nbde pathology review.pdf

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NBDE Part I ReviewNBDE Part I Review

PATHOLOGYPATHOLOGY



V. Systemic Pathology*V. Systemic Pathology*!! CardiovascularCardiovascular

!!

RespiratoryRespiratory!! GI &GI & HepatobiliaryHepatobiliary

!! GenitourinaryGenitourinary

!!BloodBlood

--lymphaticlymphatic

!! EndocrineEndocrine

!! MusculoskeletalMusculoskeletal

!! Genetic DiseasesGenetic Diseases

!! Nervous SystemNervous System

* Excludes infectiousdiseases which should becovered in microbiology

Next histology review will also cover: Inflammation/Repair ,Immunopathology and Developmental Disturbances

(Genetic, Non-neoplastic, Neoplastic)



Pathology Diagnosis ParadigmPathology Diagnosis Paradigm!! ReactiveReactive

!! Inflammatory (Inflammatory (--itisitis), non), non--inflammatory, Infectious,inflammatory, Infectious,Traumatic , AutoimmuneTraumatic , Autoimmune

!! Classic signs and symptoms of inflammation?Classic signs and symptoms of inflammation?

!! DevelopmentalDevelopmental!! Congenital or acquired malformationCongenital or acquired malformation

!! Sometimes symmetric features or cysticSometimes symmetric features or cystic

!! NeoplasticNeoplastic ((--omaoma))

!! Benign (Benign (--omaoma)) vsvs Malignant (Malignant (--sarcoma/ sarcoma/ --carcinoma)carcinoma)



Pathology Diagnosis ParadigmPathology Diagnosis Paradigm

!! Apply paradigm to cells/tissues/organsApply paradigm to cells/tissues/organs

!! Often when normal anatomy/physiologicOften when normal anatomy/physiologicfunction of tissue impaired, the signs andfunction of tissue impaired, the signs andsymptoms follow accordinglysymptoms follow accordingly

! Anatomy/Physiology is key tounderstanding most Pathology, becauseoften what the tissue normally doesindicates how it will behave when it ismessed up – or pathologic !



CardiovascularCardiovascular

DiseasesDiseases

• Inter-related group of diseases



Cardiac Circulation



LungsLungs

Systemic Circulation



Pathology Diagnosis ParadigmPathology Diagnosis Paradigm

Applied to Cardiovascular PathologyApplied to Cardiovascular Pathology

!! ReactiveReactive


!! Classic Signs and symptoms of inflammation?Classic Signs and symptoms of inflammation?

!! DevelopmentalDevelopmental

!! Congenital or acquired malformationCongenital or acquired malformation!! Sometimes symmetric features or cysticSometimes symmetric features or cystic

!! Neoplastic (Neoplastic (--omaoma))!!

BenignBenign vsvs MalignantMalignant

-- What happens after damage or impairment ofWhat happens after damage or impairment ofnormal anatomy/physiology in the heart…normal anatomy/physiology in the heart…

(muscles and vessels)…(muscles and vessels)…





Angina PectorisAngina Pectoris!! Lack of oxygen to the heart due to narrowedLack of oxygen to the heart due to narrowed

or occluded coronary artery…why?or occluded coronary artery…why?!! Intermittent chest painIntermittent chest pain

!! SubsternalSubsternal painpain -- may radiate to left arm ormay radiate to left arm orleft mandibleleft mandible

!! Associated with exertion or stressAssociated with exertion or stress!! Stable (exertion), unstable (rest), orStable (exertion), unstable (rest), or

PrintzmetalPrintzmetal variant (morningvariant (morning coronarycoronary

artery spasm)artery spasm)!! Relieved by rest and/or nitroglycerinRelieved by rest and/or nitroglycerin

!! Increased risk for cardiac coIncreased risk for cardiac co--morbiditymorbidity



Ischemic Heart DiseaseIschemic Heart Disease!! Due to decreased blood supply toDue to decreased blood supply to

the heartthe heart Coronary Artery DiseaseCoronary Artery Disease

(CAD)(CAD)!! Contributing factors:Contributing factors: HypertensionHypertension,,

diabetes, smoking, higher lowdiabetes, smoking, higher low--density lipoprotein (LDL),density lipoprotein (LDL),

cholesterolcholesterol

!! Outcomes: angina pectoris,Outcomes: angina pectoris,

myocardial infarction (heart attack),myocardial infarction (heart attack),

or sudden cardiac deathor sudden cardiac death



HypertensionHypertension

!! Sustained diastolic pressureSustained diastolic pressure>

90 mm Hg and90 mm Hg andsystolic pressuresystolic pressure

> 140 mm Hg (AHA)140 mm Hg (AHA)

!! 9090--95% (idiopathic), 595% (idiopathic), 5--10% (renal disease or renal10% (renal disease or renalarteryartery stenosisstenosis))

!! Mechanisms:Mechanisms: blood volume (Glucose, Nablood volume (Glucose, Na++),),

peripheral resistance (i.e. atherosclerosis), renalperipheral resistance (i.e. atherosclerosis), renaldisease, adrenal disease, lung diseasedisease, adrenal disease, lung disease

!! Increased risk for:Increased risk for: AtherosclerosisAtherosclerosis, Thrombosis,, Thrombosis,Myocardial Infarct (MI), Coronary artery diseaseMyocardial Infarct (MI), Coronary artery disease(CAD), Deep Venous Thrombosis (DVT),(CAD), Deep Venous Thrombosis (DVT),CerebrovascularCerebrovascular Accident (CVA, stroke),Accident (CVA, stroke),Congestive Heart Failure (CHF), andCongestive Heart Failure (CHF), and



Atherosclerosis



AtherosclerosisAtherosclerosis!! Plaque (Plaque (atheromaatheroma) development with lipids,) development with lipids,

cells, debris, new fibrous tissuecells, debris, new fibrous tissue!! Aorta, coronary, and cerebral arteries areAorta, coronary, and cerebral arteries are

most commonly affectedmost commonly affected

!! Risk factors: age (40Risk factors: age (40--60 5x60 5x risk for MI);risk for MI);sex (Msex (M

> F); heredity;F); heredity; hyperlipidemiahyperlipidemia;;hypertension; smoking; and diabetes (2xhypertension; smoking; and diabetes (2x

risk MI)risk MI)!! Can lead to many cardiovascularCan lead to many cardiovascular

complicatonscomplicatons such assuch as AneurysmAneurysm formationformation



AneurysmsAneurysms!! Abnormal dilation of arteries orAbnormal dilation of arteries or

veinsveins!! Atherosclerosis is a major riskAtherosclerosis is a major risk

factorfactor

!! Weakening of arterial wallWeakening of arterial wall

!! Abdominal aorta frequentlyAbdominal aorta frequently

affectedaffected

!! Rupture can be fatalRupture can be fatal





ThrombosisThrombosis

Virchow’sVirchow’s triad: Factors in thrombus formationtriad: Factors in thrombus formation

!! Endothelial damage Endothelial damage !!

InflammationInflammation""

ThromboplastinsThromboplastins and Factor XIIand Factor XII(Hageman) release(Hageman) release "" platelet and coagulation cascadeplatelet and coagulation cascadeactivation (hence clot/thrombus)activation (hence clot/thrombus)

!! Changes in blood flow Changes in blood flow !!

Decreased rate or increased turbulenceDecreased rate or increased turbulence!! Changes in blood viscosity Changes in blood viscosity

!! Increased viscosityIncreased viscosity "" hypertensionhypertension

Types of thrombi:Types of thrombi:

1. Pale (white):1. Pale (white): Arterial (fastArterial (fast--flowing)flowing)2. Red:2. Red: Venous (slowVenous (slow--flow trapsflow traps RBC’sRBC’s))

Pathology exemplar: Disseminated Intravascular CoagulationPathology exemplar: Disseminated Intravascular Coagulation



Recanalization

Organization

Embolism?

Which artery?



Myocardial InfarctMyocardial Infarct!! Localized area of myocardial (muscle)Localized area of myocardial (muscle)

coagulativecoagulative necrosis secondary tonecrosis secondary to

inflammationinflammation!! Most common cause of deathMost common cause of death

!! Etiology: Often secondary to thrombusEtiology: Often secondary to thrombus

!! If severe, leads to sudden cardiac deathIf severe, leads to sudden cardiac death

!! Scar Scar tissue forms at site of infarct iftissue forms at site of infarct if

patient survivespatient survives!! Muscle has poor ability toMuscle has poor ability to regenerateregenerate duedue

to cell cycle attributes of muscle cells,to cell cycle attributes of muscle cells,

thereforetherefore cancer cancer is also rare in these cellsis also rare in these cells



Red or Pale Infarct?

Scar / fibrosis

from previousMI



LungsLungs

Systemic Circulation…hemodynamics!

DVT



Congestive Heart Failure (CHF)Congestive Heart Failure (CHF)

!! Inability to eject blood, leftInability to eject blood, left--sidedsided

heart failureheart failure rightright--sided heartsided heart

failurefailure

!! Commonly caused by hypertension,Commonly caused by hypertension,

valvularvalvular disease, vessel disease,disease, vessel disease,ischemic heart disease, tumorischemic heart disease, tumor

!! Clinical signs and symptoms:Clinical signs and symptoms:dyspnea, paroxysmal nocturnaldyspnea, paroxysmal nocturnal

dyspnea,dyspnea, cardiomegalycardiomegaly, tachycardia, tachycardia



LungsLungs



RightRight--sided heart failuresided heart failure!! Commonly caused by left ventricularCommonly caused by left ventricular

failure, pulmonary congestion orfailure, pulmonary congestion orembolism,embolism, valvularvalvular disease (disease (pulmonicpulmonic

or tricuspid),or tricuspid), corcor pulmonalepulmonale (due to(due to

diseases of the lung or its vessels)diseases of the lung or its vessels)

!! Clinical signs and symptoms: SystemicClinical signs and symptoms: Systemic

venous congestion, distended neckvenous congestion, distended neckveins, enlarged liver, peripheral edemaveins, enlarged liver, peripheral edema



LungsLungs



Congenital Heart Diseases*Congenital Heart Diseases*

!! Right to Left ShuntRight to Left Shunt!! TetralogyTetralogy ofof FallotFallot

!! VentricularVentricular septalseptal defect, pulmonarydefect, pulmonary stenosisstenosis, right ventricular, right ventricular

hypertrophy, overriding aortahypertrophy, overriding aorta

!! Left to Right ShuntLeft to Right Shunt!! VentricularVentricular septalseptal defectdefect

!! AtrialAtrial septalseptal defectdefect

!! PatentPatent ductusductus arteriosusarteriosus

!! PersistentPersistent truncustruncus arteriosusarteriosus

!! No ShuntNo Shunt

!! Transposition of great vesselsTransposition of great vessels!! CoarctationCoarctation of aortaof aorta

!! PulmonaryPulmonary stenosisstenosis, aortic, aortic stenosisstenosis

!! Complete heart blockComplete heart block

*Jose Gonzales PBL case



TEST QUESTIONSTEST QUESTIONS!! 112. Which of the following has the LEAST112. Which of the following has the LEAST

ability to regenerate?ability to regenerate?a. bonea. boneb. liverb. liver

c. striated musclec. striated muscled. collagend. collagene. smooth musclee. smooth muscle

!! 16.8% correctly answered C16.8% correctly answered C



TEST QUESTIONSTEST QUESTIONS!! The next 2 questions refer to the following:The next 2 questions refer to the following:

An 80 yearAn 80 year--old female with a history ofold female with a history ofmyocardial infarction presents with a complaintmyocardial infarction presents with a complaint

of pain under her complete dentures whenof pain under her complete dentures when

biting.biting. She has worn them for 15 years, butShe has worn them for 15 years, butseldom removes or cleans them.seldom removes or cleans them. Removal ofRemoval of

the dentures reveals diffuse erythema ofthe dentures reveals diffuse erythema of

underlying mucosal tissue.underlying mucosal tissue. Bone resorption isBone resorption is

noted from detectable reduction in height of thenoted from detectable reduction in height of the

alveolar ridges due to the illalveolar ridges due to the ill--fitting denture.fitting denture.



TEST QUESTIONSTEST QUESTIONS!! 178. Each of the following statements correctly describes178. Each of the following statements correctly describes

myocardial infarction (MI) EXCEPT one. Which one is themyocardial infarction (MI) EXCEPT one. Which one is the

EXCEPTION?EXCEPTION?a. Most acutea. Most acute MIsMIs are caused by coronary arteryare caused by coronary arterythrombosis.thrombosis.

b. Acute MI is the most common cause of death inb. Acute MI is the most common cause of death inindustrialized nations.industrialized nations.

c. Pain from MI can usually be relieved by vasodilatorsc. Pain from MI can usually be relieved by vasodilatorssuch as nitroglycerin.such as nitroglycerin.

d.d. ThrombolyticThrombolytic agents such as streptokinase often limitagents such as streptokinase often limitthe size of infarction.the size of infarction.

e. Myocardial necrosis usually begins 20e. Myocardial necrosis usually begins 20

--30 minutes after30 minutes after

coronary artery occlusion.coronary artery occlusion.




TEST QUESTIONSTEST QUESTIONS!! 182. Which of the following represents the182. Which of the following represents the

MOST likely pathologic change inMOST likely pathologic change inthis patient's heart?this patient's heart?

a. vegetations of the aortic valvea. vegetations of the aortic valve

b. severeb. severe mitralmitral valve thickeningvalve thickeningc. hypertrophy of the left ventriclec. hypertrophy of the left ventricle

d. necrosis in the right ventricled. necrosis in the right ventricle

e. scarring in the left ventriclee. scarring in the left ventricle

!! 11.7% correctly answered E11.7% correctly answered E



Systemic PathologySystemic Pathology

!! CardiovascularCardiovascular

!! RespiratoryRespiratory!! GI andGI and HepatobiliaryHepatobiliary


!! BloodBlood--lymphaticlymphatic!! EndocrineEndocrine


!! Genetic DiseasesGenetic Diseases!! Nervous SystemNervous System




!! Inflammatory (Inflammatory (--itisitis), non), non--inflammatory, Infectious,inflammatory, Infectious,

Traumatic , AutoimmuneTraumatic , Autoimmune!! Classic signs and symptoms of inflammation?Classic signs and symptoms of inflammation?


!! Sometimes symmetric features or cysticSometimes symmetric features or cystic!! Neoplastic (Neoplastic (--omaoma))

!! BenignBenign vsvs MalignantMalignant

-- Apply paradigm to lungs…Apply paradigm to lungs…-- Normal anatomy/physiologic function of tissueNormal anatomy/physiologic function of tissueimpaired, so signs and symptoms followimpaired, so signs and symptoms followaccordingly…accordingly…



ReactiveReactive!! AsthmaAsthma

!! BronchitisBronchitis

!! EmphysemaEmphysema



AsthmaAsthma

!! ReversibleReversible bronchospasmbronchospasm

!! Clinical manifestations: dyspnea,Clinical manifestations: dyspnea,

cough, and wheezingcough, and wheezing

!! 5% of adults, 75% of adults, 7--10% of children10% of children!! Triggered by antigen (allergen)Triggered by antigen (allergen)

!! IgE, mast cells andIgE, mast cells and eosinophilseosinophils



Chronic ObstructiveChronic Obstructive

Pulmonary Disease (COPD)Pulmonary Disease (COPD)COPD

(Smoking)

Chronic Bronchitis(Inflammation: obstruction)

Emphysema(Dilatation: alpha-1-antitrypsin deficiency, soproteases (i.e. trypsin, elastase) unchecked)

Productive cough (chronic)Dyspnea, wheezing

Cyanosis (low O2) + Edema=“blue bloater”

Non-productive cough (chronic)

Dyspnea, tachypneaEnlarged lungs causes “barrel chest”

Tachypnea (adequate O2 )=“pink puffer”

POOR PROGNOSIS = 5-year survival < lung cancer





DevelopmentalDevelopmental!! HypoplasiaHypoplasia

!! HyperplasiaHyperplasia

!! AgenesisAgenesis

!! DysgenesisDysgenesis (malformations)(malformations)!! CysticCystic



NeoplasticNeoplasticTyped as small cell and nonTyped as small cell and non--small cellsmall cell

cancerscancers

!!CarcinomaCarcinoma

!! AdenocarcinomaAdenocarcinoma

!! MesotheliomaMesothelioma



Lung TumorsLung Tumors

!! Squamous Cell Carcinoma Squamous Cell Carcinoma

!! #1 cause of cancer deaths,#1 cause of cancer deaths,

M:F=2:1, 40M:F=2:1, 40--70 yr70 yr

!! Etiology: Cigarette smoking,Etiology: Cigarette smoking,

10x10x risk of deathrisk of death!! Symptoms: Chronic cough,Symptoms: Chronic cough,

hemoptysishemoptysis and hoarsenessand hoarseness

!! Mets: CNS, Liver, Bone, Kidney,Mets: CNS, Liver, Bone, Kidney,

AdrenalsAdrenals





Lung TumorsLung Tumors

!! Adenocarcinoma Adenocarcinoma

!! Glandular cancer, most cases relatedGlandular cancer, most cases related

to smoking, although some notto smoking, although some not

!! 22ndnd to squamous cell carcinoma ofto squamous cell carcinoma of

lunglung!! Mesothelioma Mesothelioma

!! Connective tissue cancer, rareConnective tissue cancer, rare

!! Etiology is inhalation of inorganicEtiology is inhalation of inorganic

dusts:dusts: silicosis,silicosis, anthracosisanthracosis,,

berylliosisberylliosis, asbestosis, asbestosis



Systemic PathologySystemic Pathology!! CardiovascularCardiovascular

!! RespiratoryRespiratory!! Gastrointestinal andGastrointestinal and HepatobiliaryHepatobiliary


!!BloodBlood--lymphaticlymphatic!! EndocrineEndocrine










!! Classic signs and symptoms of inflammation?Classic signs and symptoms of inflammation?


!! Sometimes symmetric features or cysticSometimes symmetric features or cystic!! Neoplastic (Neoplastic (--omaoma))

!! BenignBenign vsvs MalignantMalignant

--

Apply paradigm GI…Apply paradigm GI…

-- Normal anatomy/physiologic function of tissueNormal anatomy/physiologic function of tissueimpaired, so signs and symptoms followimpaired, so signs and symptoms followaccordingly…accordingly…



HiatalHernia

Esophageal

Carcinoma

Esophagus

ChronicGastritis

Acute

Gastritis

Peptic

Ulcers

Gastric

Carcinoma

Stomach

Hemorrhoids

Crohn's

Disease

Ulcerative

Colitis

Colonic

Diverticulosis

Colorectal

Carcinoma

Small &Large Intestines

Appendicitis

Appendix

Gastrointestinal Disease

*AchalasiaDDxcovered in

case PBL-

032: Mrs.Richardson

Hi l H iHi t l H i



Hiatal HerniaHiatal Hernia



Hiatal HerniaHiatal Hernia!! Opening for the esophagus widensOpening for the esophagus widens

!! Displacement of stomach above theDisplacement of stomach above thediaphragmdiaphragm

!! 11--20% population;20% population; with agingwith aging!! 10%10% -- heartburn, reflux of gastricheartburn, reflux of gastric

juicesjuices esophagitisesophagitis



Esophageal CarcinomaEsophageal Carcinoma!! > 50 yrs; 3:1 male predominance> 50 yrs; 3:1 male predominance

!! 11--2% of all cancer deaths2% of all cancer deaths

!! Smoking & alcohol abuseSmoking & alcohol abuse

!! Dysphagia (difficulty in swallowing)Dysphagia (difficulty in swallowing)

obstruction; anorexia; fatigue;obstruction; anorexia; fatigue;

weakness & weight lossweakness & weight loss!! Prognosis: PoorPrognosis: Poor





HiatalHernia

Esophageal

Carcinoma

Esophagus

ChronicGastritis

Acute

Gastritis

Peptic

Ulcers

Gastric

Carcinoma

Stomach

Hemorrhoids

Crohn's

Disease

Ulcerative

Colitis

Colonic

Diverticulosis

Colorectal

Carcinoma


Appendicitis

Appendix




Chronic GastritisChronic Gastritis

!! Chronic inflammatory changesChronic inflammatory changes

mucosal atrophy & metaplasiamucosal atrophy & metaplasia

!! Helicobacter pylori Helicobacter pylori , gram, gram-- bacteriabacteria

!! > 50 yrs; 50% are affected> 50 yrs; 50% are affected

!! Upper abdominal discomfort,Upper abdominal discomfort,

nausea or vomitingnausea or vomiting



Acute GastritisAcute Gastritis!! Acute Inflammatory processAcute Inflammatory process

!! TransientTransient

!! Heavy use ofHeavy use of NSAID’sNSAID’s (i.e. aspirin)(i.e. aspirin)

!! Alcohol abuseAlcohol abuse

!! Heavy smokingHeavy smoking

!! Severe stress (trauma, surgery)Severe stress (trauma, surgery)

Peptic UlcersPeptic Ulcers




!! Chronic, solitary, exposed to actionsChronic, solitary, exposed to actions

of acidof acid--peptic juicespeptic juices

!! 98% in the98% in the duodenum/stomach (4:1)duodenum/stomach (4:1)

!! Diagnosed in middleDiagnosed in middle--aged adultsaged adults

!! In US, 2% of Males & 1.5% ofIn US, 2% of Males & 1.5% ofFemales affectedFemales affected

!! Impaired secretion of gastric acidImpaired secretion of gastric acidand pepsinand pepsin

!!Infection withInfection with Helicobacter pylori Helicobacter pylori

P i UlP ti Ul




!! 22--4 cm in diameter4 cm in diameter

!! Acute , burning painAcute , burning pain!! Usually nocturnal (1Usually nocturnal (1--3 hrs after3 hrs after

meals)meals)!! Relieved by food or antacidsRelieved by food or antacids

!! Complications: Bleeding,Complications: Bleeding,

perforation through the bowel wallperforation through the bowel wall



G t i C iG t i C i



Gastric CarcinomaGastric Carcinoma

!! 3% of all cancer deaths in the US.3% of all cancer deaths in the US.

!! Early Ca is AsymptomaticEarly Ca is Asymptomatic(endoscopy)(endoscopy)

!!Advanced Ca : abdominalAdvanced Ca : abdominaldiscomfort/weight lossdiscomfort/weight loss

!! Early detection & SurgicalEarly detection & Surgical

removalremoval

!! 55--year survival rate:year survival rate: 10%10%





HiatalHernia

Esophageal

Carcinoma

Esophagus

ChronicGastritis

Acute

Gastritis

Peptic

Ulcers

Gastric

Carcinoma

Stomach

Hemorrhoids

Crohn's

Disease

Ulcerative

Colitis

Colonic

Diverticulosis

Colorectal

Carcinoma


Appendicitis

Appendix




HemorrhoidsHemorrhoids!! Dilated veins of the anal & perianalDilated veins of the anal & perianal

submucosal venous plexusessubmucosal venous plexuses

!! > 50 yrs> 50 yrs

!!

venous pressure: pregnancy;venous pressure: pregnancy;straining at stool (chronicstraining at stool (chronic

constipation)constipation)!! Bleed and become thrombosedBleed and become thrombosed

!! Surgical RemovalSurgical Removal

Crohn's DiseaseCrohn's Disease



Crohn s DiseaseCrohn s Disease

!! Inflammatory bowel disease (IBD)Inflammatory bowel disease (IBD)

!! Different than irritable bowel syndromeDifferent than irritable bowel syndrome

(IBS)(IBS)

!! Regional Enteritis,Regional Enteritis, GranulomatousGranulomatous

inflammationinflammation!! Small intestine & colonSmall intestine & colon

!! 11/33 patientspatients -- extraintestinal inflammatoryextraintestinal inflammatory

lesions in the joints, skin, liver or eyeslesions in the joints, skin, liver or eyes

!! 11--3/100,000 in US; 23/100,000 in US; 2ndnd & 3& 3rdrd DecadeDecade

Crohn’s DiseaseCrohn’s Disease



Crohn s DiseaseCrohn s Disease

!! Diarrhea, abdominal pain & feverDiarrhea, abdominal pain & fever

weight lossweight loss

!! Relapse & Remitting DisorderRelapse & Remitting Disorder

!! Complications: Fistula; abdominalComplications: Fistula; abdominal

abscesses; intestinal obstructionabscesses; intestinal obstruction

!! Sulpha drugs, corticosteroidsSulpha drugs, corticosteroids

!! SurgerySurgery

!! Prognosis: Guarded.Prognosis: Guarded.



Ulcerative ColitisUlcerative Colitis

!!Idiopathic inflammatory disease ofIdiopathic inflammatory disease ofthe colonthe colon

!! 44--6/100,000 in US; Peak incidence6/100,000 in US; Peak incidence

2020--25 years25 years

!! extraintestinal inflammatoryextraintestinal inflammatory

lesions in the joints,skin,liver, orlesions in the joints,skin,liver, oreyeseyes



Ulcerative ColitisUlcerative Colitis!! Abdominal cramps, fever, weightAbdominal cramps, fever, weight

loss, bloody stoolloss, bloody stool

!! Chronic relapsing & remittingChronic relapsing & remitting

disorderdisorder

!! Complications: severeComplications: severe

diarrhea,massive hemorrhage, severediarrhea,massive hemorrhage, severe

colonic dilation with potential rupturecolonic dilation with potential rupture!! Risk of Colon CancerRisk of Colon Cancer



Colonic DiverticulosisColonic Diverticulosis!! Outpouchings of the wall of the colonOutpouchings of the wall of the colon

!! 50% of US: > 60 yrs50% of US: > 60 yrs!! Asymptomatic;Asymptomatic; 11//55:pain:pain (left lower(left lower

quadrant)quadrant)!! Occasionally Inflamed (Diverticulitis)Occasionally Inflamed (Diverticulitis)

!!

Treatment: highTreatment: high--fiber diet or surgeryfiber diet or surgeryin severe casesin severe cases



Colorectal CarcinomaColorectal Carcinoma



Co o ecta Ca c o a

!! 150,000 case diagnosed annually150,000 case diagnosed annually

in USin US

!! 15% of all cancer deaths (58,000)15% of all cancer deaths (58,000)

!! Peak Incidence: 60Peak Incidence: 60--70 yrs70 yrs

!! Related to low fiber, highRelated to low fiber, highcarbohydrate, high fat dietcarbohydrate, high fat diet

!! Glandular originGlandular origin(Adenocarcinomas)(Adenocarcinomas)

!!Begin as Adenomatous PolypsBegin as Adenomatous Polyps

Colorectal CarcinomaColorectal Carcinoma



!! Asymptomatic for yearsAsymptomatic for years

!!Fatigue & Anemia (due to bleeding)Fatigue & Anemia (due to bleeding)

!! Detection: Digital Rectal Exam,Detection: Digital Rectal Exam,

Fecal Test (occult blood loss),Fecal Test (occult blood loss),ColonoscopyColonoscopy

!! Surgical ExcisionSurgical Excision

!! 2525--30%: disease beyond curative30%: disease beyond curative

surgerysurgery

AppendicitisAppendicitis



pppp

!! 10% of population;10% of population; 22ndnd & 3& 3rdrd DecadeDecade

!! Mild periumbilical discomfortMild periumbilical discomfort

anorexia, nausea/vomitinganorexia, nausea/vomiting rightrightlower quadrant tendernesslower quadrant tenderness deepdeep

constant ache/painconstant ache/pain!! Other GI diseases mimic AppendicitisOther GI diseases mimic Appendicitis

!!Treatment: Surgical RemovalTreatment: Surgical Removal

!! Prognosis: GoodPrognosis: Good



HepatobiliaryHepatobiliary DiseaseDisease



HepatobiliaryHepatobiliary DiseaseDisease

!!Hepatic NecrosisHepatic Necrosis

!!Viral HepatitisViral Hepatitis

!!Drugs or chemicalsDrugs or chemicals

!!Chronic Liver DiseaseChronic Liver Disease

!!CirrhosisCirrhosis alcohol or viral:alcohol or viral:

Covered in caseCovered in case PBL 118PBL 118 -- A Stitch in TimeA Stitch in Time))

!!HepatocellularHepatocellular CarcinomaCarcinoma

Alcoholic Liver Disease



Alcoholic Liver DiseaseAlcoholic Liver Disease

!! Leading cause of liver diseaseLeading cause of liver disease

!! 10 million Americans10 million Americans

!! 200,000 deaths annually:200,000 deaths annually:

!! Alcohol AbuseAlcohol Abuse!! 2525--30% hospital patients:30% hospital patients:

!! Problems related to alcoholProblems related to alcohol



CirrhosisCirrhosis

!!Chronic Liver DiseaseChronic Liver Disease

!!Loss of normal liver structureLoss of normal liver structure

!!Loss of normal functionLoss of normal function!!Normal liver parenchymaNormal liver parenchyma

replaced by:replaced by:!!Fibrosis & nodules of cellsFibrosis & nodules of cells



Normal CirrhoticNormal Cirrhotic

CirrhosisCirrhosis



Signs and Symptoms ofSigns and Symptoms of



Hepatic FailureHepatic Failure

!! JaundiceJaundice

!! SpiderSpider AngiomaAngioma

!! HypoalbuminemiaHypoalbuminemia

EdemaEdema!! GynecomastiaGynecomastia

!! TremorTremor!! CoagulopathyCoagulopathy

!! Coma, deathComa, death

BiliaryBiliary Disease:Disease:



Gallstones (Gallstones (cholelithiasischolelithiasis))!! Common cause ofCommon cause of biliarybiliary

diseasedisease

!! Abdominal painAbdominal pain

!! CholesterolCholesterol hyperseretionhyperseretionoror supersaturationsupersaturation – – 90%90%

!! PigmentPigment – – 10%10%!! Black pigmentBlack pigment – –

hemolysishemolysis

!! Brown pigmentBrown pigment – –

infectioninfection!! MixedMixed



TEST QUESTIONSTEST QUESTIONS!! 10. Each of the following is attributable to10. Each of the following is attributable to

hepatic failure EXCEPT one.hepatic failure EXCEPT one.

Which one is the EXCEPTION?Which one is the EXCEPTION?a. tremora. tremorb.b. gynecomastiagynecomastiac.c. mallorymallory bodiesbodies

d.d. hypoalbuminemiahypoalbuminemiae. spidere. spider telangiectasiatelangiectasia





y gyy gy


!! RespiratoryRespiratory

!! GI andGI and HepatobiliaryHepatobiliary!! GenitourinaryGenitourinary

!! BloodBlood--lymphaticlymphatic

!! EndocrineEndocrine!! MusculoskeletalMusculoskeletal


!!Nervous SystemNervous System

Genitourinary



GenitourinaryGe tou a y

!! Reproductive PathologyReproductive Pathology(anatomic structures?)(anatomic structures?)

!! ReactiveReactive


!! NeoplasticNeoplastic

!! Kidney PathologyKidney Pathology

(anatomic structures?)(anatomic structures?)

!! Reactive (PBL case?)Reactive (PBL case?)!! DevelopmentalDevelopmental


Signs and Symptoms foreach category?

Kidney Pathology



Kidney Pathologyy gy

! Nephrotic Syndrome :

! Proteinuria

! Increased glomerular permeability

! Nephritic Syndrome :! Hematuria, oliguria, uremia

! Acute nephritis/Acute glomerular disease

Chronic disease can lead to life-threatening renal failure.








!!

EndocrineEndocrine!! MusculoskeletalMusculoskeletal


!!Nervous SystemNervous System

HematologyHematology--LymphoidLymphoid



Red, White and Blue disordersRed, White and Blue disorders

Blood Dyscrasias

Red Cell Disorders White Cell Disorders

Neoplastic NeoplasticReactive Reactive

PolycythemiaAnemia/

ThalassemiaLeukemia/

Lymphoma/ Myeloma

Neutropenia



HematologyHematology--LymphoidLymphoid

Blue disorders (bleeding)

Platelet pathology Coagulation pathology

ThrombocytopeniaThrombocytosis

HemophiliasVon Willebrand disease

Red Cell Disorders



Red Cell Disorders

Red Cell Disorder

Increased Red Cell Destruction

Hemolytic Anemia

Decreased Red Cell Production

Diminished Erythropoiesis

Sickle Cell Iron Deficiency Megaloblastic Aplastic

Folic Acid Vitamin B12(pernicious)

Examples of Red Cell DisordersExamples of Red Cell Disorders



Variations of size, shape, or color…Variations of size, shape, or color…

Examples of Red Cell DisordersExamples of Red Cell DisordersMyelophthisic Anemia – 2°Leukemia Megaloblastic Anemia



(Normocytic, Normochromic) (macrocytic)

White Cell DisordersWhite Cell Disorders

N l iN l i



NeoplasticNeoplastic!! Lymphoma Lymphoma (solid)(solid)

!! Hodgkin’s, EBV (ReedHodgkin’s, EBV (Reed--Sternberg cell)Sternberg cell)

!! NonNon--Hodgkin’s (B or T cell)Hodgkin’s (B or T cell)

!! LeukemiaLeukemia ((marrowmarrow""bloodblood))

!! Lymphoblastic/MyeloblasticLymphoblastic/Myeloblastic

!! MyelophthisicMyelophthisic AnemiaAnemia

!! Multiple Myeloma Multiple Myeloma ((marrowmarrow""bloodblood))

!! Plasma cellPlasma cell dyscrasiadyscrasia

!! MonoclonalMonoclonal gammopathygammopathy

!! BenceBence--Jones protein in urineJones protein in urine

!! “Punched“Punched--out” lesions of boneout” lesions of bone

PBL Cases:PBL Cases:

1) Lewis Kimble1) Lewis Kimble2) Prior Walter’s2) Prior Walter’s

Mass AppealMass Appeal



Normal Lymph NodeNormal Lymph Node Hodgkin’s LymphomaHodgkin’s Lymphoma

(R d(R d St b ll )St b ll )



(Reed(Reed--Sternberg cells)Sternberg cells)





““PunchedPunched--out” lesions ofout” lesions of

M lti l M lM lti l M l



Multiple MyelomaMultiple Myeloma

TEST QUESTIONSTEST QUESTIONS



!! 170. The patient was found to be severely170. The patient was found to be severely

anemic, showinganemic, showing normocyticnormocytic,, normochromicnormochromic

erythrocytes.erythrocytes. Which of the following BESTWhich of the following BEST

characterizes this anemia?characterizes this anemia?

a. hemolytica. hemolytic

b. perniciousb. perniciousc.c. myelophthisicmyelophthisic

d. chronic blood lossd. chronic blood loss









!!EndocrineEndocrine!! MusculoskeletalMusculoskeletal



Hypothalamus





Endocrine DiseasesEndocrine Diseases

!! PituitaryPituitary



!! PituitaryPituitary!! GigantismGigantism

!! AcromegalyAcromegaly

!! DwarfismDwarfism

!! ThyroidThyroid!! HyperthyroidismHyperthyroidism

!! HypothyroidismHypothyroidism

!! ParathyroidParathyroid!! HyperparathyroidismHyperparathyroidism

!! HypoparathyroidismHypoparathyroidism

!! Adrenal CortexAdrenal Cortex!! Cushing’s DiseaseCushing’s Disease!! Addison’s DiseaseAddison’s Disease

!! PancreasPancreas!! Diabetes MellitusDiabetes Mellitus

GigantismGigantism

H i f h hH i f h h



•• Hypersecretion of growth hormoneHypersecretion of growth hormone

– – BeforeBefore the closure of thethe closure of the epiphysealepiphyseal

platesplates – – Usually caused by a benign tumor:Usually caused by a benign tumor:

pituitary pituitary adenoma adenoma

•• Manifestations:Manifestations: – – Generalized increased size of the bodyGeneralized increased size of the body

– – Disproportionately long arms and legsDisproportionately long arms and legs

•• Treatment: Surgical removal of theTreatment: Surgical removal of theadenomaadenoma

AcromegalyAcromegaly



•• Hypersecretion of growth hormoneHypersecretion of growth hormone

((somatotropinsomatotropin))-- afterafter closure of theclosure of the EpiphysealEpiphyseal PlatesPlates

•• Enlargement the bones of the hand,Enlargement the bones of the hand,

feet, facial skeletonfeet, facial skeleton – – PrognathismPrognathism withwith diastemadiastema

•• Hypertension & Congestive HeartHypertension & Congestive HeartFailureFailure






Acromegaly is due to an excessiveAcromegaly is due to an excessive

production of which of the following?production of which of the following?

A.A. ThyrotropinThyrotropin

B.B. GonadotropinGonadotropin

C.C. SomatotropinSomatotropinD.D. AdrenocorticotropinAdrenocorticotropin

!!19.5% correctly answered C19.5% correctly answered C

DwarfismDwarfism



•• HyposecretionHyposecretion of growth hormoneof growth hormone

•• Alternately tissues lack ofAlternately tissues lack ofresponsiveness to growthresponsiveness to growth

hormonehormone

•• Short stature, small jaws & teethShort stature, small jaws & teeth

•• Hormone replacement therapyHormone replacement therapy

ThyroidThyroid



!!HyperHyper--thyroidismthyroidism

!! Grave’s DiseaseGrave’s Disease

!!HypoHypo--thyroidismthyroidism

!! CretinismCretinism

!! MyxedemaMyxedema

HyperthyroidismHyperthyroidism



•• Hypersecretion of thyroid hormone:Hypersecretion of thyroid hormone:

– – Grave’s DiseaseGrave’s Disease

– – Multinodular Goiter/AdenomaMultinodular Goiter/Adenoma

•• More common in women (7More common in women (7--10x)10x)

Grave’sDi



Grave sDisease

PBL Case:TheRetired

Runner

Clinical FeaturesClinical Features



•• Wide, staring gaze (proptosis /Wide, staring gaze (proptosis /

exophthalmos)exophthalmos)•• Nervousness, tremor, irritabilityNervousness, tremor, irritability

••

Tachycardia, PalpitationsTachycardia, Palpitations

•• Weight loss with increased appetiteWeight loss with increased appetite

•• Severe hyperthyroidism can lead toSevere hyperthyroidism can lead to

Thyroid Storm Thyroid Storm : may be precipitated: may be precipitated

by stressby stress (dental procedures)(dental procedures)

HypothyroidismHypothyroidism



•• HyposecretionHyposecretion of Thyroid Hormoneof Thyroid Hormone

•• CretinismCretinism: Infants/Early Childhood: Infants/Early Childhood

•• MyxedemaMyxedema: Older children/Adults: Older children/Adults

CretinismCretinism



•• Impaired Development of CNSImpaired Development of CNS

– – Mental RetardationMental Retardation•• Impaired Development of SkeletalImpaired Development of Skeletal

SystemSystem – – Short StatureShort Stature

•• Protruding tongueProtruding tongue

Before and After Thyroid Hormone

Replacement Therapy



MyxedemaMyxedema



•• MentalMental

SluggishnessSluggishness

•• ObesityObesity

•• Sensitivity toSensitivity to

coldcold




Hypothyroidism in an adult results inHypothyroidism in an adult results in

A.A. MyxedemaMyxedema

B.B. ThyrotoxicosisThyrotoxicosis

C.C. Thyroid stormThyroid storm

D.D. Increased basal metabolic rateIncreased basal metabolic rate

ParathyroidParathyroid

•• Secretes Parathyroid Hormone (PTH)Secretes Parathyroid Hormone (PTH)



•• Secretes Parathyroid Hormone (PTH)Secretes Parathyroid Hormone (PTH)

•• CounteractsCounteracts CalcitoninCalcitonin from Thyroidfrom Thyroid

•• Controlled by the level of CaControlled by the level of Ca++

•• Decreased serum CaDecreased serum Ca++++ Release of PTH,Release of PTH,

which causes release of Ca++ fromwhich causes release of Ca++ from

mineral stores (what tissue mainly?)mineral stores (what tissue mainly?)

Two Types:Two Types:

!! PrimaryPrimary

!! SecondarySecondary

Primary HyperparathyroidismPrimary Hyperparathyroidism

•• Hyperplasia/AdenomaHyperplasia/Adenoma



•• Hyperplasia/AdenomaHyperplasia/Adenoma

•• ManifestationsManifestations:: – – PainfulPainful BonesBones

(Fractures, Giant(Fractures, Giant--cell lesions)cell lesions)

– – RenalRenal StonesStones((UrolithiasisUrolithiasis))

– – AbdominalAbdominal GroansGroans(Gallstones, Peptic Ulcer)(Gallstones, Peptic Ulcer)

– – PsychicPsychic MoansMoans (depression & lethargy)(depression & lethargy)

Brown tumor – Central Giant-cell Lesions of Bone



Note: teeth can show loss oflamina dura on radiographs

SecondarySecondary

HyperparathyroidismHyperparathyroidism



yp p yyp p y

!! Usually secondary to renal failureUsually secondary to renal failure

!! Decreased serum calciumDecreased serum calcium

!! Increased parathyroid activityIncreased parathyroid activity

•• Surgical Removal of the glandSurgical Removal of the gland

•• Renal Transplant if renal failureRenal Transplant if renal failure

•• Prognosis: GoodPrognosis: Good


!! The next question refers to the following: A 42 yearThe next question refers to the following: A 42 year--old female withold female witha history of hyperparathyroidism presents with a complaint ofa history of hyperparathyroidism presents with a complaint of



a history of hyperparathyroidism presents with a complaint ofa history of hyperparathyroidism presents with a complaint ofbilateral pain in the temporomandibular joint on closing.bilateral pain in the temporomandibular joint on closing. She reportsShe reportsthat her ears are occasionally "clogged" and she sometimesthat her ears are occasionally "clogged" and she sometimesexperiences a "ringing" sensation. The dentist determines that texperiences a "ringing" sensation. The dentist determines that thesehesesymptoms are related to her TMJ condition.symptoms are related to her TMJ condition.

162. Given her reported hyperparathyroidism, this162. Given her reported hyperparathyroidism, thispatient is likely to show each of the following signs orpatient is likely to show each of the following signs orsymptoms EXCEPT one. Which one is thesymptoms EXCEPT one. Which one is theEXCEPTION?EXCEPTION?a.a. urolithiasisurolithiasisb. elevated serum calciumb. elevated serum calciumc.c. tetanictetanic muscular convulsionsmuscular convulsions

d. central giantd. central giant--cell bone lesionscell bone lesionse. loss of lamina dura surrounding multiple teethe. loss of lamina dura surrounding multiple teeth

!! 8% correctly answered C8% correctly answered C

In a parathyroid deficiency state, there isIn a parathyroid deficiency state, there is

A.A. An increase in serum calcium and a decreaseAn increase in serum calcium and a decrease



in serum phosphatein serum phosphate

B.B. A decrease in serum calcium and an increaseA decrease in serum calcium and an increasein serum phosphatein serum phosphate

C.C. An increase in serum calcium and a normalAn increase in serum calcium and a normal

serum phosphateserum phosphateD.D. A normal serum calcium and an increase inA normal serum calcium and an increase in

serum phosphateserum phosphate

PTH=“Break bone” vs. CALCITONIN (from thyroid)=“Build bone”

Adrenal CortexAdrenal Cortex



!!Hypercortisolism:Hypercortisolism: Cushing’sCushing’sDiseaseDisease

!!Hypocortisolism:Hypocortisolism: Addison’sAddison’s

DiseaseDisease

Cushing’s DiseaseCushing’s Disease

•• Causes:Causes: Increased levels ofIncreased levels of



•• Causes:Causes: Increased levels ofIncreased levels ofglucocorticoidsglucocorticoids

•• Endogenous, ExogenousEndogenous, Exogenous

•• ManifestationsManifestations

– – Hypertension & Weight GainHypertension & Weight Gain

– – Fat in the facial areaFat in the facial area (Moon Face)(Moon Face) &&posterior neck & backposterior neck & back (Buffalo Hump)(Buffalo Hump)

– – Diabetes & OsteoporosisDiabetes & Osteoporosis

– – Mental DisturbancesMental Disturbances



Addison’s DiseaseAddison’s Disease



•• Decreased levels ofDecreased levels of

glucocorticosteroids (adrenalglucocorticosteroids (adrenal

insufficiency)insufficiency)

•• Autoimmune destruction of theAutoimmune destruction of thegland; Infections; Metastaticgland; Infections; Metastatic

NeoplasmsNeoplasms

Addison’s DiseaseAddison’s Disease

•• ManifestationsManifestations::



•• ManifestationsManifestations::

– –

Weakness; G.I. DisturbancesWeakness; G.I. Disturbances

– – Hyperpigmentation (MSH)Hyperpigmentation (MSH)

•• Treatment:Treatment:

-- Corticosteroid ReplacementCorticosteroid ReplacementTherapyTherapy



PancreasPancreas

!! Islets Of LangerhansIslets Of Langerhans



Islets Of LangerhansIslets Of Langerhans

!! Glucagon:Glucagon: Mobilization of storedMobilization of storedglucose into bloodglucose into blood!! Hypersecretion?Hypersecretion?

!! HyposecretionHyposecretion??

!! Insulin:Insulin: Glucose transportGlucose transport from bloodfrom bloodinto cellsinto cells

!!Hypersecretion?Hypersecretion?

!! HyposecretionHyposecretion??

Diabetes MellitusDiabetes Mellitus

•• 13 million people in the USA13 million people in the USA



3 o peop e t e USp p

•• Mortality rate of 54,000Mortality rate of 54,000

•• Defective/Deficient InsulinDefective/Deficient Insulin

MechanismsMechanisms

– – Impaired glucose use & HyperglycemiaImpaired glucose use & Hyperglycemia

•• Two Types:Two Types: Type IType I && IIII

– – Type II most commonType II most common

Type IType I

•• Younger onsetYounger onset

•• Manifestations: Polydipsia PolyuriaManifestations: Polydipsia Polyuria



Manifestations: Polydipsia, Polyuria,Manifestations: Polydipsia, Polyuria,

Polyphagia,Polyphagia, KetoacidosisKetoacidosis

•• Autoimmune responseAutoimmune response

– – Antibodies to Islet cellsAntibodies to Islet cells

•• Most complications related toMost complications related toHyperglycemia orHyperglycemia or GlycosylatedGlycosylated EndEnd--

ProductsProducts

•• Treatment:Treatment: – – InsulinInsulin

Type IIType II

•• Not related to autoimmuneNot related to autoimmuneh i



mechanismsmechanisms

•• Decreased Secretion/InsulinDecreased Secretion/Insulinresistance at receptor levelresistance at receptor level

•• Onset over 30 years of ageOnset over 30 years of age•• Treatment:Treatment:

– – Oral Hypoglycemic DrugsOral Hypoglycemic Drugs – – Weight lossWeight loss

GlucosuriaGlucosuria usually occurs in which of theusually occurs in which of the




GlucosuriaGlucosuria usually occurs in which of theusually occurs in which of the

following?following?A.A. Addison’s diseaseAddison’s disease

B.B. Diabetes mellitusDiabetes mellitus

C.C. Cushing’s diseaseCushing’s disease

D.D. Parkinson’s diseaseParkinson’s disease



Why this clinical picture intraorally?









!! GI andGI and HepatobiliaryHepatobiliary




!! MusculoskeletalMusculoskeletal!! Genetic DiseasesGenetic Diseases


MusculoskeletalMusculoskeletal

!! Muscle PathologyMuscle Pathology!! ReactiveReactive



!!MyositisMyositis (infection, trauma), Myasthenia Gravis(infection, trauma), Myasthenia Gravis

(autoimmune damage to Ach receptors)(autoimmune damage to Ach receptors)


!!Muscular dystrophy, congenital or acquiredMuscular dystrophy, congenital or acquiredmyopathiesmyopathies


!!RhabdoRhabdo--myoma/ myoma/ --myosarcomamyosarcoma (striated muscle)(striated muscle)

!!LeioLeio--myoma/ myoma/ --myosarcomamyosarcoma (smooth muscle)(smooth muscle)

RhabdomyosarcomaRhabdomyosarcoma

(common in children, rarer in adults)(common in children, rarer in adults)



MusculoskeletalMusculoskeletal

!! Bone (skeletal) PathologyBone (skeletal) Pathology!! ReactiveReactive



!!Osteomyelitis; OsteitisOsteomyelitis; Osteitis deformansdeformans ((Paget’sPaget’s

disease); Osteoporosisdisease); Osteoporosis


!!OsteogenesisOsteogenesis Imperfecta (PBL case?);Imperfecta (PBL case?);Osteopetrosis (Marble bone disease)Osteopetrosis (Marble bone disease)


!!Osteoma/Osteoblastoma/OsteosarcomaOsteoma/Osteoblastoma/Osteosarcoma;;Many malignancies metastasize to boneMany malignancies metastasize to bone

(more common than primary bone cancers)(more common than primary bone cancers)

OsteomyelitisOsteomyelitis




!! 160. The first clinical findings in160. The first clinical findings in prostaticprostatic cancercancerare often the result of metastasis to which of theare often the result of metastasis to which of the



are often the result of metastasis to which of theare often the result of metastasis to which of the

following?following?a. livera. liverb. brainb. brainc. testesc. testes

d. adrenal glandd. adrenal glande. bonee. bone

!! 14.6% correctly answered E14.6% correctly answered E






Respiratoryesp ato y

!! GI andGI and HepatobiliaryHepatobiliary




!! MusculoskeletalMusculoskeletal!! Genetic Diseases (covered later)Genetic Diseases (covered later)


Nervous SystemNervous System!!

ReactiveReactive!! Meningitis; Encephalitis; Neuritis (Meningitis; Encephalitis; Neuritis (GuillainGuillain--BarreBarre Syndrome)Syndrome)

!! Trauma: Contusion/Concussion/Trauma: Contusion/Concussion/HematomaHematoma



Trauma: Contusion/Concussion/ Trauma: Contusion/Concussion/ HematomaHematoma

!!DemyelinatingDemyelinating

: Multiple sclerosis: Multiple sclerosis

!! Degenerative: Alzheimer’s disease, Parkinson’s diseaseDegenerative: Alzheimer’s disease, Parkinson’s disease


!!SpinaSpina bifida; cerebral palsy; neurofibromatosis (Vonbifida; cerebral palsy; neurofibromatosis (VonRecklinghausen’sRecklinghausen’s disease); Tuberous sclerosis (multipledisease); Tuberous sclerosis (multiple

brain lesions)brain lesions)


!! SchwannomaSchwannoma,, NeuromaNeuroma,, AstrocytomaAstrocytoma,, GlioblastomaGlioblastoma,,

EpendymomaEpendymoma,, MedulloblastomaMedulloblastoma;; MeningiomaMeningioma;;

CraniopharyngiomaCraniopharyngioma



NEOPLASIANEOPLASIA

DefinitionsDefinitions

!! Hyperplasia Hyperplasia = An abnormal increase in the number= An abnormal increase in the numberof cells in a tissueof cells in a tissue

M l iM l i Th l fTh l f diff i ddiff i d



!! Metaplasia =Metaplasia = The replacement of oneThe replacement of one differentiateddifferentiated

cell typecell type with another cell typewith another cell type!! NeoplasiaNeoplasia = New tissue growth or tumor= New tissue growth or tumor

(benign or malignant)(benign or malignant)

!! Dysplasia Dysplasia = Altered tissue growth= Altered tissue growth (usually precancerous)(usually precancerous)

!! Anaplasia Anaplasia = The reversion of cells to an immature= The reversion of cells to an immatureor a less differentiated form, as occurs in mostor a less differentiated form, as occurs in most

malignant tumorsmalignant tumors!! Cancer Cancer = malignant tumor= malignant tumor



orMetaplasia

CancerCancer



NomenclatureNomenclature

!! Tumors areTumors areclassified by theclassified by the

tissue presumed totissue presumed to

--carcinomacarcinoma

sarcomasarcoma

--omaomaMalignantMalignantBenignBenign



tissue presumed totissue presumed to

be the origin of thebe the origin of thetumortumor

!! Carcinoma Carcinoma ==

Epithelial tissueEpithelial tissuecancer (includingcancer (including

ductalductal epithelium)epithelium)

!! Sarcoma Sarcoma ==Connective tissueConnective tissue

cancercancer

AdenocarcinomaAdenocarcinoma(breast or prostate(breast or prostate

cancer)cancer)

OsteosarcomaOsteosarcoma

Exceptions: Exceptions:

MelanomaMelanoma

LymphomaLymphoma

Brain tumorsBrain tumors

AdenomaAdenomaFibromaFibroma

LipomaLipoma

LeiomyomaLeiomyoma

HemangiomaHemangioma

NeuromaNeuroma

--sarcomasarcoma

BenignancyBenignancy vsvs MalignancyMalignancy



g yg y g yg y

BEHAVIOR OF BENIGNBEHAVIOR OF BENIGN

NEOPLASMSNEOPLASMS

!! An orderly tumorAn orderly tumor



yy

!! WellWell--defineddefinedborders or capsuleborders or capsule

!! Rarely infiltrativeRarely infiltrative

!! NonNon--metastasizingmetastasizing

BEHAVIOR OF MALIGNANTBEHAVIOR OF MALIGNANT

NEOPLASMSNEOPLASMS

!! Disorderly andDisorderly and

destructive growthdestructive growth



destructive growthdestructive growth

patternpattern!! No capsuleNo capsule

!! InvasionInvasion

!! MetastasisMetastasis

!! Rapid growthRapid growth

!! NecrosisNecrosis

!! Bizarre cytologyBizarre cytology

CARCINOGENESIS: How we getCARCINOGENESIS: How we get

to fullto full--blown cancer or malignancy?blown cancer or malignancy?



!! HyperplasiaHyperplasia "" DysplasiaDysplasia "" AnaplasiaAnaplasia(CANCER(CANCER))

!! MetaplasiaMetaplasia "" DysplasiaDysplasia "" AnaplasiaAnaplasia(CANCER)(CANCER)

Oncogenes, Tumor Suppressor Genes,Mutagenesis and the Cell Cycle…



orMetaplasia

The Cell Cycle

Oncogenes



g

(i.e. Cyclin-D1)

Tumor SuppressorGenes

(i.e. p53, Rb)

RETINOBLASTOMARETINOBLASTOMARETINOBLASTOMA

!! RbRb gene mutationgene mutation

causes continuouscauses continuous

cell cycling becausecell cycling because



cell cycling becausecell cycling because

of loss of tumorof loss of tumor

suppressionsuppression

!! 1/20,000 infants1/20,000 infants

!! 60% sporadic, 40%60% sporadic, 40%

inherited cancerinherited cancer

!!Knudson’s twoKnudson’s two

--hithit

hypothesishypothesis

CERVICAL DYSPLASIACERVICAL DYSPLASIA

!! Precancerous Precancerous changes andchanges andcontinuous cellcontinuous cell



continuous cellcontinuous cellcyclingcycling – –

!! HPV virus hasHPV virus hasoncogeniconcogenic

proteinsproteins!! Bizarre cytology:Bizarre cytology:HyperchromaticHyperchromaticnuclei, atypicalnuclei, atypical

mitosis,mitosis, N/C,N/C,prominent nucleoli,prominent nucleoli,pleomorphismpleomorphism

SQUAMOUS METAPLASIASQUAMOUS METAPLASIA

DYSPLASIADYSPLASIA "" LUNG CANCERLUNG CANCER



Respiratory mucosa Squamous metaplasia

PATHOLOGIC DIAGNOSISPATHOLOGIC DIAGNOSIS

--CANCERCANCER

!!



!!Biopsy (Biopsy (histopathology histopathology ) Is The Gold) Is The GoldStandard For Diagnosing Cancer ofStandard For Diagnosing Cancer of

TissuesTissues

!! Frozen SectionFrozen Section (during surgery)(during surgery)!! Permanent SectionPermanent Section (after surgery)(after surgery)



ExcisionalExcisional

vs.vs.IncisionalIncisional



BiopsyBiopsy

10% Formalin Solution





TissueTissue

EmbeddingEmbedding



MicrotomeMicrotome – – Tissue SectioningTissue Sectioning





Tissue WashingTissue Washing

and Staining (H&E)and Staining (H&E)

Microscopic Evaluation for DiagnosisMicroscopic Evaluation for Diagnosis



FrozenFrozen

SectionSection

DiagnosisDiagnosis



Freezing chamber

Tissue biopsy

Cryostat

CYTOLOGYCYTOLOGY

!! FineFine--needleneedle



aspirationaspiration(FNA) biopsy(FNA) biopsy

!! FluidsFluids

!! Pap smearsPap smears

IMMUNOHISTOCHEMISTRYIMMUNOHISTOCHEMISTRY



FLOW CYTOMETRYFLOW CYTOMETRY



CYTOGENETICSCYTOGENETICS



PATHOLOGYPATHOLOGY



GRADING and STAGINGGRADING and STAGING

PATHOLOGY GRADINGPATHOLOGY GRADING

How closely do the cancer cellsHow closely do the cancer cells



resemble the normal cells from whichresemble the normal cells from whichthey arose?they arose?

!! WellWell--differentiateddifferentiated (closely resemble normal)(closely resemble normal)

!! ModeratelyModerately--differentiateddifferentiated (sort of resemble)(sort of resemble)

!! PoorlyPoorly--differentiateddifferentiated (don’t resemble at all)(don’t resemble at all)!! This caries the worst prognosis in most casesThis caries the worst prognosis in most cases

PATHOLOGY GRADINGPATHOLOGY GRADING



PATHOLOGY STAGINGPATHOLOGY STAGING

• An anatomic assessment of the spread of



neoplasm within the body

• How much cancer is present, and where?

• i.e. TNM Staging System

• More prognostically significant than

grading usually

PATHOLOGY STAGINGPATHOLOGY STAGING

!! T = Tumor sizeT = Tumor size

!!N N d l i lN N d l i l



N = Nodal involvementN = Nodal involvement!! M = Metastasis to distant siteM = Metastasis to distant site

!! 4 Stages: I, II, III, IV4 Stages: I, II, III, IV!! The higher you go, the worse the prognosisThe higher you go, the worse the prognosis

(stage IV=widespread metastasis)(stage IV=widespread metastasis)

TUMOR SIZETUMOR SIZE



NODAL INVOLVEMENTNODAL INVOLVEMENT



DISTANT METASTASISDISTANT METASTASIS



QUESTIONS?QUESTIONS?



nbde pathology review.pdf

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