Hemorrhage, Hemostasis and Circulatory Shock

HemorrhageExtravasation of blood due to ruptured vesselsFrom hemo = blood, rrhagia = to burst forthHemorrhage may be external or internalHemorrhage may be obvious (gross) or hidden (occult)This is whole blood with RBCs, not just edemic transudates or exudates

How much blood loss?Class I: up to 15% of blood volumetypically no change in vital signsroutine blood donation amounts to ~10%Class I: 15-30% of total blood volumetachycardia (rapid heart beat) with a narrowing of the difference between the systolic and diastolic blood pressurescompensatory peripheral vasoconstriction; cool, pale skin; altered mental status, dizzy or confusedfluid resuscitation with saline or Lactated Ringer's solutionClass III: 30-40% of circulating blood volumeblood pressure drops, heart rate increases, peripheral perfusion worsens, mental status worsens fluid resuscitation and/or blood transfusionClass IV: >40% of circulating blood volumehypovolemic shock--limit of the body's compensation is reachedaggressive resuscitation is required to prevent death

Indications of internal hemorrhageDeepAnemiafewer circulating RBCsIncreased indirect bilirubin (unconjugated, albumin-bound)SurfaceHemorrhage under the skin or mucous membranes looks red (oxygenated Hb) or purple (deoxygenated Hb)

Enclosed bleeding by size and shapePetechiae are flat, tiny, 1- to 2-mm, multifocallocally increased intravascular pressure, coagulation (platelet) defects, the trauma of sudden hypoxia (strangulation) from Italian, petecchie = flea bites (puh-teek-ee-uh)petechia (s.); petechiae (pl.); petechial (adj)Purpura are flat, small, 1 mm, multifocalTerm used to describe platelet-related bleeding disorders that result in bruised skin and/or mucous membranesfrom Latin, purpleEcchymoses, contusions (bruises) are smooth and noticeably large, >1 cm, focaltrauma, vascular inflammationchymose = juicyHematoma are emergent, lumpy, hardened, focalClotted blood collected near the skin surface or internally at serosal surfaces or aneurysms

Colors of bruisingInitial hemorrhage of RBCs into tissue is cleared by macrophages, which process Hb Oxyhemoglobin and DeoxyhemoglobinDeoxyhemoglobin and BiliverdinBiliverdin and BilirubinBilirubin and HemosiderinHemosiderinWhen iron and porphyrins are completely cleared, tissue resumes normal color

Distribution of hemorrhage(s)Multifocal indicates problem affecting vessels or plateletsthrombocytopenia or thrombocytopathy reduced number or function of platelets preventing coagulationinherited coagulation defectshemorrhagic diathesisanticoagulants inhibit production of vitamin K-dependent coagulation proteinsend stage hepatic disease. With approximately 80% loss of functional hepatic tissue, production of coagulation factors can become inadequate.disseminated intravascular coagulation (DIC)coagulation out of controlvasculitisimmune mediated--precipitation of Ag-Ab complexes, which are chemotactic for neutrophils, resulting in vascular damageinfections of endotheliumFocal distributionsingle or a few focal hemorrhages are typical of trauma regional neoplasm, thrombosis, or microbial invasionproblems with protein clotting factors

Petechiae from strangulation

Petechiae

Petechiae

Petechiae or purpurae

Senile or actinic purpura

Echymoses or contusions

Hematoma--subdural

Hematoma

Subcapsular hematoma

HemopericardiumThis is hemopericardium as demonstrated by the dark blood in the pericardial sac opened at autopsy. Penetrating trauma or massive blunt force trauma to the chest (often from the steering wheel) causes a rupture of the myocardium and/or coronary arteries with bleeding into the pericardial cavity. The extensive collection of blood in this closed space leads to cardiac tamponade. A pericardiocentesis, with needle inserted into the pericardial cavity, can be a diagnostic procedure.

Gastrointestinal hemorrhageWhen rate is slow, blood is digested or lost in fecesIn upper GI, blood turns black and tarry as it is digested and is called melenaMelena is symptomatic of peptic ulcers, ruptured esophageal varices, cancersIn lower GI, blood remains red and is excreted with fecesFecal occult blood test; now fecal immunochemical testFOBT used dye adsorbed on paper to detect Fenton reaction catalyzed by heme ironFIT uses Ab against globin portion of hemoglobin

Hemorrhage into cavitiesPleural hemorrhagehemothoraxBuild-up of pressure prevents lung expansionPrevents gas exchangeMay lead to lung collapseInstigates coughing or hiccups, which exacerbates bleedingPericardial hemorrhagehemopericardiumBuild-up of external pressure inhibits fillingCardiac tamponade = compressionIntracranial hemorrhageAlways bad because of the rigid craniumCSF pressure increases rapidly if bleeding rate is greater than rate of fluid resorption

HemodynamicsMaintenance of blood volume Maintenance of blood pressureMainenance of clot-free flowplasminDevelopment of clot in response to vascular damagehemostasisthrombin-fibrin

Mechanism of hemostasisReflex sympathetic noradrenergic vasoconstrictor system activated locallyDamaged vascular endothelium releases endothelin10 times more potent than angiotensin II Platelets contact collagenprimary hemostasisAdhere: GpIb receptor tethered to collagen via vWFSecrete: ADP, TxA2, Ca++, growth and clotting factorsAggregate: Ca++ bridges with surface phosphoserineCoagulation cascadesecondary hemostasisStimulated by tissue factor (factor III)Platelets, fibrin, net of captured RBCs and WBCs

Primary hemostatic clot formationPlatelets are activated by contact with Extra Cellular MatrixCirculating von Willebrand Factor tethers platelet glycoprotein receptors to ECM collagenThrombin is released to cleave fibrinogen creating fibrin nets that capture more platelets as well as RBCs and WBCsPlatelets contract with microtubular contractile proteins, consolidating plug

Hemostatic clot resolutiontPA, tissue plasminogen activator, cleaves plasminogen to plasminPlasmin digests fibrin clotTightly regulated yin-yang of hemostasis

Platelet structureAnuclear cell fragments synthesized in marrowSurface glycoprotein Ib and IIa/IIIb receptorsInternal alpha granules containing Factors V and VIII and IVFibrinogen, fibronectin, thromboxaneA2PDGF, TGF-bInternal dense granules containing ATP, ADP and Ca++Histamine, serotonin, epinephrineInternal canaliculiopen canalsContractile cytoskeletal fibers

Platelet structure

Platelet actionsAdhesion to extracellular matrixGpIb links to collagen via vWFGpIIb/IIIa links platelets via fibrinogenSecretion from granules into canaliculi and exteriorTransition of phosphlipids to outer laminaAggregationPrimary hemostatic plugContractionSecondary hemostatic plug

Platelet aggregation

Clotting v. thrombosisTHROMBUS: Blood that has solidified within the vascular lumens or cardiac chambersCLOT: Blood that has solidified anywhere else THROMBOEMBOLISM: Portion of thrombus that travels through the vasculature to form a plug elsewhereEMBOLISM: vascular plug, not always from a thrombus

Consequences of acute hemorrhageLoss of blood beyond a certain volume will cause systemic hypotensionrapid compensation by the baroreceptor response leads to peripheral vasoconstrictionfluids shift from the interstitial into the IV compartmentslower response from the renin-angiotensin-aldosterone system results in vasoconstriction and retention of sodium and water by the kidneyantidiuretic hormone (ADH) also kicks in, acts on nephron to promote water resorptionLoss of blood beyond the body's ability to compensate will cause systemic hypotension, reduced cardiac filling, reduced tissue perfusion, loss of erythrocytes and their Hb, hypoxemia, and a further cascade of events called shock

Hypovolemic, cardiogenic shockCausesBlood lossDehydrationReduced cardiac outputDeranged peripheral vasomotor controlConsequensesInadequate perfusionHypoxia, lactic acidosisRecovery dependent on duration and severity

Stages of ShockEarly StageCompensatory mechanisms maintain perfusion of vital organsInclude increased heart rate and increased peripheral resistance Progressive StageCompensatory systems no longer adequate with tissue hypoperfusionOnset of circulatory and metabolic imbalance, especially metabolic acidosis from lactic acidemia Irreversible StageOrgan damage and metabolic disturbancesSurvival not possible

Clinical consequencesHypotensionWeak, rapid pulse (tachycardia)Shallow rapid breathing (tachypnea)Cool, damp, cyanotic skinTissue injuries are due to hypoxia

*http://usmlewiki.org/index.php?title=USMLE_Wiki:Hemodynamic_Disordershttp://www.pathguy.com/lectures/fluids.htm#introhttp://www.pathologyoutlines.com/coagulation.html**American College of Surgeons' Advanced Trauma Life Support (ATLS) classification scheme for hemorrhages**http://www.pathguy.com/sol/07554.jpg*http://www.pathguy.com/sol/21433.jpg*http://library.med.utah.edu/WebPath/ATHHTML/ATH035.html*http://www.pathguy.com/sol/14287.jpg*Senile indicates presentation in old, elderly skin, whereas actinic implies UV damage from the suns rays. Hemorrhage due to weakened vessels exposed to UV and/or oxidative stress.*http://library.med.utah.edu/WebPath/ATHHTML/ATH036.html*From PIERImage 1846, 1854Brain: Subdural Hematoma: Gross good example multiple trauma*From PIER Image# 200331 CAT scan shows resolving encapsulated hematomaImage# 16946 Brain, subarachanoid hemorrhage and hematoma due to ruptured aneurysm*From PIERImage 1658 liver of neonate, subcapsular fresh hematomaImage 8770 spleen Subcapsular Hematoma: Gross natural color sectioned spleen showing lesion very wellImage 3095 kidney Subcapsular Hematoma: Gross natural color excellent example*http://library.med.utah.edu/WebPath/FORHTML/FOR034.html*Why is FIT more specific to lower GI bleeding than FOBT?**FIGURE 45A Normal hemostasis. A, After vascular injury local neurohumoral factors induce a transient vasoconstriction. *B, Platelets bind via glycoprotein Ib (GpIb) receptors to von Willebrand factor (vWF) on exposed extracellular matrix (ECM) and are activated, undergoing a shape change and granule release. Released adenosine diphosphate (ADP) and thromboxane A2 (TxA2) induce additional platelet aggregation through platelet GpIIb-IIIa receptor binding to fibrinogen, and form the primary hemostatic plug. *C, Local activation of the coagulation cascade (involving tissue factor and platelet phospholipids) results in fibrin polymerization, cementing the platelets into a definitive secondary hemostatic plug. *D, Counter-regulatory mechanisms, mediated by tissue plasminogen activator (t-PA, a fibrinolytic product) and thrombomodulin, confine the hemostatic process to the site of injury.*http://library.med.utah.edu/WebPath/ATHHTML/ATH034.html*http://sandwalk.blogspot.com/2007/04/blood-clotting-platelets.html