Shock (PDF)

ACIDIC SURGERY NA SIYA KASI MABABA NA SCORES NATIN SHOCK, NAKAKAGULAT GRADES SA SURG :O LECTURER: DR. DAGA NI SHILOH (HAYOP KAYO PATI BA NAMAN DITO) SHOCK...

ACIDIC SURGERY NA SIYA KASI MABABA NA SCORES NATIN SHOCK, NAKAKAGULAT GRADES SA SURG :O LECTURER: DR. DAGA NI SHILOH (HAYOP KAYO PATI BA NAMAN DITO) SHOCK Can be due to pulmonary embolism or tension pneumothorax Soft tissue and bony injury lead to the Shock, regardless of its etiology, is the failure to meet the activation of inflammatory cells metabolic needs of the cell and the consequences that TRAUMATIC The release of circulating factors, such ensue as cytokines modulate the immune o Initial cellular injury that occurs is reversible response o However, the injury will become irreversible if tissue perfusion is prolonged or severe enough such that, at CORE PRINCIPLES IN THE MANAGEMENT OF THE CRITICALLY the cellular level, compensation is no longer possible ILL/INJURED PATIENT Definitive control of the airway Central component = decreased tissue perfusion (edi walang dugo), Control of active hemorrhage kapag hindi nakarating yung blood (oxygen) and other substances na kailangan sa cells, doon na magkakaroon ng shock. So TANDAAN, o “paramount priority” basically, ang shock ay due to DECREASED TISSUE PERFUSION na Volume resuscitation (blood products > crystalloid) pwedeng galing sa either cellular or direct effect, mamaya pag - o While operative control of bleeding is achieved uusapan ‘yan, which will eventually leads cellular hypoxia/ischemia. Unrecognized or inadequately corrected hypoperfusion o increases morbidity and mortality HISTORICAL BACKGROUND Excessive fluid resuscitation He documented that the shock state in hemorrhage was o may exacerbate bleeding associated with reduced CO due to volume loss, not a Management of shock. Ito ‘yung dapat mong malaman, kasi wala “toxic factor” kang alam. If nag-basic life support na kayo, alam niyo na sina ABCDE. In 1934, Blalock proposed four categories of shock: Same lang ‘yan dito, una DEFINITIVE CONTROL OF AIRWAY, like may hypovolemic, vasogenic, cardiogenic, and neurogenic obstruction, control mo through oxygen or intubation. CONTROL OF HEMORRHAGE kapag need pa rin maka-deliver ng oxygen ang blood nang maayos, kasi kapag tinanggal mo obstruction, makakahinga ka CATEGORIZATION OF SHOCK nang maayos kasi oks na airway mo, pero ang oxygen hindi naman Most common type, results from loss of delivered nang maayos kasi nga may hemorrhage, edi wala rin, kaya circulating blood volume siya “paramount priority”. Next is VOLUME RESUSCITATION, This may result from loss of whole blood replacement of volume loss lang ‘yan through fluid infusion if controlled HYPOVOLEMIC (hemorrhagic shock), plasma, na ang bleeding mo, ‘Yung INADEQUATELY CORRECTED interstitial fluid (bowel obstruction), or HYPOPERFUSION, sa blood loss kapag ‘di mo napalitan, edi a combination hypoperfused haha, may decrease sa venous return, si heart mo hindi Results from decreased resistance makakapag-pump nang maayos edi deads ka. EXCESSIVE FLUID within capacitance vessels (VEINS), RESUSCITATION naman, example na-clot ka tapos nag-bleed ulit; or sa VASOGENIC mga trauma like head trauma, kapag naglagay ka ng trauma, usually seen in sepsis pwedeng magkaroon ng cerebral edema kapag hindi controlled. Form of vasogenic shock in which spinal cord injury or spinal anesthesia CURRENT DEFINITIONS & CHALLENGES NEUROGENIC causes vasodilation due to acute loss of sympathetic vascular tone Modern definition and approach to shock acknowledges that shock consists of inadequate tissue perfusion marked: Results from failure of the heart as a o Decreased delivery of required metabolic substrates CARDIOGENIC pump, as in arrhythmias or acute o Inadequate removal of cellular waste products myocardial infarction o Failure of oxidative metabolism that can involve NEWEST ADDITION IN CLINICAL PRACTICE defects of oxygen (O2) delivery, transport, and/or Form of cardiogenic shock that results utilization from mechanical impediment to Current challenges include moving beyond fluid OBSTRUCTIVE circulation leading to depressed resuscitation based upon endpoints of tissue oxygenation cardiac output rather than primary and using therapeutic strategies at the cellular and cardiac failure molecular level KUMUNOY’S IMPROPERTY 1  ACIDIC SURGERY NA SIYA KASI MABABA NA SCORES NATIN SHOCK, NAKAKAGULAT GRADES SA SURG :O LECTURER: DR. DAGA NI SHILOH (HAYOP KAYO PATI BA NAMAN DITO) With continued hypoperfusion, which may be UNRECOGNIZED, CELLULAR DEATH AND INJURY ARE OF SHOCK ONGOING DECOMPENSATED Microcirculatory dysfunction, PHASE parenchymal tissue damage, and Regardless of etiology, the initial physiologic responses in inflammatory cell activation can May changes na shock are driven by tissue hypoperfusion and the perpetuate hypoperfusion + sa Vital signs tapos developing cellular energy deficit. nag-r’regress pa Ischemia/reperfusion injury exacerbates initial insult → Compromise of function at the Cellular Effect organ system level, thus leading to - Disruption host- the “VICIOUS CYCLE” of shock microbe equilibrium Persistent hypoperfusion results in - Trauma FURTHER HEMODYNAMIC DERANGEMENTS AND CVS COLLAPSE Direct Effect IRREVERSIBLE Extensive parenchymal and - Acute heart failure PHASE microvascular injury such that - Neurogenic volume resuscitation fails to reverse - Hemorrhage the process, leading to death Ito yung “vicious cycle” sa Cellular effect and Direct effect decompensated Sa cellular level, meron tayong trauma and disruption host-microbe phase na sinasabi, equilibrium (refer sa pic). Sa TRAUMA, alam naman natin na may tissue for example tuloy injury dito and ito ang magerelease ng DAMPS naalala sa prelims? So tuloy yung itong mga DAMPS na to can stimulate inflammatory responses which hypoperfusion, can lead to decreased tissue perfusion. Sa DISRUPTION HOST MICROBE, bleed ka lang dito pumapasok yung bacterial products or endotoxins for example NANG bleed, yung yung Lipopolysaccharides (LPS) → decreased tissue perfusion. mga sinabi under Sa direct effect naman dito derecho na ang result ay decreased tissue DECOMPENSATED PHASE bullets sa table will lead to decreased cardiac perfusion. Pwedeng acute heart failure or neurogenic or sa output. DECREASE CARDIAC OUTPUT → DECREASE TISSUE PERFUSION → hemorrhage. ACUTE HEART FAILURE, direct kasi diretso mismo, may DECREASE VENOUS RETURN, CELLULAR HYPOXIA, AND DECREASE abnormality ka sa heart mo di nag-p’pump nang maayos, decreased CORONARY PERFUSION. Tapos paulit ulit lang yang cycle na yan which perfusion agad → hypoxia → shock. Sa NEUROGENIC for example will eventually lead to irreversible phase. spinal cord injury (neurogenic shock), mag vvasodilate diba kasi nasira In addition, yung sa DECREASED TISSUE PERFUSION, ganun din yan. Dahil na nerves mo, san na dadaan yang mga sympathetic shit mo para may decrease sa perfusion nagkakaroon ng parenchymal cell injury, magpunta sa A1 adrenergic receptor para mag constrict? endothelial activation/microcirculatory damage and cellular HAHAHAHAH JOKE TANGINA di ko naman alam yan f*ck pharma aggregation, paulit ulit lang din hanggang maging irreversible na mga (RUFFAKE AMBOBO MO NAMAN). So sira na nerves mo, wala ng signal damage. Walang maayos na oxygen na rerecieve, malamang to vasoconstrict → vasodilation → decreased tissue pefusion na agad masisira. Diyan papasok syempre kaya kailangan mo magawa yung → shock. Sa hemorrhage alam niyo na yan sinabi na kanina. core principles ng management kanina, para ma-break yang cycle and eventually, bumalik sa compensated phase yung patient at 3 STAGES OF SHOCK mabuhay. Body can compensate for the initial The specific responses will differ based on the etiology of loss of blood volume primarily shock: COMPENSATED through the NEUROENDOCRINE o Cardiovascular response driven by the sympathetic PHASE RESPONSE to maintain nervous system is markedly blunted in neurogenic or hemodynamics septic shock KUMUNOY’S IMPROPERTY 2  ACIDIC SURGERY NA SIYA KASI MABABA NA SCORES NATIN SHOCK, NAKAKAGULAT GRADES SA SURG :O LECTURER: DR. DAGA NI SHILOH (HAYOP KAYO PATI BA NAMAN DITO) o Decreased perfusion may occur as a consequence of Wag lang ikaw :’) SEE TAGLANDI KA LANG DITO AMP. Babawasan cellular activation and dysfunction, such as in septic blood flow sa lahat para maibigay sa heart at brain. So ang shock and to a lesser extent traumatic shock mechanism niyan ay autonomic control daw so autonomic nervous system, increase contractility ng heart (ano receptor joke ayoko na Many of the organ-specific responses are aimed at nga, BETA 1 NUBA RUFFAKE KATANGA), syempre para mas may maintaining perfusion in the cerebral and coronary distribute kang dugo, tapos peripheral vasoconstriction para ma-limit circulation yung blood supply doon sa di naman priority. Tapos involved din mga o Stretch receptors and baroreceptors in the heart and hormones (response to stress daw epinephrine yiiee pharma). Tapos sa vasculature (carotid sinus and aortic arch) regulate regional blood flow, ayun nga, lessen yung pag bigay ng o Chemoreceptors blood sa ibang region/organs. o Cerebral ischemia responses o Release of endogenous vasoconstrictors AFFERENT SIGNALS o Shifting of fluid into the intravascular space Afferent impulses transmitted from CNS reflexive effector o Renal reabsorption and conservation of salt and water responses or efferent impulses These effector responses are designed to: o Expand plasma volume o Maintain peripheral perfusion and tissue O2 delivery o Restore homeostasis Other stimuli that can produce the neuroendocrine response include: o Pain, hypoxemia, hypercarbia, acidosis, infection, change in temperature, emotional arousal, or hypoglycemia Sensation of pain from injured tissue is transmitted via the spinothalamic tracts → activation of the HPAA axis and Eto experiment sa daga. Yung arrow na mahaba from 80 tas bumaba ANS → direct sympathetic stimulation of the adrenal yan yung percentage ng blood loss, tapos yung mga arrow na pataas medulla → catecholamine release yan yung survival rate. Wag mo ng titigan ng matagal, ang sinasabi Baroreceptors also are an important afferent pathway in lang dyan as blood loss increases, yung survival rate mo bumababa, initiation of adaptive responses to shock so at 0% blood loss, 100% survival rate, sa 10% blood loss naman, 90% o These receptors normally inhibit induction of the ANS survival rate and so on. Sa 50% blood loss, patay ka na. → When activated, these baroreceptors diminish their output, thus disinhibiting the effect of the ANS NEUROENDOCRINE & ORGAN-SPECIFIC RESPONSES → ANS increases its output via sympathetic activation at Goal of the neuroendocrine response to hemorrhage is to the vasomotor centers of the brain stem centrally maintain perfusion to the heart and the brain, even at the mediated constriction of peripheral vessels expense of other organ systems o Autonomic control of peripheral vascular tone and VOLUME RECEPTORS AORTIC & CAROTID BODIES cardiac contractility Sensitive to changes in Respond to alterations in o Hormonal response to stress and volume depletion both chamber pressure or stretch of the o Local microcirculatory mechanisms that are organ pressure and wall arterial wall specific and regulate regional blood flow stretch Responding to larger Initial stimulus = loss of circulating blood volume in Present within the area reductions in intravascular hemorrhagic shock Activated with low volume or pressure The magnitude of the neuroendocrine response is based volume hemorrhage on both the volume of blood lost and rate at which it is lost or mild reductions in right atrial pressure Uyy si big boss niyo nakakita ng “Autonomic” o di kaya “hormonal”. Autonomic control daw oh ano kaya yan simpatetik o parasimpatetik? Chemoreceptors in the aorta and carotid bodies are HAHAHA nakakaramdam yiiiee eexplain niya yannn HAHAHAH! HINDI sensitive to changes in O2 tension, H+ ion concentration, NA NGA SIGE NA, BAKA KUNG SAAN PA AKO MAPUNTA HAHA TAENA and carbon dioxide (CO2) levels MO RUFFAKE. Pero eto lang ang fake kumz explanation. Ang sinasabi o Stimulation of the chemoreceptors: lang sa neuroendocrine response sa shock ay yung pag compensate → Vasodilation of the coronary arteries nito na i-priority ang supplies sa HEART AND BRAIN, mawala na lahat! KUMUNOY’S IMPROPERTY 3  ACIDIC SURGERY NA SIYA KASI MABABA NA SCORES NATIN SHOCK, NAKAKAGULAT GRADES SA SURG :O LECTURER: DR. DAGA NI SHILOH (HAYOP KAYO PATI BA NAMAN DITO) → Slowing of the heart rate → This is compensated by ↑ cardiac heart rate and → Vasoconstriction of the splanchnic and skeletal contractility, as well as venous and arterial circulation vasoconstriction o Protein and nonprotein mediators that act as afferent → (+)sympathetics → (+)β1-adrenergic receptors → ↑ heart impulses to induce a host response (so aside sa rate and contractility↑ cardiac output neuroendocrine, meron din nitong mga inflammatory response) → ↑ myocardial O2 consumption due to increased → Histamine; Eicosanoids; Cytokines; Endothelins workload: myocardial O2 supply must be maintained o ↑ sympathetics catecholamine release from adrenal Shet neuroanatomy. Pero alam niyo na yan! Again afferent, from medulla sensory receptors papunta sa CNS. So for example pag naka sense ka Levels peak within 24-48 hours of injury and return to baseline ng pain from injured tissue, yung afferent signal na yan pupunta sa CNS Persistent elevation of catecholamine levels beyond this time para mag produce ng effector response which is yung release ng suggests ongoing noxious afferent stimuli catecholamines. May mga volume receptors din na nasa wall ng chamber ng heart, so pag nakadetect ng stretch mag gegenerate ng Catecholamine effects on peripheral tissues include: afferent signal. Aortic arch and carotid bodies receptors naman which ALAM NIYO NA TO LAHAT TO FOR ↑ GLUCOSE response to change in pressure sa arterial wall at mas nakakasense ng o (+)hepatic glycogenolysis larger reductions of volume. May mga baroreceptors din na pag o (+)gluconeogenesis naactivate, nadidisinhibit ang ANS → ANS increase in output → o (+)skeletal muscle glycogenolysis centrally mediated peripheral constriction (again to compensate o (-)suppression of insulin release diba?). Chemoreceptors naman na sensitive sa O2 tension, H+ ion and o (+)glucagon release CO2 levels. HORMONAL RESPONSE EFFERENT SIGNALS Shock stimulates the hypothalamus to release CRH release of CARDIOVASCULAR RESPONSE ACTH by the pituitary So nasa efferent na o ACTH (+) adrenal cortex to release cortisol acts tayo, responders na synergistically with epinephrine and glucagon catabolic to alam niyo na yan!! state So sa hemorrhage o Cortisol stimulates gluconeogenesis and insulin resistance paulit ulit na kanina, (aims to provide substrate for hepatic gluconeogenesis) baba venous return, → Hyperglycemia baba output, pano → Muscle protein breakdown ngayon mag → Lipolysis ccompensate? Edi o Cortisol causes retention of sodium and water by the malamang increase nephrons pumping/ o Severe hypovolemia: ACTH secretion occurs contractility ng independently of cortisol negative feedback inhibition heart. Alam na natin na ang Cortisol ang stress hormone. So in times of stress, So nasa efferent na tayo, responders na to alam niyo na yan!! So sa mag aactivate ang HPA axis. CRH → ACTH → CORTISOL. Itong cortisol hemorrhage paulit ulit na kanina, baba venous return, baba output, na to acts as synergist with epi and glucagon which all release more pano ngayon mag ccompensate? Edi malamang increase glucose in times of stress. Ang pinaka point lang nito ay maglabas ng pumping/contractility ng heart. Yung mga SYMPATHETICS nag iinitiate mga pag ukunan ng source of energy kaya sila Catabolic state, para niyan diba, B1 receptors!!! Tapos syempre tataas din myocardial O2 icatabolize ang mga energy source mo to produce energy, kaya may consumption mo, syempre mataas din workload ng heart eh. Meron proteolysis din at lipolysis. Retention of Na and H2O din to maintain fluid din release ng catecholamines from adrenal medulla dahil sa levels lalo na sa mga bleeding. sympathetic activity, dyan na ngayon papasok yung biochem responses, all for compensation. Alam niyo na dapat yan masyadong mahaba pag iisa isahin pa yan!!! take note lang sa suppression ng insulin ha, malamang suppressed yan kasi insulin promotes glycogenesis, eh kailangan mo nga glucose for energy to compensate sa mga nangyayari, so inhibit yan. Changes in cardiovascular function are a result of the neuroendocrine response and ANS response to shock: o Hemorrhage → ↓ venous return → ↓ output KUMUNOY’S IMPROPERTY 4  ACIDIC SURGERY NA SIYA KASI MABABA NA SCORES NATIN SHOCK, NAKAKAGULAT GRADES SA SURG :O LECTURER: DR. DAGA NI SHILOH (HAYOP KAYO PATI BA NAMAN DITO) Renin-angiotensin system is activated in shock HEMODYNAMIC RESPONSES TO DIFFERENT TYPES OF SHOCK Stimulus of renin release: TYPES OF Hypovo Septic Cardiogenic Neurogenic o Decreased renal artery perfusion SHOCK lemic o β-adrenergic stimulation CARDIAC ↓ ↑↑ ↓↓ ↑ o Increased renal tubular sodium concentration INDEX o Angiotensin I has no significant functional activity SVR ↑ ↓ ↑↑ ↓ o Angiotensin II VENOUS ↓ ↑ → → → Potent vasoconstrictor of both splanchnic and peripheral CAPACITANCE vascular beds CVP/ PCWP ↓ ↑↓ ↑ ↓ → Stimulates the secretion of aldosterone, ACTH, and SVO2 ↓ ↑↓ ↓ ↓ antidiuretic hormone (ADH) (preservation of CELLULAR/ intravascular volume) METABOLIC Effect Cause Effect Effect Pinagsawaan na natin to lahat last year pa kung paano tong renin- EFFECTS angiotensin na to, alam niyo na rin sa pharma, alam niyo na kung ano CIRCULATORY HOMEOSTASIS triggers nito, kung paano niya napapataas ng BP as well as yung mga pathway ng angiotensin na yan so mag focus tayo sa trip niya dito sa shock. Angiotensin II ay potent vasoconstrictor daw ng both splanchnic and peripheral vascular beds, para saan yan? Lagi yan pag sinabi dito sa shock na vasoconstrictor ng ganyan, laging to promote blood supply sa heart and brain. Aanhin mo ba blood supply sa GIT in times of shock? Tandaan na priority lagi HEART at BRAIN! Hindi yung puro heart lang masasaktan ka niyan sige ka. Tapos this stimulates the release of aldosterone and ADH. Para saan nanaman? Edi to conserve fluids through reabsorption ng sodium and water at paglabas ng potassium at H+. ALDOSTERONE & VASOPRESSIN/ADH CIRCULATORY HOMEOSTASIS Mineralocorticoid At rest, the majority of the blood Acts to promote reabsorption of sodium volume is within the venous system ALDOSTERONE and water PRELOAD Degree of tension on the muscle Potassium and hydrogen ions are lost in when it begins to contract when the urine in exchange for sodium ventricles becomes filled Ito ang filling or Released by pituitary gland in response to: End-Diastolic Wall Tension (EDV) pag puno ng o Hypovolemia o Generated by venous return to the heart coming from o Changes in circulating blood volume heart circulation in terms o Increased plasma osmolality (kasi nga o Major determinant of cardiac of venous return. diba nireretain ang sodium) output So pag mas o Epinephrine, angiotensin II marami kang Most alterations in cardiac output in o Pain, and hyperglycemia blood na pumunta the normal heart are related to ADH acts on the distal tubule and sa heart, changes in preload collecting duct to: masstretch, mas Net effect of preload on CO is o Increase water permeability malakas ang influenced by cardiac determinants VASOPRESSIN o Decrease water and sodium losses pump (systolic). of ventricular function or ADH o Preserve intravascular volume Shunts blood away from splanchnic o Coordinated atrial activity organs during hypovolemia causing o Tachycardia intestinal ischemia (eto nanaman ang blood Frank-Starling Curve: force of gusto natin nasa heart at brain!) ventricular contraction as a function Endotoxin directly stimulates ADH of its preload independently of BP, osmotic, or o Based on force of contraction intravascular volume changes (ganito VENTRICULAR being determined by initial muscle usually pag ang shock mo ay sepsis shock) CONTRACTION length Proinflammatory cytokines also contribute Cardiac dysfunction seen in burns to arginine vasopressin release. and in hemorrhagic, traumatic, and septic shock KUMUNOY’S IMPROPERTY 5  ACIDIC SURGERY NA SIYA KASI MABABA NA SCORES NATIN SHOCK, NAKAKAGULAT GRADES SA SURG :O LECTURER: DR. DAGA NI SHILOH (HAYOP KAYO PATI BA NAMAN DITO) Force that resists myocardial work source of production para mapabilis ang gawa ng ATP. Ang problem during contraction lang pag anaerobic ang gamit mas marami ngayong pyruvate → Arterial pressure: major component of lactic acid, kaya magkakaroon ng intracellular metabolic acidosis afterload influencing the ejection Depletion of ATP influences all ATP-dependent cellular fraction processes AFTERLOAD o Maintenance of cellular membrane potential Homeostasis: ↑ afterload = Ito yung peripheral maintained by increases in preload o Synthesis of enzymes and proteins vasoconstriction In shock, compensatory mechanism o Cell signaling (diastolic) to sustain cardiac output is impeded o DNA repair mechanisms o Stress response acute release of Decreased intracellular pH also influences vital cellular catecholamines sympathetic functions such as: nerve activity in the heart ↑ heart o Normal enzyme activity rate and contractility o Cell membrane ion exchange Plays an integral role in regulating o Cellular metabolic signaling cellular perfusion and is significantly Catecholamines have a profound impact on cellular influenced in response to shock MICROCIRCULATION metabolism Innervated by the sympathetics and o Increased catecholamines: Ganun lang ulit, sa has a profound effect on the larger → Hepatic glycogenolysis, gluconeogenesis, microcirculation nag arterioles ccompensate lang to in Responses during diff. types of shock: ketogenesis, skeletal muscle protein breakdown, and times of shock. Kapag ang shock mo may o Hypovolemic: large arterioles adipose tissue lipolysis volume loss, tulad sa constricts o Cortisol, glucagon, and ADH: contribute to the hypovolemic at hemorrhagic shock, o Neurogenic: vessels vasodilate catabolism during shock vasoconstriction kasi Other vasoconstrictors: vasopressin, o Epinephrine: induces further release of glucagon, while kailangan mag preserve. Sa mga shock naman na angiotensin II, and endothelin inhibiting the pancreatic β-cell release of insulin walang blood loss tulad Mechanisms lead to diminished ALAM NIYO NA TO!! GAGALITIN!!! >:( ng sepsis or neurogenic, capillary perfusion that may persist ang problema nag vvasodilate ang vessels, after resuscitation CELLULAR HYPOPERFUSION so tataas ang o Endothelial cell swelling Oxygen debt: experienced by hypoperfused cells and capacitance → babagsak BP o Dysfunction tissues o Activation marked by the o Deficit in tissue oxygenation over time that occurs recruitment of leukocytes and during shock platelets o When O2 delivery is limited: So paulit ulit ha, sa pathophysiology ng shock when it comes to → O2 consumption can be inadequate to match the hormonal and vascular effects, usually preserves fluids, metabolic needs of cellular respiration → creating a vasoconstriction, ↑ glucose tsaka taas pump ng heart, dyan lang deficit in O2 requirements at the cellular level umiikot yan wag niyo pahirapan sarili niyo, tandaan niyo lang sino nag Under normal circumstances, cells can “repay” the O2 ccause ng mga yun. So move on na tayo METABOLIC EFFECTS naman! debt during reperfusion Tangina wala pang kalahati. o The magnitude of the O2 debt correlates with the METABOLIC EFFECTS severity and duration of hypoperfusion Cellular metabolism is based primarily on the hydrolysis of o Surrogate values for measuring O2 debt include base ATP deficit and lactate levels o ↓ O2 tension ↓ oxidative phosphorylation slow Shock also induces changes in cellular gene expression generation of ATP or shift to anaerobic metabolism and o DNA binding activity of nuclear transcription factors is glycolysis to generate ATP altered by hypoxia and ROS and nitrogen radicals o Under hypoxic conditions in anaerobic metabolism, o Expression of other gene products such as: pyruvate is converted into lactate, leading to an → Heat shock proteins intracellular metabolic acidosis → Vascular endothelial growth factor Para magfunction ang cells ng maayos kailangan natin ng → Inducible nitric oxide synthase (iNOS) Magandang O2 supply, para makapag generate to ng ATP ng mabilis. → Heme oxygenase-1 Pero in times of shock di makapag distribute ng O2 ng maayos diba? → Cytokines To compensate, may shifting to anaerobic metab at glycolysis as KUMUNOY’S IMPROPERTY 6  ACIDIC SURGERY NA SIYA KASI MABABA NA SCORES NATIN SHOCK, NAKAKAGULAT GRADES SA SURG :O LECTURER: DR. DAGA NI SHILOH (HAYOP KAYO PATI BA NAMAN DITO) So through shifting to anerobic metabolism ng pag generate ng ATP o Further activation of neurons and mast cells nakakapag compensate ang cells natin makagawa ng ATP sa shock o Increasing the expression of adhesion molecules on the diba? So nagkakautang ngayon ng O2 ang cells, which can be endothelium corrected naman through hyperfusion after. Pero syempre mas o These mediators cause leukocytes to release platelet- matagal walang bayad ng utang mas malaki maaccumulate mo na activating factor platelet adhesion damage tulad niyang changes in cellular gene expression ganyan na o Coagulation and kinin cascades impact the interaction of mangyayari dyan. endothelium and leukocytes Dami nangyayari ampota pero basically ganito inaamplify ng DAMPS IMMUNE AND ang immune response through traumatic shock. Maglalabas to ng HMGB1, heparan sulfate at uric acid para mag stimulate sa macrophages to release chemokines and TNF that will stimulate lymphocytes to release cytokines which will further enhance yung inflammation. Same din with sepsis sa bacterial products. Ang difference lang nila, si Trauma ay lumabas from cells na nainjure, pero Failure to adequately control the activation, escalation, or ang bacterial products galing sa bacteria which is an external source. suppression of the inflammatory response can lead to: o Systemic inflammatory response syndrome CYTOKINES/CHEMOKINES o Multiple organ failure One of the earliest cytokines released in Several mechanisms that lead to the activation of the active response to injurious stimuli inflammatory and immune responses: Peak: 90 minutes, returns to baseline after 4 o Release of bioactive peptides by neurons in response to hrs pain Released by monocytes, macrophages, and T cells release o Release of intracellular molecules by broken cells, such as: Induced by bacteria, endotoxin, → Heat shock proteins; Mitochondrial products; Heparan haemorrhage and ischemia sulfate; High mobility group box 1; RNA Leads to the development of shock and Danger Signaling: release of intracellular products from hypoperfusion damaged and injured cells can have paracrine and TNF-a TNF-a levels correlate with mortality endocrine-like effects on distant tissues to activate the ↑TNF-a = ↑mortality inflammatory and immune responses Effects: o DAMPS: endogenous molecules are capable of signaling o Peripheral vasodilation the presence of danger to surrounding cells and tissues o Activates the release of other cytokines → They are recognized by cell surface receptors (PRRs & o Induces procoagulant activity TLRs) to effect intracellular signaling that primes and o Stimulates a wide array of cellular amplifies the immune response metabolic changes o Contributes to the muscle protein Basically ang DAMPS inaamplify niya ang immune response, breakdown and cachexia pinapataas niya to kaya nagkakaroon ng mas malaking damage pa. Has actions similar to those of TNF-a Center ito for Traumatic Shock na pag uusapan mamaya Very short half-life (6 minutes) Tissue-based macrophages or mast cells: before the recruitment Primarily acts in a paracrine fashion to IL-1 of WBC into sites of injury, they as sentinel responders, releasing: modulate local cellular responses Histamines; Eicosanoids; Tryptases; Cytokines Systemic effects: Pareho lang ng action to sa o Produces a febrile response to injury by TNF-a, activating prostaglandins in the difference lang posterior hypothalamus ay shorter half- o Causes anorexia by activating the life to and satiety center paracrine Augments the secretion of ACTH, effect so local lang, sa site glucocorticoids, and β- endorphins lang mismo ng In conjunction with TNF-a, IL-1 can stimulate injury. Ang TNF- the release of other cytokines: a umiikot sa o IL-2, IL-4, IL-6, IL-8 katawan o Granulocyte-macrophage colony- stimulating factor o Interferon-gamma Together these signals amplify the immune response by: KUMUNOY’S IMPROPERTY 7  ACIDIC SURGERY NA SIYA KASI MABABA NA SCORES NATIN SHOCK, NAKAKAGULAT GRADES SA SURG :O LECTURER: DR. DAGA NI SHILOH (HAYOP KAYO PATI BA NAMAN DITO) Produced by activated T COMPLEMENT Activates other lymphocyte subpopulations Can be activated by injury, shock, and severe infection and NK cells Contributes to host defense and proinflammatory Increased IL-2 secretion: activation IL-2 o promotes shock-induced tissue injury and the development of shock May serve as a marker for severity of injury Depressed IL-2 production o In trauma patients, the degree of complement o associated with depression in immune activation is proportional to the magnitude of injury function after hemorrhage o Significant complement consumption occurs after Elevated in response to hemorrhagic shock, hemorrhagic shock major operative procedures, or trauma Activation of the complement cascade can contribute to Elevated IL-6 levels the development of organ dysfunction correlate with mortality in shock states IL-6 o Activated complement factors C3a, C4a, and C5a: Contributes to lung, liver, and gut injury after o Potent mediators of increased vascular permeability hemorrhagic shock. May play a role in the development of o Smooth muscle cell contraction Peborit ni doc diffuse alveolar damage and ARDS o Histamine and arachidonic acid by-product release sabihin dito IL-6 and IL-1 o adherence of neutrophils to vascular endothelium mataas IL-6 sa o mediators of the hepatic acute phase Activated complement acts synergistically with endotoxin patients with response to induce the release of TNF-a and IL-1 (bacterial response) o enhance the expression and activity of: ARDS → complement, C-reactive protein, NEUTROPHILS fibrinogen, Haptoglobin, amyloid A, Neutrophil activation - early event in the upregulation of alpha1-antitrypsin, the inflammatory response o promote neutrophil activation o First cells to be recruited to the site of injury Considered an anti-inflammatory cytokine that may have immunosuppressive Polymorphonuclear leukocytes (PMNs) - remove infectious properties agents, foreign substances that have penetrated host Its production is increased after shock and barrier defenses, and nonviable tissue through trauma phagocytosis Associated with depressed immune function Activated PMNs generate and release a number of clinically, as well as an increased substances that may induce cell or tissue injury: susceptibility to infection o Reactive O2 species Secreted by T cells, monocytes, and o Lipid-peroxidation products IL-10 macrophages Inhibits the following processes: o Proteolytic enzymes (elastase, cathepsin G) o Proinflammatory cytokine secretion o Vasoactive mediators (leukotrienes, eicosanoids, and (anti-inflammatory nga eh diba) platelet-activating factor o O2 radical production by phagocytes o Adhesion molecule expression CELL SIGNALLING o Lymphocyte activation Host of cellular changes occur following shock Administration of IL-10 depresses cytokine Signaling pathways may be altered by: production and improves some aspects of o Changes in cellular oxygenation immune function o Redox state Have the ability to induce chemotaxis of o High-energy phosphate concentration leukocytes Chemokines bind to specific chemokine o Gene expression CHEMOKINES receptors and transduce chemotactic o Intracellular electrolyte concentration induced by signals to leukocytes shock Signaling pathways INFLAMMATORY MEDIATORS OF SHOCK o Alter the activity of specific enzymes PROINFLAMMATORY ANTI-INFLAMMATORY o Expression or breakdown of important proteins Interleukin-1ɑ/β; Interleukin-2 Interleukin-4; Interleukin-10 o Affect intracellular energy metabolism Interleukin-6; Interleukin-8; Interleukin-13; Interferon; TNF; PAF Prostaglandin E2; TGFβ KUMUNOY’S IMPROPERTY 8  ACIDIC SURGERY NA SIYA KASI MABABA NA SCORES NATIN SHOCK, NAKAKAGULAT GRADES SA SURG :O LECTURER: DR. DAGA NI SHILOH (HAYOP KAYO PATI BA NAMAN DITO) Alterations in Ca2+ regulation may So nadiscuss na earlier yang mga yan ha! Alam niyo na dapat yan!!! lead to: Sa classification naman of hemorrhage please memorize! Kasi lalabas sa exam yan, class 1 ang normal lang dyan pag nag donate ka dugo o direct cell injury diba 500ml kinukuha, tignan mo heart rate 120 >140 (bpm) Hypotension, marked tachycardia Severe Blood Pressure Normal Orthostatic Hypotension Loss of up to >30% (i.e., pulse greater than 110 to 120 hypotension CNS Symptoms Normal Anxious Confused Obtunded bpm), and confusion Immediately life threatening and Most common cause of shock in the surgical or trauma Loss of 40% (2L) generally requires operative control of patient is loss of circulating volume from hemorrhage bleeding (hemorrhage = whole blood loss) Other causes: loss of plasma, interstitial fluid (bowel Young healthy patients perforation), dehydration o May tolerate larger volumes of blood loss Acute blood loss reflexive decreased baroreceptor o Manifests fewer clinical signs despite the presence of stimulation from stretch receptors in the large arteries can peripheral hypoperfusion lead to: o May maintain a near-normal blood pressure until a o Decreased inhibition of vasoconstrictor centers in the precipitous CVS collapse occurs brain stem Elderly patients o Increased chemoreceptor stimulation of vasomotor o Elderly patients may be taking medications that either centers promote: o Diminished output from atrial stretch receptors → bleeding (warfarin or aspirin) → All of these will cause ↑ vasoconstriction and → mask the compensatory responses to bleeding (e.g., peripheral arterial resistance β-blockers) Hypovolemia also induces sympathetic stimulation o Factors associated w/ elderly patient’s ability to leading to catecholamine release → (+) RAAS → ↑ tolerate hemorrhage: vasopressin release → ↑ peripheral vasoconstriction → Atherosclerotic vascular disease o Lack of sympathetic effects on cerebral and coronary → Diminishing cardiac compliance with age vessels + local autoregulation → maintenance of → Inability to elevate heart rate or cardiac contractility cardiac and CNS blood flow in response to hemorrhage → Overall decline in physiologic reserve. KUMUNOY’S IMPROPERTY 9  ACIDIC SURGERY NA SIYA KASI MABABA NA SCORES NATIN SHOCK, NAKAKAGULAT GRADES SA SURG :O LECTURER: DR. DAGA NI SHILOH (HAYOP KAYO PATI BA NAMAN DITO) MANAGEMENT Patients who fail to respond to initial resuscitative efforts: Potential bleeding sources will be located along the known o Should be assumed to have ongoing active or suspected path of the wounding object hemorrhage from large vessels o Patients with penetrating injuries who are in shock o Require prompt operative intervention usually require operative intervention Appropriate priorities in these patients are as follows: o Patients who suffer multisystem injuries from blunt o Control the source of blood loss trauma have multiple sources of potential hemorrhage o Perform IV volume resuscitation with blood products in Sites of blood loss sufficient to cause shock: the hypotensive patient o External, intrathoracic, intra-abdominal, o Secure the airway retroperitoneal, and long bone fractures Procedures indicated when time are of the essence and Each pleural cavity can hold 2 to 3 L of blood and can rapid treatment is essential: therefore be a site of significant blood loss o Laparotomy o Tube thoracostomy - indicated in unstable patients o Thoracotomy o Chest radiograph - indicated in stable patients and Actively bleeding patient cannot be resuscitated until those w/ hemothorax control of ongoing hemorrhage is achieved Etiology and causes of hemorrhagic shock: Damage control resuscitation o Pelvic fractures - associated w/ major retroperitoneal o This strategy begins in the emergency department, hemorrhage, can be confirmed by pelvic x-ray continues into the operating room, and into the o Intraperitoneal hemorrhage- most common source of intensive care unit (ICU) blood loss that induces shock (sinaksak ng ice pick kasi o Initial resuscitation: gangsta ka) → limited to keep SBP around 80 to 90 mmHg. o Non-trauma - consider GI bleeding, check Hx and PE → prevents renewed bleeding from recently clotted o Internal (intracavitary) blood loss- if major blood loss is vessels (diba pag sobra sobra na-perfuse mo) not immediately visible → warm patient to prevent coagulopathy o Injuries to major artery & veins- can cause rapid → intravascular volume resuscitation is accomplished bleeding with blood products and limited crystalloids (initially Direct pressure must be applied and sustained to minimize crytalloids muna, tapos blood products) ongoing blood loss o Blunt injury (nabangga or nahulog)- major cause of death Tourniquets should be used for extremity bleeding stopped is a closed head injury by direct pressure and applied in the prehospital setting as → Cause of death is secondary to brain hypotension needed → SBP of 110 mmHg would seem to be more appropriate Diagnosis of intraperitoneal bleeding: o Irreversible shock- patients who fail to respond to o Diagnostic ultrasound resuscitative efforts despite adequate control of o Diagnostic peritoneal lavage ongoing hemorrhage → ongoing fluid requirements despite adequate control TREATMENT of hemorrhage Treatment of shock is initially empiric (ABCDE) → persistent hypotension despite restoration of o Airway, Breathing, Circulation, Disability and Exposure intravascular volume necessitating vasopressor o Priority is the initiation of volume infusion while the support search for the cause of the hypotension is pursued → may exhibit a futile cycle of uncorrectable o Shock in a trauma patient or postoperative patient hypothermia, hypoperfusion, acidosis, and should be presumed to be due to hemorrhage until coagulopathy that cannot be interrupted despite proven otherwise maximum therapy IMEMORIZE ITONG ABCDE NA TO KASI NAGTATANONG SA SAMPS!!! o Fluid resuscitation is a major adjunct to physically Control of ongoing hemorrhage is an essential component controlling hemorrhage in patients with shock of the resuscitation of the patient in shock → Crystalloids: mainstay fluid of choice Treatment of hemorrhagic shock is instituted concurrently → Increased risk of death in bleeding trauma patients with diagnostic evaluation to identify a source treated with colloid compared to patients treated with crystalloid KUMUNOY’S IMPROPERTY 10  ACIDIC SURGERY NA SIYA KASI MABABA NA SCORES NATIN SHOCK, NAKAKAGULAT GRADES SA SURG :O LECTURER: DR. DAGA NI SHILOH (HAYOP KAYO PATI BA NAMAN DITO) → Severe hemorrhage: restoration of intravascular Hypoperfusion deficit in traumatic shock volume should be achieved with blood products o Magnified by the proinflammatory activation that → Hypertonic saline: resuscitative adjunct in bleeding occurs following the induction of shock (yan na DAMPS) patients Treatment of traumatic shock benefit may be immunomodulatory o Focused on correction of the individual elements to decreased reperfusion-mediated injury with diminish the cascade of proinflammatory activation decreased O2 radical formation o Prompt control of hemorrhage less impairment of immune function vs. standard o Adequate volume resuscitation to correct O2 debt crystalloid solution o Debridement of nonviable tissue less brain swelling in the multi-injured patient o Stabilization of bony injuries resuscitation agent for combat injuries o Appropriate treatment of soft tissue injuries may contribute to a decrease in the incidence of ARDS and multiple organ failure SEPTIC (VASODILATORY) SHOCK o packed RBCs and other blood products: essential in the Vasodilatory shock is the result of: treatment of patients in hemorrhagic shock o Dysfunction of the endothelium and vasculature → target HgB for stable ICU patients- 7 to 9 g/dL secondary to circulating inflammatory mediators and → Damage control resuscitation consists of transfusion cells with RBCs, FFP, and platelet units given in equal o Response to prolonged and severe hypoperfusion. number Hypotension- results from failure of the vascular smooth plasma-platelet-RBC in a ratio of 1:1:1 improved muscle to constrict appropriately survival at 3 hours and a reduction in deaths Characterized by peripheral vasodilation with resultant Increased platelet use appears to improve hypotension and resistance to treatment with vasopressors outcome So diba nga sabi natin kanina pag ganitong wala namang fluid loss, → The benefit of platelet transfusion may be most vasodilation ang nangyayari, tumataas capacitance ng vessels, so pronounced in trauma patients with brain injury ang effect, nakikita to ng katawan as low volume tpaos resistant pa to platelets should be transfused in the bleeding sa vasopressors, wala talagang vasoconstriction na nangyayari. So patient to maintain counts above 50 × 109/L pano nag ssepsis? Sa bacterial products nagrerelease yan ng nitric kailangan >50 ang platelet oxide sa vessels. Eh ano ba ang nitric oxide? Vasodilator diba Despite the hypotension, plasma catecholamine levels are elevated, and the renin-angiotensin system is activated Septic shock- most frequently encountered form of vasodilatory shock Represents the final common pathway for profound and prolonged shock of any etiology Other causes of vasodilatory shock o Hypoxic lactic acidosis o Carbon monoxide poisoning o Decompensated and irreversible hemorrhagic shock o Terminal cardiogenic shock TRAUMATIC SHOCK o Postcardiotomy shock Etiology and causes: o small volume hemorrhage accompanied by soft tissue Causes of septic and vasodilatory shock injury (femur fracture, crush injury) o Systemic response to infection o Combination of hypovolemic, neurogenic, o Non Infectious systemic inflammation cardiogenic, and obstructive shock that precipitate → Pancreatitis rapidly progressive → Burns o Anaphylaxis Blunt trauma patients: o Acute Adrenal Insufficiency o Multiple organ failure, including acute respiratory o Prolonged, severe hypotension distress syndrome (ARDS) KUMUNOY’S IMPROPERTY 11  ACIDIC SURGERY NA SIYA KASI MABABA NA SCORES NATIN SHOCK, NAKAKAGULAT GRADES SA SURG :O LECTURER: DR. DAGA NI SHILOH (HAYOP KAYO PATI BA NAMAN DITO) → Hemorrhagic shock; Cardiogenic shock; Serum lactate should be measured as a marker of shock Cardiopulmonary bypass Blood cultures should be obtained o Metabolic Empiric antibiotics must be chosen carefully based on the → Hypoxic lactic acidosis; Carbon monoxide poisoning most likely hospital infection control (pag may sepsis na yung patient, ibigay mo na lahat ng antibiotic na malakas, yung DIAGNOSIS kayang patayin lahat, pag naidentify na yung bacteria saka mo Immune response is overly exuberant or becomes systemic lang bigyan ng specific.) rather than localized, manifestations of sepsis may be Vasopressors may be necessary to treat patients with evident septic shock after first line therapy These findings include: o Catecholamines are the vasopressors used most often o Enhanced cardiac output; Peripheral vasodilation; → norepinephrine being the first-line agent Fever, leukocytosis; Hyperglycemia; Tachycardia → followed by epinephrine Vasodilatory effects are due, in part, to the upregulation of → Arginine vasopressin- potent vasoconstrictor, is often the inducible isoform of nitric oxide synthase (iNOS or NOS added to norepinephrine 2) in the vessel wall Dobutamine therapy is recommended for patients with Criteria for the diagnosis of sepsis in the hospitalized adult: cardiac dysfunction o Manifestations of the host response to infection in Surviving Sepsis Campaign bundles of care to be initiated addition to identification of an offending organism within the first hour after presentation in the patient with The terms sepsis and septic shock are used to quantify the sepsis: magnitude of the systemic inflammatory reaction o Measure serum lactate level. Remeasure if the initial o Sepsis - have evidence of an infection, as well as lactate is >2 mmol/L systemic signs of inflammation (e.g., fever, leukocytosis, o Obtain blood culture prior to administration of and tachycardia) antibiotics → Severe- hypoperfusion with signs of organ dysfunction o Rapid administration of 30 mL/kg crystalloid for o Septic shock - requires the presence of the hypotension or lactate ≥4 mmol/L aforementioned signs, associated with more significant o Use vasopressors if the patient is hypotensive during or evidence of tissue hypoperfusion and systemic after fluid resuscitation to maintain a mean arterial hypotension pressure ≥65 mmHg Pinagkaiba ng sepsis sa septic shock, pag may hypotension na and evidence of tissue hypoperfusion yun na yung septic shock CARDIOGENIC SHOCK The Third International Consensus Definitions for Sepsis and Defined clinically as circulatory pump failure leading to Septic Shock (Sepsis-3) diminished forward flow and subsequent tissue hypoxia, in o Refined the definitions and utilize a Sequential (Sepsis- the setting of adequate intravascular volume related) Organ Failure Assessment (SOFA) score to help Puso na ang may problema, ex. may arrythmia or MI, di na makapump determine signs of organ dysfunction and to guide maayos → heart attack management Hemodynamic criteria: TREATMENT o Sustained hypotension (SBP