Path Final

Front 1

Compartments ENT

Back 1

-oral/oropharynx
-salivary gland
sinonasal
-nasopharynx
-ear
-larynx
-skin
-thyroid/parathyroid
-lymph node
-bone/soft tissue

Front 2

Oral/Oropharynx

Back 2

Infectious
-candida
Non-infectious;non-neoplastic:
-extravasation mucocele
-lingual thyroid
-sarcoidosis
Neoplastic:
-squamous cell cacinoma
-tonsillar lymphomas (heme)

Front 3

Candida sp.

Back 3

Clin: Immunocompromised patients. "Thrush" = oral candidasis
Rad: Not done
Path: Superficial infection by oral flora. Hyphal forms (spaghetti) and yeast forms (meatballs)

Front 4

Extravasation Mucocele

Back 4

Clin: lower lip mass, floor of mouth cyst ("ranula")
Rad: Not done
Path: Etio: minor salivary duct trauma Mucin extravasation (Alcian blue (+))

Front 5

Lingual Thyroid

Back 5

Clin:
-children-old age
-dysphagia, foreign body sensation
-10% are hypothyroid
Rad:
-scintigraphy to demonstrate other thyroid and function of lingual thyroid
Path:
-only thyroid gland in >70%
-unencapsulated
-low malignant potential

Front 6

Sarcoidosis

Back 6

Clin: young adults with fever, weight loss, Pulmonary, cutaneous involvement
ENT: oral, S/N, larynx, salivary gland, ear
RAD: Screen with CXR: hilar adenopahty ENT: non-destructive
Path: Well-defined, non necrotizing granulomas
-no vasculitis
-elevated angiotensin-converting enzyme
-lip biopsy (+) in ---> 50%

Front 7

Squamous Cell Carcinoma

Back 7

Clin: Lower lip most common (sun, smoking)
tongue > FOM >gingiva > palate> tonsil (smoking)
Rad: Staging: local extent, regional LNs, CXR
Path: Etio: mutagens
-prognosis a function of size, grade, stage

Front 8

Salivary glands

Back 8

Infectious
-sialadenitis +/- sialolithiasis (stones)
Non-infectious, non-neoplastic:
-sjogren's syndrome
Neoplastic:
-pleiomorphic adenoma
-mucoepidermoid CA
-adenoid cystic CA

Front 9

Sialoadenitis +/- Sialolithiasis

Back 9

Clin: inflammation, partoid or submandibular glands; Non-obstructive: staph, strep, mumps
Obstructive: duct stones +/- infection
Rad: plain films to document stone (most sumbmandiulare are radio-opaque)
Path: ductal stones: SMG>parotid
-Acinar inflammation, fibrosis, atrophy

Front 10

Sjogren's syndrome

Back 10

Clin: adults, F>M, associated with:
-keratoconjectivitis sicca
-xerostomia
-connective tissue disease (RA, SLE, PAN,etc)
Rad: Not done
Path:
- major and minor glands involved
-benign lymphoepithelial lesions
-epimyopepithelial islands

Front 11

Pleiomorphic adenoma

Back 11

Clin: Adults, F>M, with slow-grwoing, painless mass of major or minor salivary gland Parotid> others
Rad: Not done
Path:
-most common benign sal gl meoplasm
-discrete, unifocal, encapsulated
-epitheliu, myoepithelium, myxoid stroma
-local recurrence potential, rare malignancy

Front 12

Mucoepidermoid carcinoma

Back 12

Clin: children-adults, major or minor glands may have h/o prior irradiation
Rad: staging
Path:
most common malignant sal gl neoplasm
-low/intermediate grade: mucous >epidermoid
-high grade: epidermoid> mucous
-mucicarmine stain (+)

Front 13

Adenoid cystic CA

Back 13

Clin: adults, M+F, with salivary gland mass major>minor
RAD: ND
Path:
-unencapsulated, infiltrative, perineural
-tubular or cribiform architecture
-mucinous basement membrane material
-course: local recurrences, late metastases

Front 14

Sinonasal

Back 14

Infectious
-allergic fungal sinusitis
Non infectious, non-neo
-inflammatory (allergic) polyps
-(sarcoidosi)
-wegener's granulomatosis
Neoplastic
-schneiderian papillomas
-(skin lesions of nassal vestibule) (derm)

Front 15

Allergic Fungal Sinusitis

Back 15

Clin: Allergic resonse to fungi (aspergillus) Children-young adults with headache
Rad: sinus opacification, maxillary, ethmoid most common
Path: mucoid plug with fungal hyphae (GMS Silver stain (+))

Front 16

Inflammatory Polyps

Back 16

Clin: any age, rhinorrhea, headaches, airborne allergens
Children: r/o CF and Kartagener's
Rad: ST mass(es), in sinuses or nasal cavity
Path: boggy polyps up to several cm
-respiratory epith, stromal edema, eos

Front 17

Wegener's Granulomatosis

Back 17

-Adults, M>F, ENT, lung and GU
ENT: nasal cavity>sinuses>other ENT
Rad: sinus opacification, bone/ST destruction
Path:
-necrotizing granulomatous vasculitis
- increase c-ANCA in >85% with active disease

Front 18

Schneiderian papillomas

Back 18

-Adolescents, adults, local symptoms, ST mass on either nasal septum o lat wall
Rad: unilateral nasal cavity ST mass +/- sinus opacification
Path: 3 histological types
-fungiform/exophytic: septal wall, no increase risk of CA
-oncocytic: lateral wall, 5-10% risk of CA
-inverted: lateral wall, 5-10% risk of CA

Front 19

Nasopharynx

Back 19

Infectious
-infectious mononucleosis
Non-infectious, non-neoplastic
-Sarcoidosis, Wegener's granulomatosis
Neoplastic
-teratoma
-angiofibroma
-nasopharyneal carcinoma

Front 20

Infectious Mononucleosis

Back 20

Adolescents, young adults most common
-fever, sore throat, malaise
-tender posterior LNs, hepatosplenomegaly
Rad: none done
Path:
-tonsillitis/lymphadenitis
-Reactive B and T lymphocyte hyperplasia
-IgM and IgG serolgies against viral Ags
-Self-limited in immunocompetent patients

Front 21

Inflammatory Polyps

Back 21

Clin: any age, rhinorrhea, headaches, airborne allergens
Children: r/o CF and Kartagener's
Rad: ST mass(es), in sinuses or nasal cavity
Path: boggy polyps up to several cm
-respiratory epith, stromal edema, eos

Front 22

Wegener's Granulomatosis

Back 22

-Adults, M>F, ENT, lung and GU
ENT: nasal cavity>sinuses>other ENT
Rad: sinus opacification, bone/ST destruction
Path:
-necrotizing granulomatous vasculitis
- increase c-ANCA in >85% with active disease

Front 23

Schneiderian papillomas

Back 23

-Adolescents, adults, local symptoms, ST mass on either nasal septum o lat wall
Rad: unilateral nasal cavity ST mass +/- sinus opacification
Path: 3 histological types
-fungiform/exophytic: septal wall, no increase risk of CA
-oncocytic: lateral wall, 5-10% risk of CA
-inverted: lateral wall, 5-10% risk of CA

Front 24

Nasopharynx

Back 24

Infectious
-infectious mononucleosis
Non-infectious, non-neoplastic
-Sarcoidosis, Wegener's granulomatosis
Neoplastic
-teratoma
-angiofibroma
-nasopharyneal carcinoma

Front 25

Infectious Mononucleosis

Back 25

Adolescents, young adults most common
-fever, sore throat, malaise
-tender posterior LNs, hepatosplenomegaly
Rad: none done
Path:
-tonsillitis/lymphadenitis
-Reactive B and T lymphocyte hyperplasia
-IgM and IgG serolgies against viral Ags
-Self-limited in immunocompetent patients

Front 26

Teratoma

Back 26

Clin: Majority in children, rare after age 2
-dysphagia or airway obstruction
Rad: ST mas in NP
Path:
-germ cell tumor: 3 germ cell layers present
-Mature vs. immature
-pure teratoma or mixed with other GCTs
-no malignant potential in children

Front 27

Angiofibroma

Back 27

-adolescent--> young adult males
-nasal obstruction and epistaxis
-lateral or posterior NP wall mass
Rad: CT: ST mass with contrast enhancement
Angiography: vascular hypertrophy
Path
-sessile, lobulated ST mass
-benin fibrous tumor with increased numbers of thin-walled vessels without smooth muscle

Front 28

Nasopharyngeal carcinoma

Back 28

-adults, M>W, China>US, associated with EBV
Rad: ST mass of lat NP (fossa of Rosenmuller) +/- bone destruction/invasion
Path:
-undifferentiated>squamous
-undiff type has admixed benign lymphs

Front 29

Ear

Back 29

Infectious
-ottis media
Non-infectious, non-neoplastic
-sarcoidosis
Neoplastic
-cholesteatoma
-8th cranial nerve Schwannoma (neuro)
-Paraganglioma
-external canal squamous cell carcinoma

Front 30

Ottis Media

Back 30

-young children with recent URI, fever, otalgia, decrease hearing, bulging immobile TM due to undrained middle ear fluid
Rad: Nlot done
Path: never biopsied, Micro: sterile or (+) strep, staph, H. flu

Front 31

Cholesteatoma

Back 31

Any age, peak 20s-30s, M>F, Hearing loss, pain, middle ear +/- mastoid mass
Rad: Not done
Path: cyst of benign squamous epithelium with accumulation of loose keratin, may show foreing body reaction

Front 32

Jugulotympanic Paraganglioma

Back 32

-Adults, F>M, middle ear ST mass associated with jugular vein bulb
Rad: CT:ST mass with local destruction
Angio: well-vascularized
Path:
-benign but invasive paraganglioma
-Chief and sustentacular cells, "zellballen"
-synaptophysin/chromogranin AB stains

Front 33

External Ear/Ear Canal Squamous Cell Carcinoma

Back 33

Adults, M>F
-non-healing mass or ulcer of external ear
Rad: not done
Path:
Etio: sun exposure (actinic damage)
Differential: melanoma, basal cell CA

Front 34

Larynx

Back 34

Infectious
-squamous papillomas (HPV)
-epiglottis
Non-infectious, non-neoplastic
-vocal cord polyps
Neoplastic
-squamous cell carcinoma

Front 35

Squamous Papillomas

Back 35

Children: 2-3 yo, multiple lesions, frequent local recurrence
Adults: single lesions, less frequnet local recurrence, less frequent spread
Rad: not done
Path:
-bland squamous papillomata
-may have HPV changes
-10% spread distally, 2%--> CA

Front 36

Actue Epiglottis

Back 36

child or adult with fever, upper airway obstruction, stridor
Rad: Last view showing epiglottic edema
Path:
Acute inflammation, bacteria, usualy H. flu
Course: may die if airways not estbalished

Front 37

Vocal cord polyps

Back 37

adults with hoarseness and a history of voice abuse
-aka laryngeal nodule, "singer's nodule"
Rad: Not done
Path:
-benign stromal expansion
-benign surface squamous epithelium

Front 38

Squamous cel carcinoma

Back 38

Adults, M>W
smokers/drinkers with voice changes
RAd: for staging local extent, regional LNs, mets
Path:
Etio: tobacco, EtOH, prior neck irradiation
Incidence: Glottic>supraglottic>subglottic

Front 39

Lung pathology

Back 39

-airway diseases (non-infectious)
-infections (pneumonias)
-carcinomas

Front 40

Normal Anatomy Anatomic compartments

Back 40

-airways (trachea, bronchi, bronchioles)
-alveoli
-peribronchial stroma
-interstitium

Front 41

Airway Diseases

Back 41

-Asthma
-Aspiration/aspiration pneumonia
-emphysema

Front 42

Asthma

Back 42

-airway hyper-responsivenes
-triggers: antigens, exercise, drugs, infections, stress
-acute, usually reversible diffuse bronchial narrowing
-wheezing, dyspnea
Rad: alternating atelectasis and overexpansion
Path:
-edema, smooth muscle thickening, basement membrane thickening, mucous cell hyperplasia, increased submucosal eosinophils, thickened intralumenal mucous

Front 43

Aspiration

Back 43

-children-foreign bodies
-adults: -gastric acid, food, foreign bodies (lipids in nasal drops)
Rad: foreign object or resulting pneumonia ---> tpically RLL
Path:
-foreign material -->foreign body giant cell reaction with exogenous material

Front 44

Emphysema

Back 44

-increased elastase activity
-cigarette smoking, inherited alpha 1-antitrypsin deficiency
Rad: increased lung volumes, flat diaphragm
Path:
-dilation of distal airspaces with septal destruction

Front 45

Lung infections

Back 45

-types of inflammatory response
-bacterial pneumonia an dcomplications
-mycoplasma
-viral
-mycobacteria
-fungal

Front 46

Types of inflammatory response

Back 46

Neutrophils: usually bacterial and in alveoli
Lymphocytes: usually viral in interstitium/septae
Granulomatous inflammation: usually mycobacterial or fungal

Front 47

Bacterial pneumonia

Back 47

General concepts: patterns, disease progression
-pneumonococcus- the prototype
-complications

Front 48

Bacterial Pneumonia- patterns

Back 48

Bronchopneumonia
-scattered foci of consolidation in either a single lobe or multiple lobes
-terminally ill patients
-dependent regions of lung
-common ultimate cause of death
Lobar
-complete consolidation of a lobe
-encapsulated organisms

Front 49

Bacterial Pneumonia Agnets

Back 49

Community acquired
-S.pneumoniae, Klebsiella, Hemophilus
-things with capsules
Hospital acquired "nosocomial"
-drug resistant strains
-methicillin resistant Staph. Aureaus (MRSA)
Opportunistic infections
-immunocompromised patients

Front 50

Bacterial pneumonia- Agents
Pathogenesis

Back 50

-Most bacteria are normal inhabitants of the nasopharynx or oropharynx
-reach alveoli by: aspiration (most), inhalation, hematogenous seeding, direct spread from adjacent site (rare)

Front 51

Pneumococcal pneumonia

Back 51

-Streptococcus pneumoniae
-the prototype of bacterial pneumonia
-encapsulated gram + cocci (diplococcus)
-normal resident of the nasopharynx
-often preceded by a viral infection, may alter bronchial secretions

Front 52

Pneumococcal pneumonia Pathology

Back 52

Early: pulmonary edema and proliferation of bacteria, intra-alveolar accumulation of neutrophils and erythrocytes-so called "red hepatization"
Later: serum and fibrinous exudates, intra-alveolar organization, macrophages--- so called "gray hepatization"

Front 53

complication of bacterial pneumonia

Back 53

-abscess
-pyothorax or epmyema
-bacteremia

Front 54

Abscess

Back 54

-walled off area of infection with destruction of pulmonary parenchyma
-often anaerobic oral bacteria
-more common on right than left lung
-fever, cough, foul smelling sputum
-mortality 5-10%

Front 55

Pyothorax/empyema

Back 55

-purulent material within the pleural space
-may become loculated, which requires drainage as well as antibiotics to treat

Front 56

Bacteremia

Back 56

-25%
-bacteria in the bloodstream
-endocarditis, meningitis, pericarditis

Front 57

Mycoplasma

Back 57

-Mycoplasma pneumoniae
-lack cell wall, slow growing
-culture very difficult, serum antibody testing to Dx
Acute pneumonia and tracheo-bronchitis
-milder than usual bacterial pneumonia
-"walking pneumonia"
-15-20% of pneumonias in developed countries
Highly transmissible through airborne droplets
Lymphocytic infiltrate, usually of the lower lobes

Front 58

Viral pneumonias General

Back 58

-Immune compromised (HIV, organ transplants)
-infants may get CMV
-lymphocytes in the interstitium
-distinct cytologic inclusions for some viral infections

Front 59

Tuberculosis

Back 59

-mycobacterium tuberculosis
-small, acid fast bacillus
-slow growing, 3-6 weeks to culture
-decrease in 20th century due to anti-TB drugs, re-emerging as a result of HIV and drug resistant strains
-Primary and secondary forms

Front 60

Primary tuberculosis

Back 60

-infection by inhalation of aerosolized droplets containing organisms
-caseous granulomatous inflammation results
Ghon complex forms:
-peripheral focus of infection (Ghon focus, often adjacent to iterlobar fissure)
-infected lymph node (hilum or mediastinum)
-90% of primary exposure asymptomatic

Front 61

Secondary tuberculosis

Back 61

-reactivation of primary tuberculosis OR new infection in a previously sensitized patient
-caseating granulomas again: apex and posterior segments of upper lobes
-may erode into a bronchus, creating a cavity: often in apex of lung, future home for aspergillus

Front 62

Complications of tuberculosis

Back 62

Miliary TB
-multiple small granulomas in many organs
-results from hematogenous dissemination
-most any organ can be involved
Hemoptysis
-inflammatory response erodes into pulmonary artery
Aspergilloma in cavities

Front 63

Fungal pneumonia general

Back 63

-fungi are ubiquitous in soil and air
-most exposure fails to produce infection: body temperature arrests growth, phagocytosis by neutrophils and macrophages
-risks: chemo, steriods, T-cell deficiencies
Usually granulomatous inflammation
Silver stains demonstrate organisms

Front 64

Aspergillosis

Back 64

Several species (A.niger, A.fumigatus)
-septate hyphae with acute angle branching
-live in soil and decaying plant material
Causes several distinct types of disease
-invasive aspergillosis
-aspergilloma
-allergic aspergillosis

Front 65

Invasive Aspergillosis

Back 65

-organisms invade blood vessels
-infarction of lung, dissemination, exsanguination
-Immunocompromised

Front 66

Mycetoma (fugus ball)

Back 66

-within preexisting cavity, often TB cavity
-tangled mat of hyphae, non-invasive

Front 67

Allergic Aspergillosis

Back 67

susceptible patients develop immunologic reaction to Aspergillus, esp. asthma patients

Front 68

Lung Infection Points

Back 68

3 Basic inflammatory responses: neutrophils, lymphocytes, granuloma
Most agnets have a characteristic resonse
-bacteria: neutrophils
-Viral/mycoplasma: lymphocytes
-mycobacteria/fungus: granuloma
A few infections are unique
-tuberculosis: primary vs secondary
-aspergillosis: 3 different lung diseases

Front 69

Lung Carcinoma

Back 69

-malignant epithelial neoplasms
-squamous cell carcinoma
-adenocarcinoma
-small cell carcinoma

Front 70

Lung Carcinoma: Epidemiology

Back 70

-expected incidence (2010): 222,000 (US)
-expected mortality (2010): 157,000 (US)
->85% of lung carcinoma deaths (and 30% of all cancer deaths) occur in cigarette smokers
-risk is proportional to # of cigarettes smoked, 15-30x in heavy smokers
-risk decreases with cessation of cigarettesmoking: baseline after 15 years

Front 71

Tobacco: Morbidity and Mortality

Back 71

-premature atherosclerosis: major risk factor
-emphysema: linear with exposure 7% per 10years
-chronic bronchitis
-carcinoma of pharynx, larynx, lung, esophagus, bladder, kidney

Front 72

Squamous cell carcinoma

Back 72

-smokers (98%)
-20-20% of common carcinomas
Rad: central >> peripheral
Path: squamous differentiation
-desmosomes (intercellular bridges)
-keratin production, e.g. ker pearls

Front 73

Adenocarcinoma

Back 73

-30-40% of common carcinomas
-#1 lung carcinoma in non-smokers
-80% of adenoCA's ocur in smokers
Rad: peripheral > central
Path:
-gland formation
-mucin production

Front 74

Small cell carcinoma

Back 74

-20% of carcinomas
-smokers
-commonly high stage at presentation
-generally not treated with surgery
-responsive to chemo/RT, but low 5 yr survival
Rad: Central in >90%, frequent metastases to LNs and distant sites
Path:
-malignant cytology with nuclear molding
-no nucleoli, little cytoplasm
-high mitotic activity and necrosis

Front 75

Lung carcinoma Points

Back 75

-3 major types: squamous, adeno, small cell
-most related to smoking: all types
-most common in non-smoker: adenocarcinoma
-central location: squamous, small cell
-peripheral location: adenocarcinoma
-treat with surery: squamous, adenocarcinoma
-no surgery: small cell carcinoma

Front 76

Mass Lesions
(Summary)

Back 76

The cranial cavity is a closed box. Thus, the formation of a mass within the intracranial space requires that something exit from the intracranial space. CSF and blood are the first to exit, followed by shifting of parts of the brain. Such shifts or "herniations," cause serious brain dysfunction and eventuate in death if the mass effect is not reduced. Because of this potential for mass effect, some disease processes, which are relatively benign in other locations, may be lethal when located intracranially.

Front 77

Mass Effect

Back 77

The consequence of an intracranial mass (neoplasm, hematoma, abscess, edematous infarct, etc)

Mass may cause horizontal (left-right) brain shift and may cause downward herniation (Transtentorial & Tonsillar herniation)

Front 78

Transtentorial (uncal) hernation

Back 78

Downward shift of medial temporal lobe & uncus thorugh tentorial incisure.

Due to supratentorial mass

Front 79

Tonsillar herniation

Back 79

Downward shift of cerebellar tonsils through foramen magnum.

Due to posterior fossa mass

Front 80

Mass effect leads to intracranial pressure

Back 80

Increased ICP causes headache, nausea, vomiting, pepilledema

Increased ICP may cause decreased cerebral blood flow, as intracranial pressure approaches or exceeds mean arterial pressure. Decreased cerebral blood flow leads to brain ischemia, which can cause irreversible injury

Front 81

Transtentorial (uncal) hernation
(Clinical Manifestations)

Back 81

Compression of 3rd cranial nerve causes DILATED PUPIL on side of lesion

Compression of cerebral peduncle causes CONTRALATERAL HEMIPLEGIA

Distortion & downward displacement of midbrain causes abnormal respirations, coma, HEMORRHAGES IN MIDBRAIN with irreversible brainstem damage, and DEATH

Front 82

Tonsillar herniation
(Clinical Manifestations)

Back 82

Compression of medulla causes apnea & DEATH

Front 83

Scalp Wound

Back 83

INFECTION of a scalp wound may spread to the underlying skull (osteomyelitis), meninges (meningitis), or brain (brain abscess)

Front 84

Skull Fracture

Back 84

Indicates significant head trauma, but not necessarily brain injury

May be calvarial (skull cap) fracture or basilar (base of skull fracture)

Front 85

Complications of Calvarial (Skull Cap) Fracture

Back 85

Tearing of dura may lead to tearing of its middle meningeal artery, which in turn leads to an ACUTE EPIDURAL HEMATOMA

Depressed skull fragments may cause BRAIN CONTUSION (bruising of brain)

Front 86

Complications of Basilar (Base of Skull) Fracture

Back 86

Tearing of the meninges may lead to a CSF leak from ear (CSF otorrhea) or nose (CSF rhinorrhea), which predisposes to meningitis

Tearing of cranial nerves or stalk of pituitary gland

Front 87

Focal Intracranial Lesions

Back 87

Head trauma, if significant, may cause focal intracranial lesions These focal traumatic lesions may result in localized neurologic deficits or a mass effect

May include: Contusion, Acute epideral hematoma, Acute subdural hematoma, Acute intracerebral hematoma

Front 88

Contusion

Back 88

Area of cortical hemorrhage at the surface of brain.

The contusion may be loacted beneath the site of impact (Coup Lesion) or distant from the site of impact (Contrecoup Lesion).

Contusions may cause focal neurologic deficits & may later become seizure foci.

Front 89

Acute epidural hematoma

Back 89

Rapidly accumulating blood clot due to skull fracture & tearing of middle meningeal artery

Causes a mass effect

Front 90

Acute subdural hematoma

Back 90

A rapidly accumulating blood clot due to tearing of the veins "bridging" the subdural space.

Causes a mass effect

Front 91

Acute intracerebral hematoma

Back 91

Rapily accumulating blood clot within brain parenchyma due to vascular disruption within brain.

The vascular disruption results from "shearing" forces generated at time of impact

Front 92

Hematoma Diagram

Back 92

Front 93

Diffuse Brain Injury

Back 93

Head trauma, especially that associated with automobile accidents, may cause diffuse brain injury due to shearing forces generated by deceleration/acceleration. Diffuse brain injury results in global brain dysfunction rather than the localized neurological deficits typically associated with focal brain injuries. With diffuce brain injury, the patient is unconscious from the moment of impact.

May be Concussion or Diffuse Axonal Injury

Front 94

Concussion

Back 94

A clinical syndrome of transient physiological dysfunction evidenced clinically by a short-term loss of consciousness

Front 95

Diffuse Axonal Injury

Back 95

Axonal disruption resulting from the shearing forces generated within the brain at the time of impact

Front 96

Complications of Head Trauma

Back 96

1. Brain edema - magnified any mass effect
2. Mass lesions - brain shifts, herniation, & death
3. Raised intracranial pressure (ICP) - leads to decreased cerebral perfusion pressure & consequent global brain ischemia
4. Ischemic brain injury - from hypotension, raised ICP, etc
5. Infection - meningitis or brain abscess
6. Post-traumatic epilepsy

Front 97

2 Types of Strokes:

Back 97

Ischemic or hemorrhagic

1. Brain infarct - due to loss of blow flow (ischemic stroke) --> the cause of 80% of strokes
2. Intracerebral hemorrhage - due to arterial rupture (hemorrhagic stroke) --> cause of 10% of strokes
3. Subarachnoid hemorrhage - due to arterial rupture (hemorrhagic stroke) --> cause of 10% of strokes

Front 98

Stroke Diagram

Back 98

Front 99

Hodgkin lymphoma

Back 99

-malignant lymphoma characterized by a distinctive cell: the Reed-Sternberg cell
-origin of Reed-Sternberg cell was controversial (convincingly of B-cell origin)
-EBV genome is present in up to 50% of cases
-peak incidence in 20's, smaller peak at age >50 years (bimodal age distribution)
-extranodal involvement is unusual
-spreads along contiguous lymph node chains (unlike NHL(non-hodgkins lymphoma))

Front 100

Pathologic diagnosis of Hodgkin Lymphoma

Back 100

-diagnosis based on finding Reed Sternberg cells in the appropriate cellular background: lymphocytes, eosinophils, histiocytes, fibroblasts
-Morphologic subtypes correclate with prognosis
-nodular sclerosis = good prognosis
-lymphocyte predominance= very good
-mixed cellularity -intermediate
-lymphocyte depletion- worst prognosis
-therapy has largely equalized these discrepancies. therefore HD has good prognosis

Front 101

Hodgkin Stage I

Back 101

involvment of single lymph node region or single extrolymphatic site (l E)

Front 102

Hodgkin Stage II

Back 102

involvement of two or more lymph node regions on same side of diaphragm; may include localized extralymphatic involvemetn on same side of diaphram (II E)

Front 103

Hodgkin Stage III

Back 103

-invovlement of lymph node regions on both sides of the diaphragm; may include spleen (IIIs) or localized extranodal disease (III E)

Front 104

Hodgkin Stage IV

Back 104

-diffuse extralymphatic disease (in liver, bone marrow, lung, skin)

Front 105

Hodgkin lymphoma clinical staging

Back 105

5 year survival based on stage: stage is more important than histologic subtype (unlike NHL)
Stage I and II- 90%
Stage III-84%
Stage IV - 65%

Front 106

Hodgkin lymphoma imaging

Back 106

-CT scan of chest, abdomen and pelvis
-PET scanning for baseline and follow-up
-resistant disease detectable with PET

PET currently the best predictor:
Negative PET after chemo x2
95% PFS at two years
Positive PET after chemo x2
10% PFS at two years

Front 107

Hodgkin Lymphoma therapy

Back 107

easly stage issues/options
rxt/chemo vs. chemo alone
ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) is treatment of choice : low recurrence, few side effects

Front 108

Advanced stage Hodgkin lymphoma therapy

Back 108

(IIB, III, IV)
-chemoterapy- ABVD
-hybrid/ other regimens
-consolidation with rxt

If relapsed: hematopoietic stem cell transplant

Front 109

Non-hodgkin lymphomas

Back 109

-malignant clonal diseases of lymphocytes
-NOT stem cell disorders
-many subtypes: remember there are B-T and NK cells
-several classification schemes
-working formulation is used for clinical classification (1982)
-World Health Organization (WHO) is used for pathologic classification

Front 110

Classification goals

Back 110

-to group patients into prognostic groups
-to be easily/reproducibly used by pathologists
-Historically based on histology alone:
-architectural arrangement
-cell size and shape

Front 111

Precursor B cell neoplasm

Back 111

-precursor b-cell lymphoblastic leukemia/lymphoma (b-cell acute lymphoblastic leukemia) lukes collins

Front 112

Mature (Peripheral) B cell neoplasms

Back 112

-B cell chronic lymphocytic leukemia/small lymphocytic lymphoma
-lymphoplasmacytic lymphoma (Waldenstrom's macroglobulinemia)
-hairy cell leukemia
-plasma cell myeloma/plasmacytoma
-extranodal marginal zone B-cell lymphoa of MALT type
-follicular lymphoma
-mantle cll lymphoma
-diffuse large B-cell lymphoma
-burkitt lymphoma

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Precursor T-cell neoplasm

Back 113

-precurso T-cell lymphoblastic leukemia/lymphoma (t-cell ymphoblastic lymphoma)

Front 114

Mature T-cell (peripheral) neoplasms

Back 114

-T-cell granular lymphocytic leukemia
-adult t-cell lymphoma/leukemia (HTLV1+)
-Enteropathy-type t-cell lymphoma
-mycosis fungoides (sezary syndrome)

Front 115

Small lymphocytic Lymphoma

Back 115

-essentially the same disease as CLL (chronic lymphocytic leukemia)
-SLL (small lymphocytic lymphoma) and CLL both are:
-comprised of small, round lymphocytes
-have the same immunophenotype
-occur in older adults
-are considered incurable
-Mature B-cell (CD 19+, CD 20+, CD 23+) co-expressing CD5, kappa or lambda light chain

Front 116

follicular lymphoma

Back 116

-midle-aged to elderly adults
-cells resemble normal germinal center cells
-mature B-cell immunophenotype
-Cytogenetics:
t (14;18)
-translocates bcl-2proto-oncogene downstream of immunoglobulin regulatory sequences

Front 117

Follicular lymphoma low grade histology

Back 117

-indolent course- median survival 10 years
-incurable with conventional chemo
-pts typically present with high stage disease (including marrow involvement)
-may progress to difuse large cell lymphoma
-mature B-cell phenotype (CD19,20 +) CD 10 + (immature B-cells and follicle center cells) kappa or lambda light chain

Front 118

diffuse large cell lymphoma

Back 118

-most common type of NHL
-intermediate grade lymphoma
-low stage disease can be cured
-occurs in children and adults
-can be associated with immune dysfunction (HIV, SCID, BM & organ transplants)
-1/3 cases are extranodal (GI< Brain)
-most often mature b-cell phenotype

Front 119

Burkitt lymphoma

Back 119

-endemic (africa;98% EBV genome positive)
-predominantly in children
-Non-endemic (worldwide: 15-20% EBV positive) all ages
-Cytogenetics: t(8;14) most common but also t(2;8) & t(8;22)
-c-myc proto-oncogene downstream of immunoglobulin heavy chain regulatory sequences
-mature B-cell phenotype

Front 120

classification of Non-hodgkin review

Back 120

Working formulation based on clinical grade (low, intermediate, high)
WHO based on phenotype and maturity
-precursor (immature) and mature B-cell neoplasms
-precursor (immature) and mature T-cell neoplasms

Front 121

Development of B-cell

Back 121

lymphoblast --> B-lymphocyte: (naive CD19/CD10 IgM/IgD)---> Plasma cell----> CD 138

Front 122

Plasma cell dyscrasia

Back 122

-clonal disorders of terminally differentiated B-cells
-Clinical presentation: variable; features resultant of organ dysfunction;lytic lesions or fractures in 70% cases at diagnosis
-10-15% of hematologic malignancies (20,000 cases/year in US)
-mean age: 60-'s
-Men> Women
-significant racial bias: AA: Cauc = 2:1

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Classification of Plasma Cell dyscrasia depends on ...

Back 123

Identification and characterization of clonal plasma cell population
-paraprotein analysis (classically electrophoresis)
-morphology
-immunophenotype (IHC/flow cytometry
-Cytogenetic/molecular techniques
Clinical Radiographic findings
-clinical presentation
-sites of involvement
-extent of disease

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Current diagnostic criteria for plasma cell myeloma

Back 124

-M protein in serum or urine
-clonal plasma cells in bone marrow or plasmacytoma
-Related organ or tissue impairment
C: hypercalcemia
R: renal insufficiency
A: anemia
B: bone lesions

Front 125

clonal hematologic malignancies

Back 125

Front 126

Lymphomas different types

Back 126

Front 127

Cause of Brain Ischemia

Back 127

-Arterial occlusion due to ATHEROMATOUS PLAQUE or THROMBUS. Extracranial carotid arteries are common sites fro atheromatous plaques.
-Arterial occlusion due to an EMBOLUS. Embolus may arise from thrombotic material on an atheromatous plaque in the aorta or extracranial carotid arteries, from a mural thrombus in teh heart, from thrombotic material (vegetations) on heart valves,etc
-CARDIAC ARREST or severe SYSTEMIC HYPOTENSION can cause global (diffuse) ischemic brain damage

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Consequences of Brain Ischemia

Back 128

-NO EFFECT - anastomoses (circle of Willis, leptomeningeal vessels, etc) may provide sufficient blood flow to the ischemic area
-TRANSIENT ISCHEMIC ATTACK (TIA) - clinically evidenced as a transient neurologic abnormality. TIAs are reversible & are not accompanied by irreversible brain damage, i.e., infarcts, but may herald a future infarct
-INFARCT - ischemic brain undergoes necrosis, atrophy & cavitation. The neurons (gray matter) are most vulnerable to ischemic injury.

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Macroscopic & Microscopic evolution of an infarct

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-Coagulative necrosis (red neurons) is present at 12-24 hrs.
-Influx of neutrophils within infarcted tissue occurs by 24 hrs.
-Influx of macrophages occurs by 3rd day
-Edema & mass effect is maximal in 1st week & waves thereafter
-Glial proliferation (gliosis, glial scarring) occurs in brain tissue at the periphery of the cavity
-Cavitation of infarct takes weeks to months, depending on size of infarct

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Location of Brain Infarct

Back 130

Often provides a clue as to its cause

Locations:
Cortical infarct
"Borderzone" infarct
"Lacunar" infarct
Global ischemic injury

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Cortical Infarct
(Location of Brain Infarct)

Back 131

Due to occlusion of a large artery.

Usually caused by atherothrombosis or embolism

Front 132

"Borderzone" Infarct
(Location of Brain Infarct)

Back 132

Occurs int he borderzone region between 2 arterial distributions.

Due to an episode of systemic hypotension

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"Lacunar" Infarct
(Location of Brain Infarct)

Back 133

Due to occlusion of a small penetrating artery.

These deep infarcts are usually cavitary (cystic)

Front 134

Global Ischemic Injury
(Location of Brain Infarct)

Back 134

Aka Global Ischemic Encephalopathy

Due to prolonged cardiac arrest

Ischemic injury is widespread

Front 135

Consequences of a Brain Infarct

Back 135

-Brain necrosis leads to NEUROLOGIC DEFICIT of rapid onset. The type of neurologic de3ficit is determined by the location of the infarct
-Possible MASS EFFECT from edema within infarcted tissue
-DEMENTIA ("vascular dementia") may complicate multiple brain infarcts

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Causes of nontraumatic (spontaneous) Brain Hemorrhage

Back 136

-HYPERTENSION - the common cause of nontraumatic brain hemorrhage
-Bleeding disorder
-Rupture of an arteriovenous malformation
-Drug abuse (e.g., cocaine, amphetamines)
-Cerebral amyloid angiopathy - occurs in other patients
-Hemorrhage into primary or metastasis neoplasm in brain

Front 137

Berry (Saccular) Aneurysms

Back 137

Arise on large arteries in the subarachnoid space at the base of the brain (e.g., arteries of the circle of Willis)
-Aneurysms arise at the forks of arteries
-Prevalence of aneurysms in the general population is 2-5% in adults, with higher frequency in patients with polycystic kidney disease or coarctation of the aorta
-Berry aneurysms are frequently multiple (20%)

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Consequences of massive Subarachnoid Hemorrhage from Ruptured Aneurysm

Back 138

-Hemorrhage causes increased intracranial pressure
-Hemorrhage may also jet upward into brain parenchyma & produce a localized hematoma with a mass effect
-Ruptured aneurysm may rebleed
-Subarachnoid hemorrhage may cause arterial vasospasm & infarcts

Front 139

Consequences of a Brain Tumor
(Diagram)

Back 139

Front 140

All Intracranial Tumors are potentially lethal
(Diagram)

Back 140

Front 141

Histological Classification of tumors of the nervous system
(Differentiation of Tumor Cells --> Histological Classification)

Back 141

Glial differentiation --> Astrocytoma & glioblastoma, Oligodendroglioma, Ependymoma
Neuronal differentiation --> Medulloblastoma
Arachnoidal-cell differentiation --> Meningioma
Schwann-cell differentiation --> Schwannoma & neurofibroma, Malignant peripheral nerve sheath tumor (MPNST)
Miscellaneous types of differentiation --> Pituitary adenoma; Lymphoma, primary or metastatis; Hemangioblastoma; Craniopharyngioma; Germ-cell neoplasms of pineal & suprasellar areas
Metastatic tumors --> Carcinomas, sarcomas, etc.

Front 142

Incidence of Intracranial Tumors
(Diagram)

Back 142

Note that gliomas, metastases & meningiomas make up the majority of brain tumors

Front 143

Clinical & Pathologic Correlations
(Brain Tumor locations and types of neoplasms)

Back 143

Front 144

Malignant Glioma (Glioblastoma)

Back 144

Very poorly differentiated astrocytomas, with mitotic figures, necrosis, & a fast rate of growth.

Their infiltrative nature precludes complete surgical excision, giving them a very poor prognosis

Front 145

Meingioma

Back 145

Meningiomas are external to the brain & do not infiltrate underlying brain

These histologically benign tumors rarely metastasize & can often be completely surgically excised, giving them a good prognosis

Front 146

Schwannoma (Vestibular schwannoma)

Back 146

Arising on the left 8th cranial nerve.

These benign tumors are well circumscribed & can be completely excised, giving them a good prognosis

The patient presents with vertigo or hearing loss, reflecting involvement of the 8th cranial nerve

Front 147

Relative Frequency of Primary Neoplasms Metastatic to the Brain

Back 147

Front 148

"Demyelinating Disease" Definition

Back 148

1. Difference between Demyelination, where myelin breakdown occurs but the axons are preserved; & axonal (Wallerian) degeneration, where myelin breakdown occurs secondary to degeneration of the underlying axons.
2. There is potential for REMYELINATION & AXONAL REGENERATION in PNS, but no significant potential in CNS.

Front 149

Demyelination & Remyelination in PNS
(Diagram)

Back 149

Front 150

Wallerian Degeneration & Axonal Regeneration

Back 150

Front 151

Mechanisms by which myelinating glial cells of the nervous system are selectively injuried (selective vulnerability)

Back 151

1. Immune-mediated (multiple sclerosis, CNS; Guillain-Barre syndrome, PNS)
2. Viral infection of oligodendrocytes (progressive multifocal leukoencephalopathy)
3. Inherited metabolic defects (the leukodystrophies)
4. Toxins (diphtheria neuropathy)

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Multiple Sclerosis (MS)

Back 152

An immune-mediated demyelinating disease of CNS
1. Occurs between 15-50 years of age, with average age of onset at 30
2. Currently considered an autoimmune disease in which environmental factors & heredity contribute to risk
3. Pathology is that of demyelination plus the chronic inflammation typical of an autoimmune disease

Front 153

Progressive Multifocal Leukoencephalopathy (PML)

Back 153

Another type of CNS demyelinating disease
The viral disease, which typically occurs in immunocompromised patients, is most commonly found in AIDS patients.
Unlike MS, the demyelination is accompanied by viral inclusions in oligodendrocytes & bizarre reactive astrocytes.

Front 154

Leukodystrophies

Back 154

Inherited metabolic diseases in which the myelinating glia (oligodendrocytes & sometimes Schwann cells) are severely affected because of an enzyme defect, which prevents the normal catabolism of myelin.

Front 155

Alzheimer's Disease

Back 155

-Responsible for 50-60% of the cases of dementia
-Characterized primarily by a degeneration of the neurons in the CEREBRAL CORTEX & HIPPOCAMPUS, which causes dementia
-Etiology & Pathogenesis = Unknown. Most adults with Down syndrome develop the pathological changes of Alzheimer's disease by age 40. Most cases are sporadic, but a small percent of cases are familial & the genes have been identified (beta amyloid precursor protein gene; presenilin 1 & 2 genes). Apolipoprotein E4 is an established risk factor.

Front 156

Alzheimer's Disease
(Degenerative Changes in the Cytoskeleton of involved neurons, in the neuropil of the gray matter & in cerebral blood vessels)

Back 156

-NEUROFIBRILLARY TANGLES in neurons --> composed of intracytoplasmic paired helical filaments (PHF) in the neuronal cytoplasm. PHF are an abnormally phosphorylated isoform of TAU, a low molecular weight microtubule associated protein
-SENILE PLAQUES in the neuropil - composed of extracellular amyloid (amyloid Beta protein) surrounded by PHF-filled neuronal processes.
-Vascular deposits of amyloid Bta protein (Cerebral Amyloid Angiopathy)

Front 157

Huntington's Disease

Back 157

-Autosomal Dominant Inheritance. The mutated gene is on chromosome 4 & encodes for the protein, huntingtin. The mutation is an expanded CAG repeat. Clinical onset usually around 20-50 years of age. Characterized by progressive choreiform movements & dementia
-The neuronal degeneration is primarily in the basal ganglia (which produces chorea) & in the cerebral cortex (which produces dementia)
-Histopathologically, there are loss of the smaller neurons in the caudate nucleus & putamen, & loss of neurons in the cerebral cortex

Front 158

Parkinson's Disease
(Characterizations & Pathogenesis)

Back 158

-A neurogenerative disease characterized mainly by a degeneration & loss of the pigmented neurons of the substantia nigra in the midbrain. The loss of pigmented cells is so great that it can be seen grossly. The loss of neurons in the substantia nigra causes the clinical picture of parkinsonism

-The pathogenesis of this sporadically occuring disease is unknown. Rare familial forms do occur & have been linked to several different gene mutations

Front 159

Parkinson's Disease
(Histopathology & Other Diseases)

Back 159

-The degenerating neurons show characteristic LEWY BODIES, which are composed primarily of alpha-synuclein. Lewy bodies are characteristic of Parkinson's disease, but can be seen in patients without Parkinson's disease
-Other disease processes can also produce tremor, rigidity, & bradykinesia, and thus a Parkinson-like picture clinically. Among the diseases associated with the parkinsonism syndrome are certain drugs (phenothiazines, etc), postencephalitic parkinsonism, infarcts of the substantia nigra, & certain other neurodegenerative diseases.

Front 160

Infectious Diseases of the Nervous System

Back 160

A wide variety of infectious agents may invade the nervous system. Some have a predilection for the CSF & cause a leptomeningitis, whereas others preferentially infect various parts of the brain (encephalitis) or spinal cord (myelitis). Infectious agents may get to the brain via the blood stream, by direct spread from an adjacent focus of infection in the scalp, skull, or paranasal sinuses, or by direct implantation during trauma. Opportunistic agents are becoming increasingly important causes of CNS infection because of the increasing prevalence of individuals with compromised immune systems. Infections cause CNS dysfunction by destruction of brain tissue as well as by causing a mass effect.

Front 161

Acute Bacterial Meningitis (Leptomeningitis)

Back 161

-An acute inflammation of the leptomeninges (pia & arachnoid)
-Pathogenesis of the CSF infection (Bacteremia from a known or unknow distant focus of infection; Direct extension of infection from middle ear, mastoid bone, paranasal sinuses, or head wound)
-Bacteriology of acute bacterial meningitis (Neonate - Group B Strep, Listeria, enteric gram-negative rods; Child - S. pneumoniae, N. meningitidis, H. influenzae; Adult - S. pneumoniae, N. meningitidis)

Front 162

Clinico-pathologic Correlations of Acute Bacterial Meningitis

Back 162

-Meningeal inflammation --> stiff neck, headache
-"Toxins" --> brain swelling --> increased ICP --> herniation
-"Toxins" --> encephalopathy & seizures
-Inflammation of cranial nerves --> nerve palsies
-Thrombophlebitis --> brain infarcts
-Meningeal fibrosis --> hydrocephalus

Front 163

Chronic Meningitis

Back 163

May complicate infections with a protracted clinical course, such as tuberculosis, certain fungal infections & syphilis.

When these chronic infections involve the leptomeninges, a chronic inflammatory process ensues. This chronic inflammatory process in the subarachnoid space also affects the cranial nerves & blood vessels in the subarachnoid space, leading to cranial nerve palsies & brain infarcts

Front 164

Brain Abscess

Back 164

A pus-filled cavity walled off by granulation tissue

Front 165

Pathogenesis of Brain Abscess

Back 165

-Bacteremia from distant focus of infection
-Traumatic implantation
-Direct extension from infection in middle ear, sinuses, etc

Front 166

Bacteriology of Brain Abscess

Back 166

Often a mix of aerobic & anaerobic bacteria

Front 167

Clinico-Pathologic correlations of a Brain Abscess

Back 167

-Local brain destruction --> neurologic deficit
-Mass effect --> herniation --> death
-Extension into ventricle --> ventriculitis & death

Front 168

Viral Infections of the CNS
(Pathogenesis of Viral Meningitis or Viral Infection)

Back 168

Front 169

HSV 1 Encephalitis

Back 169

-The most commonly occurring sporadic viral encephalitis.
-Viral encephalitis is very destructive, causing necrosis & hemorrhage in the brain.
-Microscopically, the necrosis is accompanied by lymphocytic inflammation and, with some viruses, characteristic intranuclear or intracytoplasmic viral inclusions.

Front 170

Fungal Infections of the CNS

Back 170

These "opportunistic" infections usually occur in immunocompromised patients & may cause a chronic meningitis (e.g., Cryptococcus neoformans) or encephalitis (e.g., Candida species)

Front 171

Spongiform Encephalopathies (Prion Diseases)

Back 171

Creutzfeldt-Jacob disease

Front 172

Neuropathology of AIDS

Back 172

-HIV Encephalitis (subacute giant-cell encephalitis)
-Opportunistic infections - such as CMV encephalitis, PML, cerebral toxoplasmosis, & cryptococcal meningitis
-CNS lymphoma
-AIDS-related myelopathy & peripheral neuropathy

Front 173

Diagnosis and classifications (and ultimately management) of hemtopoietic neoplasms is dependent upon

Back 173

-clinical manifestations,
-morphology of biopsied tissue (special stains)
-flow cyometry
-molecular studies
- cytogenetics
-findings guide therapy, serve as upfront prognostic markers, and predict response to treatment
-each technology has its strengths and weaknesses

Front 174

Development and Differentiation

Back 174

-patterns of gene expression vary as cells mature and differentiate
-morphological differentiation
-differences in expression can be exploited to help classify disease

Front 175

Cluster of Differentiation: The CD designation

Back 175

-fisrt est. in 1982
-currently ~350 designated surgace antigens
-Commonly encountered markers: CD45

Front 176

CD45

Back 176

-all normal leukocytes to vary degrees
-LCA=leukocyte common antigetn

Front 177

B Cell CD designation

Back 177

- CD10+
-CD19+
-CD20+
-CD22+
-CD79a K/LPAX-5+

Front 178

T cell CD designation

Back 178

-CD2+
-CD3+
-CD4+
-CD5+
-CD7+
-CD8+

Front 179

NK cell CD designation

Back 179

-CD16+
-CD56+

Front 180

Plasma Cell CD designation

Back 180

-CD38+
-CD138+kappa/lambda

Front 181

Monocytes CD designation

Back 181

-CD4+
-CD64+

Front 182

"Blasts" CD designation

Back 182

-CD34+
-CD117+

Front 183

Megas CD designation

Back 183

-CD41+
-CD42+
-CD61+
-Factor VIII+

Front 184

Myeloid CD designation

Back 184

-MPO+
-CD10+(mature)
-CD15+
-CD33+

Front 185

Immunophenotyping

Back 185

-Low numbers: T-cell phenotype:remember CD4 counts and HIV/AIDS-low T cells (CD 1,2,3,4,5,7,8)
-Mid teens=Myelomonocytic (CD13=granulocyte, CD14=monocytic, CD15=granulocyte)
-Nineteen and early twenties: B-cell phenotype(CD19,20,21,22,23)
-Other markers (CD34 stem cell, CD33 myeloid)

Front 186

Overview of Flow Cytometry

Back 186

-measurement of cellular properties as they are moving in a fluid stream, past a stationary set of detectors
-Detectors: Positional and Fluorescence
-Positional (forward scatter {size}, side scatter {complexity})
-Fluorescence; attach a fluorescent probe to an antibody directed at a specific marker, excite with a light, measure emission, immunophenotype
-FACS - fluorescence activated cell sorting

Front 187

Immunophenotyping

Back 187

-identifying the phenotype using fluorescently labeled antibodies as probes

Front 188

Neoplastic Hematopathology

Back 188

-leukemia (acute and chronic)
-Lyphoma (hodgkin and non-hodgkin)

Front 189

Classification of Leukemias

Back 189

-diagnosed according to prominent cell type involved
-Acute: rapid onset, aggressive, usually poorly differentiated (blasts)
-Chronic: insidious onset, usually less aggressive and more mature appearing

Front 190

Acute Lymphoblastic Leukemias

Back 190

-lymphoid precursor (lymphoblast

Front 191

Acute Myeloid Leukemias

Back 191

-myeloid precursor (myeloblast

Front 192

Chronic Lymphoproliferative Disorders

Back 192

-Lymphocyte (B, T, NK)
-Plasma cell

Front 193

Myeloproliferative Disorders and Myelodysplastic Syndromes

Back 193

-Granulocytes
-basophils
-eosinophils
-platelets
-monocytes

Front 194

Chronic Myeloid Leukemia (CML)

Back 194

-myeloproliferative neoplasm that originates in bone marrow stem cell associated with BCR-ABL1 fusion gene
-20-40% of pts are symptomatic and diagnosed incidentally
-WBC: leukocytosis with blood that looks like a bone marrow aspirate
-numerous immature granulocytes
-increased basophils
-hypercellular
-increased M:E

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Benign neutrophilia

Back 195

-many etiologies left shift not marked as in CML (may see bands but infrequently see myelocytes and other immature forms)

Front 196

BCR-ABL fusion Gene

Back 196

-juxtapostions of BCR (22) with ABL(9)
-constituatively avtive tyrosine kinase (upregulating cell cycling)
-karotype, FISH, PCR
-Target for therapy
-normal karotype doesnt exclude a cryptic translocation

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Leukemia progression

Back 197

-untreated, the chronic phase disease will ultimately transform to a blast phase with :
*additional genetic abnormalities
*increased blasts
-Variants: AML and ALL (remember where the defect is)

Front 198

Chronic Lymphocytic Leukemia (CLL)

Back 198

-kidn of an outlier from the other leukemias
-disease equivalent to small lymphocytic lymphoma (SLL, tissue vs bone marrow/blood based)
-mature B cell lymphoma
-pts often older and die with disease and not from it
-more agressive subsets exists
-50% have hypoammaglobulinemia (infection) Coombs + AIHA, ITP
-can have involvement of the bone marrow, lymph nodes (SLL), spleen(white pulp), etc

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Leukemia Immunophenotype

Back 199

-Typical pattern:Mature B cell phenotype expressing and CD5 and CD23 (CD19+CD20+(weak)CD5+CD23+)
-Weak sIgM or IgM/IgD+
-light chain restricted
-CD10-Cylcin D1-CD103
-CD10: follicular, burkitt, ALL
-Cyclin D1: mantle cell lymphoma (CD5+ but CD23-)
-CD103: Hairy Cell leukemia

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Cytogenetics

Back 200

-Deletion 13q14 (found in >50% cases, good prognosis, better than nl karyotype, microRNA and BCL-2)
-Trisomy 12 (found in ~20% cases,worse prognosis, atypical morphology and IPT {FMC7+, CD38+}, unmutated IgVH)
-Deletion 11q23(~20%cases, bad prognosis, ATM, MLL and others)
-Deletion 17p13 (5% of untreated cases, bad prognosis, less responsive to therapy, p53)
-Deletions of 6 (Increased PL, bad prognosis)

Front 201

Acute Myeloid leukemia

Back 201

-Clonal expansion of meyloid blasts
-classification requires (>/=20% of blood or marrow blasts, Auer rods are seen only in a subset of cases)
-Can arise de novo or as a consequence of underlying disorder such as MDS, MPD

Front 202

Acute Myeloid WHO classification

Back 202

-Acute Myeloid with recurrent genetic abnormalities (15/17; PML/RAR alpha; Acute promyelocytic leukemia)
- Acute myeloid not otherwise specified : rest of FAB classification
-Acute myeloid with multilineage dyplasia:following MDS or MDS/MPD or w/o antecedent MDS
-Acute meyloid and myelodysplastic, therapy related (alkylating agent-related, topoisomerase type II inhibitor related)

Front 203

t(15;17)(q22;q12); PML/RAR alpha Acute Promyelocytic Leukemia

Back 203

-blocked at promyelocytic stage of granulocyte differentiation
0comprised 5-8% of AML
-Clinically associated with DIC
-95% with reciprocal translocation t(15;17), with fusion of PML gene on 15 and retinoic acid receptor alpha (RAR alpha) on 17
-Remaining 5% show RAR alpha rearrangements with other genes

Front 204

t(15;17) and ATRA

Back 204

-Promyelocytic leukemia (PML) protein :tumor suppressor that forms complexes with other proteins (P53, pRb, and others)
-Retinoic acid receptor alpha
-all-trans retinoic acid (ATRA): RA analogue:overcomes the avidity of RAR alpha binding to corepressor complex, differentiation therapy

Front 205

Retinoic Acid Receptor Alpha

Back 205

-Normally heterodimerizes with retinoid X receptor (RXR) and interacts with nuclear corepressor complex to transcriptionally block granulocyte differentiation
-Retinoic acid release teh complex and allows progression of differentiation past the promyelocyte stage

Front 206

AML with Normal cytogenetics

Back 206

-Approx. 50% of AML's have no clonal cytogenic abnormality
-clearly not devoid of genetic mutations
-Mutations at genetic level: (FLT3, NPM1, RAS, CEBPA, etc)

Front 207

AML w/normal cytogenetics: FLT3

Back 207

-FMS-like tyrosine kinase 3
-mutations occur in 20-30% of de novo AML
-most frequent molecular abnormality in AML
-Associated with POOR prognosis
-internal tandem duplication=most common form

Front 208

Acute Lymphoblastic Leukemia (ALL)

Back 208

-variable clinical presentation
-most common in kids
-frequently have peripheral blood leukocytosis with numberous circulating blast (but can be aleukemic)
-most commonly of B-cell origin, variable prognosis but generally yes, much better in children than adults
-less commonlyTcell (T-ALL) mediasinal or soft tissue masses,consideed higher risk, prognosis worse tahat B-ALL

Front 209

ALL Cytogenetics

Back 209

-karyotype and specifically targeted fluorescence in situ hybridization (FISH) and molecular studies
-B-cell acute lymphoblastic leukemia( cytogenetic abnormalities seen in majority of cases, some are recurrent, some have significant prognostic implications)
-T-cell acute lymphoblastic leukemia:clonal rearrangement of T-cell receptor gene

Front 210

Favorable prognosit cytogenetic classifications of adult ALL

Back 210

-Favorable: hyperdiploid and t(12;21)
-Unfavorable:t(9;22), abn (11q23), hypodiploid

Front 211

ALL

Back 211

-common in kids, good prognosis
-less common in adults, worse prognosis
-lymphoblasts large cells with open chromatin
-t(9;22) bad but doesnt independently drive diseae

Front 212

AML

Back 212

-look for incerased blasts and Auer rods
-cytogenetics subtype increasingly more important

Front 213

CML

Back 213

-t(9;22) BCR-ABL drives disease (not the most accurate representation of malignancy)
-Can transform to acute leukemia (lymphoid/myeloid)

Front 214

CLL

Back 214

-older pts
-CD20+CD19+CD5+CD23+flow is a great starer tooth
-differentiate from mantle and cell lymphoma

Front 215

Etiology

Back 215

Cause of a disease process

Front 216

Pathogenesis

Back 216

Mechanisms of disease development

Front 217

Morphologic changes

Back 217

Structural changes due to disease

Front 218

Clinical findings

Back 218

Functional consequences of disease

Front 219

GI Tissue Layers
(Diagram)

Back 219

Front 220

Esophagitis

Back 220

Defined: Inflammation of esophageal mucosa
Prevalence: 5% of US
Types:
-Reflux esophagitis (aka GERD)
-Infectious esophagitis
-Barrett esophagus
-Other: radiation, chemical

Front 221

Reflux Esophagitis
(Etiology & Pathogenesis)

Back 221

Etiology --> Gastric contents reflux back into esophagus
-Decreased lower esophageal sphincter (LES) tone
-Hiatal hernia
-Increased intra-abdominal pressure

Pathogenesis --> Gastric fluid causes esophageal mucosal damage

Front 222

Reflux Esophagitis
(Decrease in tone of lower esophageal spincter - LES)

Back 222

-Fatty meals
-Alcohol
-Smoking
-Presence of nasogastric tube
-Pregnancy (progesterone)

Front 223

Reflux Esophagitis
(Increase in luminal pressure)

Back 223

-Large meals
-Obesity
-Pregnancy (mass effect)
-Bending at the waist

Front 224

Reflux Esophagitis
(Morphologic changes)

Back 224

-Inflammatory cells in esophageal squamous epithelial (Lymphocytes, eosinophils, neutrophils)
-Basal zone hyperplasia
-Elongation of lamina propria papilla
-Spongiosis

Front 225

Reflux Esophagitis
(Clinical Findings)

Back 225

-Dysphagia
-Heartburn/chest pain
-Hematemesis

Front 226

Reflux Esophagitis
(Consequences/complications)

Back 226

-Bleeding
-Ulceration
-Stricture (Deep ulcers can heal with scarring leading to narrowing of the esophageal lumen)
-Barrett esophagus

Front 227

Infectious Esophagitis
(Etiology & Pathogenesis)

Back 227

Etiology:
-Fungal - candidiasis
-Viral - Herpes & CMV

Pathogenesis:
-Inflammation & resulting tissue damage in response to infectious viral or fungal agent

Front 228

Infectious Esophagitis
(Morphologic changes)

Back 228

Candida:
-Gross - white/gray adherent pseudomembranes
-Micro - yeast & pseudohyphae

Herpes virus:
-Gross - punched-out ulcers
-Micro - HSV & CMV have characteristic viral cytopathic effect

Front 229

Herpetic Viral Cytopathic Effect

Back 229

-Multinucleated squamous epithelial cells
-Margination of normal chromatin forming a peripheral rim with central ground glass appearance
-Nuclear Moulding

Front 230

Infectious Esophagitis
(Clinical findings)

Back 230

-Immunosuppressed patients
-Dysphagia
-Pain

Front 231

Barrett Esophagus
(Definition)

Back 231

Replacement of the distal esophageal squamous epithelium by metaplastic columnar epithelium (with intestinal type goblet cells)

Front 232

Barrett Esophagus
(Etiology & Pathogenesis)

Back 232

Etiology --> Chronic reflux injury (GERD)

Pathogenesis --> Injury from reflux of gastric acid results in metaplasia:
-Conversion of one differentiated cell type to another
-Benign, adaptive process

Front 233

Barrett Esophagus
(Morphologic Changes)

Back 233

Replacement of the squamous epithelium of the distal esophagus with columnar epithelium containing goblet cells

Front 234

Barrett Esophagus
(Diagnosis: 2 Criteria)

Back 234

1. Endoscopic findings (red, velvety mucosa)
-Histologic findings of columnar mucosa with goblet cells in biopsy material from specified location ("intestinal metaplasia")

Front 235

Barrett Esophagus
(Clinical findings)

Back 235

Risk factors:
-Age >40
-Caucasian
-Male
-Any underlying cause for long standing reflux esophagitis

Same symptoms as GERD

Front 236

Barrett Esophagus
(Complications)

Back 236

Dysplasia --> disordered cell growth

10% lifetime risk for development of Adenocarcinoma:
-Risk of developing adenocarcinoma is related to the length of the metaplastic segment (30-40 fold increase risk over general population if >3cm of Barrett is present)

Front 237

Esophageal Carcinoma

Back 237

-Uncommon (6% of all cancers in the GI tract)
-Usually asymptomatic until they cause obstruction (often too late to permit cure; without treatment, average survival is 4 months after diagnosis)
-Squamous cell carcinoma is more common worldwide
-Adenocarcinoma & squamous cell carcinoma exhibit comparable incidence rates in the US

Front 238

Esophageal Adenocarcinoma
(Definition, Etiology, & Pathogenesis)

Back 238

Definition --> Malignant epithelial tumor with gland formation

Etiology --> Majority arise in Barret esophagus; ???Helicobacter pylori???

Pathogenesis --> Multistep molecular "hits"

Front 239

Transition from Barrett Esophagus to Adenocarcinoma

Back 239

Front 240

Esophageal Adenocarcinoma
(Morphologic changes)

Back 240

-Gross: Flat or raised lesion
-Micro: Infiltrating glands with mucin production

Front 241

Esophageal Adenocarcinoma
(Clinical findings)

Back 241

Usually asymptomatic until luminal obstruction
-Difficulty swallowing
-Weight loss

Diagnosis often too late to permit cure
-<20% 5 year survival

Front 242

Esophageal Squamous Cell Carcinoma
(Definition, Etiology, & Pathogenesis)

Back 242

Definition --> malignant epithelial tumor with squamous differentiation

Etiology --> Diet (Vitamin deficiency, high nitrates, fungal contamination) & Lifestyle (ETOH & smoking)

Pathogenesis:
-Carcinogens (fungus & nitrosamines)
-Potentiators of carcinogens (nutritional deficiency)
-Stepwise accumulation of genetic alterations

Front 243

Squamous Cell Carcinoma
(Morphologic Findings)

Back 243

Gross:
-Polyploid, ulcerating, or flat tumor
-Middle third

Micro:
-Invasive squamous epithelial nests within fibrotic stroma
-Rich lymphatic system allows extensive tumor spread

Front 244

Gastric Diseases

Back 244

Gastritis:
-Acute
-Chronic (H. pylori)
Peptic ulcer
Tumors (Adenocarcinoma)

Front 245

Gastritis
(Definition & Etiology)

Back 245

Definition --> inflammation of the gastric mucosa

Etiology --> Numerous:
-NSAID/ASA use
-ETOH & smoking
-Infection (Helicobacter pylori)
-Autoimmune (chronic)

Front 246

Gastritis
(Pathogenesis)

Back 246

-Mucosal damage
-Increased H+ secretion with back diffusion
-Decreased bicarb buffer
-Reduced blood flow
-Alteration to adherent mucus layer
-Direct epithelial damage

Front 247

Gastritis
(Morphologic findings)

Back 247

Gross --> Acute & Chronic: Variable
-Congestion, ulceration, atrophy

Micro:
Acute/active --> neutrophils in lamina propria & in epithelium
Chronic:
-Lympocytes & plasma cells in lamina propria & in epithelium
- +/- mucosal atrophy with intestinal metaplasia

Front 248

H. Pylori Chronic Gastritis

Back 248

Most common type of chronic gastritis in US (90% of patients with chronic gastritis have H. pylori present)

Major etiologic factor in peptic ulcers

Front 249

H. Pylori Chronic Gastritis
(Pathogenesis)

Back 249

Virulence factors:
-Motility (flagella)
-Urease (Releases ammonia - causes cell injury & buffers gastric acid)
-Protease (Degrades protective mucus barrier)
-Exotoxin (Damages epithelial cells)

Front 250

H. Pylori Chronic Gastritis
(Morphologic findings)

Back 250

Early - acute/active gastritis
-Neutrophils & microorganisms

Later - chronic
-Lymphocytes & microorganisms

H. pylori in mucus layer

Front 251

H. pylori Infection & Disease
(Diagram)

Back 251

Front 252

Laboratory Medicine

Back 252

-clinical pathology
-the area of pathology dedicated to the selection, provision an dinterpretation of diagnostic testing for patient care
-clinical chemistry, molecular diagnostics, microbiology, hematology, coagulation, transfusion medicine, cytogentics, hematopathology

Front 253

Use of Laboratory data

Back 253

-part of medical decision process
-ordered to screen for disease, answer a question, verify disease, determine prognosis, stage, monitor an intervention or treatment
-70% of all diagnosis are based upon a laboratory test result

Front 254

Screening

Back 254

-amino acids: newborns
-PSA: prostate Cancer
-cortisol: Cushings

Front 255

Diagnosis (confirmation)

Back 255

-glucose: diabetes
-blood/urine cultures: infections
-TSH: thyroid disease
-hemoglobing: anemia

Front 256

Disease severity/staging

Back 256

-PSA: prostate Cancer

Front 257

Monitor

Back 257

-prothrombin time: coagulation tx
-HbA1c: diabetic glycemic control

Front 258

Prognosis/risk stratification

Back 258

-microalbumin:diabetic nephropathy
-hsCRP: cardiac

Front 259

Define "normal" reference ranges

Back 259

-define the reference population
-without disease
-exclusion criteria: recent illness, drug use (OTC, prescription, abused), obesity, etc
-partioning criteria: gender, age, ethnicity, posture, fasting, time etc
-95-97% of reference pop

Front 260

"normal" variatioN"

Back 260

-ultradian (<1d)
-circadian (over 24hr)
-cicannual (over year)
-intra-individual variation (between days):
-<5%- electrolytes, creatinine, T4
-5-10%- alkaline phosphatase, cholesterol, glucose
->10%- cortisol, ACTH, creatinine kinase, TSH

Front 261

Cholesterol

Back 261

-I lowered my cholesterol by 9 points (200-191 mg/dL)
-4.5% analytical variability 9mg/dL
-6.5% biological variability
13 mg/dL (intra-individual)

Front 262

"unexpected results"

Back 262

pre-analytical:
-patient preparation
-specimen collection an dhandling
analytical variability
-impression, error
biological variability
-physiology and unexpected pathology
pharmacological effects/interactions

Front 263

Adrenal Excess

Back 263

glucocorticoids: cushings syndrome
mineralcorticoids: Conn's syndrome
Androgens: congenital adrenal hyperplasia

Front 264

Cushing's Syndrome

Back 264

Any cause of increased glucocorticoids (cortisol)
-cushing's disease: pituitary adenoma
-adrenal tumor
-ectopic ACTH

Front 265

clinical features of Cushing's

Back 265

-Cushinoid appearance: moon face, hirsutism, acne, plethora, truncal obesity, buffalo hump, edema, excessive bruising, thin skin w/ striae
-poor wound healing
-hyperglycemia
-osteoporosis
-muscle weakness, emotional instability, cardiac hypertrophy, hypertension, polyuria

Front 266

Remember: If your patient is on a corticosteroid

Back 266

-wounds heal poorly or slowly
-consult patients MD: may ned to increase dose, may need to delay procedures

Front 267

Thyroid

Back 267

-two connected lobes
-12-20g (size), soft, highly vascular
-synthesizes, stores and releases T4 and T3 in response to TSH
-regulate and maintain overall body metabolism
-promote growth and maturation
-fetal brain development
-organ specific actions: dec levels lead to mucoprotein deposition in skin, muscles and heart

Front 268

Regulation of thyroid hormone synthesis

Back 268

-hypothalamus: TRH
-pituitary: TSH (establishes set point)
-thyroid: T3 and T4
-periphery: 5'-deiodinase type I and type II (conversion of T4 to T3)
-free T4 (FT4) about .03% of total T4
-Free T3 (FT3) about .3% of total T3

Front 269

TSH

Back 269

-serum TSH levels reflect the integrative action of both T3 and T4 on pituitary
-change in free thyroid hormone causes a logarithmic change in TSH

Front 270

Assessment of thyroid status

Back 270

Purpose:
-screening: high risk groups
-all newborns, women >45 y, pregnancy, history, elderly
-ambulatory, "health"
-doesn't apply when testing during illness
-diagnosis
-monitoring
Key Tests
-TSH (reflex to free T4, add T3 or free T3)

Front 271

Diabetes in the US

Back 271

-21 million individuals are known to have diabetes
->1 million have Type 1 with 35-50,000 new cases/ year
->19 million have Type 2 with 6 million undiagnosed
-3-5% of all pregnancies have gestational diabetes
-42 million are thought to be "pre-diabetic" (have glucose intolerance)

Front 272

Type I diabetes

Back 272

-5-10% of cases
-not age specific (onset most often in childhood or adolescence)
-destruction of pancreatic beta cells
-autoimmune process
-causing severe insulin deficiency
-80-90% destruction before symptomatic
-requires physiologic replacement of insulin

Front 273

Clinical presentation Type I diabetes

Back 273

-abrupt onset of sumptoms
-polyuria, polydipsia, rapid weight loss, ketoacidosis common
-poor healing, nephropathy, neuropathies, retinopathies, hypo and hyperglycemic events

Front 274

Type 2 diabetes

Back 274

-90% of cases (30% undiagnosed)
-complications begin before diagnosis
-age, BMI, family hx, gestational diabetes, impaired glucose tolerance, phsical inactivity, race/ethnicity (all RISK factors)
-insulin resistance
-insulin secretory defect (may require insulin)
-normal or increased insulin
-poor healing, nephropathy, neuropathies, hyperglycemia

Front 275

Complications- Type I or Type 2

Back 275

-decreased resistance to infections
-xerostomia
-poor or delayed wound healing
-increased incidence of periodontal disease with periodontal abscesses
-before major procedures consult with patient's MD
-Type 1 patients may need increased insulin
-Type 2 patients may require insulin prior to treatment
-both may need antibiotic therapy
-during long procedures- may experience hypoglycemia
-may be useful to have patient monitor glucose

Front 276

Laboratory testing

Back 276

-glucose (plasma/serum)
-goal is to tighten glucose control but minimize hypoglycemic events
-self-monitoring blood glucose
-HbA1c: indicator of glucose control over last 8-12 weeks
-microalbumin: used to judge renal impairment, correlates with risk of retinopathy

Front 277

Parathyroid and PTH

Back 277

-parathyroids
-2-7mm, 50% fat
-chief cells synthesize, store, and secrete PTH
PTH:
-direct action on bone (osteoblasts, osteocytes, and indirectly on osteoclasts)
-direct action on kidney
-indirect action on intestine

-chief cells (small round cells with finely granular cytoplasm)

Front 278

Vitamin D

Back 278

-dietary sources (ergocalciferols)
-vitamin D2, fish liver oils, egg yolks, liver
-dermal (cholecalciferols) : 7-dehydrocholesterol ---> sunlight--> vitamin D3

Front 279

Vitamin D synthesis

Back 279

- (in liver) 24-hydroxylase---> 35 (OH) D: use for vitamin D status
- (in kidney) 1-hydroxylase ---> 1,25 (OH)2D: use for mineral disorders

Front 280

Osteoporosis

Back 280

Diagnosis:
-low bone density ,fracture, physical findings (dorsal kyposis)
Symptoms:
-none to few (back pain from fractures)
-increased caries, tooth loss

Front 281

Bisphosphonate

Back 281

-used to treat osteoporosis
-alendronate

Front 282

Abbreviations

Back 282

-CRH: corticotropin releasing hormone
-GnRH- gonadotropin releasing hormone
-GHRH- growth hormone releasing hormone
-PIF- prolactin inhibiting factor
-TRH- thyrotropin-releasing hormone
-GHIH- somatotropin (growth hormone) release inhibiting factor
-IGF-1- insulin-like growth factor
-HCG- human chorionic gonadotrophin
-BMI-body mass index
-DXA-dual energy x-ray absorptiometry

Front 283

Peptic Ulcer Disease
(Definition)

Back 283

Ulcer --> disruption of the mucosa that extends through the muscularis mucosa

Peptic ulcer --> distruption of the mucosa that extends through the muscularis mucosa in region of GI tract exposed to acid secretions (stomach & duodenum)

Front 284

Peptic Ulcer Disease
(Etiology)

Back 284

-Decreased mucosal defenses
-Increased mucosal damage

Front 285

Peptic Ulcer Disease
(Morphologic changes)

Back 285

Gross:
-Anterior wall first part of duodenum
-Lesser curvature of stomach
-Sharply punched-out mucosal defect

Micro --> 4 characteristic zones:
1. Fibrinopurulent exudate
2. Necrotic tissue
3. Granulation tissue
4. Fibrotic tissue

Front 286

Peptic Ulcer Disease
(Clinical findings)

Back 286

-Epigastric pain
-Iron deficiency anemia
-Hemorrhage
-Perforation

Front 287

Gastric Adenocarcinoma
(Etiology/Risk Factors)

Back 287

-Dietary (Benzopyrene & nitroamines --> smoked, fried, grilled foods)
-Low SES
-Helicobacter infection (antral/body tumors)
-Smoking
-Other --> atrophic gastritis, pernicious anemia, subtotal gastrectomy, gastric adenomatous polyps

Front 288

Gastric Adenocarcinoma
(Pathogenesis)

Back 288

Multiple genetic alterations:
-p53 mutations
-E-cadherin expression alterations
-TGFBRII
-BAX
-IGRFII

Front 289

Peptic Ulcer vs Adenocarcinoma

Back 289

Front 290

Gastric Adenocarcinoma
(Morphologic findings)

Back 290

2 Subtypes:
1. Intestinal --> infiltrating glands with mucin production
2. Diffuse --> infiltrating poorly differentiated single cells (signet ring cells)

Front 291

Gastric Adenocarcinoma Diffuse Type

Back 291

Signet ring cell pattern of adenocarcinoma with cells filled with mucin & vacuoles that push the nucleus to one side

Front 292

Celiac Disease
(Definition)

Back 292

Immune mediated disease characterized by:
-Malabsorption
-Small intestine mucosal flattening
-Symptomatic response to removal of gluten from diet [Gluten is a protein component (gliadin) found in wheat, oat, barley & rye]

Front 293

Celiac Disease
(Etiology & Pathogenesis)

Back 293

Etiology --> Gluten sensitivity with tissue damage

Pathogenesis:
-Enterocyte damage
-Failure of crypt zone cells to regenerate

Front 294

Celiac Disease
(Gross pathology & Microscopic findings)

Back 294

Gross pathology:
-Flat mucosa with loss of ridges & convolutions

Microscopic findings:
-Shortening in villous height
-Elongation of crypts
-Increased lymphoplasmacytic infiltrate in lamina propria
-Histologic changes are patchy (Biopsy of multiple sites increases likelihood of finding characteristic changes)

Front 295

Celiac Disease
(Mucosal Architecture Diagram)

Back 295

Front 296

Celiac Disease
(Surface Epithelium)

Back 296

Front 297

Celiac Disease
(Clinical Findings)

Back 297

-Usually presents in childhood
-Disease more severe in distal duodenum & upper jejunum (Decreases distally & may be minimal in distal ileum)
-Severity of malabsorption dependent on length of small bowel involvement & correlates with variability in clinical presentation

Front 298

Acute Appendicitis
(Definition & Pathogenesis)

Back 298

Definition --> Inflammatory disease of the wall of the appendix

Pathogenesis:
-Obstruction of the appendiceal orifice (fecalith, parasites)
-Distention of the lumen & bacterial invasion

Front 299

Crypt Architecture

Back 299

Front 300

Inflammatory Bowel Disease

Back 300

Idiopathic (etiology not understood)

Divided into 2 Types:
1. Crohn disease
2. Ulcerative colitis

Diagnosis requires:
-Chronicity
-Exclusion of other etiologies (particularly infectious)

Front 301

Head Trauma
(Summary)

Back 301

Head trauma may lead to wounds of the scalp, skull fractures, large intracranial hematomas, & focal or diffuse brain lesions. Focal brain lesions are contusions, which may be "coupe" or "contrecoup," and represent localized areas of hemorrhage within the cortex. Diffuse brain injury is caused by shearing of axons within the white matter, and while not visible grossly, is a major cause of severe & irreversible brain damage. The terms "contusion" and "concussion" are often confused, but should be sharply differentiated. Traumatically induced intracranial hematomas, whether intracerebral, subdural, or epidural, are classic mass lesions & can cause devastating effects because of brain shifts & herniations. Chronic subdural hematomas often occur without clear evidence of previous head trauma & should be distinguished from acute subdural hematomas, which are typically found in patients within hours after obvious head trauma.

Front 302

Cerebrovascular Disease
(Summary)

Back 302

Stroke = leading cause of morbidity & 3rd leading cause of mortality in US. A "stroke" may be due to an infarct in the brain, a hemorrhage within the brain, or a hemorrhage within the subarachnoid apce. Infarcts are usually due to atherosclerosis-associated intravascular thrombosis or embolism. Intracerebral hemorrhage is usually associated with hypertension or a bleeding diathesis. Rupture of a saccular aneurysm on 1 of the large arteries in the subarachnoid space at the base of the brain is the usual cause of a stroke due to a major subarachnoid hemorrhage. Both infarcts & hemorrhages lead to varying amounts of brain destruction & also act as mass lesions. The location & size of the lesion is important in determining the type & extent of the neurologic deficits precipitated by the infarct or hemorrhage.

Front 303

Brain Tumors
(Summary)

Back 303

Brain tumors may be primary or metastatic. Gliomas are the commonest type of primary brain tumor. Menfingiomas & either-nerve schwannomas are other common primary brain tumors. Because of their location & infiltrative nature, gliomas are often difficult ot surgically excise & become increasingly large mass lesions; they also destroy the brain tissue locally. Some primary brain tumors grow rapidly & are very lethal, despite aggressive therapy, whereas others are more slowly growing & have a relatively good prognosis if treated appropriately. Although primary brain tumors may be very malignant in the sense that they quickily lead to death, these tumors rarely metastasize. Histologic classification is very important in predicting growth rate, & thus prognosis, for primary brain tumors, most often arise from a lung or breast primary, destroy brain tissue locally, & are mass lesions.

Front 304

Demyelinating Diseases

Back 304

Demyelination = myelin is lost from the axon, but the axon remains intact (selective vulnerability). Characterized by the common histologic findings of loss of myelin & relative sparing of axons, & by a primary injury of the myelinating glial cell (oligodendrocyte-CNS, Schwann cell-PNS) or its myelin sheath. Several different pathogenetic mechanisms involved in this selective injury. Multiple sclerosis of the CNS & the Guillain-Barre syndrome (inflammatory demyelinating neuropathy) of the PNS are the classic immunologically mediated demyelinating diseases. The leukodystrophies are a group of demyelinating diseases: myelin loss is due to an inherited metabolic defect. The loss of the myelin sheath prevents the axon from effectively conducting nerve impulses, so that the axon loses its function. Fortunately, remyelination of axons by Schwann cells can occur in the PNS; these remyelinated fibers regain their ability to conduct impulses & permit return of function...There is no significant remyelination of axons in the CNS & no return of function.

Front 305

Neurodegenerative Diseases

Back 305

A group of disease in which the primary abnormality is a selective degeneration of certain populations of neurons. The clinical presentation of each disease is dictated by the which neuronal populations are involved. Thus, diseases characterized by degeneration of neurons of the cerebral cortex (i.e. Alzheimer's disease) are associated with dementia; diseases characterized by degeneration of the neurons of the basal ganglia are associated with movement disorders (i.e. Huntington's chorea); diseases characterized by degeneration of neurons of the substantia nigra (in brain stem) are associated with Parkinsonism (Parkinson's disease); & diseases characterized by degeneration of upper & lower motor neurons are associated with paralysis (e.g., amyotrophic lateral sclerosis). In some diseases, the neuronal degeneration is accompanied by characteristic histologic changes (e.g., neurofibrillary tangles, senile plaques, Lewy bodies). Most neurodegenerative diseases are sporadically; a few have Mendelian inheritance. The pathogenesis is not well known.

Front 306

Amyotrophic Lateral Sclerosis (ALS; motor neuron disease)

Back 306

-A neurodegenerative disease in which there is a preferential loss of the Upper & Lower Motor Neurons. Loss of upper motor neurons results in spastic paralysis, while loss of lower motor neurons results in flaccid paralysis & muscular atrophy
-Most cases are sporadic, but a small percentage of cases are familial. One mutated gene causing familial ALS encodes for superoxide dismutase (SOD1). The pathogenesis of the neuronal degeneration is unknown.
-Histopathologically, there is loss of large motor neurons (Betz cells in motor cortex, motor neurons in lower brain stem, & anterior horn cells in spinal cord). Degeneration of the corticospinal tracts of the spinal cord occurs as a consequence of the loss of upper motor neurons.

Front 307

Acute Appendicitis
(Morphologic Findings)

Back 307

Gross --> congestion with a fibrinopurulent exudate on the serosal surface

Micro --> Mucosal ulceration with neutrophils infiltrating the wall of the appendix

Front 308

Endocrinology Definition

Back 308

-study of the glands and the hormones they produce
-classically includes: pituitary, thyroid, parathyroid, adrenals, pancreatic islets, and gonads

Front 309

Hormones

Back 309

-term derived from Greek "to set in motion"
-growth,maintenance of homeostasis,reproduction
-some are synthesized as precursor polypeptides

Front 310

5 Classes of Hormones

Back 310

-amino acid derivatives: catecholamines, thyroid hormones (T3/T4)
-small neuropeptides: thyrotropin -releasing hormone, somatostatin
-large proteins: insulin, parathyroid hormone
-steroid hormones: cortisol, estrogen, testosterone
-Vitamin derivatives: vitamin A, Vitamin D

Front 311

Hormone and Protein Secretion

Back 311

-peptide hormones initially stored in secretory granules and released after stimulation by releasing factor or neural signal
-steroid hormones are secreted as they are synthesized

Front 312

Hormone and Protein Binding Proteins

Back 312

-Serum-binding proteins protect hormones from premature degradation
-restrict hormone access to some receptors and other sites
-only unbound (FREE) hormone can interact with receptors and elicit a biologic response

Front 313

Endocrinology Definition

Back 313

-study of the glands and the hormones they produce
-classically includes: pituitary, thyroid, parathyroid, adrenals, pancreatic islets, and gonads

Front 314

Hormones

Back 314

-term derived from Greek "to set in motion"
-growth,maintenance of homeostasis,reproduction
-some are synthesized as precursor polypeptides

Front 315

5 Classes of Hormones

Back 315

-amino acid derivatives: catecholamines, thyroid hormones (T3/T4)
-small neuropeptides: thyrotropin -releasing hormone, somatostatin
-large proteins: insulin, parathyroid hormone
-steroid hormones: cortisol, estrogen, testosterone
-Vitamin derivatives: vitamin A, Vitamin D

Front 316

Hormone and Protein Secretion

Back 316

-peptide hormones initially stored in secretory granules and released after stimulation by releasing factor or neural signal
-steroid hormones are secreted as they are synthesized

Front 317

Hormone and Protein Binding Proteins

Back 317

-Serum-binding proteins protect hormones from premature degradation
-restrict hormone access to some receptors and other sites
-only unbound (FREE) hormone can interact with receptors and elicit a biologic response

Front 318

Hormone Regulation

Back 318

-Feedback control: positive and negative
-negative feedback tends to dominate
-positive feedback is less understood
-other control factors: immune system, cytokines, & other local factors
-maintain constant levels of hormones within a narrow range

Front 319

Biologic Rhythms

Back 319

-Environmental adaptation
-seasonal changes
-light-dark & sleep-wake cycles
-meals
-menstrual cycles
-age
circadian/diurnal patters

Front 320

Pathologic Mechanisms of Endocrine Disorders

Back 320

-Hormone excess
-hormone deficiency
-Hormone Resistance (at or post receptor)

Front 321

Hormone Excess

Back 321

-neoplasms
-autoimmune
-Iatrogenic
-infectious/inflammatory
-mutations at key receptors

Front 322

Hormone Deficiency

Back 322

-autoimmune
-iatrogenic
-infectious/inflammatory
-nutritional/vitamin deficiency
-defect/mutations
-hemorrhage/infarction
-hormone resistance

Front 323

Approach to Endocrine Patient

Back 323

-symptoms reflect amount of available hormone
-hormone measurements in serum/plasma or urine (baseline samples collected under controlled conditions)
* Deficiency = stimulation study
*Excess=suppression study
-primary disease
-secondary disease

Front 324

Pituitary Gland

Back 324

-1cm in length; .5grams
-below hypothalamus in bony sella turcica
attached to hypothalamus by infundibulum
-anterior lobe is composed of cords of secretory cells in righ vascular stroma
-secretory cells named for staining properties: Acidophils (A) or Basophils (B) or named for secretory product

Front 325

Acidophils

Back 325

-somatotrophs (GH)
-Lactotrophs (prolactin)

Front 326

Basophils

Back 326

-Thyrotrophs (TSH)
-Corticotrophs (ACTH)
-Gonadotrophs (FSH & LH)

Front 327

Releasing and inhibiting Factors

Back 327

-CRF
-GnRH
-GHRH
-PIF
-TRH
-SRIF

Front 328

Tropic Hormones

Back 328

-ACTH
-LH
-FSH
-GH
-PRL
-TSH

Front 329

Secretory Hormones

Back 329

-cortisol
-testosterone
-estradiol
-IGF-1
-T4/T3

Front 330

Anterior Pituitary Insufficiency

Back 330

-may be acquired or developmental/genetic
-acquired is most common (tumors, inflammation, vascular damage)
-hormone loss can be selective, partial, or complete
-sequence of hormone los related to compression or destructive lesions: GH then LH, FSH then TSH finally ACTH
-initial symptoms due to insufficient levels of target hormones
-Adults-usually hypogonadism
-children-growth retardation

Front 331

Anterior Pituitary Excess

Back 331

-Primary disease
* pituitary adenomas, hyperplasia (prolactin secreting adenomas, GH or ACTH secreting tumors)
-Secondary disease (damage to hypothalamus or hypothalmic - pituitary tract, decreasing inhibiting factors

Front 332

Growth Hormone

Back 332

-Action: promotes growth of soft tissues, cartilage, and bone
-released in response to exercise,stress, hypoglycemia, and other hormones (testosterone, estrogen, thyroxine)
-pulsatile secretion (peak concentrations during sleep, p meals)
-random measurments not useful
-GH stimulates IGF synthesis
-Stimulation or suppression tests

Front 333

Growth Hormone and IGF-1

Back 333

-excess: acromegaly (adults) , giantism (children)
*increased GH: multiple samples/24h, increased IGF-1: better correlation to clinical severity
-Deficiency: decreased IGF-1 not specific, r/o nutrition, psychological, hepatic dysfunction, correlate with age, GH stimulation test

Front 334

Growth Hormone excess

Back 334

-pituitary adenoma (giantism in children and acromegaly in adults)
-Features become more pronounced with time (nose, jaw, tongue{marcoglossia}, soft tissues of hands and feet become enlarged, overgrowth of mandible leads to malocclusion, teeth may become separated, generalized apical root resorption)
-compression or destruction of normal pituitary tissue will lead to hypofunction of other systems (secondary hypothyroidism etc)
-fatigue, osteoarthritis, osteoporosis

Front 335

Adrenal Glands

Back 335

-pair ~4cm (each located at superior pole of kidney)
-cortex
-medulla

Front 336

Cortex of Adrenal Glands

Back 336

-hormones synthesized from cholesterol
-zona glomerulosa: mineralcorticoids (aldosterone: Na and K regulation_
-Zona fasciculata : Glucocorticoids (cortisol: protein, fat, carb metabolism, *responsive to ACTH)
-Zona reticularis: Androgens (testosterone, dehydroepiandrosterone, androsterdeione-sexual maturation, *responsive to ACTH)

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Adrenal Medulla

Back 337

-Hormones synthesized from tyrosine (Epi, NorEpi, Dopamine)

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Cortisol

Back 338

-regulated by ACTH and immune system
-~90% bound to cortisol-binding globulin (CBG) albumin and sex hormone binding globulin
-exhibits circadian rhythm or pattern (highest in AM and lowest in PM)

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Adrenal insufficiency

Back 339

-Primary-Addison's disease
-worldwide : infectious cause: TB, histoplasmosis, crytococcosis, CMV
-US: autoimmune adenalitis, watch for other autoimmune diseases
-gradual onset
-generally affects entire cortex leading to deficiency in all adrenal sterioids
-Secondary: decreased pituitary ACTH

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Addison's Disease

Back 340

-glucocorticoid deficiency (weakness, weight loss, fatigue, hypoglycemia, nausea)
-Mineralocorticoid deficiency (hyponatremia, hyperkalemia, dehydration)
-ACTH excess (hyperpigmentation of skin and mucus membranes{melanocyte stimulating hormone})

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Crohns Disease
(Gross Pathology)

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-Discontinuous involvement of GI (can affect stomach, small intestine and large intestine)
-Transmural inflammation leads to thickening of wall (creeping fat= mesenteric fat wraps around affected area
-fistulas
-mucosal ulceration and "cobblestone" appearance

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Crohns Disease
(Microscopic Pathology)

Back 342

-active inflammation (cryptitis = intraepithelial neutrophils; occasional crypt abscess=neutrophils in crypt lumens)
-features of chronicity (crypt branching/drop-out
-mucosal ulceration
-transmural lymphoid aggregates
-non-caseating granulomas

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Chrons Disease
(Local Complications)

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-small bowel obstruction (common) * due to stricture formation
-Iron deficiency (ulceration may cause occult hemorrhage, frank rectal bleeding can occur)
-perforation (in 2% of cases)
-fissuring and fistulation can lead to intra-abdominal abscess formation
-malabsorption (if extensive small bowel involvement, vitamin B12)

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Ulcerative Coliti
(Gross Pathology)

Back 344

-continuous involvement (distal rectum to variable length proximal)
-involves colon and rectum only
-inflammation limited to mucosa
-pseudopolyps

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Pseudopolyps

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-islands of intact, regenerative mucosa surrounded by adjacent ulcerated/inflamed mucosa

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Ulcerative Colitis
(Microscopic Pathology)

Back 346

- Active inflammation (cryptitis =intraepithelial neutrophils; crypt abscess=neutrophils in crypt lumens)
-features of chronicity (crypt branching/drop-out)
-mucosal ulceration

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IBD & Colon Cancer

Back 347

-both UC and CD are associated with an increased risk of developing colon cancer
-Risk may be the result of persistent inflammation and repair
-greater risk is associated with severe disease involving the entire colon for over 10 years and onset of disease in childhood

Front 348

Diverticular Disease

Back 348

-protrusions of the mucosa through the muscle wall
-common in western societies
-50% of ppl >60 yrs
-low bulk diet
-extremely uncommon in underdeveloped nations

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Diverticular Disease
(Gross & Microscopic findings)

Back 349

Gross:
-range in number (few to many)
-arranged in parallel rows (usually sigmoid colon)
-may contain impacted and calcified stool (fecalith)

Micro:
-flask-like outpouching of mucosa and submucosa through muscularis

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Diverticular disease: Complications

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-asymptomatic in 80% of afected individuals
-inflammation (diverticulitis) resulting in perforation and pericolonic abscess, hemorrhage- erosion into major blood vessels present in the connective

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Adenomatous Polyps

Back 351

-benign gland forming, epithelial neoplasms of colonic mucosa
-dysplasia: disturbance in growth and differentiation manifest as architectural and cytologic dysplasia
-dysplasia can cary in degree: mild moderate or severe
-adenomatious polyps are the precursor lesions of the vast majority of colorectal cancers
-though not every adenoma will give rise to colorectal cancer
-remain the same size for prolonged periods or even regress

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Adenomatous Polyp Growth Patterns

Back 352

-sessile
-pedunculated

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Adenomatous Colonic Epithelium

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-pleomorphic, hyperchromatic nuclei
-nuclear pseudostratification
-loss of cytoplasmic mucin

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Colorectal Cancers

Back 354

-most arise from pre-existing adenomas
-prevalenc of adenomas in pop. typically paralles the prevalenc of colorectal cancer
-when invasive carcinoma is found at an early stage, there are usually adenomatous areas surrounding it
-development of adenomas precedes that of colorectal cancer by 5-10 yrs
-the risk of cancer is directly related to the number of adenomatous polyps
-individuals with familial adenomatous polyposis syndrome are almost certain to develop colorectal cancer
-removing adenomas decreases incidence of subsequent carcinoma

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Colorectal carcinoma

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-annumally accounts for 150,000 new cases and 60,000 deaths in US
-Sporadic : 90 - 95% of cases
-familial adenomatous polyposis syndrome

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Familial Adenomatious Polyposis syndrome

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-1% of cases
-caused by mutations of adenomatous polposis coli (APC) gene on chromosome 5q21
-affected individuals develop 100s to 1000s of adenomatous polyps by late adolescence which will progeress to carcinoma if untreated (colectomy)
-30-40% of cases result from new germline mutation and thus do not have a family history to justify aggressive screening

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Colorectal Carcinoma : herditary nonpolyposis colorectal carcinoma syndrome

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-5-10% of colorectal carcinoma
-autosomal dominant familial syndrome
-colonic malignancies often multiple and not associated with adenomas
-associated with extraintestinal carcinoma, particularly the endometrium
-

Front 358

Colorectal Carcinoma
(Gross & Microscopic Findings)

Back 358

Gross:
-polpoid, ulcerating or infiltrative appearance
-infiltrative tumors often present with annular or "napkin ring" constrictions leading to bowel obstruction

Micro:
-well, moderately or poorly differentiated invasive glands (adenocarcinoma)
-prognosis related to degree of differentiation (grade), depth of invasion and nodal involvement (stage)

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Colorectal Carcinomas
(Clinical features)

Back 359

-occult GI bleeding with gradual development of anemia
-occasionally blood loss is sufficient to yield bright red blood in stool
-obstruction
-perforation

Front 360

Adenomatous transformation to Colorectal cancer

Back 360

-approximately 10 yrs
-broad window of opportunity for prevention of colorectal carcinoma by endoscopic removal of polyp