oxygenated bloodoxygenated blood

Effected tissue is Effected tissue is bluish – red due to bluish – red due to accumulation of accumulation of deoxygenated blood.deoxygenated blood.

Will lead to Erythema Will lead to CyanosisExamples: (i) In skeletal muscle during exercise ; (ii) At sites of inflammation

Example: (i) Systemic: As in congestive cardiac failure ; (ii) Local: As in isolated venous obstruction

Hyperemia Vs CongestionHyperemia Vs Congestion

Hyperemia Vs Congestion

In both cases there is an increased volume and pressure of blood in a given tissue with associated capillary dilation and a potential for fluid extravasation.In Hyperemia: increased inflow leads to engorgement with oxygenated blood, resulting in erythema

In Congestion: diminished outflow leads to a capillary swollen with deoxygenated venous blood and resulting in cyanosis

MORPHOLOGIC CHANGES IN HYPEREMIAMORPHOLOGIC CHANGES IN HYPEREMIA AND CONGESTION AND CONGESTION

GROSS EXAMINATIONGROSS EXAMINATION:: Cut surface of hyperemic or Cut surface of hyperemic or congested tissue area haemorrhagic and wet.congested tissue area haemorrhagic and wet.

MICROSCOPIC EXAMIANTIONMICROSCOPIC EXAMIANTION: : a) a) Pulmonary CongestionPulmonary Congestion:: (i) (i) Acute Pulmonary CongestionAcute Pulmonary Congestion: Alveolar capillaries are : Alveolar capillaries are

engorged with blood. There may be associated alveolar engorged with blood. There may be associated alveolar septal edema or focal intra alveolar hemorrhage. septal edema or focal intra alveolar hemorrhage.

(ii) (ii) Chronic Pulmonary CongestionChronic Pulmonary Congestion: The septa have : The septa have become thickened and fibrotic. The alveolar spaces may become thickened and fibrotic. The alveolar spaces may contain numerous hemosidrin laden macrophages contain numerous hemosidrin laden macrophages ((Heart Failure Cells)Heart Failure Cells)

b) b) Congestion of LiverCongestion of Liver:: The central regions of the The central regions of the hepatic lobules are grossly red brown and slightly hepatic lobules are grossly red brown and slightly depressed due to loss of cells and are accentuated depressed due to loss of cells and are accentuated against the surrounding zones of uncongested against the surrounding zones of uncongested liverliver( nutmeg liver) ( nutmeg liver) .(.(so called because it resembles so called because it resembles the alternating pattern of light and dark seen when a the alternating pattern of light and dark seen when a whole nutmeg is cut) In long standing congestion due to whole nutmeg is cut) In long standing congestion due to cardiac failure there can be hepatic fibrosis cardiac failure there can be hepatic fibrosis ((Cardiac Cardiac CirrhosisCirrhosis) )

Heart Failure CellsHeart Failure CellsHaemosidrin laden macrophages seen in Haemosidrin laden macrophages seen in

alveolar spaces, in pulmonary congestionalveolar spaces, in pulmonary congestion Nutmeg liverNutmeg liverAlternating pattern of light Alternating pattern of light and dark areas seen in and dark areas seen in congestion of liver (resembles congestion of liver (resembles alternating dark and light when a whole alternating dark and light when a whole

nutmeg is cut)nutmeg is cut)

CCardiac Cirrhosisardiac CirrhosisHepatic fibrosis seen in chronic heart Hepatic fibrosis seen in chronic heart

failure failure

Liver with Chronic Passive Congestion and Haemorrhagic Necrosis

A: Central areas are red and slightly depressed compared with the surrounding tan viable parenchyma, forming a “nutmeg liver” pattern(so called because it resembles the alternating pattern of light and dark seen when a whole nutmeg is cut

B: Centrilobular necrosis with degenerating hepatocytes and haemorrhage

Left-sided heart failureLeft-sided heart failure chronic congestion of lungchronic congestion of lung lung edema, haemorrhage: lung edema, haemorrhage: weight weight

increased, sogginess subcrepitant, increased, sogginess subcrepitant, sectioning permits the free escape of a sectioning permits the free escape of a frothy hemorrhagic fluid, frothy hemorrhagic fluid,

Microscope showed alveolar walls are Microscope showed alveolar walls are dilated and alveolar space edema,full with dilated and alveolar space edema,full with red cells and can find red cells and can find ““heart failure cell””

brown induration of the lungbrown induration of the lung

““HHeart failure cell” eart failure cell” macrophages phagocytose macrophages phagocytose red cell red cell

then the red cell break then the red cell break down intodown into hemosiderin hemosiderin granulesgranules

Acute congestion of the lung with pulmonary edema. Chronic congestion with heart failure cells

Right-Sided Heart FailureRight-Sided Heart Failure Nutmeg liverNutmeg liver:Liver congestion in :Liver congestion in

centrilobular areas surrounded by fatty centrilobular areas surrounded by fatty degenerationdegeneration

peripheral regionsperipheral regions cardiac sclerosiscardiac sclerosis

persistence

Nnutmeg liver (photo is offered by )

Histologic appearance of atrophy and necrosis of cells in the central part of the liver lobule in chronic congestion

Chronic venous congestion ( nutmeg liver)

Chronic venous congestion ( nutmeg liver) with recent infarction

Section in the lung shows Thickened alveolar wall with congested dilated alveolar capillaries. The alveolar spaces contain intact and haemolysed red blood cells, brown haemosidren granules, heart failure cells and homogenous pink transudate. The heart failure cells are large, rounded phagocytic cells engulfing brown haemosidren granules and red blood cells.

Diagnosis

Chronic venous congestion, lung

Chronic venous congestion, lung

Chronic venous congestion liver

Atrophic liver cells

Dilated sinusoids

Central vein

EDEMAEDEMA

EDEMAEDEMA““Edema is the increased fluid in the Edema is the increased fluid in the

interstitial tissue spaces and or body interstitial tissue spaces and or body cavities”cavities”

Approximately 60% of lean body Approximately 60% of lean body weight is water, two thirds of which is weight is water, two thirds of which is intracellular, with the reminder in the intracellular, with the reminder in the extra cellular compartments, mostly as extra cellular compartments, mostly as interstitial fluid (only about 5% of total interstitial fluid (only about 5% of total body water is in blood plasma). The term body water is in blood plasma). The term edema signifies increased fluid in the edema signifies increased fluid in the interstitial tissue spaces.interstitial tissue spaces.

The interstitial tissue is in equilibrium with plasma on one hand and parenchymal cell cytoplasm on the other.

Movement of water and electrolytes among plasma , interstitium, cells and lymphatics is shown by arrows

Components of Interstitial tissue:A. Water ; Electrolytes; Hydrogen ions; Glucose ; LipidsB. Ground substance; Glycoprotein; Hyaluronic acid;

Fibronectins C. Fibrillar proteins ; Collagen( Osteoid in bone and chondroid

in cartilage); Elastin ; D. Interstitial cells; Fibroblasts; Macrophages ; lymphocytes;

Mast cells; Adipocytes (fat cells)

NORMAL TISSUE FLUID CIRCULATIONNORMAL TISSUE FLUID CIRCULATION

Hydrostatic blood pressure forces water out of capillaries at the arterial end, but the plasma oncotic pressure attributable to albumin sucks water back into capillary beds at the venous end . A small amount of water drains from the tissues through lymphatic channels

Variables Affecting Fluid Transit Across capillary Walls

Capillary hydrostatic and osmotic forces are normally balanced so that there is no net loss or gain of fluid across the capillary bed. However increased hydrostatic pressure or diminished plasma osmotic pressure leads to a net accumulation of extravascular fluid(edema). As the interstitial fluid pressure increases, tissue lypmhatics remove much of the excess volume via thoracic duct. If the ability of the lypmhatics to drain fluid is exceeded, persistent tissue edema results

PATHOPHYSIOLOGIC CATEGORIES OF EDEMAPATHOPHYSIOLOGIC CATEGORIES OF EDEMA

I. I. Increased Hydrostatic Pressure:Increased Hydrostatic Pressure: a. a. Impaired venous returnImpaired venous return

Congestive heart failureCongestive heart failureConstrictive pericarditisConstrictive pericarditisAscities (Liver Cirrhosis)Ascities (Liver Cirrhosis)Venous obstruction or compression , e.g., ThrombosisVenous obstruction or compression , e.g., Thrombosisb. b. Arteriolar dilatationArteriolar dilatation

HeatHeat Neurohumoral dysregulation Neurohumoral dysregulation

II. II. Reduced Plasma Osmotic Pressure Reduced Plasma Osmotic Pressure (Hypoprotenemia)(Hypoprotenemia)Protein losing Glomerulonephritis (Nephrotic Syndrome)Protein losing Glomerulonephritis (Nephrotic Syndrome)Liver Cirrhosis (Ascities)Liver Cirrhosis (Ascities)MalnutritionMalnutrition

Protein – losing GastroenterophathyProtein – losing Gastroenterophathy

III. III. Lymphatic Obstruction:Lymphatic Obstruction:InflammatoryInflammatoryNeoplasiaNeoplasiaPost surgicalPost surgicalPost irradiationPost irradiationParasitic ( Filaraisis)Parasitic ( Filaraisis)

IV.IV. Inflammation Inflammation ( increased capillary ( increased capillary permeability)permeability)Acute inflammationAcute inflammationChronic inflammationChronic inflammation

Angiogenesis Angiogenesis

V. V. Sodium RetentionSodium RetentionExcessive salt intake with renal insufficiencyExcessive salt intake with renal insufficiencyIncreased tubular reabsorption of sodiumIncreased tubular reabsorption of sodiumRenal Hypoperfusion Renal Hypoperfusion Increased renin- angiotensin – aldosterone secretionIncreased renin- angiotensin – aldosterone secretion

Arterial EndArterial End Venous EndVenous End

Hydrostatic pressure is more Hydrostatic pressure is more than osmotic pressure than osmotic pressure

Osmotic pressure is more Osmotic pressure is more than hydrostatic pressure than hydrostatic pressure

I.I. INCREASED HDROSTATIC PRESSUREINCREASED HDROSTATIC PRESSURE

Normal Hydrostatic pressure at the arteriolar end of capillaries is 35 mm of Hg and at the venular end of capillaries it is about 15 mm of HgIncreased venous pressure exceeds that of plasma oncotic pressure and so water remains in the tissues.Local increase in Hydrostatic Pressure: It result from impaired venous out flow. For example, deep venous thrombosis in the lower extremities leads to edema which is restricted to lower limbsGeneralized Increase in Venous Pressure: Generalized increase in venous pressure, with resulting systemic edema, occur most commonly in congestive Heart Failure affecting left ventricle

Congestive heart failure is associated with reduced cardiac output and therefore reduced renal perfusion. Renal hypo perfusion, then triggers the Rennin- Angiotensin – Aldosterone Axis, inducing sodium and water retention by kidneys . This process is putatively designed to increase intravascular volume and thereby improve cardiac out put ( via Frank- Starling Law) , with restoration of normal renal perfusion . If the failing heart can not increase cardiac out put , however , the extra fluid load results only in increased venous pressure and eventually Edema

Pathways leading to systemic edema due to primary heart failure, primary renal failure, or reduced plasma oncotic pressure (e.g., from malnutrition, diminished hepatic synthesis, or protein loss due to the nephrotic syndrome)

II.II.REDUCED PLASMA ONCOTIC PRESSUREREDUCED PLASMA ONCOTIC PRESSURE(Hypoalbuminaemic oedema)(Hypoalbuminaemic oedema)

The normal colloid osmotic pressure is about 20 mm of Hg. It is an opposing force to the hydrostatic pressure . Normally at arterial end filtration of tissue fluids occur because the hydrostatic pressure is higher than the osmotic pressure. At the venous end the osmotic pressure is higher than the hydrostatic pressure resulting in the withdrawal of the tissue fluid. Therefore fall in the osmotic pressure ( due to hypoprotenemia) results in oedema Low plasma albumin concentration reduces the plasma oncotic pressure so that water can not be sucked back into the capillary bed at the venous end.

Causes of hypoalbuminemia are: (i) Protein malnutrition (as in Kwashiorkor) (ii) Liver failure (reduced albumin synthesis) (iii) Nephrotic syndrome (excessive albumin

loss in urine) (iv) Protein – losing enteropathy (a variety of

diseases are responsible)

Hypoalbuminemia as the cause of oedema can be verified easily by measuring the albumin concentration in serum

III. III. LYMPHATIC OBSTRUCTIONLYMPHATIC OBSTRUCTION(Lymphatic Oedema)(Lymphatic Oedema)

Lymphatic obstruction prevents drainage of water from tissues Important causes of lymphatic obstruction are: (i) Parasitic infection Filariasis often causes impairment in lymphatic drainage and cause massive lymph edema in inguinal region (Elephantiasis) (ii) Surgical removal of axillary lymph nodes in carcinoma breast can lead to lymph edema of arms.

Lymphatic ObstructionLymphatic Obstruction

FilariasisFilariasis – – A parasitic infection A parasitic infection

affecting inguinal affecting inguinal lymphatics resulting lymphatics resulting in elephantiasisin elephantiasis

Lymphatic Obstruction NeoplasticLymphatic Obstruction Neoplastic

Resection and/or radiation to axillary Resection and/or radiation to axillary

lymphaticslymphatics in breast cancer patients can lead to in breast cancer patients can lead to

-- -- arm edemaarm edema

Carcinoma of breastCarcinoma of breast with with obstructioobstruction of n of

superficial superficial lymphaticslymphatics can lead to edema of can lead to edema of

breast skin -- --with an unusual appearance: breast skin -- --with an unusual appearance:

“peau d’orange” (orange peel)“peau d’orange” (orange peel)

IV.IV.INFLAMMATORY OEDEMAINFLAMMATORY OEDEMA

It is a feature of acute inflammation. In acutely inflamed tissues there is increased vascular (mainly venular ) permeability due to separation of endothelial cells under the influence of chemical mediators. Fluid with high protein content leaks out of the permeable vessels into the inflamed tissue causing it to swell. There is increased lymphatic drainage, but this cannot cope with all the water released into tissues and edema results

V.V.SODIUM AND WATER RETNETIONSODIUM AND WATER RETNETION Salt retention may occur with any acute reduction of Salt retention may occur with any acute reduction of

renal functionrenal function

Sodium and Water retention is clearly contributory Sodium and Water retention is clearly contributory factors in several forms of edemafactors in several forms of edema

Increased salt, with obligate accompanying water , Increased salt, with obligate accompanying water , causes both causes both

(i) increased hydrostatic pressure( due to (i) increased hydrostatic pressure( due to expansion of the intravascular fluid volume) expansion of the intravascular fluid volume)

and and (ii) Diminished vascular colloid osmotic pressure.(ii) Diminished vascular colloid osmotic pressure.

Pathophysiology of Localized EdemaPathophysiology of Localized Edema

Factors influencing accumulation in the interstitial Factors influencing accumulation in the interstitial spacespace

Pathologic Pathologic conditioncondition

Vascular Vascular permeabilipermeabilityty

Capillary Capillary HydrostatiHydrostatic Pressurec Pressure

Interstitial Interstitial Tissue Tissue Osmotic Osmotic PressurePressure

Lymphatic Lymphatic FlowFlow

Acute Acute InflammatoInflammatory Edemary Edema

IncreasedIncreased IncreasedIncreased Normal Or Normal Or IncreasedIncreased

IncreasedIncreased

Allergic Allergic EdemaEdema

IncreasedIncreased IncreasedIncreased Normal Or Normal Or IncreasedIncreased

IncreasedIncreased

Edema of Edema of Venous Venous ObstructioObstructionn

NormalNormal IncreasedIncreased NormalNormal IncreasedIncreased

Edema of Edema of Lymphatic Lymphatic ObstructioObstructionn

NormalNormal NormalNormal Normal Or Normal Or IncreasedIncreased

DecreasedDecreased

MORPHOLOGY OF OEDEMAMORPHOLOGY OF OEDEMAGross FeaturesGross Features:: Oedema causes swelling, heaviness Oedema causes swelling, heaviness

and pallor of the affected tissue . The cut surface of an and pallor of the affected tissue . The cut surface of an oedematous organ, as lung, oozes fluidoedematous organ, as lung, oozes fluid

Microscopic Features:Microscopic Features: Oedema appears as Oedema appears as homogenous pale eosinophilic substancehomogenous pale eosinophilic substance . . Eosinophilic staining is due to its protein content . Pale Eosinophilic staining is due to its protein content . Pale staining is due to fluid dilution.staining is due to fluid dilution.Microscopically oedema fluid generally manifests as cell Microscopically oedema fluid generally manifests as cell swelling with clearing and separation of extra cellular swelling with clearing and separation of extra cellular matrix elements.matrix elements.

TYPES OF OEDEMATYPES OF OEDEMAI.I. Localized Or GeneralizedLocalized Or Generalized

II.II. Pitting Or Non- pittingPitting Or Non- pitting

III.III. Transudate Or ExudateTransudate Or Exudate

I.I. Localized Or GeneralizedLocalized Or GeneralizedLocalized:Localized:a. Inflammatory Oedemaa. Inflammatory Oedemab. Lymphatic oedema due to lymphatic obstructionb. Lymphatic oedema due to lymphatic obstructionc. Oedema due to localized venous congestionc. Oedema due to localized venous congestiond. Pulmonary oedemad. Pulmonary oedema

Generalized:Generalized:a. Cardiac Oedema: Seen in right sided heart failure.a. Cardiac Oedema: Seen in right sided heart failure.b. Nutritional Oedema: Due to hypoprotenemia seen in:b. Nutritional Oedema: Due to hypoprotenemia seen in:

- Malnutrition- Malnutrition- Malabsorption- Malabsorption- Chronic liver disease ( decreased protein synthesis)- Chronic liver disease ( decreased protein synthesis)

c. Renal Oedema: It particularly starts around the eye lids c. Renal Oedema: It particularly starts around the eye lids then becomes generalized.then becomes generalized.

II.II.Pitting Or Non- Pitting OedemaPitting Or Non- Pitting OedemaPitting Oedema:Pitting Oedema: Pitting oedema occurs when venous Pitting oedema occurs when venous

pressurepressure is increased ( e.g., right sided heart failure) or osmotic pressureis increased ( e.g., right sided heart failure) or osmotic pressure is decreased ( e.g., hypoprotenemia)is decreased ( e.g., hypoprotenemia)

It is more marked in the It is more marked in the dependent partsdependent parts ( feet in an ambulant ( feet in an ambulant patient and the sacrum in a bed ridden patient)patient and the sacrum in a bed ridden patient)

If the edematous part is pressed by the thumb , a If the edematous part is pressed by the thumb , a pit pit is is formed which refills slowly after the thumb is removed. formed which refills slowly after the thumb is removed. Dorsum of the Dorsum of the

foot ,ankle, shin and sacrum are the usual sites to look for foot ,ankle, shin and sacrum are the usual sites to look for pittingpitting

edema.edema.Non – Pitting Oedema:Non – Pitting Oedema: When thumb is pressed no pitting When thumb is pressed no pitting

takes place.takes place.Non- pitting oedema takes place in different sites.Non- pitting oedema takes place in different sites.

1. In cases of lymphatic oedema, e.g., Filaraisis.1. In cases of lymphatic oedema, e.g., Filaraisis.2. Sometimes inflammatory oedema2. Sometimes inflammatory oedema3. Deposition of mucopolysaccharides ( Myxedema) 3. Deposition of mucopolysaccharides ( Myxedema)

IIIIII. . TRANSUDATE Or EXUDATETRANSUDATE Or EXUDATE

The edema fluid occurring in hydrodynamic The edema fluid occurring in hydrodynamic derangements is typically derangements is typically protein – poor protein – poor Transudate, Transudate, .. Conversely, because of Conversely, because of increased vascular permeability , increased vascular permeability , inflammatory edema is inflammatory edema is protein rich - protein rich - Exudate.Exudate.

TRANSUDATE

EXUDATE

PROTEIN Less than 3.o g/dl More than 3.0 gram/dl COLOUR : .Clear Or Straw

Turbid or Purulent

SPECIFIC GRAVITY

Less than 1.012

More than 1.012

CELL COUNT Less than 100/cmm

More than 100/cmm

TYPE OF CELL:

Lymphocytes & mesothelial

Lmphocytes & Neutrophils

RED BLOOD CELLS: Absent Often presentCLOT FORMATION None UsualTOTAL PROTEIN: Less than 3.0 g/dl More than 3.0 g/dlRIVOLTA TEST Negative PositiveGLUCOSE As in plasma ReducedLDH Less than 550 Units More than 550 units

Transudate VS ExudateTransudate VS Exudate

TRANSUDATE

EXUDATE

CAUSES

(i) Congestive Cardiac Failure

(ii) Cirrhosis

(i) Bacterial Infection (ii) Malignancies (iii) Tuberculosis

PROTEIN SOURCE Mainly Albumin Mainly FibrinogenNATURE Normal tissue fluid

butin amounts

exceeding the normal

Inflammatory Fluid

Transudate VS ExudateTransudate VS Exudate

CLINICAL CORRELATIONSCLINICAL CORRELATIONS

HYDROTHORAX:HYDROTHORAX: Accumulation of fluid in pleural Accumulation of fluid in pleural cavitycavity

HYDROPERICARDIUM:HYDROPERICARDIUM: Accumulation of fluid in Accumulation of fluid in pericardiumpericardium

ASCITIES:ASCITIES: Accumulation of fluid in peritoneal cavityAccumulation of fluid in peritoneal cavity

ANASARCA:ANASARCA: Severe and generalized edema with Severe and generalized edema with profound subcutaneous tissue swellingprofound subcutaneous tissue swelling

Edema -Edema - MorphologyMorphology

Dependent Edema Dependent Edema is a is a prominent feature of Congestive prominent feature of Congestive Heart FailureHeart Failure

Facial Edema Facial Edema is often the initial is often the initial manifestation of Nephrotic Syndromemanifestation of Nephrotic Syndrome

Subcutaneous EdemaSubcutaneous Edema Edema of the subcutaneous tissue is most easily detected Edema of the subcutaneous tissue is most easily detected GrosslyGrossly (not (not

microscopically)microscopically) Push your finger into it Push your finger into it and a depression remainsand a depression remains

Non –pitting Edema Non –pitting Edema

Periorbital edema in Nephrotic Periorbital edema in Nephrotic Syndrome Syndrome

EdemaEdema

Clinical Correlation:Clinical Correlation:Subcutaneous EdemaSubcutaneous Edema

Annoying but Points to Underlying DiseaseAnnoying but Points to Underlying Disease However, it can impair wound healing or However, it can impair wound healing or

clearance of Infectionclearance of Infection

Edema-Edema- MorphologyMorphology

Pulmonary EdemaPulmonary Edema

is most frequently seen in Congestive is most frequently seen in Congestive Heart FailureHeart Failure May also be present in renal failure, adult May also be present in renal failure, adult

respiratory distress syndrome (ARDS), respiratory distress syndrome (ARDS), pulmonary infections and hypersensitivity pulmonary infections and hypersensitivity reactionsreactions

Pulmonary Edema-Gross:Pulmonary Edema-Gross: The Lungs are typically 2-3 times the normal weightThe Lungs are typically 2-3 times the normal weight Cross sectioning causes an outpouring of frothy, Cross sectioning causes an outpouring of frothy,

sometimes blood-tinged fluidsometimes blood-tinged fluid

Pulmonary Edema

Normal

EDEMA - EDEMA - SummarySummary

INCREASEDHYDROSTATICPRESSURE

Congestive Heart FailureAscitesVenous Obstruction

DECREASED ONCOTICPRESSURE

Nephrotic SyndromeCirrhosisProtein Malnutrition

INCREASEDPERMEABILITY

Inflammation

LYMPHATICOBSTRUCTION

InflammatoryNeoplastic

HEARTHEART LIVERLIVER KIDNEYKIDNEY

GENERALIZED EDEMAGENERALIZED EDEMA

HEARTHEART LIVERLIVER KIDNEYKIDNEY

HAEMORRHAGE HAEMORRHAGE

HAEMORRHAGEHAEMORRHAGE ““Extravasations of blood from vessels”Extravasations of blood from vessels”

Occurs in variety of settingsOccurs in variety of settings

Risk of haemorrhage (often after a seemingly Risk of haemorrhage (often after a seemingly insignificant injury) is increased in a wide variety of insignificant injury) is increased in a wide variety of clinical disorders collectively called clinical disorders collectively called Haemorrhagic Haemorrhagic DiathesisDiathesis

Trauma, atherosclerosis, or inflammatory or neoplastic Trauma, atherosclerosis, or inflammatory or neoplastic erosion of a vessel wall also may lead to haemorrhage, erosion of a vessel wall also may lead to haemorrhage, which may be extensive which may be extensive

HAEMORRHAGE …. ManifestationsHAEMORRHAGE …. ManifestationsHaemorrhage may be manifested by different Haemorrhage may be manifested by different

appearances and clinical consequencesappearances and clinical consequences1. 1. Haematoma :Haematoma : Haemorrhage may be external or Haemorrhage may be external or

accumulate within a tissue as a Haematoma ; which accumulate within a tissue as a Haematoma ; which ranges in significance from trivial (e.g., a ranges in significance from trivial (e.g., a bruisebruise) to ) to fatal 9e.g., Massive Rretroperitoneal Haematoma fatal 9e.g., Massive Rretroperitoneal Haematoma resulting from resulting from RRupture of a Dissecitng Aortic upture of a Dissecitng Aortic AneurysmAneurysm))

2. 2. HemothoraxHemothorax33. Hemoperitonium. Hemoperitonium4.4.HemopericardiumHemopericardium5. 5. Hemarthrosis Hemarthrosis 6. 6. Petichiae: Petichiae: Minute (1 to 2 mm in diameter) hemorrhage Minute (1 to 2 mm in diameter) hemorrhage

into skin, mucous membranes or serosal surfaces.into skin, mucous membranes or serosal surfaces. Causes include:Causes include: (i) (i) ThrombocytopniaThrombocytopnia (ii) (ii) Platelet function defectsPlatelet function defects (iii) (iii) Loss of vascular wall support (Vitamin C Loss of vascular wall support (Vitamin C

deficiency)deficiency)

HAEMORRHAGEHAEMORRHAGE7. 7. PurpuraPurpura:: Slightly larger (3 to 5 mm) haemorrhages. Slightly larger (3 to 5 mm) haemorrhages.

Can result form the same disorders that cause Can result form the same disorders that cause petechiae, as well as trauma ,vascular inflammation petechiae, as well as trauma ,vascular inflammation (vasculitis and increased vascular fragility(vasculitis and increased vascular fragility

8. 8. EcchmosesEcchmoses:: Are larger (1 to 2 cm) subcutaneous Are larger (1 to 2 cm) subcutaneous hamatomas (colloquially called hamatomas (colloquially called BruisesBruises) )

HAEMORRHAGEHAEMORRHAGE Clinical significance of any particular haemorrhage Clinical significance of any particular haemorrhage

depends on the volume of blood lost and the rate of depends on the volume of blood lost and the rate of bleedingbleeding

Greater loss can lead to Greater loss can lead to Hypovolemic Shock Hypovolemic Shock Site of haemorrhage is also important Site of haemorrhage is also important Chronic or recurrent external blood loss (e.g., due to Chronic or recurrent external blood loss (e.g., due to

peptic ulcer or menstrual bleeding) frequently peptic ulcer or menstrual bleeding) frequently culminates in iron deficiency as a consequence of loss culminates in iron deficiency as a consequence of loss of iron in haemoglobin of iron in haemoglobin

THROMBOSISTHROMBOSIS

THROMBOSISTHROMBOSIS The formation of a clotted mass of The formation of a clotted mass of

blood within the non interrupted blood within the non interrupted cardiovascular system is termed cardiovascular system is termed thrombosis,thrombosis, and the mass itself Thrombus and the mass itself Thrombus

Thrombosis is the formation of a solid mass from Thrombosis is the formation of a solid mass from the constituents of blood (platelets, fibrin and the constituents of blood (platelets, fibrin and entrapped red and white cells) within the heart or entrapped red and white cells) within the heart or vascular system in a living organism vascular system in a living organism

THROMBOSISTHROMBOSISNormal HemstasisNormal Hemstasis is the result of a set of well is the result of a set of well regulated processes that accomplish two important regulated processes that accomplish two important functions:functions:(i) It maintain (i) It maintain blood in a fluid, clot free stateblood in a fluid, clot free state in in normal vessels.normal vessels.

(ii) It produces a localized (ii) It produces a localized Haemostatic PlugHaemostatic Plug at the at the site of vascular injury.site of vascular injury.The pathologic opposite to hemostasis is The pathologic opposite to hemostasis is ThrombosisThrombosis

Both Hemostasis and Thrombosis depend on Both Hemostasis and Thrombosis depend on

three components:three components:(i) The Vascular Wall(i) The Vascular Wall

(ii) Platelets(ii) Platelets (iii) Coagulation Cascade(iii) Coagulation Cascade

INVOLVEMENT OF BLOOD VESSELS, PLATELETSINVOLVEMENT OF BLOOD VESSELS, PLATELETS AND BLOOD COAGULATION IN HAEMOSTASIS AND BLOOD COAGULATION IN HAEMOSTASIS

Mechanism of normal HaemostasisA: In normal uninjured blood vessels sub endothelial connective tissue, especially collagen and elastin, is not exposed to the circulating blood.B: In the first few seconds after injury, exposure of sub endothelial tissue attracts platelets, which adhere at the site of injury. Endothelial injury also activates Hageman factor (factor XII) , which in turn activates the intrinsic pathway of coagulation cascade. Release of tissue thromboplastin activates the extrinsic pathway.C: Haemostasis is achieved in minutes. Platelet degranulation stimulates further platelet aggregation . Fibrin formed by activation of the coagulation cascade combines with the mass of aggregated platelets to form the definitive haemostatic plug that seals the injury . Plasmin (fibrinolysin) formed by the activation of fibrinolytic pathway prevents excessive fibrin formation.D: During healing (hours to days), the thrombus retracts , and organization and fibrosis of the thrombus occurs. Reendotheliazation of the vessels is the final step

Primary Haemostasis: Endothelial injury exposes highly thrombogenic sub-endothelial extracellular matrix , facilitating platelet adherence ,activation and aggregation .The formation of the initial platelet plug is called primary haemostasis Secondary Haemostasis: Activated thrombin promotes the formation of an insoluble fibrin clot by cleaving fibrinogen ; thrombin also is a potent activator of additional platelets, which serve to reinforce the haemostatic plug . This sequence termed secondary haemostasis , results in the formation of a stable clot capable of preventing further haemorrhage

Primary And Secondary haemostatic Primary And Secondary haemostatic Haemostasis Haemostasis

ROLE OF ENDOTHELIUM IN HAEMOSTASISROLE OF ENDOTHELIUM IN HAEMOSTASIS

Intact endothelium cells serve primarily to inhibit platelet adherence and blood clotting. While injury or activation of endothelial cell result in procoagulant effect that augments local clot formationAnti platelet substances in Endothelium: (i) Prostacyclin (ii) Nitric Oxide (iii) Adenosine diphosphateAnticoagulant substances in Endothelium: (i) Antithrombin III (ii) Thrombomodulin (iii) Protein C (iv) Protein S

Endothelial cells and Coagulation- SummaryIntact normal endothelial cell help to maintain blood flow by inhibiting the activation of platelets and coagulation factors Endothelial cells stimulated by injury or inflammatory cytokines up-regulate expression of pro-cogulant factors (e.g., tissue factor) that promotes clotting and down regulate expression of anticoagulant factors Loss of endothelial integrity exposes sub-endothelial vWF and basement membrane collagen, stimulating platelet adhesion , platelet activation and clot formation

ROLE OF PLATELETS IN HAEMOSTASISROLE OF PLATELETS IN HAEMOSTASIS

Platelets Adhesion and Aggregation: Von Willebrand’s Factor functions as a bridge between sub endothelial collagen and the Gp Ib platelet receptor. Aggregation involves linking platelets via fibrinogen bridges bound to the platelet GpIIb- IIIa receptors


Platelets Adhesion

Platelet Activation

Shape Change

Release Reaction

Platelet Aggregation


n


(I)Platelets Adhesion Defects: -Von Willebrand Disease:Congenital Deficiency/Absence of von Willebrand Factor leads to inherited bleeding disorder- von Willebrand Disease-Beranrd Soulier Disease: Absence of Gp1b- Leads to inherited bleeding disorder Bernard Soulier Disease

(II) Platelets Aggregation Defects: Absence of GpIIb/IIIa- leads to inherited bleeding disorder- Glanzmann thormobasthenia

Platelet Aggregation


Platelet Adhesion, Activation and Aggregation- Summary Endothelial injury exposes the underlying basement membrane ECM; platelets adhere to the ECM primarily through binding of platelet GpIb receptor to vWFAdhesion leads to platelet activation , an event associated with secretion of platelet granule contents, including calcium ( a cofactor for several coagulation proteins) and ADP ( a mediator of further platelet activation) ; dramatic changes in shape and membrane composition; and activation of GpIIb/IIIa receptors The GpIIb/IIIa receptors on activated platelets form bridging cross links with fibrinogen ,leading to platelet aggregation Concomitant activation of thrombin promotes fibrin deposition, cementing the platelet plug in place

ROLE OF COAGULATION SYSTEM IN HAEMOSTASISROLE OF COAGULATION SYSTEM IN HAEMOSTASIS

INTRINSIC PATHWAY EXTRINSIC PATHWAYPrekalikrein Kallikrein VII VIIa

XIII XIIa

HMWK

XI XIa

IX IXaCa+

+

X Xa

VIIICa++ ; Pl

Prothrombin (II) Thrombin ( IIa )

Ca++ ; Pl

Fibrinogen(I) Fibrin (Ia)

XIII XIIIa

COMMONPATHWAY

Tissue Factor

Ca++ ; Pl

CAOGULATION SYSTEMCAOGULATION SYSTEM

Coagulation System comprises of several proteins which Coagulation System comprises of several proteins which are normally present in the blood in an inactive form. are normally present in the blood in an inactive form. When there is injury to the blood vessels, the When there is injury to the blood vessels, the coagulation system becomes activated and results in coagulation system becomes activated and results in the formation of a fibrin clot. Fibrin enmeshes the the formation of a fibrin clot. Fibrin enmeshes the platelet aggregate at the site of vascular injury and platelet aggregate at the site of vascular injury and converts the instable primary platelet plug to firm , converts the instable primary platelet plug to firm , definitive and stable haemostatic plug.definitive and stable haemostatic plug.In the coagulation cascade first there is initiation of In the coagulation cascade first there is initiation of Intrinsic and Extrinsic Pathways. Both of these then Intrinsic and Extrinsic Pathways. Both of these then converge onto the activation of Common Pathway. The converge onto the activation of Common Pathway. The Common Pathway then at the end leads to the formation Common Pathway then at the end leads to the formation of a stable haemostatic plugof a stable haemostatic plug

EXTRINSIC PATHWAY:EXTRINSIC PATHWAY: In the Extrinsic pathway, the factors released In the Extrinsic pathway, the factors released

from damaged tissues activate factor VII which in turn from damaged tissues activate factor VII which in turn in the presence of Tissue Factor, activates factor X. in the presence of Tissue Factor, activates factor X.

INTRNISIC PATHWAY:INTRNISIC PATHWAY: In this pathway initially factor XII is activated, when it In this pathway initially factor XII is activated, when it

comes in contact with sub endothelial elements of the comes in contact with sub endothelial elements of the blood vessels including collagen, High Molecular Weigh blood vessels including collagen, High Molecular Weigh Kininogen (HMWK) and Kalikrein . The activated factor Kininogen (HMWK) and Kalikrein . The activated factor XIIa then converts factor XI into its activated form XIa. XIIa then converts factor XI into its activated form XIa. The next step is the conversion of IX into IXa by factor The next step is the conversion of IX into IXa by factor XIa. Factor IXa in the presence of calcium, platelets and XIa. Factor IXa in the presence of calcium, platelets and factor VIII then converts X to Xa. factor VIII then converts X to Xa.

COMMON PATHWAY:COMMON PATHWAY: The common pathway is initiated by the conversion of The common pathway is initiated by the conversion of

factor X in into Xa. Activated Factor X (Xa) then converts factor X in into Xa. Activated Factor X (Xa) then converts Prothrombin (II) into Thrombin (IIa), and for this Factor V, Prothrombin (II) into Thrombin (IIa), and for this Factor V, Calcium ions and Platelets are required. Thrombin then Calcium ions and Platelets are required. Thrombin then converts fibrinogen (I) into fibrin monomers (IIa). The converts fibrinogen (I) into fibrin monomers (IIa). The fibrin monomers form cross linking meshwork under the fibrin monomers form cross linking meshwork under the influence of activated factor XIII . In this meshwork blood influence of activated factor XIII . In this meshwork blood cells get entangled to form a clot.cells get entangled to form a clot.

SEQUENCE OF HAEMOSTATIC EVENTS AT SEQUENCE OF HAEMOSTATIC EVENTS AT THE SITE OF VASCULAR INJURYTHE SITE OF VASCULAR INJURY

The general sequence of events in haemostasis at the The general sequence of events in haemostasis at the site of vascular injury are:site of vascular injury are:

First Phase : Blood Vessel Wall Response:First Phase : Blood Vessel Wall Response: After injury, After injury, there is a brief period of arteriolar there is a brief period of arteriolar VasoconstrictionVasoconstriction, , largely attributable to reflex neurogenic mechanisms largely attributable to reflex neurogenic mechanisms and augmented by the local secretion of factors such and augmented by the local secretion of factors such as endothelium derived vasoconstrictors. The effect is as endothelium derived vasoconstrictors. The effect is transient and bleeding will resume if platelets and transient and bleeding will resume if platelets and coagulation system are not activated.coagulation system are not activated.

Second Phase: Platelets Adhesion, Activation, Shape Second Phase: Platelets Adhesion, Activation, Shape change, Release Reaction and Aggregation:change, Release Reaction and Aggregation: Endothelial Endothelial injury exposes highly thrombogenic subendothelial injury exposes highly thrombogenic subendothelial matrix, which allows platelets to adhere and become matrix, which allows platelets to adhere and become activated that is, to undergo a shape change and activated that is, to undergo a shape change and release secretary granules. Within minutes the release secretary granules. Within minutes the secreted products have recruited additional platelets secreted products have recruited additional platelets to form a haemostatic plug to form a haemostatic plug ((Primary Haemostatic Plug)Primary Haemostatic Plug)

Third Phase: Activation of Intrinsic and Extrinsic Pathways Third Phase: Activation of Intrinsic and Extrinsic Pathways of Coagulation:of Coagulation: Tissue FactorTissue Factor a membrane bound procagulant factor, a membrane bound procagulant factor, synthesized by endothelium, is also exposed at the site synthesized by endothelium, is also exposed at the site of injury. It acts in conjunction with the secreted platelet of injury. It acts in conjunction with the secreted platelet factors to activate the coagulation cascade, culminating factors to activate the coagulation cascade, culminating in the activation ofin the activation of ThrombinThrombin . In turn, thrombin converts . In turn, thrombin converts circulating soluble fibrinogen to insoluble fibrin resulting circulating soluble fibrinogen to insoluble fibrin resulting in local fibrin deposition. Thrombin also induces further in local fibrin deposition. Thrombin also induces further platelet recruitment and granule release. Whole this platelet recruitment and granule release. Whole this sequence is called sequence is called Secondary Haemostasis. Secondary Haemostasis. Polymerized fibrin and platelets aggregates form a solid, Polymerized fibrin and platelets aggregates form a solid, permanent plugpermanent plug to prevent any further haemorrhage. to prevent any further haemorrhage.

Dissolution of ClotDissolution of Clot:: Once the clot is formed counter Once the clot is formed counter regulatory mechanisms, like regulatory mechanisms, like Fibrinolytic SystemFibrinolytic System are set are set into action to restrict the haemostatic plug to the site of into action to restrict the haemostatic plug to the site of injuryinjury

The involvement of blood vessels, platelets and blood coagulation in hemostasis

Screening Tests Screening Tests For For Blood Blood CoagulationCoagulation

Screening Tests of Blood Screening Tests of Blood Coagulation Coagulation

Screening tests provide an assessment of the ‘extrinsic’ and Screening tests provide an assessment of the ‘extrinsic’ and ‘intrinsic’ systems of blood coagulation and also the central ‘intrinsic’ systems of blood coagulation and also the central conversion of fibrinogen into fibrinconversion of fibrinogen into fibrin. .

Prothrombin Time (PT) :Prothrombin Time (PT) :Measures factors VII, X, V, Measures factors VII, X, V, prothrombin and fibrinogen. Tissue thrombopolastin (a brain prothrombin and fibrinogen. Tissue thrombopolastin (a brain extract) and calcium are added to citrated plasma. The normal extract) and calcium are added to citrated plasma. The normal time for clotting is 10-14 seconds. (measures extrinsic & time for clotting is 10-14 seconds. (measures extrinsic & common pathway).common pathway).

Activated Partial Thromboplastin Time (APTT):Activated Partial Thromboplastin Time (APTT):Measures Measures factors VIII, IX, XI and XII in addition to factor, X, V, factors VIII, IX, XI and XII in addition to factor, X, V, prothrombin and fibrinogen. Three substances, phospholipids, prothrombin and fibrinogen. Three substances, phospholipids, a surface activator (e.g. kaolin) and calcium- are added to a surface activator (e.g. kaolin) and calcium- are added to citrated plasma. The normal time for clotting is about 30-40 citrated plasma. The normal time for clotting is about 30-40 seconds. (Measures intrinsic & common pathway).seconds. (Measures intrinsic & common pathway).

Thrombin Time (TT): Thrombin Time (TT): is sensitive to a deficiency of is sensitive to a deficiency of fibrinogen. Diluted bovine thrombin is added to citrated fibrinogen. Diluted bovine thrombin is added to citrated plasma at a concentration giving a clotting time of 14-16 plasma at a concentration giving a clotting time of 14-16 seconds with normal subjectseconds with normal subject..

Screening Tests of Blood Coagulation-Screening Tests of Blood Coagulation-InterpretationInterpretation

Prothrombin Time: (PT)Prothrombin Time: (PT)Abnormalities indicated by prolongation: Deficiency or inhibition of one or Abnormalities indicated by prolongation: Deficiency or inhibition of one or

more of the following coagulation factors: VII, X, V, IV, fibrinogen. more of the following coagulation factors: VII, X, V, IV, fibrinogen. Most common cause of prolonged PT:Most common cause of prolonged PT:1.1. Liver disease Liver disease 3.3. D.I.CD.I.C2.2. Warfarin therapyWarfarin therapy 4.4. Heparin therapy Heparin therapy Activated Partial Thromboplastin Time (APTT)Activated Partial Thromboplastin Time (APTT)Abnormalities indicated by prolongation: Deficiency or inhibition of one orAbnormalities indicated by prolongation: Deficiency or inhibition of one ormore of the following coagulation factors: XII, XI, IX (Christmas disease ormore of the following coagulation factors: XII, XI, IX (Christmas disease orHaemophilia B) VIII (haemphilia A) X, V, II, fibrinogen. Haemophilia B) VIII (haemphilia A) X, V, II, fibrinogen. Most common causes of prolonged APTT: Most common causes of prolonged APTT: 1.1. Hemophilia Hemophilia 3.3. D.I.C. D.I.C. 2.2. Christmas disease Christmas disease 4.4. Heparin therapyHeparin therapyIII)Thrombin Time (TT)III)Thrombin Time (TT)Abnormalities indicated by prolongation: Deficiency or abnormality of Abnormalities indicated by prolongation: Deficiency or abnormality of

fibrinogen. Most common cause of prolonged TT: DIC, Heparin therapy. fibrinogen. Most common cause of prolonged TT: DIC, Heparin therapy.

Anticoagulant Therapy- Monitoring Anticoagulant Therapy- Monitoring

Oral Anticoagulant Parental Anticoagulant

-Prothrombin Time (PT)-INR

-Activated Partial Thromboplastin TIME (APTT)

Anti-clotting MechanismsAnti-clotting Mechanisms One of the major functions of homeostasis is to keep the blood in fluid One of the major functions of homeostasis is to keep the blood in fluid

state. When a clot forms repair mechanisms start which close the state. When a clot forms repair mechanisms start which close the gap in the blood vessel permanently and at the same time the clot gap in the blood vessel permanently and at the same time the clot which is formed is gradually broken down so that the circulation which is formed is gradually broken down so that the circulation may be re-established. Besides this, clotting should also be limited may be re-established. Besides this, clotting should also be limited to the required site. This is achieved by anticlotting mechanisms.to the required site. This is achieved by anticlotting mechanisms.

The substances which normally keep the blood in the fluid state are:The substances which normally keep the blood in the fluid state are: (i)(i) Anti thrombin IIIAnti thrombin III (ii)(ii) Protein CProtein C (iii) (iii) Protein SProtein S(iv) (iv) Tissue factor Pathway Inhibitor Tissue factor Pathway Inhibitor Once the clot is formed then its lysis takes places by Once the clot is formed then its lysis takes places by fibrinolytic fibrinolytic

systemsystem..

Coagulation Factors- Summary-Coagulation occurs via sequential enzymatic conversion of a cascade of circulating and locally synthesized proteins -Tissue factor elaborated at sites of injury is the most important initiator of the coagulation cascade in vivo-At the final stage of coagulation , thrombin converts fibrinogen into insoluble fibrin that contributes to formation of the definitive haemostatic plug-Coagulation normally is restricted to sites of vascular injury by: - Limiting enzymatic activation to phospholipid surfaces provided by activate platelets or endothelium - natural anticoagulants elaborated at sites of endothelial injury or during activation of coagulation cascade - Expression of thrombomodulin on normal endothelial cells, which binds thrombin and converts it into and anticoagulant - Activation of fibrinolytic system ( e.g., by association of tissue palsminogen activator with fibrin_

THROMBOSISTHROMBOSISThe formation of a clotted mass of blood within The formation of a clotted mass of blood within the non interrupted cardiovascular system is the non interrupted cardiovascular system is termed thrombosis,termed thrombosis, and the mass itself Thrombusand the mass itself ThrombusThrombosis is the formation of a solid mass from the constituents Thrombosis is the formation of a solid mass from the constituents of blood (platelets, fibrin and entrapped red and white cells) within of blood (platelets, fibrin and entrapped red and white cells) within the heart or vascular system in a living organism.the heart or vascular system in a living organism.Thrombosis Vs Blood ClotThrombosis Vs Blood Clot:: The The thrombosis is usually thrombosis is usually distinguished from distinguished from Blood ClotBlood Clot although the distinction is although the distinction is somewhat arbitrary and both invoke the coagulation cascade. somewhat arbitrary and both invoke the coagulation cascade. Clotting occurs in tissues when blood escapes from an injured Clotting occurs in tissues when blood escapes from an injured vessel (hematoma formation) . It also occurs in vessels after death vessel (hematoma formation) . It also occurs in vessels after death (postmortem clotting of blood) and in vitro ( in a test tube outside (postmortem clotting of blood) and in vitro ( in a test tube outside the body) . A thrombus is generally attached to the endothelium the body) . A thrombus is generally attached to the endothelium and is composed of layers of aggregated platelets and fibrin , and is composed of layers of aggregated platelets and fibrin , whereas a blood clot contains randomly oriented fibrin with whereas a blood clot contains randomly oriented fibrin with entrapped platelets and red cellsentrapped platelets and red cellsClearly the development of a blood clot is life saving when a large Clearly the development of a blood clot is life saving when a large vessel ruptures or severed. However, when a thrombus develops in vessel ruptures or severed. However, when a thrombus develops in the unruptured cardiovascular system, it may be life threateningthe unruptured cardiovascular system, it may be life threatening

SUMMARY OF THROMBOGENESISSUMMARY OF THROMBOGENESIS

1.Endothelial injury releases tissue factor and exposes sub endothelial connective tissues2. Platelet adherence and plasma clotting

system are triggered.3. Granule release and prostaglandin generation begins 4. Platelet aggregation induced by released ADP and vasoconstriction (5HT, Thromboxane)

result in primary (temporary) haemostatic

plug.5. Thrombin, thromboxanes, and endoperoxiedes promote releases reaction and irreversible aggregation. Platelet mass and trapped red

cells are enmeshed in fibrin to form definitive

(permanent) haemostatic plug.6. Endothelial plasmnogen activator and plasma antithrombin check rapid clotting

PATHOGENESIS OF THROMBOSISPATHOGENESIS OF THROMBOSISThree primary influences predispose to thrombus formation, the so called Three primary influences predispose to thrombus formation, the so called Virchow’s Triad:Virchow’s Triad:(i) Endothelial Injury(i) Endothelial Injury(ii) Stasis or turbulence of blood flow(ii) Stasis or turbulence of blood flow(iii) Blood Hypercoagubality (iii) Blood Hypercoagubality

Virchow’s Triad in Thrombosis:Endothelial injury is the single most important factor. Note that injury to endothelial cells can affect local blood flow and/or coagulability. Abnormal blood flow (stasis or turbulence) in turn, cause endothelial injury.The factors may act independently or may combine to cause thrombus formation

I.I.ENDOTHELIAL INJURYENDOTHELIAL INJURY

Endothelial damage stimulates both platelet adhesion Endothelial damage stimulates both platelet adhesion and activation of the coagulation cascade. Endothelial and activation of the coagulation cascade. Endothelial injury is frequently an initiating factor when thrombus injury is frequently an initiating factor when thrombus occurs in the arterial circulation. When thrombosis occurs in the arterial circulation. When thrombosis occurs in veins and in microcirculation then occurs in veins and in microcirculation then endothelial injury is less conspicuous.endothelial injury is less conspicuous.Common causes of endothelial injury are:Common causes of endothelial injury are:(i) In heart and arterial circulation the endothelial (i) In heart and arterial circulation the endothelial injury is seen in myocardial infarction and valvulitis. injury is seen in myocardial infarction and valvulitis.

(ii) Toxins from inflammatory processes(ii) Toxins from inflammatory processes(iii) local compression of vessels (e.g., during (iii) local compression of vessels (e.g., during operation)operation)

II.II.ALTERATIONS IN BLOOD FLOWALTERATIONS IN BLOOD FLOWThe two factors which contributes to formation of thrombosis The two factors which contributes to formation of thrombosis by altering the normal blood flow are:by altering the normal blood flow are:(i) (i) Turbulence in Blood Flow:Turbulence in Blood Flow: Turbulence means deviation of Turbulence means deviation of the blood stream which become distorted and abnormally hits the blood stream which become distorted and abnormally hits the vascular and cardiac lining ; thus not only deviating the the vascular and cardiac lining ; thus not only deviating the platelets towards the endothelium, but also lead to platelets towards the endothelium, but also lead to endothelial damage. It contributes to endothelial damage. It contributes to arterial and cardiac arterial and cardiac thrombosisthrombosis(ii) (ii) Stasis in Blood Flow:Stasis in Blood Flow: It is the major factor in the It is the major factor in the development of development of venous thrombosisvenous thrombosis The normal blood flow is The normal blood flow is LAMINARLAMINAR. In laminar blood flow the . In laminar blood flow the cellular elements flow centrally in the vessel lumen, separated cellular elements flow centrally in the vessel lumen, separated from endothelium by a slower moving clear zone of plasma. from endothelium by a slower moving clear zone of plasma. Stasis and turbulence then leads to thrombosis in following Stasis and turbulence then leads to thrombosis in following manner:manner:a. They disrupt laminar blood flow and bring platelets ina. They disrupt laminar blood flow and bring platelets in

contact with the endothelium.contact with the endothelium.b. They prevent dilution of activated clotting factors by freshb. They prevent dilution of activated clotting factors by fresh

flowing blood.flowing blood.c. They retard the inflow of clotting factor inhibitors andc. They retard the inflow of clotting factor inhibitors and

permit the build up of thrombi.permit the build up of thrombi.d. Promote endothelial cell activation, predisposing to locald. Promote endothelial cell activation, predisposing to local

thrombosis.thrombosis.

III.III.HYPERCOAGULABILITYHYPERCOAGULABILITYHypercoagulability contributes less frequently to thrmobotic states Hypercoagulability contributes less frequently to thrmobotic states but it is an important component in thrombosis. It is defined as but it is an important component in thrombosis. It is defined as any any alteration in the coagulation pathway that predisposes to thrombosisalteration in the coagulation pathway that predisposes to thrombosisIt can be divided into primary (genetic) and secondary (acquired) It can be divided into primary (genetic) and secondary (acquired) disordersdisorders

PRIMARY (Genetic) HYPERCOAGULABLE STATES:PRIMARY (Genetic) HYPERCOAGULABLE STATES: Mutations in Factor V (Factor V Leiden)Mutations in Factor V (Factor V Leiden) Antithrombin III deficiencyAntithrombin III deficiency Protein C or S deficiencyProtein C or S deficiency HomocystenemiaHomocystenemia Allelic variation in Prothrombin levelAllelic variation in Prothrombin level

SECONDARY (Acquired) HYPERCOAGULABLE STATES:SECONDARY (Acquired) HYPERCOAGULABLE STATES: Prolonged bed rest or immobilizationProlonged bed rest or immobilization Myocardial infarctionMyocardial infarction Tissue damage( Surgery, fracture, burn)Tissue damage( Surgery, fracture, burn) CancerCancer Antiphospholipid Antibody syndrome (Lupus Anticoagulant)Antiphospholipid Antibody syndrome (Lupus Anticoagulant) Oral ContraceptivesOral Contraceptives SmokingSmoking Heparin Induced Thrombocytpenia with Thrombosis (HITT) Heparin Induced Thrombocytpenia with Thrombosis (HITT)

9898

Inherited Inherited TThrombophiliahrombophilia

- - Factor V Leiden mutation Factor V Leiden mutation (Resistance to activated protein C)(Resistance to activated protein C)

- Prothrombin gene mutation - Prothrombin gene mutation ((Hyperprothrombinemia -Hyperprothrombinemia - prothrombin variant prothrombin variant

G20210AG20210A))

- Protein S deficiency- Protein S deficiency - Protein C deficiency- Protein C deficiency - Antithrombin (AT) deficiency- Antithrombin (AT) deficiency - Dysfibrinogenemia - Dysfibrinogenemia - Hyperhomocysteinemia- Hyperhomocysteinemia

9999

Acquired Acquired Hypercoagulable Hypercoagulable DDisordersisorders

MalignancyMalignancy Presence of a central Presence of a central

venous cathetervenous catheter Surgery, especially Surgery, especially

orthopedicorthopedic TraumaTrauma ImmobilizationImmobilization Congestive failureCongestive failure PregnancyPregnancy Oral contraceptivesOral contraceptives Hormone replacement Hormone replacement

therapytherapy

Antiphospholipid antibody Antiphospholipid antibody syndromesyndrome

Myeloproliferative Myeloproliferative disorders disorders

Polycythemia vera Polycythemia vera Essential thrombocythemia Essential thrombocythemia Paroxysmal nocturnal Paroxysmal nocturnal

hemoglobinuriahemoglobinuria Tamoxifen, Thalidomide, Tamoxifen, Thalidomide,

LenalidomideLenalidomide Inflammatory bowel Inflammatory bowel

diseasedisease Nephrotic syndromeNephrotic syndrome

Mutations in Factor V Laiden:Mutations in Factor V Laiden: There is a substutitution for the normal argenine There is a substutitution for the normal argenine

residue at position 506 of factor V. residue at position 506 of factor V. Due to this Due to this mutation factor V cannot be inactivated by mutation factor V cannot be inactivated by cleavage at the usual arginine residue and cleavage at the usual arginine residue and is therefore resistant to anticoagulant is therefore resistant to anticoagulant effect of activated protein C.effect of activated protein C.

The patients with this mutation usually present with The patients with this mutation usually present with recurrent thrombosis and recurrent abortionsrecurrent thrombosis and recurrent abortions

Primary (Genetic) Hypercoagulable States Primary (Genetic) Hypercoagulable States

Antithrombin III, Protein C and S Antithrombin III, Protein C and S DeficiencyDeficiency::

Patients with this deficiency usually Patients with this deficiency usually present with deep venous thrombosis and present with deep venous thrombosis and recurrent thromboembolism in adolescence recurrent thromboembolism in adolescence or early adult life.or early adult life.


103103

Prothrombin Gene Mutation Prothrombin Gene Mutation A single –nucleotide substitution (G to A) in the 3 ‘ –A single –nucleotide substitution (G to A) in the 3 ‘ –

untranslated region of the prothrombin gene is a fairly untranslated region of the prothrombin gene is a fairly common allelecommon allele

This variant results in increased prothrombin transcription This variant results in increased prothrombin transcription and is associated with a nearly three fold increased risk for and is associated with a nearly three fold increased risk for venous thormboses venous thormboses

Prothrombin (factor II) is the precursor of thrombin, the end-Prothrombin (factor II) is the precursor of thrombin, the end-product of the coagulation cascadeproduct of the coagulation cascade

Heterozygous carriers have 30Heterozygous carriers have 30%% higher plasma prothrombin higher plasma prothrombin levels than normalslevels than normals

Heterozygous carriers have Heterozygous carriers have an increased risk of deep vein and an increased risk of deep vein and cerebral vein thrombosiscerebral vein thrombosis


104104

Hereditary thrombophiliaHereditary thrombophilia

Characteristics:Characteristics:

- thrombosis without any predisposing conditionthrombosis without any predisposing condition

- thrombosis at young agethrombosis at young age

- thrombosis in unusual sites thrombosis in unusual sites (upper extremities, mesenteric vessels, hepatic or (upper extremities, mesenteric vessels, hepatic or

portal veins)portal veins)

- family history of thrombosisfamily history of thrombosis Neonatal purpura fulminans (homozygous PC or PS Neonatal purpura fulminans (homozygous PC or PS

deficiency)deficiency)

Antiphospohlipid Antibody SyndromeAntiphospohlipid Antibody Syndrome::

Anti-phospohlipid antibodies are directed Anti-phospohlipid antibodies are directed against epitopes on the surface of plasma against epitopes on the surface of plasma proteins. These antibodies produce hyper-proteins. These antibodies produce hyper-coagulable state by direct platelet coagulable state by direct platelet activation, inhibition of prostacyclin, and activation, inhibition of prostacyclin, and interference in Protein C synthesis. The interference in Protein C synthesis. The patients with these antibodies usually patients with these antibodies usually present with recurrent thrombosis and present with recurrent thrombosis and repeated miscarriagesrepeated miscarriages

Acquired (Secondary ) Hypercoagulable Acquired (Secondary ) Hypercoagulable States States

Oral Contraceptives Use and Pregnancy:Oral Contraceptives Use and Pregnancy: In these conditions there is increased In these conditions there is increased

hepatic synthesis of many coagulant hepatic synthesis of many coagulant factors and reduced synthesis of factors and reduced synthesis of antithronbin IIIantithronbin III


Heparin Induced Thrombocytopenia with Heparin Induced Thrombocytopenia with Thrombosis (HITT)Thrombosis (HITT)

Occurs in 5% patients treated with Occurs in 5% patients treated with unfracftionated heparin (for therapeutic unfracftionated heparin (for therapeutic anticoagulation)anticoagulation)

Antibodies are formed against heprin and platelet Antibodies are formed against heprin and platelet membrane protein (platelet factor 4)membrane protein (platelet factor 4)

These antibodies may also bind similar These antibodies may also bind similar complexes present on platelet and endothelial complexes present on platelet and endothelial surfaces , resulting in platelet activation, surfaces , resulting in platelet activation, aggregation and consumption (hence aggregation and consumption (hence Thrombocytopenia), as well as causing Thrombocytopenia), as well as causing endothelial injuryendothelial injury

Overall result is a Overall result is a pro-thrombotic state, pro-thrombotic state, even in the face of heparin even in the face of heparin administration and low platelet count administration and low platelet count


TYPES OF THROMBITYPES OF THROMBI

A thrombus is easily recognized as a solid mass in the lumen A thrombus is easily recognized as a solid mass in the lumen of a blood vessel that is often attached to the vessel wall.of a blood vessel that is often attached to the vessel wall.

PALE THORMBIPALE THORMBI RED THROMBIRED THROMBI

Thrombi in the fast Thrombi in the fast flowing flowing arterial arterial circulationcirculation are are composed composed predominantly of fibrin predominantly of fibrin and platelets, with few and platelets, with few entrapped entrapped erythrocytes – hence erythrocytes – hence the term Pale the term Pale Thrombus Thrombus

Typically occurs in Typically occurs in venous circulationvenous circulation, , where the slower where the slower blood flow blood flow encourages encourages entrapment of red entrapment of red cells. They are cells. They are composed of composed of platelets, fibrin and platelets, fibrin and large numbers of large numbers of erythrocytes trapped erythrocytes trapped in the fibrin mesh.in the fibrin mesh.

SITES OF THROMBOSISSITES OF THROMBOSIS I. I. ARTERIAL THROMBOSIS:ARTERIAL THROMBOSIS: Arterial thrombosis is common and typically occurs after Arterial thrombosis is common and typically occurs after endothelial damage and local turbulence has been caused by endothelial damage and local turbulence has been caused by atheroscleorsis.Large and medium sized arteries such as the atheroscleorsis.Large and medium sized arteries such as the aorta, carotid arteries, arteries of circle of Willis, coronary aorta, carotid arteries, arteries of circle of Willis, coronary arteries, and arteries of the intestine and limbs are mainly arteries, and arteries of the intestine and limbs are mainly affectedaffected

Mural Thrombi:Mural Thrombi: When arterial thrombi arise in heart chambers or When arterial thrombi arise in heart chambers or in aortic lumen, they are usually adherent to the wall of in aortic lumen, they are usually adherent to the wall of underlying structure and are termed Mural Thrombi.underlying structure and are termed Mural Thrombi.

Lines of Zahn: When arterial thrombus is formed in the heart or aorta, thrombi may have grossly (and microscopically) apparent laminations called lines of Zahn; these are produced by alternating pale layers of platelets admixed with some fibrin and darker layers containing more red bloodcells

II.II.VENOUS THROMBOSISVENOUS THROMBOSIS1. 1. PHLEBOTHROMBOSISPHLEBOTHROMBOSIS:: It denotes venous thrombosis occurring in It denotes venous thrombosis occurring in

the absence of obvious inflammation. Phlebothrombosis occurs the absence of obvious inflammation. Phlebothrombosis occurs mostlymostly in deep veins of the leg in deep veins of the leg ((Deep Venous Thrombosis ; DVT)Deep Venous Thrombosis ; DVT)

Deep venous thrombosis is common and has important medical implications because the large thrombi that form in these veins are often easily detached. They travel in the circulation to the heart and lung and lodge in the pulmonary arteries (Pulmonary Embolism)

Venous Thrombus in Femoral Vein: Femoral vein opened to reveal a thrombus

2. 2. THROMBOPHELIBITISTHROMBOPHELIBITIS:: It denotes venous thrombosis It denotes venous thrombosis occurring secondary to acute inflammation . occurring secondary to acute inflammation . Thrombophelibitis is a common phenomenon in Thrombophelibitis is a common phenomenon in infected wounds or ulcers and characteristically infected wounds or ulcers and characteristically involves the superficial veins and the extremities . involves the superficial veins and the extremities . The effected vein is firm and cord like and shows The effected vein is firm and cord like and shows signs of acute inflammation (pain, redness, warmth, signs of acute inflammation (pain, redness, warmth, swelling). This type of thrombus is firmly attached to swelling). This type of thrombus is firmly attached to the vessel wall and they rarely embolize. the vessel wall and they rarely embolize.

III. III. CARDIAC THROMBOSISCARDIAC THROMBOSIS

In Different circumstances Thrombi are formed in In Different circumstances Thrombi are formed in different locations inside the heart:different locations inside the heart:

1.1. Thrombi may occur in ventricles after Myocardial Thrombi may occur in ventricles after Myocardial InfarctionInfarction

2.2. Thrombi may occur in Atria in Atrial Fibrillation Thrombi may occur in Atria in Atrial Fibrillation

3.3. Thrombi may be formed in Heart Valves in Thrombi may be formed in Heart Valves in Rheumatic Endocarditic or in Infective EndocarditicRheumatic Endocarditic or in Infective Endocarditic

FATE OF THROMBOSISFATE OF THROMBOSIS

If a patient survives the immediate effects of a thrombotic If a patient survives the immediate effects of a thrombotic vascular obstruction, thrombi undergo some combination of vascular obstruction, thrombi undergo some combination of the following five events in the ensuing days or weeks the following five events in the ensuing days or weeks

Thrombus- FateThrombus- FatePropagationPropagation

EmbolizationEmbolization

DissolutionDissolution

Organization and Recanalization Organization and Recanalization

1. Lysis of the thrombosis and complete resolution of normal structure usually can occur only when the thrombus is relatively small and is dependent upon the activity of Fibrinolytic System

2. Organization : The thrombus may be replaced by scar tissue which contracts and obliterates the lumen; the blood bypasses the occluded vessel through collateral circulation

3. Dystrophic Calcification

4. Recanalization: Occasionally some of the capillaries dilate and allow the passage of blood through the thrombus or the fibrosed thrombus shrinks from the vascular wall leaving a space which gets lined by endothelium.

5.Propagation: The thrombus may accumulate more platelets and fibrin and eventually leads to vessel obstruction

5. Emoblization: Emboli can result from fragmentation of the thrombus and can result in infarction at a distant site

THROMBUSTHROMBUS CLOTCLOTOccurs inside Occurs inside cardiovascular systemcardiovascular system

Occurs inside or outside Occurs inside or outside the cardiovascular systemthe cardiovascular system

Occurs during life in Occurs during life in circulating bloodcirculating blood

Occurs during life or after Occurs during life or after death in stagnant blooddeath in stagnant blood

Contains platelets ( e.g., Contains platelets ( e.g., lines of Zhan)lines of Zhan)

No plateletsNo platelets

FirmFirm SoftSoft

Firmly adherent to the Firmly adherent to the cardiovascular sitecardiovascular site

Loosely adherentLoosely adherent

Pale, red or mixedPale, red or mixed Red or yellowRed or yellow

Thrombosis – Summary A thrombus is a solid mass of blood constituents formed within the vascular system in life.Predisposing factors (Virchow’s triad) :abnormalities of the vessel wall; abnormalities of blood flow; abnormalities of the blood constituents.Arterial thrombosis is most commonly superimposed on athermoaVenous thrombosis is most commonly due to stasisClinical consequences include: arterial thrombosis (tissue infarction distally); venous thrombosis (oedema, due to impaired venous drainage); and embolism

EMBOLISMEMBOLISM““An Embolus is a detached intravascular solid, An Embolus is a detached intravascular solid, liquid or gaseous mass that is carried by the liquid or gaseous mass that is carried by the blood to a site distant from its point of origin”blood to a site distant from its point of origin”

Virtually 99% of the emboli represent some part of a Virtually 99% of the emboli represent some part of a dislodged thrombus, hence the commonly used term dislodged thrombus, hence the commonly used term ThromboembolismThromboembolism..

Inevitably, emboli lodge in vessels too small to permit Inevitably, emboli lodge in vessels too small to permit further passage, resulting in partial or complete vascular further passage, resulting in partial or complete vascular occlusion. The potential consequences of such occlusion. The potential consequences of such thromboembolic events is the ischemic necrosis of distal thromboembolic events is the ischemic necrosis of distal tissue known as tissue known as InfarctionInfarction

ThrombosisThrombosis

EmbolismEmbolism

Emboli lodge in vessels too smallEmboli lodge in vessels too small to permit further passageto permit further passage

Partial or complete vascular occlusionPartial or complete vascular occlusion

Infarction Infarction

TYPES OF EMBOLITYPES OF EMBOLI

1.1. Thromboembolism Thromboembolism (i) Pulmonary Thromboembolism(i) Pulmonary Thromboembolism (ii) Systemic Thromboembolism(ii) Systemic Thromboembolism

2.2. Fat Embolism Fat Embolism

33. Air Embolism. Air Embolism

4.4. Amniotic Fluid Embolism Amniotic Fluid Embolism

5.5. Nitrogen Gas Embolism (Decompression Sickness) Nitrogen Gas Embolism (Decompression Sickness)

I. I. PULMONARY THROMBOEMBOLISMPULMONARY THROMBOEMBOLISM

Cause and Incidence:Cause and Incidence: The most serious form of The most serious form of thrombembolism is pulmonary embolism, which may thrombembolism is pulmonary embolism, which may cause sudden death. It has an incidence of 20 to 25 cause sudden death. It has an incidence of 20 to 25 per 100,000 hospitalized patientsper 100,000 hospitalized patients

Over 90% of Pulmonary Emboli originate in the deep Over 90% of Pulmonary Emboli originate in the deep veins of the leg (phelebothrombosis)veins of the leg (phelebothrombosis).. More rarely, More rarely, thrombi in pelvic venous plexus are the source.thrombi in pelvic venous plexus are the source.

Pulmonary embolism is common in the following Pulmonary embolism is common in the following conditions that predispose to the development of conditions that predispose to the development of phlebothrombosis:phlebothrombosis:(i)(i) Immediate post operative period Immediate post operative period(ii)(ii) Immediate post partum period Immediate post partum period(iii)(iii) Lengthy immobilization in bed Lengthy immobilization in bed(iv)(iv) Cardiac Failure Cardiac Failure(v)(v) use of Oral Contraceptives use of Oral Contraceptives

CLINICAL EFFECTS OF PULMONARY EMBOLISMCLINICAL EFFECTS OF PULMONARY EMBOLISMThe size of the embolus is the factor most influencing The size of the embolus is the factor most influencing the clinical effects of pulmonary embolismthe clinical effects of pulmonary embolism

1. 1. Massive Emboli:Massive Emboli: Large emboli (several centimeter Large emboli (several centimeter long) may long) may lodge in the outflow tract of the right lodge in the outflow tract of the right ventricle or in the main pulmonary artery,ventricle or in the main pulmonary artery, where they where they cause circulatory obstruction and cause circulatory obstruction and Sudden DeathSudden Death . .

2. 2. Medium Sized Emboli:Medium Sized Emboli: obstruction of medium sizedobstruction of medium sized arteriesarteries may cause may cause Pulmonary InfarctPulmonary Infarct

3. 3. Small Emboli:Small Emboli: Small emboli lodge in minor branches Small emboli lodge in minor branches of pulmonary artery with no immediate effects. In of pulmonary artery with no immediate effects. In many instances, the emboli either fragment soon many instances, the emboli either fragment soon after lodgment of dissolve during fibrinolysis, in after lodgment of dissolve during fibrinolysis, in which case clinical effects are minimal. If numerous which case clinical effects are minimal. If numerous small emboli occur over a long period, however, the small emboli occur over a long period, however, the pulmonary microcirculation may be so severely pulmonary microcirculation may be so severely compromised that compromised that Pulmonary Hypertension resultsPulmonary Hypertension results

II.II.SYSTEMIC THROMBOEMBOLISMSYSTEMIC THROMBOEMBOLISM

Causes:Causes:Thromboembolism occurs in systemic arteries Thromboembolism occurs in systemic arteries when the detached thrombus originates in the left when the detached thrombus originates in the left side of the heart or a large artery.side of the heart or a large artery.Systemic arterial thromboembolism commonly occurs:Systemic arterial thromboembolism commonly occurs:

1.1. In patients who have infective endocarditic with In patients who have infective endocarditic with vegetations on the mitral and aortic valves.vegetations on the mitral and aortic valves.

2.2. In patients who have suffered myocardial infarction in In patients who have suffered myocardial infarction in which mural thrombus has occurred.which mural thrombus has occurred.

3.3. In patients with mitral stenosis and arterial In patients with mitral stenosis and arterial thrombosis.thrombosis.

4.4. In patients with aortic and ventricular aneurysms, In patients with aortic and ventricular aneurysms, which contain mural thrombi which contain mural thrombi

Clinical Effects of Systemic Thromboembolism:Clinical Effects of Systemic Thromboembolism:In contrast to venous emboli,which tend to In contrast to venous emboli,which tend to

lodge primarily in one vascular bed (the lung), lodge primarily in one vascular bed (the lung), arterial emboli can travel to a wide variety of sites . arterial emboli can travel to a wide variety of sites . The site of arrest depends on the point of origin of The site of arrest depends on the point of origin of the thromboembolism and the volume of blood flow the thromboembolism and the volume of blood flow through the down stream tissues. The major sites for through the down stream tissues. The major sites for arterial embolization are the lower extremities (75%) arterial embolization are the lower extremities (75%) and the brain (10%)., with intestines, kidneys, and the brain (10%)., with intestines, kidneys, spleen and upper extremities involved to a lesser spleen and upper extremities involved to a lesser extent.extent.

The consequences of systemic emboli depend The consequences of systemic emboli depend on any collateral vascular supply in the affected on any collateral vascular supply in the affected tissue, the tissue vulnerability to ischemia, and the tissue, the tissue vulnerability to ischemia, and the caliber of the vessel occluded. In general, however, caliber of the vessel occluded. In general, however, arterial emboli cause infarction of tissues in the arterial emboli cause infarction of tissues in the distributution of the obstructed vessel.distributution of the obstructed vessel.

III.III.FAT EMBOLISMFAT EMBOLISMCauses:Causes: Fat Embolism occurs when globules of fat enter Fat Embolism occurs when globules of fat enter

the bloodstream, typically the bloodstream, typically after fractures of large after fractures of large bones(eg, femur) have exposed the fatty bone marrowbones(eg, femur) have exposed the fatty bone marrow.. Although fat globules can be found in the circulation in Although fat globules can be found in the circulation in as many as 90% of patients who have sustained serious as many as 90% of patients who have sustained serious fractures, few patients demonstrate clinically significant fractures, few patients demonstrate clinically significant signs of fat embolism.signs of fat embolism.

Clinical Effects of Fat Embolism:Clinical Effects of Fat Embolism: Fat embolism syndrome Fat embolism syndrome typically begins 1 to 3 days after injury, with sudden typically begins 1 to 3 days after injury, with sudden onset of tachypnea, dyspnea and tachycardia . Besides onset of tachypnea, dyspnea and tachycardia . Besides pulmonary insufficiency, the syndrome is characterized pulmonary insufficiency, the syndrome is characterized by neurological symptoms,including irritability and by neurological symptoms,including irritability and restlessness, which can prgress to delirium or coma. A restlessness, which can prgress to delirium or coma. A diffuse petechial rash in non dependent areas occurring diffuse petechial rash in non dependent areas occurring in the absence of thrombocytopenia is seen in 20 to 30% in the absence of thrombocytopenia is seen in 20 to 30% of cases and is useful in establishing a diagnosis.of cases and is useful in establishing a diagnosis.The typical clinical features of fat embolism include a The typical clinical features of fat embolism include a Haemorrhagic skin rash, dyspnea, tachycardia, Haemorrhagic skin rash, dyspnea, tachycardia, tachypnea, irritability and restlessness.tachypnea, irritability and restlessness.

IV.IV.AIR EMBOLISMAIR EMBOLISM

CAUSESCAUSES:: a. a. Surgery of or Trauma to internal Jugular vein:Surgery of or Trauma to internal Jugular vein: In injuries In injuries

to the internal jugular vein, the negative pressure in the to the internal jugular vein, the negative pressure in the thorax tends to suck air into the jugular vein. This thorax tends to suck air into the jugular vein. This phenomenon does not occur in injuries to other systemic phenomenon does not occur in injuries to other systemic veins because they are separated by valves from the veins because they are separated by valves from the negative pressure in the chestnegative pressure in the chest

b. b. Child birth or Abortion:Child birth or Abortion: Air embolism may occur during Air embolism may occur during childbirth or abortion, when air may be forced into childbirth or abortion, when air may be forced into ruptured placental venous sinuses by forceful ruptured placental venous sinuses by forceful contractions of uterus.contractions of uterus.

c. c. Blood Transfusion:Blood Transfusion: Air embolism during blood transfusion Air embolism during blood transfusion occurs only if positive pressure is used to transfuse the occurs only if positive pressure is used to transfuse the blood and only if the transfusion is not discontinued at blood and only if the transfusion is not discontinued at its completion.its completion.

Clinical Effects of Air Embolism:Clinical Effects of Air Embolism: When air enters the blood When air enters the blood stream, it passes into the right ventricle, creating a stream, it passes into the right ventricle, creating a frothy mixture that effectively obstructs the circulation frothy mixture that effectively obstructs the circulation and causes death.and causes death.

V.V.NITROGEN GAS EMBOLISMNITROGEN GAS EMBOLISM (DECOMPRESSION SICKNESS)(DECOMPRESSION SICKNESS)

CAUSE:CAUSE: Decompression sickness is a form of embolism that Decompression sickness is a form of embolism that occurs in Caisson workers and undersea divers if they occurs in Caisson workers and undersea divers if they ascend too rapidly after being submerged for long ascend too rapidly after being submerged for long periods. This disorder is also called the periods. This disorder is also called the BendsBends or or Caisson Caisson DiseaseDisease..

(Caissons are high pressure underwater chambers used (Caissons are high pressure underwater chambers used for deep water construction work)for deep water construction work)

When air is breathed under high underwater pressure, When air is breathed under high underwater pressure, an increased volume of air, mainly oxygen and an increased volume of air, mainly oxygen and nitrogen, goes into solution in the blood and nitrogen, goes into solution in the blood and equilibrates with the tissues . If decompression to sea equilibrates with the tissues . If decompression to sea level is too rapid, the gases that equilibrated in the level is too rapid, the gases that equilibrated in the tissues come out of solution. Oxygen is rapidly absorbed tissues come out of solution. Oxygen is rapidly absorbed into the blood, but nitrogen gas coming out of solution into the blood, but nitrogen gas coming out of solution can not be absorbed rapidly enough and forms bubbles can not be absorbed rapidly enough and forms bubbles in the tissues and blood stream that acts as emboli. in the tissues and blood stream that acts as emboli.

Clinical Effects of Nitrogen Gas EmbolismClinical Effects of Nitrogen Gas Embolism

Platelets adhere to nitrogen gas bubbles in the Platelets adhere to nitrogen gas bubbles in the circulation an activate coagulation cascade. The circulation an activate coagulation cascade. The resulting disseminated intravascular coagulation resulting disseminated intravascular coagulation aggravates the ischemic state caused by impaction aggravates the ischemic state caused by impaction of gas bubbles in capillaries. Involvement of brain in of gas bubbles in capillaries. Involvement of brain in severe cases may cause extensive necrosis and severe cases may cause extensive necrosis and death. In less severe cases, nerve and muscle death. In less severe cases, nerve and muscle involvement causes involvement causes severe muscle contractions with severe muscle contractions with intense pain (the bends)intense pain (the bends). Nitrogen gas emboli in . Nitrogen gas emboli in lungs cause lungs cause Severe difficulty in breathing (the Severe difficulty in breathing (the chokes)chokes) that is associated with alveolar edema and that is associated with alveolar edema and haemorrhagehaemorrhage

VI. VI. AMNIOTIC FLUID EMBOLISMAMNIOTIC FLUID EMBOLISM

Cause:Cause: The underlying cause is infusion of amniotic The underlying cause is infusion of amniotic fluid into the maternal circulation via a tear in the fluid into the maternal circulation via a tear in the placental membranes and rupture of uterine veins.placental membranes and rupture of uterine veins.

Clinical Effects:Clinical Effects: Amniotic Fluid Embolism is a grave but Amniotic Fluid Embolism is a grave but uncommon complication of labour and the immediate uncommon complication of labour and the immediate postpartum period. It has a mortality of over postpartum period. It has a mortality of over 80%.With the vastly increased pressures in the 80%.With the vastly increased pressures in the uterus during labour, amniotic fluid may be forced uterus during labour, amniotic fluid may be forced into the maternal uterine veins. These amniotic fluid into the maternal uterine veins. These amniotic fluid emboli travel in the circulation and lodge in the emboli travel in the circulation and lodge in the lungs, causing respiratory distress. The onset is lungs, causing respiratory distress. The onset is characterized by sudden severe dyspnea, cyanosis, characterized by sudden severe dyspnea, cyanosis, and hypotensive shock, followed by seizures and and hypotensive shock, followed by seizures and coma. coma.

AMNIOTIC FLUID EMBOLISM

Two small pulmonary arterioles are packed with laminated swirls of foetal squamous cells. There is marked edema and congestion and elsewhere in the lung tissue there are small orgainzing thrombi , consistent with disseminated intravascular coagulation.

SummarySummary

An Embolus is a mass of material in the An Embolus is a mass of material in the vascular system able to become lodged vascular system able to become lodged within a vessel and block its lumen. within a vessel and block its lumen.

Most Emboli are derived from Thrombi.Most Emboli are derived from Thrombi.

Other types of embolic material include: Other types of embolic material include: Atheromatous plaque material, Vegetations Atheromatous plaque material, Vegetations on heart valves(infective endocarditic), on heart valves(infective endocarditic), Amniotic Fluid , Gas and Fat.Amniotic Fluid , Gas and Fat.

Most common occurrence is Pulmonary Most common occurrence is Pulmonary Embolism from deep leg vein thrombosisEmbolism from deep leg vein thrombosis

INFARCTIONINFARCTIONDefinition: Definition: An Infarct is an area of ischemic An Infarct is an area of ischemic

necrosis caused by occlusion of either the necrosis caused by occlusion of either the arterial supply or venous drainage in a arterial supply or venous drainage in a particular tissueparticular tissueNearly 99% of all infarcts result from thrombosis or Nearly 99% of all infarcts result from thrombosis or embolic events and almost all result from arterial embolic events and almost all result from arterial occlusion. More rarely, obstruction of venous drainage occlusion. More rarely, obstruction of venous drainage results in infarction.results in infarction.Tissue infarction is a common and extremely Tissue infarction is a common and extremely important cause of clinical illness. Important clinical important cause of clinical illness. Important clinical entities which are attributable to infarction are:entities which are attributable to infarction are:

1.1. Myocardial Infarction Myocardial Infarction2.2. Cerebral Infarction Cerebral Infarction3.3. Pulmonary Infarction Pulmonary Infarction4.4. Intestinal Infarction Intestinal Infarction5.5. Ischemic Necrosis of Extremities (Gangrene) Ischemic Necrosis of Extremities (Gangrene)

CLASSIFICATION OF TYPES OF INFARCTCLASSIFICATION OF TYPES OF INFARCT

The appearance of infarcts varies with the site .The appearance of infarcts varies with the site .Various classification schemes are usedVarious classification schemes are used

A.A. PALE Versus RED INFARCT PALE Versus RED INFARCT

B.B. SOLID Versus LIQUIFIED INFARCT SOLID Versus LIQUIFIED INFARCT

C.C. STERILE Versus SEPTIC INFARCT STERILE Versus SEPTIC INFARCT

A. A. PALE Versus RED INFARCTPALE Versus RED INFARCTPale Infarct:Pale Infarct: Occur as a result of arterial obstruction in Occur as a result of arterial obstruction in

solid organs such as heart, kidney, spleen and brain. solid organs such as heart, kidney, spleen and brain. These organs lack significant collateral circulation, and These organs lack significant collateral circulation, and the solidity of the tissue limits the amount of the solidity of the tissue limits the amount of haemorrhage that can seep into the area of ischemic haemorrhage that can seep into the area of ischemic necrosis from adjoining capillary beds necrosis from adjoining capillary beds

Red or Haemorrhagic Infarct:Red or Haemorrhagic Infarct: (i) In tissues that have a double blood supply , e.g., lung, (i) In tissues that have a double blood supply , e.g., lung,

intestines and liver permitting some continued flow intestines and liver permitting some continued flow into the area although the amount is not sufficient to into the area although the amount is not sufficient to prevent infarction . The infarct is red because of prevent infarction . The infarct is red because of extravasation of blood in the infarcted area from extravasation of blood in the infarcted area from necrotic small vessels.necrotic small vessels.

(ii) With venous occlusion (such as in ovarian torsion)(ii) With venous occlusion (such as in ovarian torsion)(iii) In loose tissues (such as lung), which allow blood to (iii) In loose tissues (such as lung), which allow blood to

collect in the infarcted zone.collect in the infarcted zone.(iv) In tissues that were previously congested because of (iv) In tissues that were previously congested because of

sluggish venous outflowsluggish venous outflow(v) When flow is reestablished to a site of previous (v) When flow is reestablished to a site of previous

arterial occlusion arterial occlusion

B . B . SOLID Versus LIQUEFIED INFARCTSOLID Versus LIQUEFIED INFARCTIn all tissues other than brain, infarction usually In all tissues other than brain, infarction usually produces coagulative necrosis of cells, leading to solid produces coagulative necrosis of cells, leading to solid infarct. In brain, on the other hand, liquefactive infarct. In brain, on the other hand, liquefactive necrosis of cells leads to the formation of a fluid mass necrosis of cells leads to the formation of a fluid mass in the area of infarction. The end result is a cystic in the area of infarction. The end result is a cystic cavitycavity

C. C. STERILE Versus SEPTIC INFARCTSTERILE Versus SEPTIC INFARCTMost infarcts are sterile. Septic infarcts are Most infarcts are sterile. Septic infarcts are characterized by secondary bacterial infection of the characterized by secondary bacterial infection of the necrotic tissue. Septic infarcts are characterized by necrotic tissue. Septic infarcts are characterized by acute inflammation that frequently converts the acute inflammation that frequently converts the infarcts to an abscess. Secondary bacterial infection of infarcts to an abscess. Secondary bacterial infection of an infarct may also result in gangrene (e.g., intestine).an infarct may also result in gangrene (e.g., intestine).

Septic infarcts occur:Septic infarcts occur:1. Due to presence of microorganisms, as in lesions of 1. Due to presence of microorganisms, as in lesions of

infective endocarditisinfective endocarditis2. When infarction occurs in a tissue that normally 2. When infarction occurs in a tissue that normally

contain bacteria , e.g., intestinecontain bacteria , e.g., intestine

Pale infarct : Spleen

Infarct brain

MORPHOLOGY OF INFARCTSMORPHOLOGY OF INFARCTS●●Infarction occurs in tissue supplied by an Infarction occurs in tissue supplied by an artery that, when occluded leaves an artery that, when occluded leaves an insufficient collateral blood supply. Infarcts in insufficient collateral blood supply. Infarcts in kidney, spleen and lungs are kidney, spleen and lungs are Wedge ShapedWedge Shaped , , with the occluded artery situated near the with the occluded artery situated near the apex of the wedge and the base of the infarct apex of the wedge and the base of the infarct located on the surface of the organlocated on the surface of the organ . The . The characteristic shape of infarcts in these organs characteristic shape of infarcts in these organs is due to symmetric dichotomous branching is due to symmetric dichotomous branching pattern of the arteries supplying them.pattern of the arteries supplying them.

●The cerebral and myocardial infarcts are irregular shaped and determined by the distribution of the occluded artery and the limits of collateral arterial supply.

Infarct of Intestine: Infarction may follow thrombosis of or embolization to the mesenteric arteries. The sequence of changes usually seen in solid organs is altered by the effects of anastomosis and, in later stages by Bacterial InvasionInfarct of Heart (Myocardial Infarction)

Evolution of Myocardial Infarction: Changes are not evident in the initial hours. The dead tissue elicits an inflammatory reaction, characterized first by neutrophils then by macrophages. If no complications take place then the infarct heals by fibrosis and scar is formed

Infarct of Brain: These are usually due to thrombosis of diseased vessels or due to embolism from the left heart. The usual changes of infarction takes place, but the necrosis is liquefactive- cerebral softening.

EVOLUTION OF INFARCTEVOLUTION OF INFARCT ThrombosisThrombosis

EmbolismEmbolism

Occlusion of Blood Supply (Ischemia)Occlusion of Blood Supply (Ischemia)

Necrosis of Parenchymal cells and Connective Tissue frame Necrosis of Parenchymal cells and Connective Tissue frame workwork ( INFARCTION) ( INFARCTION)

Inflammatory responseInflammatory response Superadded BacterialSuperadded Bacterial InfarctionInfarction

Releases of Lysosomal EnzymesReleases of Lysosomal Enzymes GangreneGangrene

Heterolysis or AutolysisHeterolysis or Autolysis

Macrophages Phagocytose liquefied debrisMacrophages Phagocytose liquefied debris

In growth of granulation TissueIn growth of granulation Tissue

Scar FormationScar Formation

FACTORS THAT INFLUENCE DEVELOPMENT FACTORS THAT INFLUENCE DEVELOPMENT OF AN INFARCTOF AN INFARCT

The consequences of a vascular occlusion can range The consequences of a vascular occlusion can range from no or minimal effect, all the way up to death of a from no or minimal effect, all the way up to death of a tissue or even death of the individualtissue or even death of the individualThe major determinants include:The major determinants include:

(i)(i) The nature of the vascular supply The nature of the vascular supply(ii)(ii) The rate of development of the occlusion The rate of development of the occlusion(iii)(iii) The vulnerability of a given tissue to hypoxia The vulnerability of a given tissue to hypoxia(iv)(iv) Blood oxygen content Blood oxygen content1.1.Nature of Vascular Supply;Nature of Vascular Supply; The availability of an The availability of an

alternative blood supply is the most important factor alternative blood supply is the most important factor in determining the extent of damage. Lungs in determining the extent of damage. Lungs (Pulmonary and Bronchial arteries), Liver ( Hepatic (Pulmonary and Bronchial arteries), Liver ( Hepatic and Portal arteries), and hand and forearm (Radial and Portal arteries), and hand and forearm (Radial and Ulnar arteries) are relatively insensitive to local and Ulnar arteries) are relatively insensitive to local occlusion. occlusion. In contrast, renal and splenic circulation are end In contrast, renal and splenic circulation are end arterial, and obstruction of such vessels generally arterial, and obstruction of such vessels generally causes infarction. causes infarction.

2.2. Rate of Development of Occlusion:Rate of Development of Occlusion: Slowly developing Slowly developing occlusions are less likely to cause infarction since occlusions are less likely to cause infarction since they provide time for the development of they provide time for the development of alternative perfusion pathways.alternative perfusion pathways.

3.3. Vulnerability to Hypoxia:Vulnerability to Hypoxia: The susceptibility of a The susceptibility of a tissue to hypoxia influences the likelihood of tissue to hypoxia influences the likelihood of infarction. Neurons undergo irreversible damage infarction. Neurons undergo irreversible damage when deprived of their blood supply for only 3 to 4 when deprived of their blood supply for only 3 to 4 minutes. Myocardial cells are also quite sensitive minutes. Myocardial cells are also quite sensitive and die after only 20 to 30 minutes of ischemia.and die after only 20 to 30 minutes of ischemia.

4.4. Oxygen Content of Blood:Oxygen Content of Blood: Partial flow obstruction of Partial flow obstruction of a small vessel in an anaemic or cyanotic patient may a small vessel in an anaemic or cyanotic patient may lead to tissue infarction, whereas it would be lead to tissue infarction, whereas it would be without effect under conditions of normal oxygen without effect under conditions of normal oxygen tissuetissue

SHOCKSHOCKDefinition:Definition: Shock is a clinical state Shock is a clinical state characterized by systemic hypo perfusion due characterized by systemic hypo perfusion due to reduction either in cardiac output or in to reduction either in cardiac output or in effective circulating blood volume.effective circulating blood volume.

The end results are hypotension, followed by The end results are hypotension, followed by impaired tissue perfusion and cellular hypoxia.impaired tissue perfusion and cellular hypoxia.

Reduced Cardiac OutputReduced Cardiac Output Reduced Effective BloodReduced Effective Blood VolumeVolume

Systemic Hypo perfusionSystemic Hypo perfusion

HypotensionHypotension Impaired Tissue PerfusionImpaired Tissue Perfusion

Cellular HypoxiaCellular Hypoxia

SHOCK SHOCK

Shock is the final common Shock is the final common pathway for a number of potentially lethal pathway for a number of potentially lethal clinical events, including severe clinical events, including severe haemorrhage, extensive trauma or burns, haemorrhage, extensive trauma or burns, large myocardial infarction, massive large myocardial infarction, massive pulmonary embolism or microbial sepsispulmonary embolism or microbial sepsis

TYPES OS SHOCKTYPES OS SHOCK

1.1. HYPOVOLEMIC SHOCK HYPOVOLEMIC SHOCK

2.2. CARDIOGENIC SHOCK CARDIOGENIC SHOCK

3.3. OBSTRUCTIVE SHOCK OBSTRUCTIVE SHOCK

4.4. SEPTIC SHOCK SEPTIC SHOCK

5.5. NEUORGENIC SHOCK NEUORGENIC SHOCK

66. ANAPHYLACTIC SHOCK. ANAPHYLACTIC SHOCK

Mechanisms causing Shock

1. 1. HYPOVOLEMIC SHOCK:HYPOVOLEMIC SHOCK:Hypovolemia may be due to :Hypovolemia may be due to :

(i) (i) Haemorrhage:Haemorrhage: Either External or Internal Either External or Internal(ii) (ii) Excessive Fluid Loss:Excessive Fluid Loss: As occurs in diarrhea, As occurs in diarrhea,

vomiting, burns, dehydration, or excessive sweatingvomiting, burns, dehydration, or excessive sweating

2. 2. CARDIOGENIC SHOCK:CARDIOGENIC SHOCK: Cardiogenic Shock results from a severe reduction in Cardiogenic Shock results from a severe reduction in cardiac output due to primary cardiac disease, for cardiac output due to primary cardiac disease, for example:example:

(i)(i) Acute Myocardial Infarction Acute Myocardial Infarction(ii)(ii) Acute Myocarditis Acute Myocarditis(iii)(iii) Ventricular Rupture Ventricular Rupture(iv)(iv) Arrhythmias Arrhythmias

3. 3. OBSTRUCTIVE SHOCK:OBSTRUCTIVE SHOCK: Obstruction to blood flow in Obstruction to blood flow in the heart or main pulmonary artery, as occurs in the heart or main pulmonary artery, as occurs in massive pulmonary embolism.massive pulmonary embolism.

4. 4. NEUROGENIC SHOCKNEUROGENIC SHOCKShock due to neurogenic stimuli is seen:Shock due to neurogenic stimuli is seen:

(i) During anesthesia(i) During anesthesia(ii) In spinal cord injury(ii) In spinal cord injury(iii) During simple fainting(iii) During simple fainting

The underlying mechanism which leads to shock in The underlying mechanism which leads to shock in these these

conditions is conditions is Peripheral VasodilatationPeripheral Vasodilatation . Widespread . Widespread vasodilatation in small vessels leads to excessive vasodilatation in small vessels leads to excessive

pooling of blood in peripheral capacitance vessels. pooling of blood in peripheral capacitance vessels. The result is reduction of effective blood volume and The result is reduction of effective blood volume and therefore a decreased cardiac output therefore a decreased cardiac output ((Peripheral Peripheral Circulatory Failure)Circulatory Failure)

Simple fainting is self correcting. When the Simple fainting is self correcting. When the patient falls on the ground the recumbent position patient falls on the ground the recumbent position increases venous return and thereby restores increases venous return and thereby restores cardiac outputcardiac output

6. 6. SEPTIC SHOCK:SEPTIC SHOCK:It is usually seen in:It is usually seen in:

(i)(i) Overwhelming Microbial infection. Overwhelming Microbial infection.(ii)(ii) Endotoxic Shock due to Gram Negative infections Endotoxic Shock due to Gram Negative infections(iii)(iii) Gram – Positive septicemia Gram – Positive septicemia(iv)(iv) Fungal Sepsis Fungal Sepsis(v(v) Super antigens) Super antigens

In Septic shock, circulating endotoxin (bacterial lipopolysaccharide) In Septic shock, circulating endotoxin (bacterial lipopolysaccharide) binds with the CD 14 receptor on macrophages, producing massive binds with the CD 14 receptor on macrophages, producing massive release of cytokines, particularly Tumour Necrosis Factor (TNF), and release of cytokines, particularly Tumour Necrosis Factor (TNF), and some other cytokines like Interleukin – 1 (IL-1), Interleukin – 6(IL-6) some other cytokines like Interleukin – 1 (IL-1), Interleukin – 6(IL-6) and Interleukin – 8 (IL-8). The net effect of their release is and Interleukin – 8 (IL-8). The net effect of their release is permeability changes and intravascular coagulation.permeability changes and intravascular coagulation.The factors which leads to shock in infective conditions include:The factors which leads to shock in infective conditions include:

(i)(i) Peripheral vasodilatation and pooling of blood Peripheral vasodilatation and pooling of blood(ii)(ii) Endothelial injury/activation Endothelial injury/activation(iii)(iii) Leucocytes induced damage Leucocytes induced damage(iv)(iv) Disseminated Intravascular Coagulation Disseminated Intravascular Coagulation(v)(v) Activation of Cytokine Cascade Activation of Cytokine Cascade

Activation of lipopolysacchardies (LPS) initiates cytokine cascade. These in turn activates Nitrous Oxide (NO) and Platelet Activating Factor (PAF). At low levels of NO and PAF only inflammatory effects are seen.At Moderate levels of NO and PAF more systemic events occur in addition to local vascular effectsAt High Concentrations of NO and PAF the syndrome of Septic Shock is seen(DIC- Disseminated Intravascular Coagulation; ARDS – Adults Respiratory Distress Syndrome)

STAGES OF SHOCKSTAGES OF SHOCK

Shock develops in three stages:Shock develops in three stages:

(i) Stage of compression or (i) Stage of compression or Non- Progressive ShockNon- Progressive Shock

(ii) Stage of impaired tissue perfusion or (ii) Stage of impaired tissue perfusion or Progressive Progressive ShockShock

(iii) Stage of Decompensation or (iii) Stage of Decompensation or Irreversible ShockIrreversible Shock

STAGE OF COMPENSATION OR NON- PROGRESSIVE SHOCK:STAGE OF COMPENSATION OR NON- PROGRESSIVE SHOCK:In this phase a variety of neurohumoral mechanisms In this phase a variety of neurohumoral mechanisms ((compensatory mechanismscompensatory mechanisms)) help to maintain cardiac help to maintain cardiac output an blood pressure. These include: output an blood pressure. These include:

(i) Baro receptor reflexes.(i) Baro receptor reflexes.(ii) Release of catecholamine(ii) Release of catecholamine

(iii) Activation of renin- angiotensin axis(iii) Activation of renin- angiotensin axis (iv) Antidiuretic hormone release(iv) Antidiuretic hormone release (v) Generalized sympathetic stimulation.(v) Generalized sympathetic stimulation.

The net effect is tachycardia, peripheral The net effect is tachycardia, peripheral vasoconstriction and renal conservation of fluid. vasoconstriction and renal conservation of fluid. Cutaneous vasoconstriction is responsible for the Cutaneous vasoconstriction is responsible for the characteristic coolness and pallor of skin in well characteristic coolness and pallor of skin in well developed shock. developed shock. Vasoconstriction in renal arterioles decreases the Vasoconstriction in renal arterioles decreases the pressure and rate of glomerluar filtration with resulting pressure and rate of glomerluar filtration with resulting decreased urine output (oliguria) decreased urine output (oliguria)

STAGE OF IMPAIRED TISSUE PERFUSION OR STAGE OF IMPAIRED TISSUE PERFUSION OR PROGRESSIVE PHASEPROGRESSIVE PHASE

If the underlying causes are not corrected, shock If the underlying causes are not corrected, shock passes imperceptibly to the progressive phase. During passes imperceptibly to the progressive phase. During which there is widespread tissue hypoxia. In the this which there is widespread tissue hypoxia. In the this stage anaerobic respiration is replaced by anaerobic stage anaerobic respiration is replaced by anaerobic glycolysis with excessive production of lactic acid glycolysis with excessive production of lactic acid (Metabolic Acidosis)(Metabolic Acidosis)With widespread tissue hypoxia, vital organs are With widespread tissue hypoxia, vital organs are affected and begin to fail; clinically patient becomes affected and begin to fail; clinically patient becomes confused and the urinary output declines. confused and the urinary output declines. STAGE OF DECOMPENSATION OR STAGE OF DECOMPENSATION OR

IRREVERSIBLE SHOCKIRREVERSIBLE SHOCK Unless there is intervention the process enters Unless there is intervention the process enters irreversible stage. Lysosomal enzymes release further irreversible stage. Lysosomal enzymes release further worsens the shock state. At this stage patient develops worsens the shock state. At this stage patient develops complete renal shut down due to tubular necrosis. complete renal shut down due to tubular necrosis. Despite all measures, the downward clinical spiral Despite all measures, the downward clinical spiral almost almost inevitably culminates in death inevitably culminates in death

MORPHOLOGICAL CHANGES IN SHOCKMORPHOLOGICAL CHANGES IN SHOCK

The cellular and tissue changes induced by shock are The cellular and tissue changes induced by shock are essentially those of hypoxic injury; since shock is essentially those of hypoxic injury; since shock is characterized by characterized by failure of multiple organ systemsfailure of multiple organ systems , , the cellular changes may appear in any tissue. The the cellular changes may appear in any tissue. The changes are more evident in following tissues;changes are more evident in following tissues;

1. 1. Brain:Brain: Ischemic encephalopathy Ischemic encephalopathy2. 2. Heart:Heart: Necrosis and subendocardial haemorrhage Necrosis and subendocardial haemorrhage3. 3. Kidneys:Kidneys: Acute tubular necrosis Acute tubular necrosis4. 4. Lungs:Lungs: Edema; Haemorrhage; Alveolar damage Edema; Haemorrhage; Alveolar damage5. 5. Gastrointestinal Tract :Gastrointestinal Tract : Patchy mucosal haemorrhage Patchy mucosal haemorrhage

and necrosisand necrosis6. 6. Liver:Liver: Central Necrosis Central Necrosis

CLINCAL COURSECLINCAL COURSE

The clinical manifestations depend on the The clinical manifestations depend on the precipitating insult. In hypovolemic and cardiogenic precipitating insult. In hypovolemic and cardiogenic shock the patient presents with hypotension; a shock the patient presents with hypotension; a weak, rapid pulse; tachypnea; and cool, clammy weak, rapid pulse; tachypnea; and cool, clammy skin, cyanotic skin.In septic shock, however, the skin skin, cyanotic skin.In septic shock, however, the skin may initially be warm and flushed because of may initially be warm and flushed because of peripheral vasodilatation. peripheral vasodilatation.

If the compensatory mechanisms fail then If the compensatory mechanisms fail then eventually electrolyte imbalances and metabolic eventually electrolyte imbalances and metabolic acidosis also deteriorates the situation. Then acidosis also deteriorates the situation. Then patient enters into renal failure. patient enters into renal failure.

If the cause of shock can be treated, e,g., If the cause of shock can be treated, e,g., hypovolemia, then patient will survive. But patients hypovolemia, then patient will survive. But patients in whom cause can not be treated , e.g., massive in whom cause can not be treated , e.g., massive myocardial infarction, the patient will die. myocardial infarction, the patient will die.

haemodynamic disorders , thromboembolism and shock by dr nadeem (rmc)

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