Physio Pat Review

7/28/2019 Physio Pat Review

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Physiopathology

Review

Itisaveryfast,quickreviewofthewholethingItisnotacompleteworkforYour

prepara;on,butausefulpre-examlecture

BasedonDoc.JipasmaterialandRobbinsPathology

AlessandroMoa,UVVG,3rdyear

1

Chapterssummarizedinthiswork:

Anemia Hemostasis Lungdiseases RespiratoryFailure RenalDiseases RenalFailure Jaundice PancreasProblems PortalCirculaon Arrhythmias Cardiomyopathies Valvulopathies


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AnemiaBloodComponents:

Plasma:55%;BloodCells:45%

Threetypes:

Erythrocytes/RBCs Leukocytes/WBCs

Thrombocytes/Platelets

Hematopoiesisis theprocessbywhichmaturebloodcellsaregeneratedandfunconal,assumingtheexistenceofcellsoforiginwhohavealongseriesoftransformaonsandhematopoecmicroenvironment(composedofstromalcellsandsmulangfactors).Bone marrow is the central component generang blood cells: red cells, granulocytes,monocytes, lymphocytes, platelets and hematopoiec funcons are proliferaon,differenaonandcellreleaseintocirculaon.Bonemarrowconsistsof:reculovascularstroma(withsupporngrole,nutrionandmovementofhematopoieccells);medullarparenchyma-composedofacvecellsformingislandsofhematopoiesis,

usually arranged around a trophic cell - "nurse cell." Nurse cells are involved inerythropoiesis (iron stores) in myelopoesis and megacaryopoesis (liberate smulangfactors-e.g..IL-3).Pluripotentstemcells(PSCs)arethecellsoforiginofallbloodcells.

TheRBClifecycle:Inthebonemarrow,erythropoienenhancesthegrowthofdifferenaonofburstformingunits-erythroid(BFU-E)andcolonyformingunits-erythroid(CFU-E)intoreculocytes.Reculocytespendsthreedaysmaturinginthemarrow,andthenonedaymaturingintheperipheralblood.AmatureRedBloodCellcirculatesintheperipheralbloodfor100to120days.Understeadystatecondions,therateofRBCproduconequalstherateofRBCloss.

Whatisanemia?Isapathologicalstate,accompaniedbydecreasein:thelevelofhemoglobin,thequantyoferythrocytes,perunitofvolumeoftheblood.Result:deficiencyintheoxygen-carryingcapacityoftheblood(hypoxia)

Hemoglobin=gramsofhemoglobinper100mLof

wholeblood(g/dL)

Hematocrit=percentofasampleofwholeblood

occupiedbyintactredbloodcells

RBC=millionsofredbloodcellspermicroLofwhole

bloodMCV=Meancorpuscularvolume

If>100Macrocycanaemia If80100Normocycanaemia

If


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Decreasedproduconofredbloodcells Normocyc Macrocyc

Hypochromic

Normochromiccombined

mechanisms

Lossofredbloodcells(bleeding,lysis)

Hyperchromic

Microcyc

Iron

deficiency,

Thalassemia,

Chronic

disease,

Copper

deficiency

Malignancy,

Chronicdisease,

Renalfailure,

Bloodloss,

Hemolyc

disorders,

Hemoglobinopat

hies

Folatedeficiency,VitaminB12deficiency,Inheritedbonemarrowfailure,Hypothyroidism,Druginduced,

Acvehemolysis

Aplascanaemia:Erythropoiendeficiency.Marrowinfiltraon-malignancy:injury-infecons,toxins;Nutrionaldeficiency(iron,proteins);Ineffecveerythropoesis(thalassemias);

Labs:Lowreculocytecount,variableMCV.

InbloodLoss:Reculocytecount

usuallyelevated,bonemarrow

tryingtocompensate,MCVusually

normaltoslightlyelevated.For

Hemolysis:Acquired,Autoimmune

process,vesselinjury,InheritedRBC

defect,Reculocytecountusually

elevated,MCVnormaltoslightlyelevated

AnemiasClassificaon

ComplicaonsinAnemicSyndrome:biochemicalchanges,hemodynamicchanges,respiratoryandrenalchanges,alteraonsofssueperfusion,increasedproduconofRBCs,immunesystemabnormaliesandendocrinechanges(hypofuncons).

IscharacterizedbyPancytopenia(loweringofallbloodcellstypes).Couldbecongenitaloracquired,hasaverylowincidenceandcanbemanagedbyEPOorbloodtransfusion.Cricalinbloodlossandsepsis.

Aplasc

Type

Irondeficiencyisthemostcommoncauseofanaemia,20%ofwomen(50%ofpregnantwomen)and3%ofmendonothaveenoughironinthebody.Disruponofironmetabolismcausesanaemiaanddisturbcytochromesacvity(cellrespiraon).Ironisobtainedthroughdietaryintake(muscle,liver)andironabsorponrequiresthepresenceofHClandtransferrin.Ironisabsorbedinproximalsmallbowel.Itmayinstallsaersmallandconnuouslossofblood,inadequateintake,metabolismdisordersorinsituaonsofincreasedneeds(pregnancy).Labfindings:SerumIron=LOW(360micrograms/dL).SerumFerrin=LOW(


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4

UnderproduconofRBCs,shorteningofRBCsurvival,2ndmostcommoncauseofanaemia(aerirondeficiencyanaemia.Generallydevelopsaer1-2monthsofsustaineddisease.Itisanormochromic,normocycorhypochromic,microcycanaemia,whichdevelopsthroughmulplemechanisms.Newestname,inflamma&onassociatedanaemia,ismorerepresentavebecauseitreflectspathophysiologicalmechanisms.Couldbesecondary(chronicinfecons,collagendiseases,malignancies,elderlypaents).Ironreplacementisnotnecessary.Maybenefitfromerythropoiensupplementaon.

Anemiain

chronic

diseases

VitaminB12andfolicacidareimportantnutrientsrequiredintheprocessofnuclearmaturaon.Theyarerequiredduring

erythropoiesis(duringDNAsynthesis).Theseanaemiasmaybecausedbecauseofanutrionaldeficiencyorimpairedabsorponmainly.ImpairedDNAsynthesisleadstodefecvecellmaturaonandcelldivision.Nuclearmaturaondelays

fromthecytoplasmicmaturaonNUCLEO-CYTOPLASMICASYNCHRONY.Abnormallylargeerythroidprecursorsandred

cells.Cobalamin(VitB12)deficiencyisformerlyknownasPerniciousAnemia.Anaemiaisnormochromic,macrocyc

definedbyincreasingMCVover100fl->Macrocytosisistypicalin:Megaloblascanaemia,Alcoholism,Liverdisease.

Megaloblas;canaemiaischaracterizedbynucleo-cytoplasmicasincronismduetodeficiencyinDNAsynthesiswithnormal

RNAandproteinsynthesis(immaturenucleiandmaturecytoplasm).

Megalobl

asc

subtype

Eology:Autosomalrecessivegenec

disorderofinadequateproduconof

normalhemoglobin

weakeninganddestruconofredblood

cells.Paentshavedefectsineitherthe

orglobinchain(unlikesickle-celldisease,

whichproducesaspecificmutantformofglobin),causingproduconofabnormalred

bloodcells.FoundinMediterraneanethnic

groups.ClinicalManifestaons:

Asymptomac->majorretardaon->life

threatening:Splenomegaly,hepatomegaly.

Thalassemia


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HemostasisTheprocessbywhichthebodystopsbleedinguponinjuryandmaintainsbloodinthefluid

stateintothevascularcompartment.Processisrapidandlocalized.Itisruledby:blood

vessels,plateletsandplasmaproteins(coagulaon,fibrynolyc,serineproteaseinhibitors).

AndotherminorprocesseslikeKininandComplementsystems.

Four

Stages1

2

3

4

Primaryhemostasis:Responsetovascularinjury(vasoconstricon),Formaonoftheplateletplug

adheringtotheendothelialwall,Limitsbleedingimmediately

SecondaryHaemostasis(coagulaon):resultsinformaonofastableclot.Involvestheenzymacacvaonofcoagulaonproteinsthatfuncontoproducefibrinasareinforcementoftheplateletplug(FIBRINCASCADE).

Graduallythestableplugwillbedissolvedbyfibrinolysis.

ClotRetracon

Fibrinolysistodissolvetheclot

Fibrinolysispreventsexcessivethrombus(clot)formaon.ItisacvatedbysmulithatacvatetheIntrinsicpathway(exposuretosubendothelialcollagenandtheplateletplug).PlasminogenisacvatedandbecomesPlasmin,whichisresponsibleforlysisofaclot;aswellasinhibionofplateletaggregaonandacvaonofclongfactorsintheaffectedarea

Theyinteractwithinjuredvesselwall,interactwitheachothertoproducetheprimaryhemostacplug,whichisfragileandcaneasilybedislodgedfromthevesselwall.AreSmall,anucleatedcytoplasmicfragments,releasedfrommegakaryocytesinthebonemarrow.Megakaryocyteproliferaonissmulatedbythrombopoien(TPO).Normalplateletcountis150-400x109/L.Survive9-12days.Nonviableoragedplateletsremovedbyspleen&liver.2/3ofplateletscirculateintheperipheralblood;1/3aresequesteredinthespleen.Spontaneoushemorrhagingoccurswhenplateletcountgets


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BleedingDisorders

CloZngfactorsabnormalies

DIC=disseminatedintravascular

coagulaon

Vascularabnormalies

Plateletsdisorders

producon destruction (Primary/Idiopathic:ITPAcute/ChronicORSecondary:Drugs,HIV)Clinicalsigns:

Petechiae,ecchymoses,haematomas Bleedingfrommucosalsurfaces(epistaxis,gingivalbleeding,hematuria,

melena,hematochezia,hyphema)

ProlongedbleedingaervenipunctureorminorsurgeryIntheory,spontaneousbleedingasaresultofprimaryhaemostacdefect

couldbeduetooneofthreemechanisms:vasculardefect,thrombocytopenia

(mostcommon)orthrombopathia

Congenital:VonWillebranddisease(MCwithminimalbleeding),

FactorVIIIDeficiency(HemophiliaAorClassicType),FactorIXDeficiency

(HemophiliaB)

Acquired:Vit.Kdeficiency=DuetodeficientcarboxylaonoffactorsII,VII,IX&X;

Oralan-coagulant;Coumarinderivaves=warfarininhibitVit.Kfactors.Liverdiseasessynthesisoffactors.

Isastate/syndromewhichis

characterizedbyaccelerated

intravascularcoagulaonassociated

withincreasedconsumponofplatelets

andplasmaclongfactors.

Characteriscfeatures: acvaonofcoagulaonsystem acvaonoffibrinolycsystem consumponofclongfactors consumponofnaturalinhibitors ThrombocytopeniaItscourseisdeterminedby:platelet

produconvsdestrucon;fibrindeposit

vsfibrinolysis;synthesisofcoagulaon

factorversustheirdepleon

Causes:

Infecons(Meningococcemia,Rickesioses,Infecve

endocardis)

DrugReacons Hereditaryhemorrhagic

telangiectasia

Cushingsyndrome Henoch-SchnleinPurpura ScurvyandtheEhlers-Danlos

syndrome

Amyloidinfiltraonofbloodvessels

6

IntheDIC:

Systemic

acvaon

of

Coagulaon

Intravascular

Depositoffibrin

Depleonof

platelets/coagulaonfactor

1.Thrombosisofsmall,midsizevesselsandorganfailure

2.Contributestomulpleorganfailure

inconjunconwithhaemodynamicand

metabolicconsequences

Severebleeding


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andalso

FactorsII,VII,IX,XareallK-vitamindependent.SynthesisofVitaminK-dependentfactorsoccursintheliver.VitaminKisanessenalcofactor(forcarboxylaon)toacvatethesefactors.AncoagulantrodencidesinterferewithrecyclingofVitaminK,resulnginrapiddepleon.ProteinsCandSarealsovitaminK-dependent.Clinicalscenario:Obstrucve

jaundice,Fatmal-absorpon,Broadspectrumanbiocs,Hemorrhagicdiseaseofnewborn.Coagulaontests:ProlongaonofPTandAPTT,normalTT

VitaminK

deficiency

HaemophiliaA(factorVIIIdeficiency)isthemostcommonformofthedisorder,presentinabout1in5,00010,000male

births;amountoracvityoffactorVIII;factorVIII=cofactorforacvaonoffactorXinthecoagulaoncascade.HaemophiliaB(factorIXdeficiency)occursinaround1inabout20,00034,000malebirths;Clinically=indisnguishable

fromHemophiliaAwithsimilarlabfindings;DiagnosisbyfactorIXlevels.Likemostrecessivesex-linked,X

chromosomedisorders,haemophiliaismorelikelytooccurinmalesthanfemales.Haemophilialowersblood

plasmaclongfactorlevelsofthecoagulaonfactorsneededforanormalclongprocess.Thuswhenabloodvesselis

injured,atemporaryscabdoesform,butthemissingcoagulaonfactorspreventfibrinformaon,whichisnecessaryto

maintainthebloodclot.

Haemophi

lia

VWFactorisproducedbymegakaryocytesandendothelialcells,anditcirculatesinplasmacomplexedtofactorVIIIItisimportantintheformaonoftheprimaryplateletplug(causesplateletstoadheretosubendothelialcarlage).VonWillebrandfactor'sprimaryfunconisbindingtootherproteins,inparcularfactorVIII,anditisimportantinplateletadhesiontowoundsites;itisnotanenzymeand,thus,hasnocatalycacvity.

Von

Willebranddisease

Severedamagetohepatocytesorobstruconofbileductresultsinvariablefactordeficienciesand/orabnormaliesinVitaminKmetabolism.Disordersofplateletnumberandfunconmayoccur.PTandPTTcanbeprolonged.FDP,D-dimer,andfibrinogenconcentraonsmaybeincreasedduetoreducedclearanceofplasminogenacvators,aswellasreducedsynthesisoffibrinolycinhibitors.Basedonresultsofcoagulaontests,maybedifficulttodifferenatefromDIC.Looktophysicalexamfindings,chemistryprofilechanges,andliverfuncontesng.

Hepac

Diseases

Causes:Plateletdysfunconorabnormalplatelet-vesselwallinteraconduetolowHb(alteredbloodrheology)Clinicalfeature:mucocutaneousbleeding.Coagulaontests:normalPTandAPTT;prolongedskinbleedingme

Uremiableeding

Diagnosc

tests

Wholebleedingme

PlateletCount

Vesselwall:usuallyonlyecchymoses

Coagulaon

Fibrinogen

Thrombocitopenia:platelets(80.000;mm3)/Thrombocitosis

PT=normal10-15sec(prothrombinme)/PTT=normal;3-50sec.(paralthromboplasnme)

7


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LungDiseases

ChronicBronchits

COPD

Emphysema

ARDS

Asthma

A.IntrinsicasthmanoenvironmentalcausescanbeidenfiednegaveskintesttocommonairbornallergensrathernegavefamilyhistoryB.Extrinsicasthmaatopy,genecpredisposionIgE,mastcellsandeosinophilsresponsetoallergensC.Occupaonalasthmasensibilisaonofairwaystoinhalantchemicals

IntrinsicAsthma Noallergicor

(personalfamily)history

Usuallyadultonset

Oenfollowssevererespiratory

illness Symptoms

usuallyperennial Morerefractory

totreatment

ExtrinsicAsthma Strongfamilyhistoryof

allergies Usuallyonsetatayoung

age Otherallergic

manifestaonsinpaents

Historyofspecificallergicassociaontriggers(e.g.pollen,animaldander)

Correlaonwithskinandinhalaonresponsestospecificangens

Whendoesitoccurs?Instabilityoftheairways=exaggeratedbronchoconstrictorresponsetoawidevarietyofsmuli1. Acute

bronchoconstricon2. Swellingoftheairway

wall

3. Chronicmucusplugformaon4. Airwaywallremodeling

Earlyphaseresponse:3060minutes,allergenorirritantacvatesmastcells,inflammatorymediatorsarereleased(histamine,bradykinin,leukotrienes,prostaglandins,platelet-acvang-factor,chemotaccfactors,cytokines).Intenseinflammaonoccurs+BronchospasmLatephaseresponse:56hours,itischaracterizedbyinflammaon,eosinophilsandneutrophilsinfiltrate,mastcellsreleasehistamineandaddionalmediators,Self-perpetuangcycle,Lymphocytesandmonocytesinvadeaswell,Futureaacks

maybeworsebecauseofincreasedairwayreacvitythatresultsfromlatephaseresponse 8


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ChronicBronchis

Presenceofchronicproducve

coughfor3ormoremonthsin

eachof2successiveyearsina

paentwhomothercausesofchroniccoughhavebeen

excluded.Riskfactors:

cigareesmokeorair

polluon.

Anatomicalalteraonsof

lungs:Chronicinflammaon

andswellingoftheperipheral

airways,excessivemucus

produconandaccumulaon,

paralortotalmucus

plugging,hyperinflaonof

alveoli(air-trapping),smooth

muscleconstriconof

bronchialairways(mild

bronchospasm)

Pathophysiology:

Chronicinflammaon:Hypertrophy&hyperplasiaofbronchialglandsthatsecretemucus.IncreasenumberofGobletcells(secrete

mucin).Ciliaaredestroyed

Narrowingofairway:Starngw/bronchi->smallerairways:moreairflowresistance&workofbreathing+Hypovenlaon&CO2retenon->hypoxemia&hypercapnea.

Bronchospasmoenoccurs,asendresult:Hypoxemia,hypercapnea,polycythemia(increaseRBCs),cyanosis,Corpulmonale.

Emphysema

Abnormalpermanentenlargementofthe

airspacedistaltothe

terminalbronchioles.

Accompaniedby

destruconof

bronchioles.

Abnormaldistension

ofairspaces.Actual

causeisunknown

Pathophysiology:

Structuralchanges:Hyperinflaonofalveoli,destruconof

alveolar&alveolar-capillarywalls,smallairwaysnarrow,lung

elascitydecreases.

Mechanismsofstructuralchange:

Obstruconofsmallbronchioles Proteolycenzymesdestroyalveolarssue Elasn&collagenaredestroyedTheendresult:alveoliloseelascrecoil,thendistend,&

eventuallyblowout.Smallairwayscollapseornarrow.

Hyperinflaonofalveoli(air-trapping).Decreasedsurface

areaforvenlaon

Thereisalsoapermanentenlargementanddeterioraonof

theairspacesdistaltotheterminalbronchioles;Destruconofpulmonarycapillaries.AndBronchospasm.

Eology:cigareesmoking,genec

predisposionandotherchemicals

irritants.Classificaon:

Centrilobular(mostcommon) Perilobular 9


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10

COPD

Characterizedbypresence

ofairflowobstrucon.

Causedbyemphysema

and/orchronicbronchis.Generallyprogressive.May

beaccompaniedbyairway

hyperacvity.Maybe

parallyreversible

1. Itischronic2. Itisprogressive3. Mostlyfixedairway

obstrucon

4. Nonreversiblebybronchodilators

5. Exposuretonoxiousagentisa

must

6. TwoenesinCOPDnamely

7. ChronicBronchis8. Emphysema

IrreversibleCOPDWhy?

Fibrosisandnarrowingoftheairways

Lossofelascrecoilduetoalveolardestrucon DestruconofalveolarsupportthatmaintainspatencyofsmallairwaysReversibleBronchialAsthma

Accumulaonofinflammatorycells,mucus,andexudatesinbronchi Smoothmusclecontraconinperipheralandcentralairways Dynamichyperinflaonduringexercise

Causes:

Cigareesmoking

(mostcommon

anddangerous)

InfeconHeredity

Iknowitsenoughwith

pictures:D


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RespiratoryFailure

NormalValues

pH 7.35-7.45 PaO2 >70mmHg PaCO2 35-45mmHg HCO3 22-28mmol/l

Minutevenlaon=Tidal

volumeXRespiratoryrate

pH =Acidosis

pH =Alkalosis

PaO2=Hypoxemia

PaCO2=Hypercapnia

pH+PaCO2R.acidosis

--HCO3

pH+PaCO2R.Alkalosis

--HCO3

Notadiseasebutacondion.Majorthreatistheinabilityofthelungstomeettheoxygen

demandsofthessues.Resultofoneormorediseasesinvolvingthelungsorotherbody

systems.Resultsfrominadequategasexchange,insufficientO2transferredtotheblood

(Hypoxemia),inadequateCO2removal(Hypercapnia)

ClinicalcondionsinwhichPaO250mmHg

Failureofoxygenaonandcarbondioxideeliminaon

AcuteorChronicType1or2(hypercapnicorHypoxemic)

ObstrucveorRestricve

Causes:

1. Hypovenlaon2. CNS3. Disordersofperipheralnervoussystem,

respiratorymuscles,andchestwall

4. Venlaon/perfusionMismatch(V/Q)5. Shunt6. Diffusionabnormalies

Incongesveheartfailure:

Vascularcongeson:increasedcapillary

bloodvolume,mildbronchoconstricon,milddecreaseinlungcompliance;PaO2

normalorevenincreased

Intersaledema:decreasedcompliance

andlungvolumes,worseningdyspnea,V/Q

abnormalityandwidenedA-aO2gradient

Alveolarflooding:lungunitsthatare

perfusedbutnotvenlated,shunt

physiologywithprofoundgasexchange

abnormalies,decreasedcomplianceandlungvolumes

Compensatorymechanism,clinicalsigns:

Respiratorycompensaon:tachypnea,useofaccessorymuscles,intercostalrecession Sympathecsmulaon:HR,BP,sweang Tissuehypoxia:alteredmentalstate,HRandBP

(late)

Haemoglobindesaturaon:cyanosis

Classificaon:

Hypoxaemicvs.HypercapnicAcutevs.Chronic

Obstrucvevs.restricve

Type1=Hypoxemic

RF

PaO250mmHg

Hypoxemiais

common

Drugoverdose,

neuromuscular

disease,chest

walldeformity,

COPD,and

Bronchialasthma

ClinicalSignsandSymptoms:Hypoxemia:Dyspnea,Cyanosis,

Confusion,somnolence,fits,

Tachycardia,arrhythmia,

Tachypnea(goodsign),Useofaccessoryms,Nasalflaring,

Recessionofintercostalms,

Polycythemia,PulmonaryHTN,

Corpulmonale,Rt.HF

Hypercapnia:Cerebralblood

flow,andCSFPressure,Headache,

Asterixis,Papilloedema,Warm

extremies,collapsingpulse,

Acidosis(respiratory,and

metabolic),pH,laccacid

11


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Spirometry

Disncveclinicaland

physiologicalfeaturesdefine:

Obstrucvelungdisease:

decreasedFEV1andFEV1/VCRestricvelungdisease:

decreasedFEV1.NormalFEV1/

VC.DecreasedTco.

TotalLungCapacity(TLC)-thetotalvolumeofthelung,thevolumeofaircontainedinthelungattheendofmaximalinspiraonInspiratoryReserveVolume(IRV)-volume,whichcanbeinspiredbeyondaresulinspiraonTidalVolume(TV)volumeofasinglebreath,usuallyatrestFunconalResidualCapacity(FRC)-Theamountofairleinthelungsaeradalbreathout,theamountofairthatstaysinthelungsduringnormalbreathing

VitalCapacity(VC)maximumvolumewhichcanbevenlatedinasinglebreathInspiratoryCapacity(IC)-themaximalvolumethatcanbeinspiredfollowinganormalexpiraonExpiratoryReserveVolume(ERV)volume,whichcanbeexpiredbeyondaresulexpiraonResidualVolume(RV)volumeremaininginthelungsaeramaximumexpiraonForcedVitalCapacity(FVC)-thevolumeofairthatcanforciblybeblownoutaerfullinspiraon,measuredinlitresForcedExpiratoryVolumein1Second(FEV1)-themaximumvolumeofairthatcanforciblyblowoutinthefirstsecondduringtheFVCmanoeuvre,measuredinlitersFEV1/FVC(FEV1%)-inhealthyadultsthisshouldbeapproximately7580%.

Inobstrucvediseases(asthma,COPD,chronicbronchis,emphysema)FEV1isdecreasedbecauseofincreasedairwayresistancetoexpiratoryflowandtheFVCmaybeincreased(forinstancebyairtrappinginemphysema).FEV1/FVCisdecreased(


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RenalDiseases

Tubular

Intersal

Vessels

Diabetesproblems

Glomerulopathies

Glomerulonephris,GN,isarenaldiseasecharacterizedbyinflammaonoftherenalglomeruli.

ImpairmentofselecvefilteringproperesofthekidneyleadingtoadecreasedGFR

Moleculesnormallynotfilteredsuchasconstuentsoftheblood,passintotheurineandare

excreted:

Haematuria(especiallydysmorphicredcells):redcellcasts

Proteinuria(maybeinnephrocrangeof>3.5g/24hours)

Lipiduria(glomerularpermeabilitymustbeincreasedtoallowthefiltraonoflargelipoproteins)

Primaryconfinedtothekidney SecondaryduetoasystemicdiseaseClinicalmanifestaons:Proteinuriaasymptomac;Haematuriaasymptomac;Hypertension

Nephrocsyndrome:grossproteinuria,hyperlipidemia

Nephricsyndrome:Oliguria,Haematuria,Proteinuria,Oedema.

Acuterenalfailure:Oliguria,lossofKidneyfuncon-withinweeks

Rapidlyprogressiverenalfailure:OvermonthsandyearsUremia.Endstagerenalfailure

NephricSyndrome:

haematuriaisusuallymacroscopicwithpinkorbrownurine(likecocacola);

oliguriamaybeoverlookedorabsentinmildercases(transientrenalimpairment);

oedemaisusuallymildandisoenjustperi-orbital-weightgainmaybedetected;+/-

fluidoverload

hypertensioncommonandassociatedwithraisedureaandcreanine;

proteinuriaisvariablebutusuallylessthaninthenephrocsyndrome.

NephrocSyndrome:

Isnotadiseasebutagroupofsignsandsymptomsseeninpaentswithheavyproteinuria

presentswithoedema proteinuriausually>3.5g/24hrs(>0.05g/kg/24hrsatchildren) serumalbumin


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lotsofdifferentdiseasesoftubulesandintersum,verydiverseaeologies,pathogenesesand

appearances,togethertheyaccountforsignificantnumbersofcasesofrenalimpairment.Tubulo/intersal

IntersalNephris,causes:Infecon,mechanical(obstrucon),drugs,autoimmune,metabolic(diabec,uric),radiaon,neoplascinfiltraon

Acutetubularnecrosis(ATN):mostimportantcauseofacute

renalfailure;characterizedbyacutedestruconoftubular

epithelialcells;mostcommonlysecondarytoischaemia,butcan

alsobeduetodirecttoxiccelldamage;potenallyreversible,sincetubularcellscanregenerate(ifgivenme).Types:

1. Ischemic:Stateofhypoperfusion(shockandreduconinintrarenalbloodflow)

2. Nephrotoxic(heavymetals,solvents,drugs,anbiocs,NSAIDs,diurecs,mediumcontrastforradiology,pescides)

Inbothtypeswewillfind:tubularcelldegeneraonanddeath,

tubularcastsofdeadcells&debris,intersaloedema&

secondaryinflammaon,paleswollenkidneys,reversiblelesion,

destruconoftubularepithelium,acutesuppressionofrenal

funcon(urineoutput>400ml/day)

Bacterialinfecons:bacterialinfeconoftherenalparenchymacausesintersalnephris.Infeconwithout

anatomicalabnormalityseldomproducespermanentdamage.

Obstrucon(stones,prostateetc)incombinaonwith

infeconcancauseprogressivedisease.Tuberculosiscauses

extensivedestruconbecauseofgranulomas,fibrosisand

caseaon.

Pyelonephris:Commonlybacterial(Gramnegave:E.coli,

Proteus,Klebsiella,Pseudomonas,Enterobacter)Riskfactors:Anomalies,Instrumentaon,Obstrucon,

bladderdysfuncon,reflux,Pregnancy

Symptoms:painatthecostovertebralangle,fever,chills,

malaise,Urine:pyuria,bacteria,Dysuria

Naturalhistory:Self-liming,recurrent,chronic

uricacidcalculi,parenchymaldepositsofuricacidandtubularobstruconwithuratecancauserenaldamage

anelevatedplasmauricaciddoesnotinitselfseemtocauserenaldamage

1/4ofpaentswithgoutgeturicacidstones 1/4ofpaentswithuricacidstoneswillhavegoutacutenephropathywithoverproduconofuricacidandkidney

obstruconwithuricacidcrystals;canoccurfollowingtreatment

ofmalignantdiseaseswithcytotoxics,heatstrokeorstatus

epilepcus;treatwithfluidsandprophylaxiswithallopurinol;

roleofuricacidinchronicrenalfailureisdisputed,butdoesoccur

withsomefamilialdisorders;

Gout,UricAcidandRenalDisease

PolycyscRenalDisease

Adult:

Autosomaldominant.Huge

kidneysfullofcysts.Usually

nosymptomsunl30years.

Associatedwithbrain

aneurysms.

Childhood:

Autosomalrecessive.

Numeroussmallcorcal

cysts.Associatedwithliver

cysts

Paentsoendieininfancy

AutosomalDominantPolycyscKidneyDisease:accountsfor

7-10%ofpeopleondialysis.50%ofsufferershaverenalfailure

byage60.Cystsmayoccurinliverandpancreasbutdonot

usuallygiveproblems 14


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Acute:suddenonset,rapidreduconinurineoutput.Usuallyreversible.Tubularcelldeath

andregeneraonChronic:Progressive.Notreversible.Nephronloss(75%offunconcan

belostbeforeitsnoceable)

Inabilityofkidneytomaintainhomeostasisleadingtoabuildupofnitrogenouswastes

Differenttorenalinsufficiencywherekidneyfunconisderangedbutcansllsupportlife

Occursoverhours/days Labdefinion1. Increaseinbaselinecreanineofmorethan50%2. Decreaseincreanineclearanceofmorethan50%3.

DeterioraoninrenalfunconrequiringdialysisAnurianourineoutputorlessthan100mls/24hours

Oliguria-


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Itisyellowishdiscoloraonof:skin,mucousmembranes,sclera;duetoexcessplasmabilirubinJaundice

Thedifferenaldiagnosisforyellowingoftheskinislimited.Inaddion

tojaundice,itincludesCarotenoderma,theuseofthedrug,

Quinacrine,excessiveexposuretophenols.Isnotadiseasebutrathera

signthatcanoccurinmanydifferentdiseases.Normalfindingsfor

bilirubinis5-17mmol/l,whileclinicallyobviousresultsare:50mmol/l

(2.5mg/dl).Bilirubinisabilepigment,lipidsolubleandisaproductof

hememetabolism(checktheHEMEmetabolismpicture->)

75%isderivedfromRBCs.Innormaladultsthisresultsinadailyload

of250-300mgofbilirubin.Normalplasmaconcentraonsarelessthen

1mg/dL Interferencesatanyoneofthepointsofbilirubin

processingdescribedabovecanleadtoacondionknown

asHYPERBILIRUBINEMIA.Causes:

Infirst3->unconjugatedN. Increasedbilirubinproducon

Reducedbilirubinuptakebyhepaccells Disruptedintracellularconjugaon

Last2->Conjugated

Disruptedsecreonofbilirubinintobilecanaliculi Intra/extra-hepacbileductobstrucon

TypesPre-Hepac(hemolyc):excessproduconofbilirubin

(beyondtheliversabilitytoconjugateit)

Hepac:ageneralizedliver(hepatocyte)dysfuncon

Post-Hepac(obstrucve):byanobstruconofthe

biliarytree


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Pancreas

Problems

WhatisSphincterofOddiDysfuncon?

ThesphincterofOddihasthreemajorfuncons:1)regulaonofbileandpancreacflowintothe

duodenum,2)diversionofhepacbileintothegallbladder,and3)theprevenonofrefluxof

duodenalcontentsintothepancreacobiliarytract.Themajorphysiologicroleofthesphincteris

theregulaonoftheflowofbileandpancreacjuice.TherearetwotypesofsphincterofOddi

dysfuncon:1)papillarystenosisand2)sphincterofOddidyskinesia.Papillarystenosisisafixed

anatomicnarrowingofthesphincter,oenduetofibrosis.SphincterofOddidyskinesiareferstoa

varietyofmanometricabnormaliesofthesphincterofOddi

Pancreas!Whentheacvaonofdigesveproenzymesoccursinpancreacductsystemoracinercells,theinflammaonistheresult.Oedema

orobstruconofampullaofVaterresulnginreflexesOfbileintopancreacductortoacinarcells.Pancreasshowsedema&necrosis.

(10%-30%mortalityrate).Thereleaseofdigesveenzymesleadtofatnecrosisinthepancreas&peritonealcavity.

Pathophysiology:insultleadstoleakageofpancreacenzymesintopancreacandperipancreacssueleadingtoacuteinflammatoryreacon,Steps:STAGE1:PancreacInjury(Edema,Inflammaon)STAGE2:LocalEffects(retroperitonealedema,Ileus)STAGE3:SystemicComplicaons(Hypotension/shock,Metabolicdisturbances,Sepsis/organfailure)

Autodigesontheory: Acvatedenzymesdigestcellularmembranes,cause

proteolysis,edema,intersalhemorrhage,vascular

damage,coagulaon&fatnecrosis,parenchymalcell

necrosis

Liberaonofbradykininpepdes,increasedvascularpermeability,andedemawithprofoundeffectsonmany

organs,esp.thelungs

SIRS,ARDS,MulorganFailure,otherdistanteffects

ACUTE

Pathophysiology:irreversibleparenchymaldestrucon

leadingtopancreacdysfuncon.Persistent,recurrent

episodesofseverepain.Anorexia,nausea.Conspaon,

flatulence.Steatorrhea.Diabetes.Causes: #1-eologyischronicEtOHabuse(90%) Gallstones Hyperparathyroidism Congenitalmalformaon (pancreasdivisum) IdiopathicComplicaons:Shock&renalfailure,hypoCa,hypoalbuminemia,hyperglucemia,hypoxia.Othersareexocrineinsufficiency(steatorrhea)andendocrineinsufficiencymayresultfromisletcelldestruconwhichleadstodiabetes

CHRONIC


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Portal

Circulaon

Aportalsystemofveinsisonewhichbeginsandalsoendsincapillaries.Theportalvenousbranchesramifyinanarteriallikepaernandendindilatedchannelscalledsinusoids,whichareequivalenttosystemiccapillaries.Fromhereblooddrainsintothehepacvenoussystem.Thenormalportalpressureis5-7mmHg(8-12cmofwater).Portalhypertensionispresentwhentheportalveinpressureexceeds12mmHg

Portalhypertensionisahighbloodpressureintheportalveinanditstributaries(portalvenous

system).Itisdefinedasaportalpressuregradient(thedifferenceinpressurebetweentheportal

veinandthehepacveins)of5mmHgorgreater.PRESSUREABOVE40mmHg.Causes:

1.INCREASEDRESISTENCE:

Pre-hepac(pre-sinusoid):portalveinobstrucon,congenital,thrombosis,extrinsic Intra-hepac(sinusoid):livercirrhosis,bilharzialperiportalfibrosis Post-hepac(post-sinusoid):Budd-Chiarisyndrome(hepacveinthrombosis),Veno-occlusive

diseaseandcardiacproblems

2.INCREASEDBLOODFLOW:

Arterial-portalvenousfistula

Increasedsplenicflow:BanssyndromeorsplenomegalyConsequences:

Porto-systemiccollaterals(caputmedusae,oesophagealvarices,haemorrhoids).Splenomegaly(congesve).Congesonofthewhole

GIT.Bleedingvarices.Ascites.

Invesgaons:

Assessmentofliverfuncontests:(a)Hypoalbuminaemia=theliveristheonlysiteofalbuminsynthesis.(b)ALT&ASTaremoderatelyraised.(c)Prothrombinmeandconcentraonaredisturbed=thistestisthemostsensiveliverfuncon.

Deteconofoesophagealvaricesbyopcfibreendoscopyorbybaritateswallow(radiology)orduplextechnique. Deteconofsplenicsequestraonandhypersplenism:bloodanalysis,bonemarrowexaminaonandradioacveisotopesstudies Diagnosisoftheaeologyofliverdiseaseisperformedbyimmunologicaltest(hepas)orliverbiopsy

Ascites

Describesthecondionofpathologicfluidcolleconwithintheabdominalcavity.CandevelopsforIncreasedhydrostacpressure,Decreasedcolloidosmocpressure,Increasepermeabilityofperitonealcapillaries,Leakageoffluidintotheperitonealcavityormiscellaneouscauses.InCirrhocascitesitdevelopsbecauseoftheportalhypertension,thelymphformaon,renalabnormalies

withNaretenonandwaterretenon.Alsorenalvasoconstriconincreasetheprobabilityofascites(latephenomena).

TheSerum-ascitesalbumingradient(SAAG)isbeerdiscriminantthanoldermeasures(transudateversusexudate)forthecausesofascites.Classificaon:a.Ahighgradient(1.1g/dL)indicatestheascitesisduetoportalhypertension.

b.Alowgradient(


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ArrhythmiasRe-entry

Automacity

Parasystole

Mostcommonmechanism:short

circuitthatformsbetweentwo

pathwaysthatareeither

anatomicallyorfunconally

disnct

Typically:Path1:Slowconducon,short

refractoryperiod

Path2:Rapidconducon,long

refractoryperiod

Heartcellsotherthan

thoseoftheSAnode

depolarizefasterthan

SAnodecells,andtake

controlasthecardiac

pacemaker.Factors

thatenhance

automacityinclude:

SANS,PANS,CO2,O2,H+,

stretch,hypokalemia

andhypocalcaemia.

Examples:Ectopic

atrialtachycardiaor

mulfocaltachycardia

inpaentswith

chroniclungdisease

ORventricularectopyaerMI

Isabenigntypeofautomacity

problemthataffectsonlyasmall

regionofatrialorventricular

cells.3%ofPVCs

Islikeadominoeffectwherethearrhythmiaisduetotheprecedingbeat.Delayedaer-depolarizaonsariseduringtheresngphaseofthelastbeatandmaybethecauseof

digitalis-inducedarrhythmias.Earlyaer-depolarizaonsariseduringtheplateauphaseor

therepolarizaonphaseofthelastbeatandmaybethecauseoftorsadesdepointes

TriggerAcvity Classificaon

Whatisanarrhythmia?

Anyabnormalityofthecardiacrhythmiscalledacardiacarrhythmia.Abnormaliesofelectrical

rhythm:generangrhythm,conduconoftheelectricity.Therearetwomaintypesofarrhythmia: Bradycardias:theheartrateisslow(100bpm)Commonnamesperregion:

Atrial:AF,Paroxs.Supra-Ventricular-TachycardiasorSVT(AVNRT,AVRT(WPW),Mulfocalatrial

tachycardia)

Ventricular:VT,VF,Torsades

Bradyarrythmia:Medicaon,AVblock,SSS

ClinicalManifestaons:Palpitaons,Syncope,Ifgoingfastenough,canprecipitatecardiac

ischaemiaandchestpain,Cardiacfailure,Decreasedlevelofconsciousness,Hypoperfusionofall

organs,Cardiacarrest.

***IhasnotinsistedoneachsubtypeofARandecgfindings,youcanfindmostoftheminmy

previousreviewfrom1stsemester


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Cardiomyopathies

Dilated

Primary(idiopathic)isadiseaseofunknowneologythat

principallyaffectsthemyocardiumleadingtoLVdilaonand

systolicdysfuncon.Secondarycausesincludeischemia,

alcoholic,peripartum,post-infecous,viral.Mostcommonof

thecardiomyopathies.Dilaonandimpairedcontraconof

ventricles:

Reducedsystolicfunconwithorwithoutheartfailure Characterizedbymyocytedamage Mulpleeologieswithsimilarresultantpathophysiology

Genecdiseasecharacterizedbyhypertrophyoftheleventricle

withmarkedvariableclinicalmanifestaonsmorphologicand

hemodynamicabnormalies.Mostcommoncauseofdeathin

youngpeople.Themagnitudeofleventricularhypertrophyis

directlycorrelatedtotheriskofsuddencardiacdeath(SCD).

Youngptswithextremehypertrophyandfewornosymptoms

areatsubstanallong-termriskofSCD.Vigoroussystolic

funcon,butimpaireddiastolicfuncon,impairedrelaxaonof

ventricles,elevateddiastolicpressures.

Mostrareformof

cardiomyopathy.Characterized

byfibroadiposereplacementof

segmentsofthefreewallof

therightventricle.Exam

usuallynormal.EKG-RBBBmay

bepresent.Echo-necessaryfor

diagnosis.Regionalwallmoon/funconisreduced.

Familialandprogressive.

Predominatelyfoundinyoung

adults.Ventriculararrhythmias:

causeofyoungadultsudden

death

Arrhythmogenic/others

Restricve

Leastcommontypeofcardiomyopathy.Increasedsffnessof

themyocardium->impaireddiastolicfilling.Ventricular

volumesareusuallynormalorreduced.Wallthicknessis

normalormildlyincreased.Systolicfunconistypically

preserved.Usuallydilatedatria..Hallmark: abnormaldiastolicfuncon Rigidventricularwallwithimpairedventricularfilling Bearsomefunconalresemblancetoconstricvepericardis Importanceliesinitsdifferenaonfromoperable

constricvepericardis

Characterizedby:impairedventricularfillingduetoan

abnormallysff(rigid)ventricle,normalsystolicfuncon(early

onindisease),intraventricularpressurerisesprecipitouslywith

smallincreasesinvolume

Areaheterogeneousgroupofdiseasesofthemyocardium,

associatedwithmechanical&/orelectricaldysfuncon

Hypertrophic


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Valvulopathies

ValveStenosis:obstrucontovalveflowduringthatphaseofthecardiaccyclewhenthevalveis

normallyopen.Hemodynamichallmark-pressuregradient~flow//VA

ValveRegurgitaon:Insufficiency,Incompetence,Inadequatevalveclosurebackleakage

Asinglevalvecanbebothstenocandregurgitant;butbothlesionscannotbesevere!!Combinaons

ofvalvelesionscancoexist

LimitedflowintotheLVhas3majorsequale:ElevaonofLt.Atrialpressure,SecondaryRVpressureoverload,hemopsy,ReducedLVejeconperformance.Duetodiminishedpreload.TachycardicresponsetocompensatetodecreasedSVworsensthetransmitralgradient.Eology:rheumac,infecveendocardis,mitralcalcificaon.Naturalhistory:Progressive,lifelongdisease,Usuallyslow&stableintheearlyyears.Progressiveacceleraoninthelateryears20-40yearlatencyfromrheumacfevertosymptomonset.Addional10yearsbeforedisablingsymptomsMortality:Duetoprogressivepulmonarycongeson,infecon,andthromboembolism

Mitral

Stenosis

PureVolumeOverload.CompensatoryMechanisms:Leatrialenlargement,LVHandincreasedcontraclity.Eology:Valvular-leaflets(MyxomatousMVDisease,Rheumacendocardis,congenital-cles);Chordaedefects;Annuluscalcificaon;PapillaryMusclesproblems;LVdilataon&funconalregurgitaonorTrauma.

ChronicMRdefinion:BackflowofbloodfromtheLVtotheLAduringsystole,aMild(physiological)MRisseenin80%ofnormalindividuals.

Mitral

Regurgita

on

Isanarrowingoftheaorcvalveopeningcausedbythefailureofthevalveleafletstoopennormally.ConcentricLVHthendevelopsduetoanincreaseinLVpressure.ThickeningandsffeningoftheLVinthefaceofincreasingobstruconresultsinincreasedLVEDP.Result=LAHanddiastolicdysfuncon.InsignificantAo.stenosis,thecardiacoutputmaybefairlywellmaintainedatrestbutfailstoaugmentwithexercise.Eology:congenital,rheumac,degeneraveorcalcific.

Aorc

stenosis

Definion:LeakageofbloodfromaortaintoLVduringdiastoleduetoineffecvecoaptaonoftheaorccusps.CombinedpressureANDvolumeoverload.CompensatoryMechanisms:LVdilaon,LVH.Progressivedilaonleadstoheartfailure.Eology:Infecveendocardis(majorityofcases),AorcDisseconoftherootoftheaorta,Trauma.Thereisanacuteandachronicsubtype.

Aorc

Regurgita

on

HTN,ECGandIschemicheartdiseasearenotdevelopedinthisreview.YouBelovedColleague

MaytheForceBeWithYouAlessandro Moa UVVG 3rdyear

Physio Pat Review

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