Hypocalcemia: Acute Care Considerations PDF

→Hypocalcemia: Acute Care Considerations: 1.Head/Neck Surgeries 2.Autoimmune disease 3.Parathyroid Cancer (or treatment of) 4.Heavy metals (copper) 5.Magnesium abnormality 6.Multiple drug transfusions (citrate) 7.Drugs < 8.8 dL/L Ionized Ca < 4.7 mg/dL Chronic etiology: Hypoparathyroid...

→Hypocalcemia: Acute Care Considerations: 1.Head/Neck Surgeries 2.Autoimmune disease 3.Parathyroid Cancer (or treatment of) 4.Heavy metals (copper) 5.Magnesium abnormality 6.Multiple drug transfusions (citrate) 7.Drugs < 8.8 dL/L Ionized Ca < 4.7 mg/dL Chronic etiology: Hypoparathyroidism Vitamin D Deficiency Often hypocalcemia is chronic and we typically don’t see it and they’re not symptomatic Think about whether they simply have primary hypoparathyroidism, the parathyroid gland is just simply not putting out enough PTH or do they have a vitamin D deficiency. (Don't commit table to memory) This chart gives the etiologies for calcium disorders and you’re looking at whether the serum PTH is high or low With metastatic disease, the serum PTH is going to be high and its going to release calcium from the bones, increasing absorption, and increasing the amount of resorption in the kidneys and we’ll have a normal vitamin D, but they’re going to be hypercalcemic. → Hypocalcemia- Clinical Presentation Paresthesias, circumoral tingling/numbness Cramping, muscle spasm (laryngospasm, tetany) AMS, cognitive impairment, seizure: Prolonged QT Intervals- mess up cardiac cycle leading to life threatening dysrhythmias Chvostek’s (tap/stroke side of cheek & they have a twitch) and Trousseau’s signs (BP cuff pumped up and their fingers twitch and have carpopedal spam) With hypercalcemia there’s slowing of CNS, with hypocalcemia we see seizures, tetany, cramping Diagnostic Approach to hypocalcemia You want to start with the parathyroid hormone level and you want to think about whether they have Vit D issues. Is that hypoparathyroidism? Then look at etiology, do they have a nutritional deficiency or is it that they simply can't absorb it? Caveats Overall, PO supplementation if possible IV supplementation for severe hypocalcemia (< 7.5 mg/dL) Calcium Gluconate preferred and less caustic. ○ Much more tolerated and safer drug to give if IV supplementation is needed ○ Central access highly recommended CaCl provides higher levels of elemental calcium per gram ○ Very caustic ○ Requires central access ○ Risk for cardiac toxicity Correct Magnesium! Won't correct calcium w/o mag being corrected! Corrected Calcium Serum PTH is the most reliable estimate of calcium levels with hypercalcemia Ionized calcium most reliable in determining if the patient is hypocalcemic ○ If you have a patient with really abnormal calciums, you probably want to look at what a corrected calcium is, particularly if they have cancer, emaciated, or has malnutrition, alcoholic w/ poor nutrition. Corrected Calcium= Serum Ca + 0.8 (4 - serum albumin) 4= “Normal” serum albumin ○ Need to know that calcium is 50% bound to albumin and bound to protein, so when you look at a calcium level you don’t really see what's getting to the cells. Diagnostic Approach to Acute Calcium Disorders Check comprehensive chemistries (liver, renal function) Correct for serum albumin Ionized calcium/free calcium in ECF Magnesium, Phosphate Alk. Phos PTH*** VBG/ABG for pH CBC Consider 24 hour urine calcium, Endocrine/HemOnc consult Summary: Calcium is one electrolyte that is essential to core life processes ○ Physiologic functions ○ Indications of abnormalities ○ Approach must include consideration of other factors (Mag, Phos, renal and liver function, developmental stage, co-morbidities) PTH is the decision point from which to work up etiology Consider free/effective calcium by correcting for albumin If giving IV calcium supplementation, provide safe and reliable access (central line) RHEUMATOID ARTHRITIS Overview ○ Destruction of synovial tissue and joint space​ Attack interphalangeal joints (knuckles, IP joints, DIP, MCP, PMP, etc.)​ MCP joints at base of fingers overtime will have ulnar deviation turning out toward lateral aspect of hand​ Big bumpy rheumatoid nodules ​ Articular and articular cartilage overlying bone broken down by collagenases – if have enzymes in inflammatory response, articular collages broken down and see bone erosion & loss of bone​ Synovial membrane – hold synovial fluid that lubricates the join and facilitate free movement – all enclosed in articular capsule where we'll see ​ As synovial lining replaced w thick fibrous pannus -> deformity, further fibrosis, bone erosion​ *Destruction of synovial tissue & joint space + chronic inflammatory response w/ cytokines, macrophages, etc. *Chronic pain – makes you tired, not wanting to eat -> malnutrition; movement restriction – higher likelihood developing comorbidities; dec quality of life and duration of life​ ○ Systemic inflammatory response​(e.g. fatigue, anorexia, fever etc.) ○ Autoimmune attack by Rheumatoid Factors (RF)- IgG or IgM, leading to enzymatic breakdown​ Autoimmune attack: rheumatoid factors (RFs) are antibodies – autoantibodies attacking our own antibodies lead to enzymatic  breakdown; mediated or caused by abnormal protein production [citrullination – arginine converted to citrulline – more of inflammatory response)​ ○ Abnormal citrullination (conversion of protein arginine to citrulline)​ Risk Factors ○ Age, Sex (2-3 x risk in women), increased in women who never give birth​ ○ Heredity​ ○ HLA Class II genotypes​[exogenous antigens -- even though this is an autoimmune response] ○ Epigenetic influences increase expressivity​ ○ Smoking, obesity​ ○ Early life exposure to smoking, lower income households in childhood​ ○ Breastfeeding decreases risk​(even if you have the gene to code for autoantibodies & RFs - you have dec expressivity w/ breastfeeding) Health Disparities ○ SDOHs, lack of access to care -- people of color likely to be diagnosed after already having significant issues compared to white non-Hispanic people Pathophysiology of RA ○ Chemotaxis​ Interferon-y, IL-17 draw monocytes, macrophages, neutrophils​ CD4 and CD14 – draws in IL-17 & interferon gamma – chief cytokines responsible for chemotaxis – acute inflamm ->  chronic -> TNF-alpha & IL-1 (proinflammatory cytokines) -> destruction of hyaline cartilage (articular cartilage) once worn down ○ TNF and IL-1 produce cytokines​ Destruction of hyaline cartilage​ ○ RANKL​ Resorption of bone, erosion​ Inc prod of RANKL – lead to resorption of bone or breakdown of bone (erosion) - causing deformity of articular surface of joint -> citrullination of proteins -> inc enzymatic production [see collagenases, proteases -> further inflamm & breakdown -> Lectin cascade activation [even if no mannose involved] -> inc. WBCs and cytokines ​ ○ Citrullination of proteins​ Acts as auto-antigen​ ○ Complement cascade activated (Lectin)​ Pannus Formation Long-term see fibrosis and pannus formation (thick fibrous lining/overgrowth - become stiff, painful) RA: The Autoimmune Response ○ T-Cells RANKL, other cytokines Enzyme production Collagenases -- breakdown of collagen -- lose cartilage Elastase -- breakdown of elastin -- joint stiffness Pannus formation ○ B-Cells Activated Rheumatoid Factors (RFs) [IgM & IgG] Autoimmune Complexes: self autoantibodies vs our antibodies Clinical Manifestations of RA  ○ Morning Stiffness​ accumulation of inflammatory products in joint space from overnight – thus morning stiffness and then to loosen up throughout day w/ activity; can do well with NSAIDs long-term; can see in the PIP joints; systemic symptoms + localized symptoms; warm feeling in joint​ ○ Pain Fatigue​ ○ Low Grade Fevers​ ○ Pain- myalgias, arthralgias​ ○ Eyes- dryness, uveitis​ ○ Rheumatoid nodules (characteristic)​ Fingers, heels, elbows, knees, forearms ○ Ulnar deviation ○ Possible complication: septic arthritis -- further bone destruction ○ *Difference to Osteoarthritis: Inc stiffness throughout the day as they use their joints since there’s no immune response & they have bone on bone + loss of synovial space GOUT Who gets gout/ risk factors ○ Male sex (females post menopause)  Rare before 30-40 yo ○ Chronic renal failure ○ Hypertension, CAD ○ Obesity, High Triglycerides ○ Diuretic use ○ Beer consumption ○ Diet heavy in shellfish, prepared or red meats, ETOH Urate= Anion Uric acid ○ Breakdown product of purine (nucleotide) metabolism ○ Weak organic acid, but poorly soluble in its undissociated form ○ More soluble in acid environments Blood, urine, synovial fluid core component is hyperuricemia or high levels of uric acid in the blood, serum levels greater than 6.8 are where we start to see clinical manifestations of gout Patho ○ Environment: Hypeuricaemia Overproduction of uric acid Underexcretion of uric acid ○ ○ Excretion largely dependent on renal function -proximal renal tubule reabsorption -urate anion transporters and exchange molecules ○ Crystal formation- more acid environment, lower temps pH temperature ○ can see over-reabsorption of uric acid- if we have a large amount of uric acid that is not reabsorbed and continues to be secreted and its not very soluble- can see uric acid kidney stones ○ with a more acidic environment and lower temperature, the more likely we are to see crystal formation ○ MSU crystal deposits- renal, joint ○ Cytokine production TNF, chemokines, IL-1B, IL-18 ○ Chemotaxis Macrophages, monocytes ○ Formation of inflammasome Propagation of inflammatory response Lysosomal enzymes Prostaglandin production (PGE2) IL-1Beta ○ crystal deposits are made of monosodium urate (like to deposit in renal tubules and synovial joints) ○ Presence of crystals leads to cytokine production (draws in wbcs)  ○ Inflammasome- mediated by presence of macrophages which phagocytize the crystals and form this pathological structure Clinical manifestations ○ Monoarticular Arthritis ○ Pain! ○ Rapid onset Worst at night ○ MTP of great toe,heel, instep, knee, wrist ○ Renal stones ○ Stages Stage I- Asymptomatic Hyperuricaemia Stage II- Acute Flares Stage III- Tophaceous (Chronic) Stage 3- chronic, tophi- develop and crystallize and lead to little white, hard nodules, can be in more than one joint at this stage pseudogout ○ pseudogout is the accumulation of calcium pyrophosphate deposits rather than monosodium urate crystals ○ First line of therapy is NSAIDs because it blocks production of prostaglandins and reduces the amount of inflammation overview ○ Gout is a condition associated with increased production or decreased elimination of urate, which forms highly insoluble uric acid salts ○ Deposition of MSU crystals causing pathology is usually focused on the kidneys and joints (synovium) ○ Production of inflammasome leads to increased chemotaxis and production of cytokines OSTEOGENESIS IMPERFECTA Osteogenesis imperfecta (OI), also known as brittle bone disease, is a genetic disease of collagen synthesis Some severe forms of OI can be diagnosed in utero based on fractures visible on ultrasound, while other milder forms may not be diagnosed until later in childhood. Genes involved in each stage of collagen synthesis and processing ○ The genes indicated in the diagram are associated with various stages of collagen synthesis and processing. Mutations in these genes can lead to OI or related diseases: Signal Transduction and Gene Expression (Gray): WNT1 and SP7 influence osteoblast differentiation. Translation (Brown): COL1A1 and COL1A2 encode the α1 and α2 chains of type I collagen Post-Translational Modifications (Red): SERPINH1, SPARC, P3H1, P4HB, and PPIB are involved in hydroxylation and folding.  ER Homeostasis (Purple): CREB3L1, SEC24D, and TMEM38B maintain ER function and intracellular balance. Proteolytic Processing (Blue): BMP1 is involved in cleaving procollagen. ECM Structure and Mineralization (Green): PLOD2 and SPARC contribute to ECM formation and mineralization. Osteogenesis imperfecta (OI) is a genetic disorder primarily affecting collagen synthesis, with critical implications for bone strength and structure. Collagen, particularly Type I collagen, plays an essential role in forming the extracellular matrix of skin, bones, and tendons, creating the stability required for structural support. Genetic defects ○ Autosomal Dominant Forms: Result from direct mutations in the type I collagen genes. ○ Autosomal Recessive Forms: Result from mutations in non- collagen proteins that play roles in collagen modification or helix formation ○ Autosomal Recessive inheritance requires two copies of the mutated gene (one from each parent) for the disorder to manifest. Parents of a child with an autosomal recessive form of OI are usually carriers, meaning they each have one mutated gene but do not show symptoms. If both parents are carriers, each child has a 25% chance of inheriting the disorder. ○ Autosomal recessive forms of OI are often caused by mutations in non- collagen-related genes that affect collagen modification or processing. ○ Autosomal Dominant inheritance means that only one copy of the mutated gene (from either parent) is enough to cause the disorder. In OI, autosomal dominant forms typically result from mutations in the COL1A1 or COL1A2 genes, which directly affect type I collagen production. A parent with an autosomal dominant form of OI has a 50% chance of passing the mutation to each child. Types of mutations ○ Frameshift Mutations: These mutations result in the reduced production of structurally normal type I collagen. ○ Glycine Substitution or Deletion: This mutation leads to structurally altered collagen, with more severe defects arising from substitutions closer to the carboxyl-terminal end. ○ Rare mutations account for less than 5% of OI cases and affect proteins essential for helix assembly, such as the collagen 3-hydroxylation complex. This leads to types of OI (types VI-XI) associated with autosomal recessive inheritance. ○ Heterozygous Mutations: The most common cause of OI involves heterozygous mutations in genes COL1A1 and COL1A2. These mutations can include: Loss-of-function mutations (e.g., stop mutations) lead to haploinsufficiency, where patients have a reduced amount of collagen. Glycine substitutions that lead to structural alterations in the extracellular helix due to improper collagen assembly, resulting in more severe cases. Pathology of bone remodeling in OI  ○ The instability and poor quality of collagen trigger the body to increase bone resorption, as it attempts to remove structurally flawed bone. Reduced bone strength and persistent breakdown of bone tissue lead osteoblasts to work harder to produce new bone (osteoid), yet this new osteoid is of lower quality due to the collagen defect. This cycle leads to "high turnover osteoporosis," with bones being weaker and less dense, thus increasing fracture risk. Collagen biosynthesis, modification, and secretion in OI ○ OI can also arise from mutations that affect the biosynthesis and secretion of collagen, rather than altering its sequence directly. ○ These pathways involve proteins critical for collagen’s post- translational modification, folding, transport, and quality control, with disruptions leading to a range of OI phenotypes Mutations can happen on these genes ○ Chaperone Proteins for Collagen Stability: Chaperones stabilize the collagen triple helix and prevent premature fibril assembly: FKBP10 (FKBP65): Prevents premature assembly of procollagen chains. FKBP10 mutations can lead to Bruck syndrome, with brittle bones and joint contractures. SERPINH1 (HSP47): This chaperone prevents collagen misfolding. Mutations in SERPINH1 cause moderate to severe OI, with fractures occurring early in life. ○ Lysine Hydroxylation and Cross-Linking: PLOD2 (Lysyl Hydroxylase 2): Modifies lysine residues to allow strong collagen cross-linking. PLOD2 mutations lead to Bruck syndrome type 2, causing joint contractures and moderate bone fragility. ○ Calcium and Intracellular Signaling: TMEM38B: Mutations impair collagen modification and are associated with a mild form of OI. MBTPS2: Reduces hydroxylation of lysine residues, impacting osteoblast differentiation, leading to moderate to severe OI. ○ Bone-Specific Collagen Production: CREB3L1: Activated during ER stress, essential for bone-specific collagen production. Mutations in CREB3L1 result in reduced bone collagen and moderate to severe OI. ○ Collagen Transport and Secretion: SEC24D: Necessary for ER-to-Golgi transport. Mutations cause retention of procollagen in the ER, leading to deformities and classic OI characteristics. ○ Extracellular Matrix (ECM) Interactions: SPARC (Osteonectin): Binds collagen, aiding bone matrix mineralization. SPARC mutations delay collagen secretion, causing moderate OI Autosomal recessive types of OI  ○ Type III: Severe fragility with growth deformities, scoliosis, and a triangular facial shape. This type can also occur in autosomal dominant forms but is commonly recessive. ○ Types V and VI: Characterized by distinct bone abnormalities, including mesh-like bone structure, calcification, and mineralization issues, leading to skeletal symptoms. ○ Types VII, VIII, and IX: Common Defect: A mutation in the prolyl 3-hydroxylation complex in the endoplasmic reticulum, necessary for collagen triple helix assembly. ○ Type VII: Moderate to severe, with rhizomelia (shortened limbs) and coxa vara (hip deformity). Type VIII: Severe to lethal, with rhizomelia. ○ Type IX: Severe form with significant bone fragility. ○ Types X and XI: Common Defect: Mutations in collagen chaperones required to transport procollagen from the ER to the Golgi apparatus. ○ Type X: Severe bone dysplasia, dentinogenesis imperfecta, blue sclera, and issues such as renal stones. ○ Type XI: Bone dysplasia with ligament laxity, scoliosis, and flattened vertebrae, with normal sclera and no dental involvement. Autosomal dominant types of OI ○ Type I: Involves reduced collagen production with a normal structure. Clinical Features: Generalized osteoporosis, blue sclera, and hearing loss. ○ Type II: Severe form often lethal in the perinatal period, caused by a dominant negative mutation. Clinical Features: Blue sclera, extreme bone fragility, and high risk of perinatal death. ○ Type III (can also occur as autosomal recessive, but dominantly inherited forms exist): Severe bone fragility, growth deformities, scoliosis, and a triangular facial shape. ○ Type IV: Moderate to severe bone fragility with a normal sclera and potential dentinogenesis imperfecta Genes Influencing Osteoblast Differentiation and Bone Matrix Stability ○ Genes in Osteoblast Differentiation and WNT Signaling: SP7 (Osterix): Essential for osteoblast maturation. Mutations lead to increased bone porosity and fractures. WNT1: Regulates osteoblast differentiation. WNT1 mutations destabilize bone remodeling, often causing cognitive impairments. MESD: Acts as a chaperone for WNT signaling receptors; mutations reduce function, leading to fragility similar to LRP5/6 deficiencies. ○ Bone Matrix Stability and Mineralization Genes:  TENT5A: Involved in bone homeostasis; mutations cause skeletal dysplasia, activating pathways essential for bone formation. ○ Genes Influencing Bone Resorption and Osteoclast Function: IFITM5: Supports osteoblast differentiation; mutations lead to OI type V, with callus formation and ossification abnormalities. SERPINF1 (PEDF): Regulates osteoclastogenesis, inhibiting bone resorption. Loss-of-function mutations increase osteoclast activation, with fractures worsening over time. PLS3: Regulates the cytoskeleton in bone cells, where mutations reduce bone thickness and alter remodeling. Clinical manifestations and cellular pathology ○ OI is marked by collagen defects that lead to weakened bones, blue sclera, skeletal deformities, and in some cases, dentinogenesis imperfecta. ○ Cellular disruptions, including ER stress, altered osteoclast activity, collagen misfolding, and reduced secretion, result in a fragile skeletal structure. High turnover osteoporosis and impaired collagen synthesis culminate in the typical bone fragility and fracture susceptibility seen in OI ○ Classic manifestations: Osteopenia Increased rate of fractures (including potential in utero) ○ Other possible manifestations include: Blue sclerae Hearing loss Triangular/elfin face Poor dentition Bowing and deformation of bones Ligament laxity Short stature Vascular weakness which can lead to aortic aneurism Heart valve insufficiency Easy bruising Fatigue Pain Week 15: Shock, Acid-Base, and Electrolyte Abnormalities SHOCK STATES I, II, & III Shock A state in which impaired perfusion can not meet the demands of tissue and cellular metabolism Common pathways ○ decreased delivery of oxygen and nutrients ○ Increased demand/consumption  ○ Decreased removal of cellular waste products Cardiac output CO (ml/min) = HR x SV HR- controlled by nerves and hormones Stroke volume (ml/beat)- blood volume and vascular resistance Frank-starling law Volume of blood ejected by the ventricle depends on the volume present in the ventricle at the end of diastole Underlying principle= length-tension relationship in cardiac muscle fibers SV and CO correlate directly with end diastolic volume End diastolic volume correlates with vascular resistance Cardiac output= vascular resistance (FS law ensures this) Cardiac muscle normally operates only on the ascending limb of the systolic curve Preload and afterload Preload- volume of blood in ventricles at end of diastole (end diastolic volume) ○ Increased in hypervolemia ○ Regurgitation of cardiac valves ○ Heart failure Afterload- resistance left ventricle must overcome to circulate blood ○ Increased afterload=increased cardiac workload ○ Increased in hypertension and vasoconstriction Types of shock Cardiogenic  ○ Heart failure, heart cannot fill and pump ○ Leads to bradycardia and asystole Distributive- shock- fluid is in wrong place, lost cardiac output because we don’t have enough fluid in the vascular space ○ Neurogenic or vasogenic fluid/pressure (blood or plasma) is in the wrong place, directed to perhaps third spaces and the smooth muscle of the arterioles cannot vasoconstrict (if we cant vasoconstrict, we have hypotension and cannot tighten up that vascular bed) –don’t have neuro-conduction that tells us to vasoconstrict Alterations in smooth muscle tone ○ Anaphylactic Hypersensitivity or allergic response that sends fluid to the wrong spaces (third spacing of fluids) ○ Septic Infection Obstructive ○ shock- a clot that is preventing cardiac output (pulmonary embolism, cardiac tamponade- patient building up fluid in the sac, -obstructing movement and therefore we cant get good cardiac output) Hypovolemic ○ not enough volume in vascular space to maintain adequate systemic circulation, so cardiac output drops Hyperdynamic vs hypodynamic shock ○ Hyperdynamic- initially very warm, tachycardia, hypertensive, metabolizing very quickly- becomes a hypodynamic form of shock late on where they get clammy, diaphoretic, and gray in color, bradycardia ○ Hypodynamic- youre not going to get fill or pressure really from the onset if you become profoundly hypovolemic  Impairment of cellular metabolism Shift from aerobic to anaerobic metabolism ○ -Acidosis (Lactic) Loss of ability to maintain electrochemical gradient Cellular Accumulations of toxic byproducts of metabolism (o2 free radicals/ROS) Glycogenolysis (increases in blood sugar) Extracellular potassium shifts (Hyperkalemia) Activation of coagulation pathway Release of lysosomal enzymes Lipolysis- can cue apoptosis and cause cellular necrosis Cardiogenic shock Pump Failure Decreased Cardiac Output Neurohormonal Responses Sympathetic Release of Catecholamines RAAS activation ○ Sodium, fluid retention Activates inflammatory response  Until we revascularize tissues and try to increase the blood pressure, stroke volume, and increase cardiac output the patient will very quickly move towards death ○ Neurohormonal and endocrine response Clinical manifestations  ○ Chest pain, dyspnea, and faintness, along with feelings of impending doom ○ Beck’s Triad (represents cardiac Tamponade) Hypotension/ Narrow Pulse pressure JVD Muffled Heart Tones ○ Classic hallmarks: Tachycardia, tachypnea, hypotension, jugular venous distention, dysrhythmia, and low cardiac output ○ Becks triad represents cardiac tamponade ○ -there is usually some type of a collection or pericardial effusion- as the fluid collects around the heart, the heart cannot fill and stretch against it and cardiac output decreases Hypovolemic shock Insufficient intravascular volume Loss of blood, plasma, insterstitial fluid Compensatory vasoconstriction, increased systemic vascular resistance (SVR), and afterload so that CO can increase and be delivered to tissues ○ -increase in heart rate ○ -release of epinephrine and norepinephrine (catecholamines from adrenal medulla) ○ -activation of RAAS system and vasoconstriction ○ -release of antidiuretic hormone- retaining sodium and fluid ○ -fluid from the interstitial spaces will shift into the vascular space Clinical manifestations ○ Poor skin turgor, thirst, oliguria ○ Low systemic and pulmonary preloads ○ Rapid heart rates Distributive shock fluid is in wrong place, we cant generate a perfusion to get to the tissues we initially see a hyperdynamic state in response to the blood/fluid being in the wrong place and leaky capillary permeability- heart rate and blood pressure increase (cardiac output will initially go up)- increase in afterload not seen right away, will have a low afterload because fluid volume not staying in intravascular space in response Types of distributive shock ○ neurogenic/vasogenic Widespread vasodilation Imbalance between parasympathetic and sympathetic stimulation. Persistent vasodilation, relative hypovolemia. Reduction in SVR Pressure inadequate to drive nutrients across capillary membranes Dont have neural input to tell our arterioles to vasoconstrict  ○ Anaphylactic Widespread hypersensitivity Extensive immune/inflammatory response Interstitial fluid shifts Massive vasodilation Peripheral pooling, relative hypovolemia ○ Septic shock Sepsis: life-threatening organ dysfunction caused by a dysregulated host response to infection.- systemic inflammatory response to infection Septic Shock: a subset of sepsis in which underlying circulatory and cellular/metabolic abnormalities are profound enough to substantially increase mortality.- see involvement of the end organs  Common sites lungs, bloodstream, intravascular catheter, intraabdominal, urinary tract, and surgical wounds Bacteremia, endotoxins, and exotoxins cause the host to initiate the inflammatory process. Activation of complement, coagulation, and kinin systems Innate and adaptive immunity. Initiates and promotes widespread vasodilation. massive vasodilation brought out by activation of different plasma protein systems All results in a pro-inflammatory response that becomes harmful to the host and results in lack of perfusion to the organs and risk of death Clinical manifestations Persistent low arterial pressure Elevated serum lactate Increased HR, fever low tissue perfusion low SVR from vasodilation altered oxygen extraction Overtime, become cold with low blood pressure Obstructive shock  something preventing or blocking perfusion from getting to the tissues and decreasing cardiac output (e.g. pulmonary embolism, tension pneumothorax) Note: Nothing is absolutely one form of shock or the other, its very rare that its one form of shock Multiple organ dysfunction syndrome This is what shock leads to Also known as end organ failure Dysfunction of two or more organ systems ○ Due to uncontrolled inflammatory response Shock and sepsis: Two most common causes ○ Trauma, burns, acute respiratory disorder (ARDS), major surgery, circulatory shock, necrotic tissue, disseminated intravascular coagulation (DIC), acute renal failure, acute pancreatitis Primary (immediately) vs Secondary MODS (gradual) Clinical manifestations ○ 24 hours Low-grade fever, tachycardia, tachypnea, dyspnea, altered mental status, general hyperdynamic and hypermetabolic state ○ 24–72 hours Beginning of lung failure; possible appearance of ARDS ○ 7- 10 days Development of hepatic, intestinal, and renal failure ○ 14–21 days Increased severity of renal failure and liver failure; also possible occurrence of death  ○ Later: Hematologic failure and myocardial failure ○ ○ Hypermetabolism When we are in shock, we have hypermetabolism An endocrine response where we are pushing out catecholamines Pituitary gland is releasing ACTH because we need cortisol to increase metabolism because the tissues are not generating enough ATP Excessive endocrine response Circulating catecholamines Cortisol ○ tachycardia, hypermetabolism, and increased oxygen consumption. Also mediated by TNF and IL-1. Alterations in carbohydrate, fat, and lipid metabolism. Increased burden of work on the system Plasma protein activation  Includes increased risk of either coagulopathy and DIC or consumption of coagulation products because of activation of the coagulation pathway DIC- microembolisms and using coagulation and clotting factors in a dysfunctional way that consumes and utilizes all of the platelets which causes an increased risk for abnormal bleeding and moving towards death Myocardial depression Exhaustion of oxygen stores SHOCK IN CHILDREN Most Common Etiology ○ Severe dehydration ○ Hemorrhage ○ Progressive heart failure: heart defects ○ Pulmonary hypertension ○ Drug toxicity ○ Electrolyte or acid-base imbalance ○ Dysrhythmia ○ Obstruction of blood flow ○ Multi-organ failure Types of shock ○ Hypovolemic: Loss of circulating blood volume, leading to inadequate perfusion. Pathophysiology: Decreased preload → reduced stroke volume → decreased cardiac output → impaired tissue perfusion. ○ Cardiogenic: Failure of the heart to pump effectively. Patho: Decreased cardiac output despite normal or increased blood volume → inadequate perfusion.  ○ Distributive: results from inappropriate vasodilation, leading to relative hypovolemia. Septic: Severe allergic reaction with systemic histamine release. Patho: Excessive cytokine release → vasodilation → decreased systemic vascular resistance → maldistribution of blood flow. Anaphylactic: Severe allergic reaction with systemic histamine release. Widespread vasodilation, increased vascular permeability → decreased circulating volume. Neurogenic: Loss of sympathetic tone due to spinal cord injury or central nervous system damage. Patho: Unopposed parasympathetic activity → vasodilation and bradycardia. ○ Obstructive: Physical obstruction to blood flow in large vessels or the heart. Patho: Mechanical obstruction → impaired ventricular filling or outflow → reduced cardiac output. Type of Shock Primary Problem Treatment Focus Hypovolemic Loss of blood/fluids Fluid resuscitation (crystalloids, blood) Cardiogenic Pump failure Improve cardiac function (inotropes, revascularization) Septic (Distributive) Infection and Treat infection, vasopressors vasodilation Anaphylactic Allergy and Epinephrine, fluids, antihistamines (Distributive) vasodilation Neurogenic Loss of sympathetic Vasopressors, atropine (Distributive) tone Obstructive Physical obstruction Relieve obstruction (e.g., chest tube, thrombolysis) Shock Clinical Manifestations: Newborn ○ Jittery, lethargy, hypotonic- tone is important ○ Apnea and bradycardia- resp < 20 ○ Hypothermia and hypoglycemia- signs of sepsis infection with potential shock ○ Poor feeding Infants and children  ○ Irritability and lethargy ○ Mottled color – pallor ○ Initally: Tachycardia, delayed capillary refill, diminished peripheral pulses ○ LATE: hypotension and bradycardia Pediatric Vital Signs HypoVolemic shock- Most common Most common type of shock in children Etiology – dehydration and trauma Hypotension – severe, decompensated shock Bradycardia – impending cardiovascular collapse Hypoglycemia - /= 150mg/dl3 Mild/Moderate dehydration ○ Thirst-lethargy, eyes sunken, diminished tears, mucous membranes sticky-dry, decreased urine, cap refill > 2 Severe dehydration  ○ Limp, cold, cyanotic, poor turgor, sunken fontanels and eyes, absent tears, no urine output in 8 hours, hypotension, bradycardia Cardiogenic Shock Impaired myocardial function/cardiac output Post-op cardiac surgery, cardiomyopathy, myocarditis Complication of other types of shock: can move from hypovolemic to cardiogenic Distributive/Septic Shock Septic, anaphylactic or neurogenic Vasodilation and increased capillary permeability Loss of vasomotor tone – severe head/spinal cord injury Septic shock mortality rate 8.9-24%, rapid Obstructive Shock Inadequate cardiac output Obstruction of blood flow to or from the heart or lungs Congenital heart defect, pulmonary embolism or pneumothorax Hypoxemia, dyspnea, cool extremities, faint pulses Pediatric Burns Partial and full thickness burns Move Hypovolemia shock to septic shock d/t loss of skin barrier Primary complication is inhalation injury- heat damages airways Infants and children have thinner skin, renal system is immature, larger body surface area than adults, limited glycogen stores. Rule of Nines: is a quick method for estimating the total body surface area (TBSA) affected by burns. In pediatrics, this rule is modified from the adult version due to differences in body proportions. ○ Head and Neck: 18% (compared to 9% in adults) ○ Each Arm (front and back): 9% (4.5% front, 4.5% back) ○ Each Leg (front and back): 14% (7% front, 7% back) ○ Anterior Torso (front): 18% ○ Posterior Torso (back): 18% ○ Perineum: 1%