chapter 7 general principles of...

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Chapter 7Chapter 7General Principles of PathophysiologyGeneral Principles of Pathophysiology

Copyright © 2007, 2006, 2001, 1994 by Mosby, Inc., an affiliate of Elsevier Inc.

ObjectivesObjectivesDescribe normal cell environmentDescribe normal cell environment

Outline how alterations in water and electrolyte Outline how alterations in water and electrolyte balance affect body functionbalance affect body function

Describe treatment of fluid/electrolyte Describe treatment of fluid/electrolyte imbalancesimbalances

Describe body mechanisms to maintain acidDescribe body mechanisms to maintain acid--base balancebase balance


ObjectivesObjectivesOutline alterations in acidOutline alterations in acid--base balancebase balance

Describe management of patients with acidDescribe management of patients with acid--base base imbalanceimbalance

Describe cell or tissue alterations due to Describe cell or tissue alterations due to adaptation, injury, neoplasia, aging, deathadaptation, injury, neoplasia, aging, death

Outline effect of cell injury on local/systemic body Outline effect of cell injury on local/systemic body functionfunction


Mosby, Inc. items and derived items © 2007, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.

Sanders: Mosby's Paramedic Textbook, Revised 3rd Edition PowerPoint Lecture Notes

Chapter 7: General Principles of Pathophysiology

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ObjectivesObjectivesDescribe alterations in body function due to Describe alterations in body function due to genetic/familial disease factorsgenetic/familial disease factors

Outline hypoperfusion syndromeOutline hypoperfusion syndrome

Describe inflammatory and immune responses to cell Describe inflammatory and immune responses to cell injury or antigenic stimulationinjury or antigenic stimulation

Explain how altered immunity and inflammation can harm Explain how altered immunity and inflammation can harm body functionbody function

Describe impact of stress on response to illness or injuryDescribe impact of stress on response to illness or injury


ScenarioScenario

Your patient appears acutely ill. His physician Your patient appears acutely ill. His physician says he has a diagnosis of diabetic says he has a diagnosis of diabetic ketoacidosis. He is breathing rapidly, has a ketoacidosis. He is breathing rapidly, has a dry, furrowed tongue, and tenting skin. The dry, furrowed tongue, and tenting skin. The physician tells you to watch for rhythm physician tells you to watch for rhythm disturbances.disturbances.


ConsiderConsiderWhat signs and symptoms of dehydration should you What signs and symptoms of dehydration should you watch for?watch for?

How should you treat the dehydration?How should you treat the dehydration?

Why is the patient breathing so fast?Why is the patient breathing so fast?

Should you attempt to slow his breathing?Should you attempt to slow his breathing?

Why might this patient have increased potassium levels Why might this patient have increased potassium levels that can cause rhythm problems?that can cause rhythm problems?



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The CellThe Cell

Fundamental unit Fundamental unit found in higher life found in higher life formsforms


Tissue TypesTissue Types

EpithelialEpithelial

ConnectiveConnectiveIncluding hematologic tissueIncluding hematologic tissue

MuscleMuscle

NervousNervous


Intracellular Fluid (ICF)Intracellular Fluid (ICF)

Fluid found in all Fluid found in all body cellsbody cells

40% of total body 40% of total body weightweight



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Extracellular Fluid (ECF)Extracellular Fluid (ECF)

Intravascular Intravascular Blood plasmaBlood plasma

Interstitial fluidInterstitial fluidBetween cells Between cells Cerebrospinal fluid Cerebrospinal fluid Intraocular fluidIntraocular fluid20% of total body weight20% of total body weight


Aging and Distribution of Body FluidsAging and Distribution of Body Fluids

Water is the main component of body Water is the main component of body massmass

AdultsAdults•• 50% to 60% of total body weight 50% to 60% of total body weight

NewbornNewborn•• About 80% of total body weightAbout 80% of total body weight

Childhood Childhood •• 60% to 65% of total body weight60% to 65% of total body weight

Further declines with age Further declines with age


Water Movement Between ICF and ECFWater Movement Between ICF and ECF

OsmosisOsmosisFlow of fluid across a semipermeable membrane from a lower Flow of fluid across a semipermeable membrane from a lower solute concentration to a higher solute concentrationsolute concentration to a higher solute concentration

Partial pressures of gases determine osmotic pressurePartial pressures of gases determine osmotic pressure

Nongaseous particles (e.g., electrolytes)Nongaseous particles (e.g., electrolytes)Osmotic pressure determined by:Osmotic pressure determined by:

•• Number and molecular weights Number and molecular weights •• Permeability of membranePermeability of membrane



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OsmosisOsmosis


SolutionsSolutionsHypertonic solutionHypertonic solutionHypotonic solutionHypotonic solutionIsotonic solutionIsotonic solution


DiffusionDiffusion

Due to constant motion of atoms, molecules, Due to constant motion of atoms, molecules, ions in solutionions in solution

Passive processPassive processMoves particles from area of higher concentration Moves particles from area of higher concentration to area of lower concentrationto area of lower concentration

Concentration gradientConcentration gradient



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DiffusionDiffusion


Mediated Transport MechanismsMediated Transport Mechanisms

Carrier moleculesCarrier moleculesProteinsProteinsGlucoseGlucose

Two kinds of mediated transport: Two kinds of mediated transport: Active transportActive transportFacilitated diffusionFacilitated diffusion


Mediated Transport by aMediated Transport by aCarrier Molecule Carrier Molecule



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Molecule Released on Other Side of Molecule Released on Other Side of Plasma MembranePlasma Membrane


Water Movement between Plasma Water Movement between Plasma and Interstitial Fluidand Interstitial Fluid

Fluid transfer between blood and interstitial Fluid transfer between blood and interstitial fluid fluid

Due to pressure changes at arterial and Due to pressure changes at arterial and venous ends of the capillaryvenous ends of the capillary


Capillary NetworkCapillary Network

Blood enters capillary network from arteriolesBlood enters capillary network from arteriolesFlows through capillary network into venulesFlows through capillary network into venulesArteriolar capillaries Arteriolar capillaries Venous capillariesVenous capillariesTrue capillariesTrue capillariesThoroughfare channelsThoroughfare channelsCapillary sphinctersCapillary sphincters



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Sympathetic InnervationSympathetic Innervation

Sympathetic fibers Sympathetic fibers innervate all blood innervate all blood vessels except:vessels except:

CapillariesCapillariesCapillary sphinctersCapillary sphinctersMost metarteriolesMost metarterioles

Vasoconstrictor and Vasoconstrictor and vasodilator fibersvasodilator fibers


Diffusion across Capillary WallDiffusion across Capillary Wall

Capillary flowCapillary flowHydrostatic pressureHydrostatic pressureOsmotic pressureOsmotic pressure

Oncotic pressureOncotic pressure

Capillary and membrane permeabilityCapillary and membrane permeability


Diffusion across Capillary WallDiffusion across Capillary Wall



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Starling HypothesisStarling Hypothesis

Net filtration = Net filtration = FForces favoring filtration orces favoring filtration −− Forces opposing filtration Forces opposing filtration


Alterations in Water MovementAlterations in Water Movement

EdemaEdemaFluid accumulation in interstitial spacesFluid accumulation in interstitial spacesDue to any condition that leads to:Due to any condition that leads to:

•• Net movement of fluid out of capillaries into interstitial Net movement of fluid out of capillaries into interstitial tissuestissues


Pathophysiology of EdemaPathophysiology of Edema

Normal interstitial space fluid depends on:Normal interstitial space fluid depends on:Capillary hydrostatic pressureCapillary hydrostatic pressureOncotic pressure by blood plasma proteins Oncotic pressure by blood plasma proteins Capillary permeabilityCapillary permeabilityLymphatic channels collect fluid forced from Lymphatic channels collect fluid forced from capillaries by blood hydrostatic pressure and capillaries by blood hydrostatic pressure and return it to circulationreturn it to circulation



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Mechanisms Responsible for EdemaMechanisms Responsible for EdemaIncreased hydrostatic pressureIncreased hydrostatic pressure

Decreased plasma oncotic pressureDecreased plasma oncotic pressure

Increased capillary permeabilityIncreased capillary permeability

Lymphatic obstructionLymphatic obstruction

Increased capillary hydrostatic pressureIncreased capillary hydrostatic pressureVenous obstructionVenous obstructionSodium and water retentionSodium and water retention


Clinical Manifestations of EdemaClinical Manifestations of Edema

Edema may be localized or generalizedEdema may be localized or generalized

Localized edemaLocalized edemaUsually limited to:Usually limited to:

•• Injury site (e.g., a sprained ankle)Injury site (e.g., a sprained ankle)•• Organ system (e.g., cerebral edema, pulmonary edema)Organ system (e.g., cerebral edema, pulmonary edema)


Generalized EdemaGeneralized Edema

More widespreadMore widespread

Dependent parts of bodyDependent parts of bodyOften:Often:•• Weight gainWeight gain•• SwellingSwelling•• PuffinessPuffiness

Other symptoms from underlying illnessOther symptoms from underlying illness



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Water Balance, Sodium, and ChlorideWater Balance, Sodium, and Chloride

Water follows osmotic gradient established by Water follows osmotic gradient established by changes in sodium concentrationchanges in sodium concentration

Sodium and water balance are closely relatedSodium and water balance are closely related


Water BalanceWater Balance

Regulated by antidiuretic hormone Regulated by antidiuretic hormone Secretion of ADHSecretion of ADHPerception of thirstPerception of thirst

Release of ADH initiated by:Release of ADH initiated by:Increase in plasma osmolality Increase in plasma osmolality Decrease in circulating blood volume Decrease in circulating blood volume Lowered venous and arterial pressureLowered venous and arterial pressure


ADHADH

Increased plasma osmolalityIncreased plasma osmolalityStimulates hypothalamic neurons (osmoreceptors)Stimulates hypothalamic neurons (osmoreceptors)Causes thirst perceptionCauses thirst perceptionIncreases ADH release from posterior pituitary Increases ADH release from posterior pituitary



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ADHADH

After ADH release:After ADH release:Water is reabsorbed into plasma from distal Water is reabsorbed into plasma from distal renal tubules and kidney collecting ducts renal tubules and kidney collecting ducts Amount of water lost in urine decreasesAmount of water lost in urine decreasesPlasma osmolality returns to normal as water is Plasma osmolality returns to normal as water is reabsorbedreabsorbed


Sodium and Chloride BalanceSodium and Chloride Balance

SodiumSodiumMajor ECF cationMajor ECF cationSodium balance regulated by aldosteroneSodium balance regulated by aldosterone

•• Hormone secreted from the adrenal cortexHormone secreted from the adrenal cortex

Regulates:Regulates:•• Osmotic forcesOsmotic forces•• Water balanceWater balance


ChlorideChloride

Major ECF anionMajor ECF anionProvides electroneutrality with sodiumProvides electroneutrality with sodiumIncreases or decreases in chloride are Increases or decreases in chloride are proportional to changes in sodiumproportional to changes in sodium



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Sodium and Chloride BalanceSodium and Chloride Balance

Aldosterone is secreted when sodium levels Aldosterone is secreted when sodium levels decrease or potassium levels increasedecrease or potassium levels increase

Increases reabsorption of sodium, secretion of Increases reabsorption of sodium, secretion of potassium by distal tubules of kidneyspotassium by distal tubules of kidneys

Renin is secreted by kidneys when blood Renin is secreted by kidneys when blood volume or water balance is reducedvolume or water balance is reduced


ReninRenin--AngiotensinAngiotensin

Renin stimulates formation of angiotensin I:Renin stimulates formation of angiotensin I:Then converted to angiotensin IIThen converted to angiotensin II

Angiotensin II is a potent vasoconstrictor Angiotensin II is a potent vasoconstrictor Stimulates ADH secretionStimulates ADH secretion

Results in:Results in:Reabsorption of sodium and waterReabsorption of sodium and waterElevation in blood pressure Elevation in blood pressure Activation of reninActivation of renin--angiotensin systemangiotensin system


Role of Adrenal Medulla in Regulating BPRole of Adrenal Medulla in Regulating BP



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ReninRenin--AngiotensinAngiotensin--Aldosterone Aldosterone Mechanism Mechanism


Vasopressin (ADH) Mechanism Vasopressin (ADH) Mechanism


Natriuretic HormoneNatriuretic Hormone

Promotes urinary secretion of sodiumPromotes urinary secretion of sodiumDecrease in sodium tubular reabsorptionDecrease in sodium tubular reabsorptionLoss of sodium and waterLoss of sodium and water



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Sodium, Chloride, and Water BalanceSodium, Chloride, and Water Balance

Homeostatic mechanisms Homeostatic mechanisms Maintain constant balance between water Maintain constant balance between water intake and excretion intake and excretion Water gained each day approximately equals Water gained each day approximately equals water lostwater lost


Alterations in Water BalanceAlterations in Water Balance

Gain water primarily by:Gain water primarily by:Drinking fluidsDrinking fluidsIngesting food containing moistureIngesting food containing moistureForming water through oxidation of Forming water through oxidation of hydrogen in food during metabolic processhydrogen in food during metabolic process



Body loses water through:Body loses water through:Kidneys as urineKidneys as urineBowel as fecesBowel as fecesSkin as perspirationSkin as perspirationExhaled air as vaporExhaled air as vaporExcretion of tears and salivaExcretion of tears and saliva



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Abnormal states of body fluid balance Abnormal states of body fluid balance If the water lost exceeds the water gained, there is If the water lost exceeds the water gained, there is a water deficit (dehydration)a water deficit (dehydration)If the water gained exceeds the water lost, there is If the water gained exceeds the water lost, there is a water excess (overhydration)a water excess (overhydration)


DehydrationDehydration

Dehydration classificationsDehydration classificationsIsotonicIsotonic

•• Excessive loss of sodium and water in equal amountsExcessive loss of sodium and water in equal amounts

HypernatremicHypernatremic•• Loss of water in excess of sodiumLoss of water in excess of sodium

HyponatremicHyponatremic•• Loss of sodium in excess of waterLoss of sodium in excess of water


Isotonic DehydrationIsotonic Dehydration

Vomiting, diarrhea, infection, bowel obstructionVomiting, diarrhea, infection, bowel obstruction

Signs and symptomsSigns and symptomsSkin turgor, oliguria, anuria, weight lossSkin turgor, oliguria, anuria, weight loss

TreatmentTreatmentIsotonic fluidsIsotonic fluids



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Hypernatremic Dehydration Hypernatremic Dehydration

Diuretic use, sodium intake without water, Diuretic use, sodium intake without water, diarrhea diarrhea

Dry, sticky mucus membranes, flushed skin, Dry, sticky mucus membranes, flushed skin, thirst, oliguria, increased thirst, altered LOCthirst, oliguria, increased thirst, altered LOC

Treat with isotonic fluidsTreat with isotonic fluids


Hyponatremic DehydrationHyponatremic Dehydration

Diuretic use, perspiration, renal problems, Diuretic use, perspiration, renal problems, increased water intakeincreased water intake

Muscle cramps, seizures, rapid pulse, Muscle cramps, seizures, rapid pulse, diaphoresis, cyanosisdiaphoresis, cyanosis

Treatment with NS or LRTreatment with NS or LRRarely, use hypertonic salineRarely, use hypertonic saline


OverhydrationOverhydrationIncreased body waterIncreased body water

Excess intake, impaired cardiac or renal function, Excess intake, impaired cardiac or renal function, endocrine dysfunctionendocrine dysfunction

Dyspnea, edema, polyuria, crackles, weight gainDyspnea, edema, polyuria, crackles, weight gain

Treatment varies by cause:Treatment varies by cause:Fluid restrictionFluid restrictionDiureticsDiuretics



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Electrolyte ImbalancesElectrolyte Imbalances

In addition to water and sodium imbalances, In addition to water and sodium imbalances, other electrolyte imbalances may occurother electrolyte imbalances may occur

PotassiumPotassiumCalciumCalciumMagnesiumMagnesium


PotassiumPotassium

Major intracellular cationMajor intracellular cation

Needed for nerve, cardiac, skeletal functionNeeded for nerve, cardiac, skeletal function

Excess excreted by kidneysExcess excreted by kidneys

Imbalance can cause sudden deathImbalance can cause sudden death


HypokalemiaHypokalemia

Poor absorption, vomiting, diarrhea, renal Poor absorption, vomiting, diarrhea, renal disease, diureticsdisease, diuretics

Malaise, weakness, dysrhythmias, decreased Malaise, weakness, dysrhythmias, decreased reflexes, faint heart sounds, hypotension, reflexes, faint heart sounds, hypotension, anorexia, vomitinganorexia, vomiting

Hospital treatmentHospital treatmentOral or IV potassiumOral or IV potassium



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HyperkalemiaHyperkalemiaRenal failure, burns, crush injuries, infections, Renal failure, burns, crush injuries, infections, excessive use, acidosisexcessive use, acidosis

Dysrhythmias, irritability, abdominal distention, Dysrhythmias, irritability, abdominal distention, nausea, diarrhea, oliguria, weakness, paralysisnausea, diarrhea, oliguria, weakness, paralysis

TreatmentTreatmentLife threats Life threats –– calcium, glucose, insulin IV, albuterolcalcium, glucose, insulin IV, albuterolHospital Hospital –– K+ restriction, exchange resins, dialysisK+ restriction, exchange resins, dialysis


CalciumCalcium

Essential for:Essential for:Neuromuscular transmissionNeuromuscular transmissionCell membrane permeabilityCell membrane permeabilityHormone secretionHormone secretionBone growthBone growthMuscle contractionMuscle contraction


HypocalcemiaHypocalcemia

Endocrine dysfunction, renal disease, Endocrine dysfunction, renal disease, malabsorptionmalabsorption

Paresthesia, tetany, cramps, neural Paresthesia, tetany, cramps, neural excitability, seizure, abnormal behaviorexcitability, seizure, abnormal behavior

TreatmentTreatmentCalcium administration in hospitalCalcium administration in hospital



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HypercalcemiaHypercalcemiaTumors, endocrine dysfunction, diuretics, Tumors, endocrine dysfunction, diuretics, excess vitamin Dexcess vitamin D

Muscle weakness, renal stones, altered mental Muscle weakness, renal stones, altered mental status, seizures, bone pain, arrhythmiasstatus, seizures, bone pain, arrhythmias

TreatmentTreatmentUnderlying problemUnderlying problemDiuresis with furosemide and NSDiuresis with furosemide and NS


MagnesiumMagnesium

Activates enzymesActivates enzymes

50% in bone50% in bone

Excreted by kidneysExcreted by kidneys

CNS effect similar to calciumCNS effect similar to calcium


HypomagnesemiaHypomagnesemiaAlcoholism, diabetes, malabsorption, starvation, Alcoholism, diabetes, malabsorption, starvation, diarrhea, diuresis, disease with hypocalcemia, diarrhea, diuresis, disease with hypocalcemia, hypokalemiahypokalemia

Tremors, nausea, vomiting, diarrhea, hyperactive Tremors, nausea, vomiting, diarrhea, hyperactive reflexes, confusion, seizures, dysrhythmiasreflexes, confusion, seizures, dysrhythmias

TreatmentTreatmentMagnesium sulfateMagnesium sulfate



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HypermagnesemiaHypermagnesemia

Patients with chronic renal insufficiencyPatients with chronic renal insufficiency

Ingestion of magnesiumIngestion of magnesium--containing compounds containing compounds

CNS depression, dysrhythmias, muscle weakness, CNS depression, dysrhythmias, muscle weakness, confusion, sedation, respiratory paralysisconfusion, sedation, respiratory paralysis

Most effective treatment: hemodialysisMost effective treatment: hemodialysis

Also IV glucose and insulinAlso IV glucose and insulin


AcidAcid--Base BalanceBase BalanceAcidsAcids

Release hydrogen ions Release hydrogen ions

BasesBasesReceive hydrogen ionsReceive hydrogen ions

A solution increases in:A solution increases in:Acidity as hydrogen ions increaseAcidity as hydrogen ions increaseAlkalinity as hydrogen ions decreaseAlkalinity as hydrogen ions decrease


Hydrogen Ion ConcentrationHydrogen Ion Concentration

Hydrogen ion Hydrogen ion concentrationconcentration

Expressed by pHExpressed by pH•• pH is negative logarithm pH is negative logarithm

(base 10) of hydrogen ion (base 10) of hydrogen ion concentrationconcentration

Strength of acid or base Strength of acid or base changes by 10 times with changes by 10 times with each unit change of pHeach unit change of pH



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Buffer Systems Buffer Systems

Carbonic acidCarbonic acid––bicarbonate bufferbicarbonate buffer

Protein bufferingProtein buffering

Renal bufferingRenal buffering

Bicarbonate buffer system


AcidAcid--Base ImbalanceBase Imbalance

Any condition that increases carbonic acid or Any condition that increases carbonic acid or decreases base bicarbonate causes decreases base bicarbonate causes acidosisacidosis

Any condition that increases base Any condition that increases base bicarbonate or decreases carbonic acid bicarbonate or decreases carbonic acid causes causes alkalosisalkalosis


Respiratory AcidosisRespiratory Acidosis

Carbon dioxide Carbon dioxide retentionretention

PCOPCO2 2 increaseincrease

Increase ventilationIncrease ventilation



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Respiratory AcidosisRespiratory Acidosis

Possible causesPossible causesRespiratory depressionRespiratory depressionRespiratory arrestRespiratory arrestCardiac arrestCardiac arrestMedicationsMedicationsChest wall injuriesChest wall injuriesPulmonary illnesses, obstructed airwayPulmonary illnesses, obstructed airway


Metabolic AcidosisMetabolic AcidosisCausesCauses

BuildBuild--up of acid or loss of baseup of acid or loss of base

Common formsCommon formsLactic acidosisLactic acidosisDiabetic ketoacidosisDiabetic ketoacidosisAcidosis related to renal failureAcidosis related to renal failureAcidosis related to ingestion of toxinsAcidosis related to ingestion of toxins

Treat causeTreat cause


Lactic AcidosisLactic AcidosisCausesCauses

Ischemia, circulatory failure, shockIschemia, circulatory failure, shockExtreme exertional states (seizures)Extreme exertional states (seizures)

Associated complicationsAssociated complicationsDecreased cardiac contraction, hypotension, cardiac muscle Decreased cardiac contraction, hypotension, cardiac muscle refractory to defibrillationrefractory to defibrillation

TreatmentTreatmentIdentify and treat underlying causeIdentify and treat underlying causeReestablish perfusion, cardiac outputReestablish perfusion, cardiac outputHyperventilation (possible), vigorous rehydration, sodium Hyperventilation (possible), vigorous rehydration, sodium bicarbonate (possible) for cardiac arrestbicarbonate (possible) for cardiac arrest



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Diabetic KetoacidosisDiabetic Ketoacidosis

CausesCausesComplication of diabetes mellitus, alcoholismComplication of diabetes mellitus, alcoholismLack of adequate insulinLack of adequate insulin

TreatmentTreatmentAdminister NSAdminister NS


Renal Failure AcidosisRenal Failure Acidosis

CausesCausesFailure of kidneys to keep acidFailure of kidneys to keep acid--base balancebase balanceInability to efficiently excrete waste productsInability to efficiently excrete waste products

TreatmentTreatmentIdentify and treat underlying causeIdentify and treat underlying cause


Ingestion of ToxinsIngestion of Toxins

TypesTypesEthylene glycol, methanol, salicylateEthylene glycol, methanol, salicylate

TreatmentTreatmentGI evacuation, hemodialysis , diuresis, hydration, GI evacuation, hemodialysis , diuresis, hydration, specific antidotesspecific antidotes



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Respiratory AlkalosisRespiratory Alkalosis

Hyperventilation Hyperventilation decreases PCOdecreases PCO22

Sepsis, shock, Sepsis, shock, peritonitis, respiratory peritonitis, respiratory problemsproblems

Treat cause, oxygenate, Treat cause, oxygenate, calmcalm


Metabolic Alkalosis (Rare)Metabolic Alkalosis (Rare)Loss of hydrogen ions Loss of hydrogen ions (usually stomach)(usually stomach)

Sodium bicarbonate or Sodium bicarbonate or calcium carbonate calcium carbonate ingestioningestion

Excess IV alkaliExcess IV alkali

DiureticsDiuretics

Treat causeTreat cause


Mixed AcidMixed Acid--Base Disturbances Base Disturbances

Combination of respiratory and metabolic Combination of respiratory and metabolic disordersdisorders

ShockShock

Cardiac arrestCardiac arrest

OthersOthers



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Alterations in Cells and TissuesAlterations in Cells and Tissues

Cellular adaptationCellular adaptationAtrophyAtrophyHypertrophyHypertrophyHyperplasia Hyperplasia MetaplasiaMetaplasiaDysplasia Dysplasia


Cellular InjuryCellular Injury

Cell unable to maintain homeostasis because Cell unable to maintain homeostasis because ofof

Hypoxic injuryHypoxic injuryChemical injuryChemical injuryInfectious injury (bacteria, viruses)Infectious injury (bacteria, viruses)Immunologic and inflammatory injuryImmunologic and inflammatory injuryGenetic factorsGenetic factorsNutritional imbalancesNutritional imbalancesPhysical agentsPhysical agents


Manifestations of Cellular InjuryManifestations of Cellular Injury

Accumulation of excess lipids, electrolytes, Accumulation of excess lipids, electrolytes, fluidsfluids

Phagocytes engulf dying cellsPhagocytes engulf dying cells

Cell swellsCell swells

Fatty changesFatty changes



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Cellular InjuryCellular Injury——Systemic ManifestationsSystemic Manifestations

FeverFeverMalaiseMalaiseLoss of wellLoss of well--beingbeingAltered appetiteAltered appetiteAltered heart rateAltered heart rateLeukocytosisLeukocytosisPainPain


Cellular Death/NecrosisCellular Death/NecrosisCell dies if it is irreparably damagedCell dies if it is irreparably damaged

After cell death, structural changes occur in the After cell death, structural changes occur in the nucleus and cytoplasmnucleus and cytoplasm

Lysosome membrane breakdownLysosome membrane breakdown

Enzymes digest cellEnzymes digest cell

NecrosisNecrosis


HypoperfusionHypoperfusionInadequate blood and nutrients to tissuesInadequate blood and nutrients to tissues

Cardiac outputCardiac outputDepends on several factorsDepends on several factors

•• Strength of contractionStrength of contraction•• Rate of contractionRate of contraction•• Amount of venous return (preload)Amount of venous return (preload)

Compensatory mechanismsCompensatory mechanisms



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Negative Feedback MechanismsNegative Feedback MechanismsBaroreceptor reflexesBaroreceptor reflexes

Chemoreceptor reflexesChemoreceptor reflexes

Central nervous system ischemic responseCentral nervous system ischemic response

Hormonal mechanismsHormonal mechanisms

Reabsorption of tissue fluidsReabsorption of tissue fluids

Splenic discharge of stored bloodSplenic discharge of stored blood


Baroreceptor Reflexes Baroreceptor Reflexes Maintain BP by Maintain BP by negative feedback negative feedback mechanismsmechanisms

Lower BP if arterial Lower BP if arterial pressure increasespressure increasesIncrease BP if arterial Increase BP if arterial pressure decreasespressure decreases


Chemoreceptor ReflexesChemoreceptor Reflexes

Low arterial pressure Low arterial pressure stimulates peripheral stimulates peripheral chemoreceptor cells in chemoreceptor cells in carotid and aortic carotid and aortic bodiesbodies

If oxygen or pH If oxygen or pH decreases, vasomotor decreases, vasomotor center of medulla is center of medulla is stimulatedstimulated



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CNS Ischemic ResponseCNS Ischemic ResponseActivated with BP< 50 mm HgActivated with BP< 50 mm Hg

Ischemia in medullary vasomotor centerIschemia in medullary vasomotor center

Activates vasomotor centerActivates vasomotor center

Elevates arterial pressureElevates arterial pressure

If it persists, vagal centers are activatedIf it persists, vagal centers are activated


Hormonal MechanismsHormonal Mechanisms

AdrenalAdrenal--medullary mechanismmedullary mechanismEpinephrine, norepinephrine releaseEpinephrine, norepinephrine releaseIncreased heart rate, stroke volumeIncreased heart rate, stroke volumeVasoconstrictionVasoconstriction

ReninRenin--angiotensinangiotensin--aldosterone mechanismaldosterone mechanismVasoconstrictionVasoconstrictionWater, sodium conservationWater, sodium conservation


Hormonal MechanismsHormonal Mechanisms

Vasopressin mechanismVasopressin mechanismADH causes vasoconstrictionADH causes vasoconstrictionDecreases urine productionDecreases urine production



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Compensatory MechanismsCompensatory Mechanisms

Reabsorption of fluidsReabsorption of fluidsDecreased capillary hydrostatic pressureDecreased capillary hydrostatic pressureFluid moves from interstitial to vascular spaceFluid moves from interstitial to vascular space

Splenic discharge of bloodSplenic discharge of bloodBlood stored in venous sinusesBlood stored in venous sinuses> 200 mL can be released after vasoconstriction> 200 mL can be released after vasoconstriction


Types of ShockTypes of Shock

Classified by primary causeClassified by primary causeTwo or more types may be combinedTwo or more types may be combinedPrimary problem is inadequate tissue perfusionPrimary problem is inadequate tissue perfusion


Types of ShockTypes of ShockHypovolemic Hypovolemic

Cardiogenic Cardiogenic

Neurogenic Neurogenic

Anaphylactic Anaphylactic

Septic Septic



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Multiple Organ Dysfunction Syndrome Multiple Organ Dysfunction Syndrome (MODS)(MODS)

Failure of two or Failure of two or more organ systems more organ systems after severe illness after severe illness or injuryor injury

Septic shock is a Septic shock is a common causecommon cause


MODS PathophysiologyMODS Pathophysiology

Inflammatory response is triggeredInflammatory response is triggeredFluid and cells leak into interstitial spaceFluid and cells leak into interstitial spaceHypotension/hypoperfusionHypotension/hypoperfusionComplement, coagulation, kallikrein/kininComplement, coagulation, kallikrein/kininThrombus formation, tissue ischemiaThrombus formation, tissue ischemiaEdema, cardiovascular instability, clotting Edema, cardiovascular instability, clotting abnormalitiesabnormalitiesTissue hypoxia, organ failureTissue hypoxia, organ failure


GlucoseGlucose

Important fuel for Important fuel for producing energyproducing energy

Krebs cycleKrebs cycleBreaks down pyruvic acid Breaks down pyruvic acid into carbon dioxide and into carbon dioxide and waterwaterMuch more efficient in Much more efficient in producing ATP than producing ATP than glycolysis glycolysis Needs oxygenNeeds oxygen



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BodyBody’’s Selfs Self--Defense MechanismsDefense Mechanisms

Defense against illness and injuryDefense against illness and injuryFirstFirst--line external barriers include:line external barriers include:

•• SkinSkin•• Mucous membranes of the respiratory, digestive, and Mucous membranes of the respiratory, digestive, and

genitourinary (GU) tractgenitourinary (GU) tract

SecondSecond——Inflammatory responseInflammatory responseThirdThird——Immune responseImmune response


Stages of Inflammatory ResponseStages of Inflammatory ResponseCellular response to injuryCellular response to injury

Energy depletion, autolysisEnergy depletion, autolysis

Vascular response to injuryVascular response to injuryHyperemia, vessel dilationHyperemia, vessel dilationLeukocyte migrationLeukocyte migration

PhagocytosisPhagocytosisLeukocytes destroy pathogensLeukocytes destroy pathogensExudate (pus) formsExudate (pus) forms


Inflammatory ResponsesInflammatory Responses

Acute inflammationAcute inflammationLocal responsesLocal responsesSystemic responsesSystemic responses

Chronic inflammationChronic inflammationInflammation Inflammation >> 2 wks2 wks



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Immune ResponseImmune Response

Types of immunityTypes of immunityNatural (native)Natural (native)AcquiredAcquired

•• Humoral immunityHumoral immunity•• CellCell--mediated immunitymediated immunity

Age and the immune responseAge and the immune response


Induction of Immune ResponseInduction of Immune Response

AntigenAntigenReacts with preformed components of immune Reacts with preformed components of immune system system

ImmunogenImmunogenAntigen that can also induce formation of Antigen that can also induce formation of antibodiesantibodies


Induction of Immune ResponseInduction of Immune Response

To be immunogenic, the antigenic molecule To be immunogenic, the antigenic molecule must bemust be

Sufficiently foreign to the hostSufficiently foreign to the hostSufficiently largeSufficiently largeSufficiently complexSufficiently complexPresent in sufficient amountsPresent in sufficient amounts

B lymphocytes B lymphocytes

T lymphocytes T lymphocytes



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Blood Group AntigensBlood Group Antigens

When combined with foreign plasma, red When combined with foreign plasma, red blood cells either clump together blood cells either clump together (agglutinate), or they do not(agglutinate), or they do not

Two distinct agglutinins (substances on red Two distinct agglutinins (substances on red blood cells acting as antigens) are blood cells acting as antigens) are responsible for this clumpingresponsible for this clumping



Four types of human blood have been Four types of human blood have been identified: A, B, AB, and O identified: A, B, AB, and O

Type A blood has antiType A blood has anti--B antibodies in the plasma B antibodies in the plasma and will clump type B bloodand will clump type B bloodType B blood has antiType B blood has anti--A antibodies and will clump A antibodies and will clump type A bloodtype A blood





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Rh FactorRh Factor

Presence or absence of Rh antigen on Presence or absence of Rh antigen on surface of red blood cellssurface of red blood cells

85% of Americans are Rh positive85% of Americans are Rh positive


HypersensitivityHypersensitivityAltered immunologic reactivity to antigen Altered immunologic reactivity to antigen

Causes pathologic immune response after Causes pathologic immune response after reexposurereexposure

Abnormal responses include:Abnormal responses include:AllergyAllergyAutoimmunityAutoimmunityIsoimmunityIsoimmunity


Mechanisms of HypersensitivityMechanisms of Hypersensitivity

Immediate hypersensitivity reactionsImmediate hypersensitivity reactionsItching, hivesItching, hivesAnaphylaxisAnaphylaxis

Delayed hypersensitivity reactionsDelayed hypersensitivity reactionsTake several hours to 1 to 2 days to appearTake several hours to 1 to 2 days to appearAt maximum several days after antigen At maximum several days after antigen reexposure reexposure



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ImmunoglobulinsImmunoglobulins

Antibodies, or immunoglobulins (Ig), respond Antibodies, or immunoglobulins (Ig), respond to antigenic stimulationto antigenic stimulation

IgGIgGIgMIgMIgAIgAIgDIgDIgEIgE


ImmunoglobulinsImmunoglobulinsIgGIgG

Secondary immune Secondary immune responseresponse

IgMIgMABO incompatibilitiesABO incompatibilities

IgAIgADefends body Defends body surface against surface against organismsorganisms

IgEIgEImmediate Immediate hypersensitivity hypersensitivity reactionsreactions

IgDIgDFunction unknownFunction unknown


Immunity and Inflammation DeficienciesImmunity and Inflammation Deficiencies

BodyBody’’s selfs self--defense mechanisms fail to defense mechanisms fail to function at normal capacityfunction at normal capacity

Sources of the deficiency:Sources of the deficiency:Congenital Congenital AcquiredAcquired•• Infection (e.g., HIV)Infection (e.g., HIV)•• Cancer (e.g., leukemia)Cancer (e.g., leukemia)•• Immunosuppressive drugsImmunosuppressive drugs•• AgingAging



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Acquired Immune DeficienciesAcquired Immune DeficienciesNutritional deficiencies Nutritional deficiencies

Iatrogenic deficienciesIatrogenic deficiencies

Deficiencies caused by traumaDeficiencies caused by trauma

Deficiencies caused by stress Deficiencies caused by stress

Acquired immunodeficiency syndrome (AIDS)Acquired immunodeficiency syndrome (AIDS)


Neuroendocrine Regulation of StressNeuroendocrine Regulation of Stress

Sympathetic nervous system activated by stressSympathetic nervous system activated by stress

Adrenal gland releases catecholamines Adrenal gland releases catecholamines

Hypothalamus stimulates pituitary gland to release:Hypothalamus stimulates pituitary gland to release:ADHADHProlactinProlactinGrowth hormoneGrowth hormoneACTHACTH


CatecholaminesCatecholamines

Stimulate:Stimulate:AlphaAlpha--adrenergic receptorsadrenergic receptors

•• AlphaAlpha--1 and alpha1 and alpha--2 2

BetaBeta--adrenergic receptorsadrenergic receptors•• BetaBeta--1 and beta1 and beta--22



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Alpha ReceptorsAlpha ReceptorsAlphaAlpha--1 receptors1 receptors

PostsynapticPostsynapticOn the effector organsOn the effector organsStimulate contraction of smooth muscleStimulate contraction of smooth muscle

AlphaAlpha--2 receptors2 receptorsPresynaptic nerve endingsPresynaptic nerve endingsStimulate alphaStimulate alpha--2 receptors 2 receptors Inhibit release of norepinephrine Inhibit release of norepinephrine


Beta ReceptorsBeta Receptors

BetaBeta--1 receptors1 receptorsPrimarily in heartPrimarily in heart

BetaBeta--2 receptors2 receptorsBronchiolar and arterial Bronchiolar and arterial smooth musclesmooth muscle

Beta receptorsBeta receptorsStimulate the heartStimulate the heartDilate bronchiolesDilate bronchiolesDilate blood vessels in Dilate blood vessels in the skeletal muscle, the skeletal muscle, brain, and heartbrain, and heartAid in glycogenolysisAid in glycogenolysis


Cortisol (Hydrocortisone)Cortisol (Hydrocortisone)Circulates in the plasmaCirculates in the plasma

Mobilizes substances needed for cellular metabolismMobilizes substances needed for cellular metabolism

Stimulates gluconeogenesisStimulates gluconeogenesisDecreases glucose utilizationDecreases glucose utilization

ImmunosuppressantImmunosuppressant

Decreases migration of macrophages Decreases migration of macrophages Decreases phagocytosisDecreases phagocytosis



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Role of the Immune SystemRole of the Immune System

Immunologic conditions may be triggered by Immunologic conditions may be triggered by stressstress

Immune, nervous, and endocrine systems Immune, nervous, and endocrine systems may be affected by stress reactionmay be affected by stress reaction


Stress, Coping, Illness InterrelationshipsStress, Coping, Illness Interrelationships

IllIll--effects of stress determined by:effects of stress determined by:Nature, intensity, and duration of stressors and Nature, intensity, and duration of stressors and individualindividual’’s perceptions perceptionIndividual coping skillsIndividual coping skills

Person must:Person must:Recognize signs and symptoms of stressRecognize signs and symptoms of stressUse stress management techniques:Use stress management techniques:

•• MeditationMeditation•• ImageryImagery


Factors Causing DiseaseFactors Causing Disease

Genetic factorsGenetic factorsChromosomalChromosomalPolygenicPolygenic

Environmental factorsEnvironmental factorsMicroorganismsMicroorganismsLifestyleLifestylePhysical environmentPhysical environmentPsychosocial environmentPsychosocial environment



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Analyzing Disease RiskAnalyzing Disease Risk

Disease ratesDisease rates

Statistics commonly used to assess societal Statistics commonly used to assess societal impact of disease:impact of disease:

Incidence rateIncidence ratePrevalence ratePrevalence rateMortality rateMortality rate


Causal and Noncausal Risk FactorsCausal and Noncausal Risk Factors


Disease RiskDisease Risk

Familial disease tendencyFamilial disease tendency

Aging and ageAging and age--related disordersrelated disorders



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ConclusionConclusionParamedics should appreciate the Paramedics should appreciate the

correlation of pathophysiology with disease correlation of pathophysiology with disease processes to better understand, anticipate, processes to better understand, anticipate,

direct, and provide appropriate care to direct, and provide appropriate care to patients.patients.


Questions?Questions?



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