Hemodynamics

Blood supplyFluid imbalance

Pathologies

EdemaVascular congestionHemorrhageThrombosisEmbolismInfarction Shock

Edema

60% BW is water2/3 intracellular rest is extracellular5% plasmaEdema means fluid in the interstitial space hydrothorax hydropericardium hydroperitoneum (ascites)Anasarca generalized edema with profound subQ swelling

Causes of edemaIncreased hydrostatic pressure impaired venous return arteriolar dilatationReduced plasma oncotic pressure (hypoproteinemia)Lymphatic obstructionSodium retentionInflammation

Transudate edema fluid occuring in hemodynamic derangement. Protein poor , spfc. grav. of 1.012.Exudate inflammatory edema fluid protein rich spfc. grav . of 1.020

Increase hydrostatic pressureImpaired venous outflow deep venous thrombosisGeneralized increase in venous pressure CHF right sided HF, dec CO , reduced renal perfusion, kidney tend to retain water and Na Tx diuretics, salt restriction, aldosterone antagonist

Reduced plasma oncotic pressureExcessive loss or reduced synthesis of albumin - nephrotic syndrome , liver cirrhosis , protein malnutritionAlso cause decrease renal perfusion water and Na retention cant correct the conditionHypoproteinemia is exacerbated by salt and fluid retention

Lymphatic obstruction

Lymphedema is usually localizedFilariasis - elephantiasisCancer - Tx irradiation

Sodium and water retentionSalt retention may be a primary contributor of edemaPost streptococcal glomerulonephritisAcute renal failure

Clinical correlationSubQ edema or renal failure signals underlying dse.Pulmonary edema can be fatal collects fluid to alveolar septa and impede O2 diffusionImpair wound healing and clearance of infectionBrain edema fatal herniation

Hyperemia and CongestionH and C indicate a local increased volume of blood in a particular tissueHyperemia is an active process resulting from augmented tissue inflow arteriolar dilation ( sk. mcle in exercise/ inflamm.) tissue is redderCongestion is a passive process resulting from impaired outflow from the tissue tissue is blue red (cyanosis) cardiac failure

Congestion of capillary beds is related to edema or they may occur togetherChronic passive congestion long standing congestion , stasis of poorly oxygenated blood chronic hypoxiaHypoxia results cell degeneration and deathCongestion may result to hge. , phagocytosis of red ( hemosiderin laden macrophage)

Hemorrhage

Extravasation of blood because to vessel ruptureCapillary bleeding can occur under conditions of chronic congestionBleeding diatheses increased tendency to hemorrhage from usually insignificant injuryTrauma, atherosclerosis, inflammation and neoplastic process - HGE

Hge maybe external or enclose within a tissue (hematoma) maybe benign or fatalPetechiae 1-2mm (thrombocytopenia, clotting fx def)Purpura - > or equal 3mm slightly larger than petechiae ( vasculitis)Ecchymoses - >1-2cm subQ hematomas (trauma)Accumulation of blood in spfc. Areas hemarthrosis, hemoperitoneum,hemothorax,hemopericardium

Clinical significance of hge depends on the volume rate of blood loss20% loss is still no significant changeGreater loss hypovolemic shockHemorrhage site is impt. intracranial hge. Inc intracranial pressureIron defeciency

Hemostasis and ThrombosisNormal hemostasis 1. maintain blood in a fluid , clot free state in normal vessels 2. they are poised to induced a rapid and localized hemostatic plug at the site of vascular injuryThrombosis - is a pathologic form of hemostasis , inappropriate activation of normal hemostatic process (thrombus)

Normal Hemostasis

Endothelium is both procoagulant and anti platelet (fibrinolytic system)Counterregulatory mech. t-PA

Antithrombotic propertiesIntact BV 1. anti-platelets platelets are inactivated- they dont adhere with each other brought about by subs PGI2 and Nitric oxide. Also adenosine diphosphatase which inhibits plt. Aggregation 2. anticoagulants a. membrane asso. Heparin like molecules anti thrombin III b. thrombomodulin spfc. Thrombin receptor

3. Fibrinolytic t-PA which clears out clot

Prothrombotic propertiesvon Willebrand factor cofactor for platelet binding with collagen and other surfaces bacterial endotoxins and cytokines cause synthesis of tissue factor activate extrinsic clotting cascade inhibit plasminogen activator and inhibits fibrinolysis

PlateletsPlay impt. role in hemostasis 2 granules a-granules fibrinogen, fibronectin, factor V, VwF, heparin binding chemokine, PDGF d-granules ADP & ATP , ionized Ca, histamine, serotonin, epinephrine

Platelets during contact of extracellular matrix1. adhesion and shape change - vWF2. secretion Ca & ADP plt.aggregation (phospholipid complexes)3. aggregation TXA2 primary hemostatic plug thrombin plt.contraction- 2ndary hemostatic plug - fibrin

Platelets adhere to extracellular matrix at sites of endothelial injury and become activatedOn activation they secrete granule product (ADP) and synthesize TXA2Platelets also expose phospholipid complexes impt.in the intrinsic coagulation pathwayInjured or activated endothelial cells are expose to tissue factors which triggers the extrinsic coagulation cascadeReleased ADP stimulates formation of primary hemostatic plug, which is eventually converted (via ADP, thrombin and TXA2) into larger definitive secondary plug.Fibrin deposition stabilizes and anchors the aggregated platelets

Coagulation cascade

Thrombosis

1. endothelial injury2. stasis or turbulence of blood flow3. blood hypercoagulability

virchows triad

Endothelial injuryHypertensionTurbulent flow scarred valvesBacterial endotoxinsHomocystinuriaHypercholesterolemiaRadiationCigarrete smoking

Injury cause subendothelial collagen exposure platelet aggregation , plt. adhesion, activation of tissue factor

Alterations of normal blood flowTurbulenceStasis(pool areas) countercurrent

Normal flow laminar flow cells flow at the center plasma at periphery ( clear zone)

Laminar flowcells flow at the centerplasma at periphery ( clear zone

Stasis and turbulenceDisrupts laminar flow plts may draw towards the endotheliumPrevents dilution factors fresh bloodRetard inflow of clotting factorsPromote endothelial cell activation local thrombosis and leukocyte adhesion

Ulcerated atherosclerotic plaque - exposed subendothelial extracellular matrixAbnormal aortic and arterial dilatations aneurysmsMyocardial infarctionsMitral valve stenosis left atrial dilatationsHyperviscousity syndromes polycythemia and sickle cell anemia

HypercoagulabilityPrimary genetic, mutation of factor V, antithrombin III def., protein c & s def., fibrinolysis def., homocysteinuria, variations in prothrombin levelSecondary high risk bed rest and immobilization, MI, tissue damage, cancer, prosthetic heart valves, DIC, heparin induced thrombocytopenia, antiphospholipid antibody ( lupus anticoagulant)

Low risk atrial fibrillation, cardiomyopathy, nephrotic syndrome, hypercoagulable state, oral contraceptive, sickle cell anemia , smokingHeparin induced thrombocytopenia- given heparin body produce antibodies against heparin and complexes with factor 4 resulting in platelet activation or endothelial cell injury (procoagulant)

Antiphospholipid antibody syndrome- antibodies to cardiolipin causing hypercoagulable states SLE recurrence venous and aterial thrombi formation miscarriages cardiac valvular vegetationsTx anticoagulant, aspirin, heparin , coumadinPrednisone miscarriagesimmunosuppression

Fate thrombus1. propagation accumulate more platelet and fibrin leading to vessel obstruction2. embolization thrombi may dislodge and travel to other sites3. dissolution thrombi may be removed by fibrinolytic system4. organization and recanalization Thrombi may induced inflammation and fibrosis and recanalized (reestablish blood flow or may incorporate into a thickened vascular wall)

Venous thrombosisPhlebothrombosis superficial veins saphenous v.- thrombi- pain and tenderness, swelling and congestion- forming varicose ulcersDeep veins (popliteal,femoral,iliac v) more tendency to embolized 50% are asymptomatic

Tumor associated procoagulant released increased risk thrombosis migratory thrombophlebitis ( trousseau syndrome )Arterial thrombosis MI dyskinetic contraction of myocardium mural thrombi rheumatic heart dse - mitral valve stenosis left atrial dilatation- atrial fibrillation - stasis atherosclerosis major initiator of thrombosis loss of endothelial integrity embolized to tissues

Disseminated Intravascular CoagulationMultiple thrombi formation consumption of platelets and factor fibrinolytic systemHemorrhageThrombotic disorder that leads to bleeding disorder

Clinical correlationObstructionEmboli fatal pulmonary embolism

Embolism

Embolus detached intravascular solid, liquid, or a gaseous mass that is carried by the blood to a site distant from its point of origin.99% - dislodged thrombus (thromboembolism)Rare droplets of fats, bubbles of air, atherosclerotic debris (cholesterol emboli), tumor fragment, bits of bone marrow, foreign bodies ( bullets)Potential consequence - infarction

Pulmonary Thromboembolism20 -25% / 100,000 hospitalized patientVenous emboli from deep leg veins goes to the right side of the heart pulmonary vasculature via pulmonary artery (at bifurcation Saddle emboli) some are multiple , small or largeParadoxical embolism pass through an interatrial or interventricular defect- systemic circulation

60-80% are clinically silent because they are just small organized in vascular wall forms webSudden death right sided heart failure cor pulmonale (60%)Pulmonary hemorrhage no infarction due to dual blood flowEmbolic obstruction - does not cause infarctionMultiple emboli pulmonary hypertension right sided heart failure

Systemic ThromboembolismEmboli with an arterial circulation80% intracardial mural thrombi2/3 asso with left ventricular wall infarct dilated left atrium (RHD) and remainder due to aortic aneurysms, thrombi on ulcerated atherosclerotic plaques, fragmentation of valvular vegetationSmall fraction due to paradoxical embolism75% lower extremities, 10% brainGIT , spleen, kidneys, upper extremities are rarely affectedIschemia is the endpoint

Fat EmbolismFracture fatty marrow adipose goes to the circulation90% skeletal traumaManifest 1-3days after injuryTachypnea, dyspnea, tachycardia( lung )Neurological signs irritability, restlessness - delirium and comaMay also precipitate petechial rash, thrombocytopenia - platelets adhering to fat globulesAnemia erythrocyte aggregation and hemolysisCause obstruction and biochemical injury to endotheliumFatal up to 10% cases

Air EmbolismGas bubbles may obstruct vascular flow causing distal ischemic injuryAir - enter circulation obstetric procedure or chest wall injury100cc of gas clinical effectBubbles as frothy mass may occlude major vesselsDecompression syndrome scuba diving/deep sea diving inc. gas like nitrogen dissolved in blood and tissues immediately goes up it expands inside forming bubbles forming gas emboli

Formation of painful gas bubbles within skeletal muscles and supporting tissues like joints BendsMay induce focal ischemia to heart and brainIn lungs - edema , focal hemorrhage, emphysema leading to respiratory distress known as chokesTx compression chamber barometric pressures may be raised to turn gas bubbles into solution. Allows gradual resorption and exhalation of gasCaissons dse chronic form persistence of gas in the heads of the femur, tibia, humerus causing ischemic necrosis

Amniotic fluid Embolism1 in 50,000 deliveriesMortality rate of >80%Sudden onset of dyspnea, cyanosis, hypotensive shock seizures and comaIf survives suffer pulmonary edema, DIC, - due to thrombogenic subs. In amniotic fluidInfusion of amniotic fluid in maternal circulation via tear in placental membrane and rupture of uterine veins

Presence of squamous epithelial cells in the pulmonary circulationAlso seen lanugo, fat ( vernix caseosa) and mucin fetal respiratory and GI tractMarked pulmonary edema diffuse alveolar change , DIC

InfarctionInfarct area of ischemic necrosis caused by occlusion of either arterial supply or venous drainage in a particular tissueMore than half common cause of death CVD99% due to thrombotic or embolic eventsOccasionally due vasospasm, hemorrhage due to plaque, compression by a tumor

Twisting of BV testicular torsion, volvulusCompression by edema Traumatic rupture of blood vessel

Factors that Influence Development of an Infarct1. nature of blood supply2. the rate of development of the occlusion3. the vulnerability of tissue to hypoxia4. blood oxygen content

Nature of Vascular SupplyPresence of alternative blood supply lungs pulmonary and bronchial arteries liver has hepatic artery and portal vein circulation both resist infarction kidneys and spleen are end organs- prone to infarction if blood supply is compromised

Rate of Development of OcclusionPresence of anastomosis will prevent infarctionIf one vessel is occluded collateral circulation may flow sufficiently to prevent infarction

Vulnerability to IschemiaSusceptibility of tissue to ischemia is likely to cause infarctionNeurons goes irreversible damage with in 3-4minHeart 20-30minFibroblast within myocardium maybe viable for many years even after ischemia

Oxygen content of BloodPartial pressure of O2 partial obstruction of small vessel of anemic or cyanotic infarctionCHF - infarction

ShockShock is a cardiovascular collapseFinal common pathway for number of lethal clinical events ( severe Hge, trauma, or burns, MI, massive pulmonary embolism, and microbial sepsisConstitutes systemic hypoperfusion reduced cardiac outputEnd results are hypotension, impaired tissue perfusion reversible cell injury irreversible cell injury

Types of shockCardiogenic shock results from myocardial pump failure MI , ventricular fibrillations, extrinsic compression (cardiac tamponade), outflow obstruction (PE)Hypovolemic shock loss of blood and plasma volume cause by Hge, fluid loss, severe burns, traumaSeptic shock systemic microbial infection gram negative infxn ( endotxin) but also in fungal and gram+ infxn

Neurogenic shock anaesthetic accident or spinal cord injury , affecting vascular tone and peripheral pooling of bloodAnaphylactic shock IgE mediated hypersensitivity response , asso with systemic vasodilation and increased vascular permeability inc vascular bed capacitance not adequately filled by normal circulating bloodHypotension , tissue hypoperfusion and cellular anoxia are the outcome

Septic shockEndotoxic shock gm negative bacteria Endotoxins are Lipopolysaccarides LPS

Stages of shockNon progressive stageProgressive stageIrreversible stage

Non progressive phaseReflex compensatory mechanismPerfusion of vital organs is maintainedBaroreceptor reflexesRelease of cathecholaminesRenin angiotensin axis , ADH , symphathetic stimulationNet effect tachycardia, peripheral vasoconstriction and renal conservation of fluid

Progressive stageHypoperfusion Onset of worsening circulatory and metabolic imbalance (acidosis)Widespread tissue hypoxiaAnaerobic glycolysis lactic acidPh lowered and blunted vasomotor responseArterioles dilate and blood begins to pool in circulationPooling affects CO anoxia - DIC

Irreversible stageIncurred cellular and tissue injury and even hemodynamic defects are corrected survival is not possibleWidespread cellular injury Lysosomal enzyme leakageMyocardial contractile function worsens by NOIschemic bowel may allow intestinal flora to enter circulation endotoxic shockRenal shutdown acute tubular necrosis

Clinical courseHypovolemic and cardiogenic shock presents hypotension ( weak rapid pulse) tachypnea, cold clammy cyanotic skinSeptic shock initiallly warm and flushed due peripheral vasodilationCatastrophe renal insufficiencyHypovolemic shock 70-80% may survive in young individualsCardiogenic and septic shock 75% mortality