it 11 - haemodynamic - krs

Click here to load reader

Post on 02-Dec-2015

15 views

Category:

Documents

1 download

Embed Size (px)

DESCRIPTION

njjjj

TRANSCRIPT

Haemodynamic, ....

Hemodynamic Disorders,Thromboembolism and ShockKrisna Murti

Department of Anatomical Pathology, Faculty of Medicine, University of SriwijayaFluidsWaterApproximately 60% of lean body weight is waterTwo thirds of the body's water is intracellularThe remainder is in extracellular compartments, mostly the interstitium (or third space) that lies between cells; only about 5% of total body water is in blood plasma.2This unit addresses factors affecting the distribution between intravascular and interstitial spacesEdema and EffusionsEdema: accumulation of fluid in the interstitial tissue spacesEffusions is accumulation of fluid in body cavitiesDepending on the site, fluid collections are variously designated hydrothorax, hydropericardium, and hydroperitoneum (ascites)Anasarca: severe, generalized edema with profound subcutaneous tissue swelling.

Pulmonary edema

4http://peir.path.uab.edu:3555/images/med/00011603.jpghttp://peir.path.uab.edu:3555/images/med/00011785.jpgElephantiasis--Lymphedema

5From GRIPELeft: elephantiasis; Right: elephantiasis secondary to carcinomahttp://peir.path.uab.edu:3555/images/med/00010326.jpghttp://peir.path.uab.edu:3555/images/med/00011028.jpg Peau dorange and Post-Mastectomy Lymphedema

6http://www.jaapa.com/inflammatory-breast-cancer-a-race-against-time/article/131006/http://peir.path.uab.edu:3555/images/med/00010442.jpg

Ascites is the accumulation of excess fluid within the peritoneal cavity

It is most frequently encountered in patients with cirrhosis and other forms of severe liver diseaseAscites due to Portal Congestion

8http://www.pathguy.com/sol/19381.jpg

American Gastroenterological Association, AGA Teaching Project, 1975 UI Medical Library call # WI, 720, P8423, 1975

Ascites with "caput madusae" (medusa head), also known as "Cruveilhier-Baumgarten Syndrome". Cirrhosis and portal hypertension sometimes create anastomoses of portal drainage with the umbilical vein. Also note protrusion of the naval from abdominal pressure.Pleural Effusions and Edema

9This is a right pleural effusion (in a baby). Note the clear, pale yellow appearance of the fluid. This is a serous effusion.Here is an example of bilateral pleural effusions. Note that the fluid appears reddish, because there has been hemorrhage into the effusion. This is a serosanguinous effusion.

http://library.med.utah.edu/WebPath/INFLHTML/INFL062.htmlhttp://library.med.utah.edu/WebPath/INFLHTML/INFL013.htmlhttp://peir.path.uab.edu:3555/images/med/00010608.jpg

Pleural Effusion

10http://library.med.utah.edu/WebPath/INFLHTML/INFL005.htmlDilated Lymphatic Vessels

11http://www.pathguy.com/lectures/lymphatic_vessels_in_edema.jpg

Normal:

balance of vascular hydrostatic presure to push water and salt out of capillaries into the interstitial spaces plasma colloid osmotic pressure to pull water and salts back into vessels

Edema:

Elevated hydrostatic pressure or diminished colloid osmotic pressure disrupts this balanceresults in increased movement of fluid out of vesselsto the interstitial and accumulateTransportation of Fluid12

Pathologies Categories of Edema

Mechanisms of Systemic Edema in Heart Failure, Renal Failure, Malnutrition, Hepatic Failure and Nephrotic Syndrome14Types of EdemaTransudate: protein poor (1.020 results from endothelial damage and alteration of vascular permeability e.g. inflammatory and immunologic pathologyHyperemia and CongestionHyperemia

An active process resulting from tissue inflow because of arteriolar dilation e.g. skeletal muscle during exercise or at sites of inflammation.

The affected tissue is redder because of the engorgement of vessels with oxygenated blood. Congestion

A passive process resulting from impaired outflow from a tissueSystemic: e.g. cardiac failure, Local: e.g. an isolated venous obstruction The tissue has a blue-red color (cyanosis) due to accumulation of deoxygenated hemoglobin in the affected tissues.

Nutmeg Liver

17Here is an example of a "nutmeg" liver seen with chronic passive congestion of the liver. Note the dark red congested regions that represent accumulation of RBC's in centrilobular regions. Microscopically, the nutmeg pattern results from congestion around the central veins, as seen here. This is usually due to a "right sided" heart failure.http://library.med.utah.edu/WebPath/LIVEHTML/LIVER041.htmlhttp://library.med.utah.edu/WebPath/LIVEHTML/LIVER042.htmlHepatic congestion

18http://library.med.utah.edu/WebPath/LIVEHTML/LIVER147.htmlIf chronic hepatic passive congestion continues for a long time, a condition called "cardiac cirrhosis" may develop in which there is fibrosis bridging between central zonal regions, as shown below, so that the portal tracts appear to be in the center of the reorganized lobule. This process is best termed "cardiac sclerosis" because, unlike a true cirrhosis, there is minimal nodular regeneration.http://library.med.utah.edu/WebPath/LIVEHTML/LIVER043.htmlIf the passive congestion is pronounced, then there can be centrilobular necrosis, because the oxygenation in zone 3 of the hepatic lobule is not great. The light brown pigment seen here in the necrotic hepatocytes around the central vein is lipochrome.

Morphology: LungThe cut surfaces are hemorrhagic and wetLUNGS: Microscopically, acute pulmonary congestion is characterized by alveolar capillaries engorged with blood,alveolar septal edema and/or focal intra-alveolar hemorrhageIn chronic pulmonary congestion, the septa are thickened and fibrotic, and the alveolar spaces may contain numerous hemosiderin-laden macrophages (heart failure cells)Morphology: LiverIn acute hepatic congestion: central vein and sinusoids are distended with blood with or without central hepatocyte degeneration. In chronic passive congestion of the liver: on cut surface central regions of the hepatic lobules are red-brown and surrounded by zones of uncongested tan liver (nutmeg liver). Microscopically: centrilobular necrosis with loss of hepatocytes, hemorrhage and hemosiderin-laden macrophages Long-standing cases (most commonly associated with heart failure), hepatic fibrosis (cardiac cirrhosis) may developed HemorrhageHemorrhage generally indicates extravasation of blood due to vessel ruptureHematoma: accumulation of blood within tissuePetechiae: Minute 1- to 2-mm hemorrhages into skin, mucous membranes, or serosal surfacesPurpura: Slightly larger (3 mm) hemorrhagesEcchymoses: Larger (>1 to 2 cm) subcutaneous hematomas (i.e., bruises).Large accumulations of blood in one or another of the body cavities are called hemothorax, hemopericardium, hemoperitoneum, or hemarthrosis (in joints)

ThrombosisRepresents hemostasis in the intact vascular systemA process by which a thrombus is formedA thrombus is a solid mass of blood constituents which developes in artery or veinIs intravascular coagulation of blood often causing sinificant interuption to blood flow

Thrombi come to clinical attention when they obstruct arteries or veins, or give rise to emboli23Pathogenesis of ThrombosisThree primary influences predispose to thrombus formation,the so-called Virchow triad: endothelial injury stasis or turbulence of blood flowblood hypercoagulability

Thrombus results from interaction: PlateletsDamaged endothelial cells Coagulation cascade

Thrombus (arrow)24

Virchow Triad in Thrombosis

Endothelial integrity 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) can, in turn, cause endothelial injury

The elements of the triad may act independently or may combine to cause thrombus formation25Primary (Genetic) Hypercoagulable States Mutation in factor V gene (factor V Leiden)Mutation in prothrombin geneMutation in methyl tetrahydrofolate geneAntithrombin III deficiencyProtein C deficiencyProtein S deficiencyFibrinolysis defects)Secondary(Acquired) Hypercoaguable StatesHigh risk for thrombosis

Prolonged bed rest or immobilizationMyocardial infarction, Atrial fibrillationTissue damage (surgery, fracture, burns)CancerProsthetic cardiac valvesDisseminated intravascular coagulationHeparin-induced thrombocytopeniaAntiphospholipid antibody syndrome (lupus anticoagulant syndrome)

Lower risk for thrombosis

Cardiomyopathy

Nephrotic syndrome

Hyperestrogenic states (pregnancy)

Oral contraceptive use

Sickle cell anemia

SmokingPathogenesis cont

1) PlateletsMaintain the integrity of the vascular endotheliumParticipate in endothelial repair through the contribution of PDGFForm platelet plugsPromote the coagulation cascade through the platelet phospholipid complex.

Pathogenesis cont 2) Endothelial cellsResistant to the thrombogenic influence of platelets and coagulation proteins

Intact endothelial cells act to modulate several aspects of hemostasis and oppose coagulation after injury by thrombo-resistancePathogenesis cont 3) Coagulation CascadeThe coagulation cascade constitutes the third component of the hemostatic process and is a major contributor to thrombosis

The coagulation cascade is essentially a series of enzymatic conversions, turning inactive proenzymes into activated enzymes and culminating in the formation of thrombin

Thrombin then converts the soluble plasma protein fibrinogen precursor into the insoluble fibrous protein fibrin

Intrinsic pathway

Extrinsic pathway

Pathogenesis cont

3) Coagulation Cascade contBesides inducing coagulation, activation of the clotting cascade also sets into motion a fibrinolytic cascade that limits the size of the final clotThis is primarily accomplished by the generation of plasminPlasmin is derived from enzymatic breakdown of its inactive circulating precursor plasminogen, either by a factor XII-dependent pathway or by two distinct types of plasminogen activators Fibrinolysis (thrombus dissolution)Runs concurrently with thrombogenesisRestores blood flow in vessels occluded by a thrombus and facilitates healing after inflammation and injuryThe proenzyme plasminogen is converted by proteolysis to plasmin, the most important fibrinolytic proteasePlasmin split fibrinThrombotic DisordersCan be anti-thrombotic (hemorrhagic), leading to pathologic bleeding states such as hemophilia, Christmas disease and von Willebrand disease

Can also be prothrombotic, leading to hypercoagulability with pathologic thrombosisHereditary ThrombophiliaIs a prothrombotic familial syndromeCharecterized by recurrent venous thrombosis and thromboembolismCan be caused by deficiency of antithrombotic proteins including antithrombin 3, protein C, and protien SAntiphospholipid Antibody SyndromeIs a prothrombotic disorder characterized by autoantibodies directed against a number of protein antigens complexed to phospholipidsIs further characterized by recurrent venous and arterial thromboembolism, fetal loss, thrombocytopenia and a variety of neurological manifestationsIt is most often diagnosed because of an incidental finding of prolonged PTTIt is sometimes associated Systemic Lupus Erythematosus and so this antibody is also known as lupus anticoagulant

Disseminated Intravascular Coagulation (DIC)Is both prothrombotic and antithrombotic disorder characterized by widespread thrombosis and hemorrhage resulting from the consumption of platelets and coagulation factorsMorphology of ThrombusThrombi may develop anywhere in the cardiovascular system, the cardiac chambers, valve cusps, arteries, veins, or capillaries. They vary in size and shape, depending on the site of originArterial or cardiac thrombi usually begin at a site of endothelial injury (e.g., atherosclerotic plaque) or turbulence (vessel bifurcation)Venous thrombi characteristically occur in sites of stasisArterial and Venous ThrombiArterial thrombi grow in a retrograde direction from the point of attachmentVenous thrombi extend in the direction of blood flow (i.e., toward the heart)The propagating tail of either thrombi may not be well attached (particularly in veins) is prone to fragmentation, creating an embolus Thrombi contWhen 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 cells

When arterial thrombi arise in heart chambers or in the aortic lumen, they usually adhere to the wall of the underlying structure and are termed mural thrombiArterial ThrombiUsually occlusiveThe most common sites in descending order, are coronary, cerebral, and femoral arteriesUsually superimposed on an atherosclerotic plaque and are firmly adherent to the injured arterial wall and are gray-white and friable, composed of a tangled mesh of platelets, fibrin, erythrocytes, and degenerating leukocytesAtherosclerosis is the major causative factorVenous ThrombosisAlso called phlebothrombosis, is almost invariably occlusive the thrombus often takes the shape of the veinBecause these thrombi form in a relatively static environment, they contain more enmeshed erythrocytes and are therefore known as red, or stasis thrombiPhlebothrombosis most commonly affects the veins of the lower extremities (90% of cases)Postmortem ClotsAt autopsy, postmortem clots may be confused for venous thrombi Postmortem clots are gelatinous with a dark red dependent portion where red cells have settled by gravity and a yellow chicken fat supernatant resembling melted and clotted chicken fat. They are not attached to the underlying wallRed thrombi are firmer, almost always have a point of attachment, and on transection reveal vague strands of pale gray fibrinThrombi on Heart ValvesBacterial or fungal blood-borne infections may result in the development of large thrombotic masses on heart valves, called as vegetations (infective endocarditis)Sterile vegetations can also develop on noninfected valves in patients with hypercoagulable states, so-called nonbacterial thrombotic endocarditisLess commonly, noninfective, verrucous (Libman-Sacks) endocarditis attributable to elevated levels of circulating immune complexes may occur in patients with systemic lupus erythematosus

Potential Outcomes of Venous Thrombosis.44

Fate of ThrombusEmbolizationEmbolismAn embolus is a detached intravascular solid, liquid, or gaseous mass that is carried by the blood to a site distant from its point of originAlmost all emboli represent some part of a dislodged thrombus, hence the commonly used term thromboembolism The emboli ultimately lodge in vessels too small to permit further passage, resulting in partial or complete vascular occlusion leading to ischemic necrosis of distal tissue, (infarction)Depending on the site of origin, emboli may lodge in the pulmonary or systemic circulations

Pulmonary ThromboembolismDepending on size of embolus, it may occlude main pulmonary artery, or impact across the bifurcation (saddle embolus), or pass out into the smaller, branching arteriolesRarely, embolus may pass through an interatrial or interventricular defect to gain access to the systemic circulation (paradoxical embolism)Most pulmonary emboli (60% to 80%) are clinically silent because they are smallSudden death, right heart failure (cor pulmonale), or CVS occurs when 60% or more of the pulmonary circulation is obstructed with emboli Embolic obstruction of small end-arteriolar pulmonary branches may result in infarction

Systemic Thromboembolism Refers to emboli traveling within the arterial circulationMost (80%) arise from intracardiac mural thrombiThe major sites for arteriolar embolization are the lower extremities (75%) and the brain (10%) The consequences of systemic emboli depend on the extent of collateral vascular supply in the affected tissue, the tissue's vulnerability to ischemia, and the caliber of the vessel occluded; in general, arterial emboli cause infarction of tissues supplied by the arteryFat Embolism Microscopic fat globules may be found in the circulation after fractures of long bones (which have fatty marrow) or, rarely, in soft tissue trauma and burnsFat is released by marrow or adipose tissue injury and enters the circulation through rupture of the blood vesselsLess than 10% of patients with fat embolism have any clinical findings Fat embolism syndrome is characterized by pulmonary insufficiency, neurologic symptoms, anemia, and thrombocytopeniaAir Embolism Gas bubbles within the circulation can obstruct vascular flow (and cause distal ischemic injury) acting as thrombotic masses. Bubbles may coalesce to form frothy masses sufficiently large to occlude major vesselsAir may enter the circulation during obstetric procedures or as a consequence of chest wall injuryAn excess of 100 cc is required to have a clinical effectDecompression Sickness Occurs when individuals are exposed to sudden changes in atmospheric pressure Scuba and deep sea divers, underwater construction workers, and individuals in unpressurized aircraft in rapid ascent are all at riskWhen air is breathed at high pressure (e.g., during a deep sea dive), increased amounts of gas (particularly nitrogen) become dissolved in the blood and tissuesIf the diver then ascends (depressurizes) too rapidly, the nitrogen expands in the tissues and bubbles out of solution in the blood to form gas emboli Bends and chokes

Decompression Sickness contTreatment: placing the individual in a compression chamber where the barometric pressure may be raised, thus forcing the gas bubbles back into solution followed by subsequent slow decompression A more chronic form of decompression sickness is called caisson disease in which, persistence of gas emboli in the skeletal system leads to multiple foci of ischemic necrosis; the more common sites are the heads of the femurs, tibia, and humeriAmniotic Fluid Embolism A grave and uncommon complication of labor and the immediate postpartum period, characterized by sudden severe dyspnea, cyanosis, and hypotensive shock, followed by seizures and comaIf the patient survives the initial crisis, pulmonary edema develops, along with DIC, owing to release of thrombogenic substances from amnioticCaused by infusion of amniotic fluid or fetal tissue into the maternal circulation via a tear in the placental membranes or rupture of uterine veins. Microscopy: presence in the pulmonary microcirculation of squamous cells shed from fetal skin, lanugo hair, fat from vernix caseosa, and mucin derived from the fetal respiratory or gastrointestinal tractMarked pulmonary edema and diffuse alveolar damage are also presentSystemic fibrin thrombi indicative of DIC can also be seen

InfarctionAn infarct is an area of ischemic necrosis caused by occlusion of either the arterial supply or the venous drainage in a particular tissue e.g. myocardial, cerebral, pulmonary and bowel infarction Most infarcts result from thrombotic or embolic events, and almost all result from arterial occlusionVenous thrombosis may cause infarction, it more often merely induces venous obstruction and congestion

MorphologyInfarcts are classified on the basis of their color (reflecting the amount of hemorrhage) and the presence or absence of microbial infectionTherefore, infarcts may be either red (hemorrhagic) or white (anemic) and may be either septic or bland

Red InfarctsRed (hemorrhagic) infarcts occur with venous occlusions (such as in ovarian torsion)in loose tissues (such as lung), and in tissues with dual circulations (e.g., lung and small intestine), permitting flow of blood from the unobstructed vessel into the affected zone White InfarctWhite (anemic) infarcts occur with arterial occlusions in solid organs with end-arterial circulation (such as heart, spleen, and kidney)where the solidity of the tissue limits the amount of hemorrhage that can seep into the area of ischemic necrosis from adjoining capillary bedsMorphologyGross: Most infarcts are wedge-shaped, with the occluded vessel at the apex and the periphery of the organ forming the base

Micro: An inflammatory response begins along the margins of infarcts within a few hours and is usually well defined within 1 or 2 days, followed by gradual degradation of the dead tissue with phagocytosis of the cellular debris by neutrophils and macrophages

Most infarcts are ultimately replaced by scar tissueSeptic InfarctSeptic infarctions may develop when embolization occurs by fragmentation of a bacterial vegetation from a heart valve or when microbes seed an area of necrotic tissue

The septic infarct is converted into an abscess, with a correspondingly greater inflammatory response

Infarct (cont.)The consequences of a vascular occlusion can range from no or minimal effect, all the way up to death of a tissue or even the individual. The major determinants include: (1) the nature of the vascular supply (2) the rate of development of the occlusion (3) the vulnerability of a given tissue to hypoxia (4) the blood oxygen content

Defect due to InfarcShockor cardiovascular collapseis the final common pathway for a number of potentially lethal clinical events: including severe hemorrhageextensive trauma or burnslarge myocardial infarctionmassive pulmonary embolismmicrobial sepsis

Events in SchockSystemic hypoperfusion caused by reduction either in cardiac output or in the effective circulating blood volume The end results are hypotension, followed by impaired tissue perfusion and cellular hypoxia Initially the cellular injury is reversible, persistence of shock eventually causes irreversible tissue injuryTypes of ShockCardiogenic s: results from myocardial pump failure e.g intrinsic myocardial infarction, ventricular arrhythmiasHypovolemic s: results from loss of blood or plasma volume e.g. hemorrhage, fluid loss from severe burns, or trauma Septic shock is caused by systemic microbial infection. Most commonly due to gram-negative infections (endotoxic shock), but it can also occur with gram-positive and fungal infectionsNeurogenic s: anesthetic accident or spinal cord injury can lead to loss of vascular tone and peripheral pooling of blood. Anaphylactic s: initiated by a generalized IgE-mediated hypersensitivity response, is associated with systemic vasodilation and increased vascular permeability.

Major Pathogenic Pathway in Septic ShockPAMPs: pathogen-associated molecular patternsHMGB1: Hihg mobility group box 1 proteinNO: Nitric oxidePAF: Platelet activating factorPAI-1: plasminogen activator inhibitor 1TF: Tissue factorTFPI: Tissue factor pathway inhibitorSeptic/Endotoxic ShockSeptic shock results from spread and expansion of an initially localized infection (e.g., abscess, peritonitis, pneumonia) into the bloodstreamMost cases of septic shock (approximately 70%) are caused by endotoxin-producing gram-negative bacilliEndotoxins are bacterial wall lipopolysaccharides (LPSs) that are released when the cell walls are degraded (e.g., in an inflammatory response)

Stages of Shock If uncorrected, leads to death. Unless insult is massive and lethal (e.g. a massive hemorrhage), shock tends to evolve through three general phasesA nonprogressive phase: reflex compensatory mechanisms are activated and perfusion of vital organs is maintained A progressive stage: tissue hypoperfusion and onset of worsening circulatory and metabolic imbalances, including acidosis An irreversible stage: sets in after body has incurred cellular and tissue injury so severe that even if the hemodynamic defects are corrected, survival is not possible

MorphologyThe cellular and tissue changes induced by shock are essentially those of hypoxic injury, since shock is characterized by failure of multiple organ systems, the cellular changes may appear in any tissue

They are particularly evident in brain, heart, lungs, kidneys, adrenals, and gastrointestinal tract

Heart - coagulation necrosis, may exhibit subendocardial hemorrhage and/or contraction band necrosis

Kidneys - tubular ischemic injury (acute tubular necrosis, therefore oliguria, anuria, and electrolyte disturbances constitute major clinical problems.

Liver: centrilobular sinusoidal congestion (grossly visible) with hepatocellular vacuolar degeneration and necrosis (may be grossly apparent)

Stomach and intestines: congestion, edema (particularly severe in the equine colon), and mucosal necrosis with hemorrhage (all of these changes are grossly visible)

Lungs are seldom affected in pure hypovolemic shock because they are resistant to hypoxic injury. When shock is caused by bacterial sepsis or trauma, however, changes of diffuse alveolar damage may appear, the so-called shock lung

Brain - ischemic encephalopathy

Morphologycont

Clinical CourseIn hypovolemic and cardiogenic shock, the patient presents with hypotension; a weak, rapid pulse; tachypnea; and cool, clammy, cyanotic skin. In septic shock, the skin may initially be warm and flushed because of peripheral vasodilationAs shock progresses, electrolyte disturbances and metabolic acidosis (lactic acidosis) complicate the situation followed by progressive fall in urine output PrognosisThe prognosis varies with the origin of shock and its duration80% to 90% of young, otherwise healthy patients with hypovolemic shock survive with appropriate managementCardiogenic shock associated with extensive myocardial infarction and gram-negative shock carry mortality rates of up to 75%, even with the best care currently available