Oedema, Infarction, and Shock PDF

Dr. Zuriel 2023  Oedema -Discuss causes -Look at gross features  Infarction -list causes -Brief look of its different types  Shock -discuss the types and their various causes. -Pathophysiology of septic shock. OEDEMA  Signifies increased fluid in the interst...

Dr. Zuriel 2023  Oedema -Discuss causes -Look at gross features  Infarction -list causes -Brief look of its different types  Shock -discuss the types and their various causes. -Pathophysiology of septic shock. OEDEMA  Signifies increased fluid in the interstitial tissue spaces  Categorised according to pathophysiologic mechanism: -Increased hydrostatic pressure -Reduced plasma oncotic pressure(hypoprotenemia) -lymphatic obstruction -Sodium retention -Inflammation  Increased hydrostatic pressure -Local increase may result from impaired venous outflow e.g in DVT -Generalised increases in venous pressure,with resulting systemic edema e.g in congestive heart failure  Reduced plasma oncotic pressure -From excessive loss or reduced synthesis of albumin. e.g nephrotic syndrome,cirrhosis  Lymphatic obstruction -impaired lymphatic drainage and consequent lymphedema is usually localised. -Can result from neoplastic obstruction e.g.Ca breast or inflammatory e.g parasitic infection,filariasis  Sodium and water retention -May occur with any acute reduction in renal function e.g in glomerulonephritis & acute renal failure.  Microscopically oedema fluid manifests only as subtle cell swelling with clearing & separation of the extracellular matrix elements.  Oedema is most easily recognised grossly. >Subcutaneous oedema - finger pressure displaces the interstitial fluid and leaves a depression(pitting edema) -or as periorbital oedema. >Pulmonary edema: -The lungs are 2-3 times their normal weight. -Sectioning reveals frothy blood tinged fluid(a mixture of air,edema fluid & extravasated red blood cells.) Brain edema -Grossly the brain appears swollen with narrowed sulci and distended gyri INFARCTION  An infarct is an area of ischaemic necrosis caused by occlusion of blood supply to a particular tissue.  99% result from thrombotic or emboli events.  Almost all result from arterial occlusion.  Other occasional causes include mechanisms such as -local vasospasm -extrinsic compression of a vessel e.g. by a tumour.  Other uncommon causes include: -Twisting of the vessel e.g. testicular torsion. -Entrapment in a hernial sac -Traumatic rupture of the blood supply.  Infarcts from venous occlusion are rare due to by-pass channels providing collateral flow. -they are seen in organs with single venous outflow channels e.g. testis & ovary  Most infarcts tend to be wedge shaped.  When the base is a serosal surface,  here is often an overlying fibrinous exudate.  The lateral margins can be irregular,reflecting the pattern of vascular supply from adjacent vessels.  At the outset,all infarcts are poorly defined & slightly hemorragic -the margins become better defined with time.  Most are ultimately replaced by scar tissue.  Can be classified on: 1. basis of colour(reflecting the amount of hemorrage): -Red(haemorrhagic) -White(anemic) 2. Presence or absence of microbial infection into -Septic -Bland  With venous occlusion e.g in ovarian torsion  In tissues with dual circulation e.g lung & small intestine permitting blood flow from the unobstructed vessel into the necrotic zone.  In tissues previously congested because of sluggish venous outflow.  When flow is re-established to a site of previous arterial occlusion & necrosis e.g following angioplasty of a thrombotic lesion  Occur with arterial occlusions in solid organs with end arteries e.g heart,spleen & kidney  The solidity of the tissue limits the amount of hemorrage that can seep into the area of ischemic necrosis from adjoining tissues.  May develop when: > embolisation occurs by fragmentation of a bacterial vegetation from a heart valve > or when microbes seed an area of necrotic tissue.  In these cases,the infarct is converted into an abscess.  The dominant histologic characteristic of infarction is ischemic coagulative necrosis.  Ultimately,most infarcts are replaced by scar tissue.  The brain is an exception. -ischaemic injury in the CNS results in liquefactive necrosis. SHOCK  Shock a.k.a cardiovascular collapse  is the final common pathway in potentially lethal clinical events such as -severe hemorrage -extensive trauma or burns -large myocardial infarction -massive pulmonary embolism - and microbial sepsis  Shock gives rise to systemic hypoperfusion -through reduction in the effective circulating blood volume.  The end results are hypotension -followed by impaired tissue perfusion and cellular hypoxia.  Initially reversible but persistent shock culminates in death.  Grouped into general categories: -Cardiogenic shock -Hypovolemic shock -septic shock -neurogenic -Anaphylactic  Results from myocardial pump failure due to: -intrinsic myocardial damage(infarction) -Ventricular arrythmias -Extrinsic compression(cardiac tamponade) -or outflow obstruction e.g. pulmonary embolism.  Results from loss of blood or plasma volume due to: -hemorrage -fluid loss from severe burns -Trauma  Is caused by systemic microbial infection.  Most commonly occurs in the setting of gram negative infection( endotoxic infection)  Can also occur with gram positive & fungal infections.  Less common.  Is shock that occurs in the setting of anesthetic accidents or spinal cord injury - owing to loss of vascular tone and peripheral blood pooling.  Due to a generalised IgE-mediated hypersensitivity response.  Is associated with systemic vasodilation & increased vascular permeability -widespread vasodilation causes sudden increase in the vascular bed capacitance -This is not adequately filled by the normal circulating blood volume -Hypotension,tissue hypoperfusion & cellular anoxia result.  The cellular & tissue changes induced by shock are essentially those of hypoxic injury. May appear in any tissue >Heart - may undergo focal or widespread coagulation necrosis >Kidneys – typically exhibit extensive tubular ischemic injury(acute tubular necrosis)  >GIT – may suffer patchy mucosal hemorrages & necroses (hemorragic enteropathy) >Lungs – when shock is caused by bacterial sepsis or trauma,changes may appear of diffuse alveolar damage (shock lung) >Liver – May develop fatty changes & with severe deficits,central hemorragic necrosis.  Septic shock ranks first among the causes of mortality in ICU.  It results from spread & expansion of an initially localised infection into the bloodstream  Approx. 70% are caused by endotoxin- producing gram negative bacilli hence the term endotoxic shock.  Endotoxins are bacterial wall lipopolysaccharides (LPS) that are released when the cell walls are degraded (e.g in inflammatory response)  At low doses, LPS activate monocytes and macrophages intended to enhance the ability to eliminate invading bacteria. -LPS also directly activate complement which likewise contributes to local bacterial eradication. -The mononuclear phagocytes respond to LPS by producing cytokines mainlyTNF,IL-1,IL-6 and chemokines. -TNF & IL-1 act on endothelial cells to stimulate adhesion molecules, more cytokines & chemokines. -The initial release of LPS is thus intended to enhance the local acute inflammatory response & clear infection.  With moderately severe infections & therefore higher levels of LPS there is a consequent augmentation of the cytokine cascade. -Cytokine induced secondary effectors e.g. nitric oxide become significant. -Systemic effects of cytokines such as TNF & IL-1 begin to be seen;these include fever & increased synthesis of acute phase reactants. -LPS at higher doses also results in diminished endothelial cell production of thrombomodulin & TFPI(Tissue factor pathway inhibitor) tipping the coagulation cascade towards thrombosis.  Finally at higher levels of LPS,the syndrome of septic shock intervenes. -The same cytokines & secondary mediators at high levels cause:  -systemic vasodilation(hypotension) -Diminished myocardial contractility -Widespread endothelial injury & activation, causing systemic leukocyte adhesion & pulmonary alveolar capillary damage(ARDS) -activation of the coagulation system culminating in DIC.  Hypoperfusion from the widespread vasodilation,myocardial pump failur & DIC result in multiorgan system failure.