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Clinical Pathophysiology Review 3 8:30 AM, March 4, 2003

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Title: Clinical Pathophysiology Review 3 8:30 AM, March 4, 2003


1
Clinical PathophysiologyReview 3830 AM, March
4, 2003
  • Fred A. Zar, MD, FACP
  • Director, M2 Clinicopathophysiology Course
  • Professor of Clinical Medicine
  • University of Illinois at Chicago

2
Respiratory Pathophysiology
3
COPD Pathophysiology and Consequences
  • Airway inflammation
  • Increased mucus and protease activity
  • Cough and sputum
  • Increased Airway Resistance
  • Wheeze and rhonchi
  • Pursed lip breathing
  • Increased Work of Breathing
  • Decreased exercise yet increased metabolism
  • Breathing may require 2535 of energy (nml 35)
  • Weight loss
  • Hyperinflation
  • Inspiratory muscle dysfunction
  • Hoovers sign, increased AP diameter
  • Impaired Regional Ventilation
  • V/Q mismatch gt hypoxemia gt pulmonary HTN

4
Smoking and COPD
  • Smoking leads to activation of macrophages and
    neutrophils
  • Pulmonary inflammation
  • gt chronic bronchitis
  • Proteases released elastase, cathepsins,
    metalloproteinases
  • gt inhibited by antiproteases
  • alpha1 antitrypsin, elafin, secretory
    leukoprotease inhibitor
  • gt injury to extracellular matrix gt emphysema

5
Emphysema
  • Definition
  • Airspace enlargement distal to terminal
    bronchiole
  • Due to destruction of alveolar wall
  • Locations
  • Centrilobular
  • Panacinar

6
Chronic Bronchitis
  • Definition
  • Cough and sputum
  • Most days for 3 months
  • 2 consecutive yrs
  • Pathologic Correlate
  • Mucus gland hypertrophy
  • Goblet cell hyperplasia

7
COPD Therapy
  • Drug Mechanism Clinical Effect
  • ß2 agonists Smooth muscle relaxation Bronchodilat
    ion
  • Decreases mast cell degran
  • Anticholinergics Muscarinic antagonists Bronchodil
    ation
  • Corticosteroids Inhibit cytokine production Do
    not alter course
  • Decreases eosinophils Decreases reactivity
  • Increases ß responsiveness Decreases
    inflammation
  • Theophylline Phosphodiesterase
    inhib. Bronchodilation
  • Adenosine receptor inhib. Better resp. muscle
    function
  • Skeletal muscle contraction

8
Asthma
  • Chronic inflammatory disorder with reversible
    airways obstruction
  • Cell mediated
  • Mast cells, eosinophils, T lymphs, macros, PMNs,
    epithelial
  • Increased bronchial responsiveness to a variety
    of stimuli
  • Allergens, exercise, cold, pollution, infection,
    drugs, GERD
  • Symptoms and signs
  • Wheeze, SOB, coughing, chest tightness
  • Can be induced with histamine or methacholine
    challenge
  • Pulsus paridoxicus drop of SBP with inspiration
    of gt 10 mm Hg
  • Dual response
  • Early(5 min) due to mast cell release of
    histamine, LT, PG, PAF
  • Late (4 hr) due to eosinophil release of LT and
    cytokines

9
Asthma Classification
  • Class Symptoms Night Sx FEV1 Therapy
  • Mild Intermittent lt 2x/wk lt 2x/mo gt 80 PRN
    ß-agonist
  • Mild Persistent 36x/wk gt 2x/mo gt 80 Daily
    GC or LA
  • or MCD
  • PRN ß-agonist
  • Moderate Persistent Daily gt 1x/wk 6080 Above
    long
  • acting ßagonist
  • anticholinergic
  • theophylline
  • Severe Persistent Continuous Nightly lt
    60 Above high
  • dose inhaled GC

10
Asthma Blood Gases
  • Stage pO2 pCO2 pH
  • I Nml Nml Nml
  • II Nml Low High
  • III Low Low High
  • IV Low High Low

11
Asthma Therapy
  • Drug Mechanism Clinical Effect
  • ß2 agonists Smooth muscle relaxation Bronchodilat
    ion
  • Decreases mast cell degran
  • Anticholinergics Muscarinic antagonists Bronchodil
    ation
  • Corticosteroids Inhibit cytokine
    production Decreases inflammation
  • Decrease eosinophils Decreases reactivity
  • Increases ß responsiveness
  • Theophylline Phosphodiesterase
    inhib. Bronchodilation
  • Adenosine receptor inhib. Better resp. muscle
    function
  • Skeletal muscle contraction
  • Leukotreine inh Decrease leukotreine
    effect Antiinflammatory
  • Cromolyn/ Mast cell stabilization Antiinflammato
    ry
  • Nedocromil

12
Pulmonary Fibrosis
  • Pathogenesis
  • Initial insult gt immune response gt alveolitis
    gt WBC/macro cytokine releasegt injury to
    epithelial cells and alveolar basal lamina gt
    repair with fibrosis
  • Associated Diseases
  • Idiopathic (cryptogenic fibrosing alveolitis)
  • CTD RA, scleroderma, PMS
  • Sarcoidosis
  • Occupational lung disease silicosis, asbestosis
  • Hypersensitivity pneumonitis
  • Eosinophilic granuloma
  • Drugs

13
Pulmonary Fibrosis Manifestations
  • Dyspnea
  • Rapid shallow breathing
  • Inspiratory crackles (Velcro)
  • Digital clubbing
  • Later right heart failure

14
PressureVolume CurveObjectively assesses
elastic recoil
  • Parameters
  • Xaxis lung volume
  • Yaxis pleural (esophageal) pressure
  • Compliance slope (?Y/?X or ?P/?V)
  • Vmax maximum expiratory flow rate
  • Dependent on recoil and airway resistance
  • Alterations in disease states
  • Emphysema loss of elastic recoil
  • Increased slope, shift to left, higher volumes
  • Pulmonary fibrosis increased elastic recoil
  • Decreased slope, shift to right, lower volumes

15
PressureVolume CurvesObstructive vs.
Restrictive Disease
  • Obstructive Restrictive
  • Example Emphysema Pulmonary fibrosis
  • Elastic recoil Decreased Increased
  • Compliance Increased Decreased
  • PV slope Increased Decreased
  • Curve shift Left Right
  • Volumes Higher Lower

16
Pathophysiologic Consequences(Emphysema,
Decreased Elastic Recoil)
  • Increased lung compliance
  • Increased lung distension
  • Increased airway collapse
  • Decreased Vmax
  • Increased work of breathing
  • Increased ventilatory drive
  • Increased FRC and RV
  • V/Q mismatch
  • Decreased diffusion capacity

17
Pathophysiologic Consequences(Pulmonary
Fibrosis, Increased Elastic Recoil)
  • Decreased lung compliance
  • Decreased lung distension
  • Increased Vmax
  • Increased work of breathing
  • Increased ventilatory drive
  • Decreased TLC, FRC, RV
  • V/Q mismatch
  • Decreased diffusion capacity

18
Respiratory Muscles
  • Inspiratory
  • Diaphragm
  • Contractsgt increased intraabd pressure gt
    pushes abd out gt pushes lower rib cage
    and chest wall out
  • Contractility best with low lung volumes
  • Accessory muscles (SCM)
  • Recruited during increased ventilatory demands
  • Elevate rib cage
  • Expiratory
  • Abdominal muscles
  • Increase abd pressure, displace diaphragm upward

19
Pulmonary Function Testing
  • Dynamic Lung Function
  • Spirometry
  • Flow loops
  • Maximum voluntary ventilation
  • Static Lung Function
  • Lung volumes
  • Lung capacities
  • Gas exchange
  • Diffusion capacity (CO)
  • Arterial blood gases

20
Indications For Pulmonary Function Testing
  • Assess SOB
  • Determine presence/degree of pulmonary disease
  • Determine pathophysiology of pulmonary disease
  • Assess course, prognosis and response to therapy
  • Assess disability

21
Dynamic Lung Function Abnormalities
  • Obstructive Lung Diseases
  • Decreased FEV1/FVC
  • Decreased Vmax (FEF2575,FEF50)
  • Inwardbowed decrease slope of exp flowvolume
    loop
  • Restrictive Lung Disease
  • Decreased FVC and FEV1
  • Normal to high FEV1/FVC
  • Preserved Vmax (FEF2575,FEF50)
  • Outwardbowed increase slope of exp flowvolume
    loop

22
PFT Classification of Pulmonary Diseases
  • Obstructive Lung Disease
  • Chronic Bronchitis
  • Emphysema
  • Asthma
  • Acute Bronchitis
  • Bronchiectasis
  • Bronchiolitis Obliterans
  • Restrictive Lung Disease
  • Pulmonary
  • Pulmonary Fibrosis
  • Pulmonary Edema
  • Focal Lung Disease
  • Tumor
  • Pneumonia
  • Atelectasis
  • Lung Resection
  • ExtraPulmonary
  • Obesity
  • Kyphoscoliosis
  • Neuromuscular Disease
  • Pleural Effusion

23
Spirometry in Pulmonary Diseases
  • Obstructive Restrictive
  • FVC
  • FEV1
  • FEV1/FVC
  • FEF50
  • MVV

24
Lung Volumes in Pulmonary Diseases
  • Obstructive Restrictive
  • TLC
  • VC
  • FRC
  • RV
  • DLCO

25
Respiratory Failure
  • Definitions
  • Hypoxemic respiratory failure PaO2 lt 50 mmHg
  • Hypercapnic respiratory failure PaCO2 gt 50 mmHg
  • Mechanisms of Hypoxemia
  • Hypoventilation
  • V/Q Mismatch
  • Pulmonary Shunts

26
Hypoventilatory Respiratory Failure
  • Due to inappropriate volume and/or frequency of
    respirations
  • Increased PaCO2 with concomitant decrease PaO2
  • Acutely causes acidosis, pulmonary hypertension
  • Causes
  • CNS disease any destructive process
  • Endocrine/metabolic hypothyroidism, metabolic
    alkalosis
  • Neuromuscular lesions of anterior horn cells,
    peripheral nerves, motor end plate, muscle itself
  • Structural COPD, kyphoscoliosis, obesity

27
V/Q Mismatch Respiratory Failure
  • The most common respiratory failure
  • Usually with some hypoventilation
  • Ideal gas exchange occurs with a V/Q ratio of 0.8
  • 4L/min alveolar ventilation and 5l/min cardiac
    output
  • If V/Q decreases
  • Less air reaches alveoli per given amount of
    perfusion
  • Less exchange of O2 and CO2
  • Alveolar endcapillary PO2 drops and PCO2
    increases
  • Healthier alveoli can compensate for CO2 but
    not O2
  • ABG shows low PaO2 and low PaCO2
  • If V/Q increases
  • More air reaches alveoli per given amount of
    perfusion
  • More exchange of O2 and CO2
  • Alveolar endcapillary PO2 increases and PCO2
    drops
  • O2 dissociation curve flat at high levels, cant
    compensate

28
Pulmonary Shunt Respiratory Failure
  • Completely unventilated alveoli (extreme V/Q
    mismatch)
  • Causes
  • Atelectasis, edema, consolidation, ARDS
  • Venous blood is shunted from pulmonary into
    systemic arterial system without getting
    oxygenated
  • V/Q 0 (no ventilation to a perfused alveolus)
  • Results in hypoxemia and hypocapnia like V/Q
    mismatch

29
Clinical Approach to Respiratory Failure
  • Whats the PaCO2?
  • If normal or low gt excludes hypoventilation
  • If high, compute alveolararterial O2 gradient
  • Calculating the Aa gradient
  • PaO2 is measured via an arterial blood gas
  • PAO2 is calculated
  • (Pb PH2O)FIO2 PACO2/r
  • (747 47)0.21 PaCO2 x 1.2
  • 147 (PaCO2 x 1.2)
  • Normal gradient is 1015 mmHg
  • If increased poor gas exchange V/Q mismatch
    or shunt

30
Treatment of Respiratory Failure By Type
  • Type Treatment
  • Hypoventilation Mechanical ventilation
  • V/Q mismatch Controlled increased FIO2
  • Target PAO2 5060 mmHg
  • Bronchodilators, antibiotics, Rx CHF
  • Shunting Mechanical ventilation
  • Positive EndExpiratory Pressure (PEEP)
  • Target PAO2 5060 mmHg
  • Target FIO2 lt 60

31
Respiratory Acidosis and Alkalosis
  • Acute Respiratory Acidosis
  • pH decreases 0.08 pH units / 10 mmHg PCO2
    increase
  • HCO3 increases 1 meq/L / 10 mmHg PCO2 increase
  • Compensated (Chronic) Respiratory Acidosis
  • pH decreases 0.03 pH units / 10 mmHg PCO2
    increase
  • HCO3 increases 3.5 meq/L / 10 mmHg PCO2 increase
  • Acute Respiratory Alkalosis
  • pH increases 0.08 pH units / 10 mmHg PCO2
    decrease
  • HCO3 decreases 2 meq/L / 10 mmHg PCO2 decrease
  • Compensated (Chronic) Respiratory Alkalosis
  • pH usually normal
  • HCO3 decreases 5.0 meq/L / 10 mmHg PCO2 decrease

32
Consequences of Acute CO2 Retention
  • Acidosis
  • Impaired tissue metabolism
  • Cerebral Vasodilation
  • Cerebral edema
  • Pulmonary Vasoconstriction
  • Pulmonary hypertension
  • CO2 Narcosis
  • Lethargy gt coma
  • Hypoxemia
  • Organ dysfunction

33
Dyspnea
  • Definition
  • Synonyms Breathlessness, shortness of breath
    (SOB), difficulty in breathing (DIB)
  • Uncomfortable awareness of breathing difficulty
  • Pathophysiologic Cause
  • Discrepancy between the drive to breath and the
    level of ventilation achieved.

34
Acute And Chronic Dyspnea
  • Acute Dyspnea
  • Pulmonary edema
  • Asthma
  • Chest wall injury
  • Pneumothorax
  • Pulmonary embolism
  • Pneumonia
  • ARDS
  • Pleural effusion
  • Pulmonary hemorrhage
  • Chronic, Progressive Dyspnea
  • COPD
  • CHF
  • Interstitial Fibrosis
  • Asthma
  • Effusions
  • Thromboembolic disease
  • Pulmonary vascular disease
  • Psychogenic dyspnea
  • Anemia (Hb lt 7.0)
  • Tracheal stenosis
  • Hypersensitivity disorders

35
Systemic vs. Pulmonary Circulation
  • Systemic Circulation
  • Normal pressures 120/80
  • SVR 19.6 torr/L/min
  • Pulmonary Circulation
  • Normal pressures 25/15
  • SVR 2.6 torr/L/min

36
Pulmonary Vascular Resistance
  • Normal parameters
  • Pressures 25/15
  • Vascular resistance 2.6 torr/L/min
  • Decreased vascular resistance
  • Parasympathetic tone
  • Acetylcholine
  • Beta2 agonists
  • Bradykinin
  • Prostaglandins PGE1, PGI2
  • Nitric oxide
  • Increased vascular resistance
  • Sympathetic tone
  • Prostaglandins PGF2a, PGF2
  • Thromboxane
  • Angiotensin
  • Histamine
  • Serotonin
  • Alveolar hypoxia or hypercapnia
  • Acidosis

37
Pulmonary Hypertension Etiologies
  • Increased Left Atrial Pressure
  • Congestive heart failure
  • Mitral stenosis
  • Increased Pulmonary Flow
  • Left to right shunt
  • Increased Pulmonary Vascular Resistance
  • Vasoconstriction
  • Hypoxia
  • Obstructive
  • Primary pulmonary hypertension
  • Pulmonary embolism (clot, tumor, fat, parasite)
  • Obliterative
  • Emphysema
  • Pulmonary fibrosis

38
Pulmonary Hypertension Signs
  • Heart Exam
  • Increased P2
  • Wide split of S2
  • R ventricular heave
  • S4
  • Pressures
  • Increased R ventricular enddiastolic pressure
  • Increased RA pressure
  • Increased CVP

39
Risk Factors for DVT/Pulmonary Embolism
  • Venous Stasis
  • Immobility age, obesity, bed rest, trauma,
    surgery, neuro Dx
  • Heart disease CHF, atrial arrhythmia, myocardial
    infarction
  • Pregnancy
  • Vein Wall Injury
  • Prior DVT
  • Pelvic, hip, leg fracture or surgery
  • Hypercoagulable States
  • Malignancies
  • Estrogen pregnancy, exogenous
  • Nephrotic syndrome
  • Hereditary Ptn C and S deficiencies, factor V
    Leiden, homocystinemia, prothrombin gene
    mutations, high factor levels, antiphospholipid Ab

40
Pulmonary Embolism Pathophysiology
  • Release of Platelet Factors
  • Serotonin and thromboxane A2
  • Vasoconstriction gt pulmonary HTN, RV
    dysfunction, chest pain, low BP, hypoxemia
  • Decreased alveolar perfusion
  • Increased dead space (increased V/Q) gt hypoxemia
    and hypocapnia
  • Reflex bronchoconstriction gt wheezing
  • Loss of surfactant
  • Atelectasis, alveolar edema and bleed gt SOB,
    crackles, chest pain
  • Decreased V/Q gt hypoxemia
  • Irritant and J receptor stimulation gt
    hyperventilation and SOB

41
Pulmonary Embolism Symptoms
  • Dyspnea
  • Pleuritic chest pain
  • Cough
  • Hemoptysis
  • Syncope

42
Pathophysiology of Chronic Pulmonary HTN
  • Phenomenon Physical Exam (Sx)
  • Increased pulmonary artery pressure gt Increased
    P2
  • Right ventricular hypertrophy gt RV S4
  • Right heart failure gt RV S3
    Increased JVP, edema Hepatomegaly
    (Fatigue and dyspnea)

43
Sleep Medicine
44
Sleep Architecture(Cycles every 90120 minutes)
  • NonRapid Eye Movement (NREM) Sleep
  • Stage 1 Transition from wakefulness
  • EEG fast theta (47 Hz) easily aroused and deny
    being asleep
  • Stage 2 Intermediate sleep, 4050 of total
    sleep time
  • EEG slower and higher amplitude, sleep spindles
    1214 Hz bursts, kcomplexes double negative
    wave
  • Stage 3 and 4 Deep sleep, 20 of sleep
  • EEG High amplitude, slow (13 Hz)
  • Rapid Eye Movement (REM) Sleep
  • EEG Low voltage, high frequency wakefulness
  • EMG atonic
  • EYE rapid eye movements

45
Determinants of Sleep
  • Homeostasis
  • Enough sleep amount that allows alertness for
    the day
  • 8 hours, yet highly variable
  • Circadian Rhythms
  • Suprachiasmatic nucleus near hypothalamus
  • Receives input via the retinohypothalamic tract
  • Changes With Age
  • Arousals increase, deep sleep decreases, latency
    increases

46
Obstructive Sleep Apnea
  • Definition
  • Repetitive episodes of upper airway obstruction
  • Frequent apnea and hypoxemia
  • Symptoms
  • Nighttime symptoms
  • Snoring, apnea/gasping, flailing of limbs,
    frequent awakenings, GE reflux urination
  • Daytime symptoms
  • Tiredness upon awakening, morning HA, excessive
    sleepiness, loss of libido/impotence
  • MVA, work accidents, school/work problems, social
    embarrassment, marital problems,
    memory/concentration trouble, depression

47
OSA Predisposing Factors
  • Age
  • Obesity
  • MgtF 21
  • Upper airway obstruction
  • Craniofacial anomalies
  • Medications
  • Alcohol
  • Smoking
  • Genetics

48
OSA Physical Exam
  • Short fat neck
  • Obesity
  • Upper airway narrowing
  • Large tonsils
  • Enlarged uvula
  • Long soft palate
  • Micrognathia/retrognathia

49
Sleep Apnea Clinicopathologic Effects
  • Acute
  • Brady/tachyarrhythmias
  • Chronic
  • Systemic HTN
  • Pulmonary HTN
  • CHF
  • Myocardial infarction
  • Stroke
  • Hypercapneic respiratory failure

50
OSA Polysomnographic Findings
  • Apneas
  • gt 30 per hour
  • Terminated by arousal
  • Often occur over 50 of sleep time
  • Architecture
  • Destroyed
  • Decreased Stage 3 and 4
  • Decreased REM

51
OSA Therapy
  • Discontinue medications and alcohol
  • Weight loss
  • Tennis ball on back
  • Nasal CPAP
  • Surgical correction
  • Uvulopharyngoplatoplasty
  • Tracheotomy

52
Narcolepsy Manifestations(Due to sudden onset of
REM sleep)
  • Cataplexy
  • Bilateral loss of muscle tone after strong
    emotion
  • Laughter, anger, amusement, exertion
  • Last seconds to minutes
  • Hypnagogic hallucinations
  • Vivid nightmares at sleep onset
  • Sleep Paralysis
  • Unable to move at sleep onset (hypnagogic) or
    offset (hypnapompic)
  • Sleep Attacks
  • Episodic overwhelming sleepiness during the day

53
Multiple Sleep Latency Criteria for Narcolepsy
  • Mean sleep latency of lt 8 minutes
  • gt 2 sleep onset REM periods during naps
  • No other apparent cause (i.e. sleep deprivation)

54
Narcolepsy Treatment
  • Behavioral
  • Structured sleep schedule with naps
  • Diet avoid heavy meals
  • Physical activity during the day
  • Pharmacological
  • Sleep attacks pemoline, methylphenidate,
    dexamphetamine, metamphetamine, modafinil
  • Cataplexy TCAs, fluoxetine, GHB
  • Psychosocial

55
Sports Medicine
56
Sports Medicine Ligament Sprains
  • Definition of a ligament
  • Dense fibrous collagen, connects bone to bone
  • Grading of sprain injuries
  • Grade 1 partial tear, no functional
    laxity heals in 24 weeks
  • Grade 2 partial tear, some laxity, intact
    endpoint heals in 46 weeks
  • Grade 3 complete ligament injury heals in 23
    months
  • Evaluation
  • History of injury
  • Exam for site of pain and laxity
  • Image

57
The Ligament Healing Process
  • Hemorrhagic Phase
  • Immediate
  • Clot forms in injured area
  • Inflammatory Phase
  • 12 weeks
  • WBCs enter and phagocytize debris
  • Clot converted to granulation tissue
  • Reparative Phase
  • 18 weeks
  • Fibroblasts lay down extracellular matrix and
    immature collagen fibers
  • Remodeling Phase
  • 4 weeks to 1 year
  • Maturation to mature collagen

58
Treatment of Ligament Sprains
  • RICE
  • Rest, Ice, Compression, Elevation
  • Immobilization
  • Some initially yet not too long (prevents full
    healing)
  • Antiinflammatories
  • OK, but need to allow some inflammation
  • Prolotherapy
  • Injections of sugar/salt solutions to increase
    inflammation

59
Sports Medicine Tendon Strains
  • Definition of a tendon
  • Dense fibrous collagen, connects muscle to bone
  • Grading of strain injuries
  • Grade 1 partial tear, no weakness
  • Grade 2 partial tear, some weakness
  • Grade 3 complete tear, loss of motor function,
    palpable defect
  • Evaluation and diagnosis
  • History of injury
  • Exam for function
  • Image usually not necessary
  • Repair mechanism
  • Same as for sprains
  • Muscles will atrophy from disuse
  • Treatment
  • RICE, ? NSAIDs, steroid injections vs.
    prolotherapy
  • Surgical repair

60
Tendinosis
  • Tendon degeneration from tendon overuse
  • Minimal inflammatory cells
  • Normal repair does not occur

61
Dislocation
  • Background
  • Usually due to major trauma
  • Named by distal bone over proximal bone
  • Common injury to multiple ligaments
  • Examination
  • Gross joint deformity
  • Check neurovascular integrity
  • Treatment
  • Emergent joint reduction

62
Bone Fractures Descriptions
  • Bone name
  • Comminution
  • Number of pieces
  • Angulation
  • Which way is it pointing
  • Translation
  • Bones separated and not overlapping
  • Shortening
  • Other Descriptors
  • Segmental (a series of Fx)
  • Impaction
  • Avulsion (bone pulled off)
  • Pattern
  • spiral/oblique/transverse

63
Fracture Healing and Treatment
  • Day 1 3
  • Bleeding and clot formation
  • Week 1
  • Macrophage migration
  • Weeks 1 6
  • Clot reorganizes into callous
  • Months 2 12
  • Remodeling to mature bone
  • Treatment
  • RICE
  • Immobilize
  • NSAIDs
  • Bone stimulation

64
Developmental Bone Disease
65
Achondroplasia
  • Genetics
  • Autosomal dominant
  • Mutation on chromosome 4 of fibroblast growth
    factor receptor 3 (FGFR3) (Arg gt gly)
  • Pathophysiology
  • Failure of enchondrial bone ossification (long
    bones)
  • Intramembranous ossification (skull/spine) normal
  • Thus, normal head and trunk size, small arms and
    legs

66
Spina Bifida
  • Pathophysiology
  • Failure of posterior neural tube closure (weeks 3
    6)
  • 1 1,000 births
  • Decreased by prenatal AFP screening and folate
    administration
  • Clinical manifestations
  • Occulta occult failure of arches to fuse, no Sx,
    hair tuft
  • Meningocele Meninges herniate through defect, no
    neurologic defect
  • Meningomyelocele Meninges and cord herniate, leg
    paralysis and hydrocephalus

67
Other Congenital Bone/Joint Diseases
  • Downs Syndrome
  • Weak C1C2 ligaments gt subluxation
  • Osteogenesis imperfecta
  • Defective type I collagen
  • Brittle bones, osteoporosis, transparent sclera
  • Congenital clubfoot
  • 1800 births
  • Adducted, inverted forefoot
  • No motor or nerve deficit
  • Developmental Dysplasia of the Hip
  • Due to external or inherited forces
  • Legg Calve Perthes Disease
  • Avascular necrosis of femoral head
  • Slipped Capital Femoral Epiphysis

68
Scoliosis
  • Lateral curvature of spine
  • Measured by Cobbs angle gt
  • Treatment
  • Immature spine
  • Brace if gt 25o
  • Mature spine
  • Fusion if gt 40o

Scoliosis
Kyphosis
69
Breast Disease
70
Nipple Discharge
  • Normal
  • Physiologic, pregnancy
  • Spontaneous
  • Papilloma 70
  • Ductal ectasia fibrocystic disease (20)
  • Cancer 10
  • Workup
  • Exam
  • Mammogram

71
Breast Cancer Epidemiology
  • The most common female nonskin cancer
  • The second most common cancer death (lung)
  • The most common cause of death in women 4555
  • Known Risk Factors
  • Sex, age, genetics
  • Proliferative breast diseases with or without
    atypia
  • Lobular carcinoma in situ
  • Prolonged estrogen
  • menarche, menopause, parity, exogenous

72
The National Surgical Adjuvant Breast Project
Antiestrogens and breast cancer
  • The Study
  • 13,388 woman at risk for breast CA
  • Over 60 or 3559 with 5year risk gt 1.66,
    lobular CA in situ
  • Randomized to tamoxifen vs. placebo x 5 years
  • The results
  • Less breast CA by 50, bone Fx
  • More Endometrial CA x 2.5, DVT/PE

73
Prognostic Factors for Breast CA
  • Number of axillary lymph nodes
  • Tumor size
  • TNM stage
  • Histologic grade
  • Nuclear grade
  • Absence of estrogen and/or progestin receptors
  • HER2 positivity (coded for by c-erbB-2 oncogene)

74
Treatment of Invasive Breast CA
  • Breast Conserving Therapy (BCT)
  • Excision with clean margins and XRT
  • BCT vs. mastectomy
  • diseasefree survival
  • overall survival
  • Contraindications for lumpectomy
  • Locally far advanced CA by exam or mammogram
  • Multicentric carcinoma
  • Persistent () margins during surgery
  • Pregnancy (1st and 2nd trimester)
  • CTD (esp. scleroderma)
  • Large tumorbreast ratio

75
Adjuvant Systemic Therapy for Breast Cancer
  • Indications for Chemotherapy
  • Tumor gt 2 cm or positive lymph nodes
  • Indications for Hormone Therapy
  • Receptor positivity

76
Family Hx Reasons to screen for BRCA1/2
  • BRCA 1 or BRCA 2 mutation
  • Breast AND ovarian cancer
  • Male breast cancer
  • gt 2 members lt 50 with breast cancer
  • Ashkenazi and gt 1 members lt 50 with breast cancer
  • Ashkenazi and ovarian cancer

77
Other Female Malignancies
78
Ovarian Cancer Risk Factors(The most common
fatal genital cancer)
  • Age
  • Peaks at 56, declines after 80
  • Incessant Ovulation
  • Early menarche, late menopause, nulliparous
  • Fertility drugs
  • Risk declines with OCPs
  • Genetic
  • Family history, BRCA 1 and BRCA 2
  • Caucasian

79
Ovarian Neoplasms
  • Epithelial (85)
  • 4555 malignant (M) vs. benign (B)
  • Serous (MB) gt mucinous (B)gt endometrioid (M),
    Brenner (B), Clear cell (M), Undifferentiated (M)
  • Germ Cell
  • Teratoma (dermoid) (B) all others (M)
    teratocarcinoma, dysgerminoma, endodermal sinus
    tumor, choriocarcinoma, embryonal cell CA,
    gonadoblastoma
  • Stromal
  • Granulosa cell (makes Est), SertoliLeydig Cell
    (makes Tt), ovarian fibroma, ovarian sarcoma

80
Ovarian Cancer Management
  • Surgery
  • Debulking as much as possible
  • Adjuvant chemotherapy
  • If metastatic or highrisk
  • Radiation Therapy
  • Dysgerminomas

81
Endometrial Carcinoma(The most common
gynecologic CA in USA)
  • Risk Factors
  • Unopposed estrogen
  • Anovulatory cycles, nulliparous, tamoxifen,
    obesity
  • Familial
  • e.g. Lynch syndrome
  • OCPs are protective
  • Clinical Presentation
  • Abnormal uterine bleeding
  • Postmenopausal or heavy premenopausal
  • Prognosis (5year survivals)
  • Stage 1 95, Stage IIIIV 26)

82
Squamous Intraepithelial Neoplasia (SIN) and
Cervical CA
  • SIN Definition
  • Dysplasia confined to the epithelium of GI/CU
    tract
  • Gynecologic foci cervix, endometrium, vaginal
  • Risks
  • HPV, immunosuppression
  • Early sex, multiple partners, high risk partners,
    prior STDs, high parity
  • Smoking, low SE status
  • Other gynecologic malignancies
  • Clinical Manifestations
  • Usually asymptomatic
  • Vaginal bleed, postcoital bleed, vaginal DC

83
Papanicolaou Smear Indications
  • Beginning
  • Age 18 or sexual activity, whichever is first
  • Frequency
  • Every year until 3 negative and not high risk
  • Cessation
  • Age 60 75
  • ? Total hysterectomy

84
Reproductive Endocrinologyand Gynecology
85
Gonadotropin Physiology
  • Hypothalamus
  • Pulsatile release of GnRH
  • Stimulates pit FSH and LH
  • Inhibited by Est and Prog
  • Anterior Pituitary
  • Releases FSH and LH
  • Stimulates ovarian Est and Prog
  • Inhibited by Est and Prog
  • Ovaries
  • Release Est and Prog
  • Release androgens

86
Menstrual Phases
  • Follicular Phase Luteal Phase
  • Pituitary FSH gt LH secretion LH surge (also FSH)
  • Ovary Estradiol secretion Prog gt Est secretion
  • Follicular maturation Ovulationgtcorpus luteum
  • Uterus Proliferative Secretory

87
Ovarian Hormone Synthesis
  • Theca Cells
  • Respond to LH
  • Produce androgens from cholesterol
  • Androstenedione, testosterone
  • Granulosa Cells
  • Respond to FSH
  • Produce estrogen from androgens
  • Requires aromatase enzyme

88
Abnormal Uterine Bleeding
  • Dysfunctional Uterine Bleeding
  • Vaginal bleeding not associated with an
    anatomical source or a systemic disease. Usually
    anovulatory. Dx of exclusion.
  • Menorrhagia/Hypermenorrhea
  • Heavy cyclic bleeding (gt 80 ml)
  • Metrorrhagia
  • Bleeding that is prolonged menstrual or
    intramenstrual
  • Menometrorrhagia
  • Combination of the above
  • Oligomenorrhea
  • Cycles gt 35d, often unpredictable
  • Polymenorrhea
  • Cycles lt 21d 24d

89
Uterine Leiomyomatas (Myomas, Fibroids)
  • Epidemiology
  • 20 over 30, gt40 over 40
  • African American 36 fold higher
  • Anatomy
  • Submucosal, intramural, subserosal, pedunculated,
    parasitic
  • Pathogenesis
  • Estrogen dependent
  • Symptoms
  • Abnormal uterine bleeding
  • Pelvic pain, urinary frequency, rectal discomfort
  • Diagnosis
  • PE, US, hysterosalpingogram, hysteroscopy, MRI
  • Therapy
  • Hormones, minimally invasive surgery, myomectomy,
    hysterectomy

90
Endometriosis Clinical
  • Definition
  • Presence of ectopic uterine mucosal tissue
  • Locations
  • Ovarian gt uterine gt ureterosacral ligaments,
    peritoneum, retroperitoneum, bowel, pleura
  • Pathogenesis
  • Retrograde menstruation
  • Vascular or lymphatic dissemination
  • Coelemic metaplasia
  • Symptoms
  • Pain, dysmenorrhea, dyspareunia, abnormal uterine
    bleeding, infertility

91
Endometriosis Treatment
  • Observation
  • Hormonal
  • OCPs, depoprovera, danazol, GNRH agonist,
    pregnancy
  • Surgical
  • Excision, fulguration, TAHBSO

92
Puberty
  • Definitions and sequence
  • Thelarche breast development, mean age 10
  • Adrenarche Body hair development, mean age 10
  • Menarche Menses onset, mean age 13
  • Age of onset one year earlier in African
    Americans
  • Precocious puberty
  • 2.5 SD below mean age
  • Delayed puberty
  • No changes at 14
  • No thelarche age 15
  • No menses within 2 years of thelarche and
    adrenarche or by age 16

93
Menopause
  • Definitions
  • Menopause cessation of menstrual cycles for one
    year
  • Perimenopause Menstrual irregularities, Sx of
    Est loss
  • Mean age 51 52
  • Related ovarian follicular physiology
  • Fetus has 7,000,000 follicles
  • At menarche 400,000 follicles
  • At menopause 10,000 follicles (nonfunctional)

94
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95
Primary Amenorrhea(No menarche by age 16,
usually genetic or anatomic)
  • Chromosomal abnormalities (45)
  • Androgen insensitivity syndrome 46 XY, defective
    Tt receptor, testes make MIF
  • Vanishing testes syndrome 46 XY, failure of full
    testicular development
  • Absent testes determining factor 46 XY, no
    testes so no Tt or MIF
  • 5alpha reductase deficiency 46 XY, female
    phenotype yet virilization after puberty with
    deep voice, baldness, increase muscle mass
  • 17OHase deficiency 46 XX or XY, cannot make
    gonadotropins, female with HTN
  • Turners 45 XO, streak ovary
  • Physiologic delay in pregnancy (20)
  • Müellarian agenesis (15)
  • Absence of fallopian tubes, uterus, upper 1/3
    vagina
  • Transverse vaginal septum/imperforate hymen (5)
  • Hypothalamic GnRH deficiency (5)
  • 1o congenital (with anosmia Kallmans)
  • 2o Anorexia nervosa, exercise, wt loss, stress,
    invasion
  • Hypopituitarism (2)

96
Approach to Primary Amenorrhea
  • Puberty present (eugonadal, makes Est)
  • Check uterine/vaginal anatomy
  • Check karyotype, testosterone level
  • Pregnancy test
  • Puberty absent (hypogonadal, no Est)
  • Check LH and FSH (cant measure GnRH)
  • Low stress?, low BW?, pit failure?
  • High Gonadal failure
  • Check karyotype (XO or XY)
  • Check prolactin and TSH

97
Secondary Amenorrhea(No menses x 6 months or 3
cycles)
  • Pregnancy most common
  • Ovarian (40)
  • Polycystic ovary syndrome (40)
  • High testosterone gt anovulation, endometrial
    atrophy
  • Ovarian failure (if lt 40 yo primary)
  • Autoimmune oophoritis
  • Hypothalamic (35)
  • Functional GnRH deficiency (same reasons as under
    1o amenorrhea)
  • Infiltrative
  • Pituitary (20)
  • Hyperprolactinemia (90) gt decreased GnRH
  • Empty sella, hypothyroidism, other pituitary
    tumors, Sheehans, infiltrative
  • Uterine (5)
  • Ashermans (gt90), endometriosis

98
Approach to Secondary Amenorrhea
  • Rule out pregnancy
  • ßHCG
  • Physical exam
  • R/O Ashermans
  • Prolactin level
  • If very high, CT or MRI of pituitary
  • TSH
  • If very high hypothyroidism
  • FSH and LH
  • If very high ovarian failure, if lt 30 gt
    karyotype
  • If low stress?, low BW?, pit failure?
  • DHEAS and testosterone
  • Only if virilized, looking for PCOS
  • 17OHprogesterone
  • Looking for congenital adrenal hyperplasia

99
Progestin Withdrawal Test
  • If bleeding occurs
  • Uterus and endometrium are intact
  • Estrogen is sufficient, progesterone was lacking
  • Anovulation
  • Hypothalamic dysfunction (stress)
  • Polycystic ovarian syndrome
  • LateOnset Congenital Adrenal Hyperplasia (17OH)
  • If bleeding does not occur
  • Insufficient estrogen or uterine cause
  • Hypothalamic dysfunction (stress)
  • Pituitary dysfunction
  • Uterine cause

100
Geriatrics
101
Pathophysiology of Bedrest
  • Pulmonary
  • Decreased oxygenation
  • Decreased ability to clear secretions
  • Vascular
  • Venous stasis gt DVT gt PE
  • Orthostasis
  • Skin
  • Pressure ulcers
  • Musculoskeletal
  • Atrophy and contractures
  • Osteoporosis
  • Electrolytes
  • Hypercalciuria gt stones
  • Gastrointestinal
  • Reflux esophagitis
  • Constipation
  • Anorexia

102
Geriatrics Vision Changes in the Elderly
  • Visual Acuity
  • Decreased accommodation (presbyopia)
  • Color Vision
  • Lens yellows, blue green blending
  • Extraocular Muscles
  • Weaken
  • Tear ducts
  • Less tear production gt corneal irritation
  • Illumination disturbances
  • Require more light yet more glare
  • Poor night vision

103
Geriatrics Hearing Changes in the Elderly
  • Presbycusis
  • Agerelated hearing loss, usually gt 65 yo
  • Higher frequency loss
  • Loss of speech discrimination
  • Interview techniques
  • Turn off all background noise
  • Sit them in a corner and at eye level
  • Well-lighted area
  • Speak clearly and slowly, low tone
  • Mime
  • Use amplifiers

104
Neurology
105
Pyramidal Motor System
  • Anatomy
  • Corticospinal and corticobulbar system
  • Originates motor, premotor, sensory cortex
  • Terminates on alpha motor neurons in the
    intermediate gray of spinal cord and brain stem
  • Function
  • Executes isolated dextrous muscle movements
  • Present only in primates and above
  • Modified by reticulospinal, tectospinal and
    vestibulospinal tracts
  • Effect of lesions
  • Upper motor neuron paralysis

106
Extrapyramidal Motor System
  • Anatomy
  • Originates basal ganglia and cerebellum
  • Links indirectly to pyramidal system via thalamus
    and cortex
  • Function
  • Basal ganglia initiation and planning of
    movement
  • Cerebellum monitors, smoothes and terminates
    movements
  • No direct initiation of movements
  • Lesions
  • Basal ganglia bradykinesia
  • Cerebellum ataxia

107
Basal Ganglia Dysfunction
  • Anatomy
  • Caudate nucleus
  • Putamen
  • Globus pallidus
  • Substantia nigra
  • Subthalamic nucleus
  • (Thalamus)
  • Effects of dysfunction
  • Involuntary movements
  • Altered voluntary movements
  • Slow
  • Interrupted
  • Uncoordinated
  • Posture and tone altered
  • Neurotransmitter correlates
  • Dopamine gt Ach hyperkinetic
  • Ach gt Dopamine hypokinetic

108
Upper Motor Neuron (Central) Weakness
  • Hemiparesis
  • Hyperreflexia
  • Unilateral clasp knife spasticity (rigidity)
  • May see spontaneous spasms
  • Anatomic associations
  • LE external rotation
  • UE decreased arm swing, internal rotation when
    extended
  • Facial spares forehead, eye wider, nasolabial
    fold flat

109
Localizing an Upper Motor Neuron (Central)
Weakness
  • Cerebral Cortex
  • Trouble with language, spatial attention, touch
    recognition, vision
  • Internal Capsule
  • Face, UE and LE weak but no other cranial nerve
    or cortical symptoms
  • Brainstem
  • Cranial nerves involved
  • Spinal cord
  • Face not involved

110
Lower Motor Neuron (Peripheral) Weakness
  • Anterior horn cell to muscle
  • Muscle atrophy
  • Fasciculations and fibrillations
  • Decreased/absent reflexes
  • Flaccidity
  • Cramping

111
UMN vs. LMN Weakness
  • UMN LMN
  • Location Cortex gt SC Ant. horn cellgtmuscle
  • Muscle size Normal Atrophic
  • Reflexes Increased Decreased
  • Fasciculations Absent Present
  • Tone Clasp knife rigidity Decreased (flaccid)

112
Babinskis Sign
  • Primitive defensive flexion of hip, knee and
    dorsiflexion of ankle
  • In primates, dorsiflexion of toes
  • When we start walking, the latter is inhibited to
    allow toe plantar flexion
  • Thus a normal response in an adult is flexion of
    the hip, knee and dorsiflexion of the ankle with
    plantar flexion of the toes.
  • Abnormal upgoing toes

113
GuillainBarré Syndrome
  • Pathogenesis
  • Immunologic attack on peripheral myelinated
    fibers
  • Etiology
  • Campylobacter jejuni, other infections,
    vaccinations
  • Clinical Manifestations
  • Ascending weakness
  • Peripheral sensory loss
  • Loss of reflexes
  • CSF increased protein but not cells

114
Peripheral Neuropathies
  • Axonal Degeneration (Dying Back)
  • Toxic injury to neurons
  • Etiologies EtOH, DM, Pb, paraneoplastic
  • Symmetric, longest fibers first
  • Ischemic
  • Loss of peripheral vascular or vaso nervorum
    blood supply
  • Etiologies DM, pressure induced neuropathies,
    vasculitis
  • Asymmetric
  • Demyelination
  • Immune mediated injury to myelinated fibers
  • Etiologies e.g. Guillain Barré syndrome
  • Symmetric loss of motor and sensory function and
    DTRs

115
Muscle Motor Weakness
  • Etiologies
  • Inflammation dermatomyositis, inclusion body
    myositis
  • Abnormal proteins muscle dystrophies
  • Toxins
  • Metabolic high Ca, low K, low glucose,
    hypothyroid
  • Neuromuscular junction myasthenia gravis,
    EatonLambert
  • Clinical Manifestations
  • Proximal gt distal muscle weakness
  • No sensory loss
  • Preservation of reflexes

116
Brain EdemaIncreased brain volume due to
increased water content
  • Vasogenic Cytotoxic Interstitial
  • Pathophysiology Endothelial Neuronal Pressure
  • injury injury
  • Causes Tumor Hypoxia Hydroceph-
  • Infection Hypoosmo alus
  • Trauma larity Meningitis
  • Infarct
  • HTN
  • Therapy Steroids None Shunt

117
Aphasia
  • Definition
  • Disorder of language due to brain dysfunction
  • Classification
  • Expressive (Broca)
  • Receptive (Wernicke)
  • Global
  • Other Characteristics
  • Fluent vs. nonfluent
  • Comprehension
  • Repetition

118
Memory Types
  • Episodic
  • Memory of events
  • Remote (mos to yrs), longterm memory, hardest to
    lose
  • Recent (min to days), new learned ability, test
    by asking patient to remember 3 common words for
    a few minutes
  • Immediate (s), not encoded, max 7 items,
    easiest to losetest via digit repetition
  • Easiest to lose
  • Semantic
  • Memory of words and meanings
  • Test via naming of objects or persons
  • Procedural
  • Skills
  • Toughest t lose

119
Memory Loss
  • Failure to create memories
  • Hippocampal system
  • Failure to have adequate storage
  • Loss of neurons
  • Failure to retrieve
  • Loss of neurons that used to contain memories

120
Acute Pain Types
  • First pain
  • Adelta fibers
  • Immediate, brief, sharp, localized
  • Second pain
  • C fibers
  • Seconds later, enduring, dull/burning, not
    localized

121
Pain Pathways
  • Ascending Pathway
  • Pain receptors
  • Synapse in dorsal horn
  • Cross to form ascending spinothalamic tract
  • Thalamus
  • Lateral thalamic nucleus
  • To somatosensory cortex gt feel pain
  • Medial thalamic nucleus
  • To frontal cortex gt realize pain
  • Descending Pathway
  • Periaqueductal gray region
  • Serotonin
  • To frontal cortex
  • Suppress response to pain
  • To spinal cord
  • Suppress sensation of pain

122
Diseases of the Pain Pathways
  • Reflex Sympathetic Dystrophy (Causalgia)
  • Postnerve injury hypersensitivity to
    catecholamines released by sympathetic nervous
    system
  • Hypereshtesia, vasoconstriction, muscle atrophy,
    contracture
  • Rx analgesics, sympathetic blockade
  • Fibromyalgia
  • Decreased descending serotonin release
  • Increased perception of pain from nonnoxious
    stimuli
  • Rx SSRIs

123
Myasthenia Gravis
  • Pathophysiology
  • Autoimmune destruction of postsynaptic
    neuromuscular junction nicotinic acetylcholine
    receptors (AchRs)
  • Antibody binds and induces cell mediated attack
  • Accelerated loss of AchRs
  • Clinical Manifestations
  • Weak proximal muscles, eye lids and EOM, cranial
    nerves, diaphragm
  • Diagnosis
  • Improvement after acetycholinesterase inhibitor
    (edrophonium, Tensilon) challenge
  • EMG Decrement in action potentials with
    repetitive stimulation
  • Assay for antiacetylcholine receptor antibodies
    (8090 )
  • Therapy
  • Long acting acetylcholinesterase inhibitors,
    steroids, cytotoxics, thymectomy, plasmapheresis,
    IVIG

124
Duchenne Muscular Dystrophy
  • Pathophysiology
  • Variable mutations of dystrophin gene at Xp21
    locus (Xlinked rec)
  • Dystrophin protects sarcolemmal membrane from
    degradation by intracellular proteases, absence
    gt muscle necrosis, Ca influx
  • Clinical Manifestations
  • Male onset 23 years, wheelchair in teens, death
    in 20s
  • Proximal weakness with calf pseudohypertrophy
    (fat, fibrosis, inflam)
  • Protruberant abdomen, lumbar lordosis
  • Cardiac CHF, arrhythmias
  • CPK elevated
  • EMG myopathic small polyphasic potentials
  • Treatment and Prognosis
  • Symptomatic, prednisone slows progression
  • Usually death in 3rd decade from respiratory or
    cardiac disease

125
Duchenne Muscular Dystrophy
Gowers Sign
Calf pseudohypertrophy
126
Polymyositis
  • Pathophysiology
  • Tcell mediated muscle injury
  • Secondary Ab formation (Jo1, Mi2, SRP)
  • Clinical Diagnostic Findings
  • Symmetric proximal muscle weakness with pain
  • Elevated plasma muscle enzymes
  • Myopathic changes on electromyography
  • Characteristic muscle biopsy abnormalities and
    the absence of histopathologic signs of other
    myopathies
  • Dermatomyositis
  • Gottrons papules and heliotrope eyelids
  • Humorally mediated vasculitis
  • Adult form associated with malignancy
  • Therapy
  • Steroids, cytotoxics, plasmapheresis, IVIG

127
Dermatomyositis
Gottrons papules
Heliotrope eyelids
128
Myophosphorylase Deficiency(McArdles Disease)
  • Pathophysiology
  • Autosomal recessive mutation of myophosphorylase
    gene on 11q13
  • Phosphorylase removes 1,4 glucosyl residues from
    glycogen releasing G1 phosphate.
  • Absence drastically reduces glucose availability
    for muscle
  • Clinical Manifestations
  • Exercise intolerance with cramping and
    myoglobinuria
  • Second wind once FFA utilization kicks in
  • Elevated CPK
  • Treatment
  • None

129
Tremor Characteristics
  • Toandfro oscillation around a joint
  • Regular or irregular
  • Predictable and simple

130
Resting (Repose) Tremor
  • Characteristics
  • Occurs with inactivity of limb
  • Examination
  • Resting hand pill rolling
  • Resting tongue
  • Etiology
  • Parkinsonism (4 6 Hz)
  • Parkinsons disease, heavy metal toxicity (Fe,
    Cu), drug (MPTP)
  • Midbrain stroke
  • Treatment
  • Dopamine agonists

131
Parkinsonism
  • Classical Characteristics
  • Bradykinesia
  • Tremor (46 Hz, initially unilateral)
  • Cogwheel rigidity
  • Loss of postural reflexes
  • Etiology
  • Death of dopaminergic neurons in substantia nigra
  • Dopamine antagonists
  • Therapy
  • Ldopa, dopamine agonists
  • Amantadine (blocks DA reuptake)
  • COMT inhibitors
  • Selegeline (MOA inhibitor)

132
Intention (Action) Tremor
  • Characteristics
  • Occurs with action of an extremity
  • Examination
  • Fingertonose and heeltoshin test
  • Etiology
  • Cerebellar disease (34 Hz)
  • EtOH, trauma, stroke, tumor, degeneration, MS
  • Midbrain stroke
  • Treatment
  • Physical therapy

133
Postural Tremor
  • Characteristics
  • Occurs with antigravity posturing
  • Examination
  • Outstretched arms and fingers
  • Tongue protrusion
  • Etiology
  • Exaggerated physiologic tremor (1012 Hz)
  • Catecholamine excess
  • Endocrine pheo, hyperthyroid, hypoglycemia
  • Drugs ßagonists, reuptake inhibitors, xanthine
    oxidase inhibitors, catecholamines
  • Stress
  • Essential tremor (410 Hz)
  • Etiology unknown
  • 50 inherited (familial tremor)
  • Treatment
  • ßblockers, EtOH, primidone

134
Tremor Summary
  • Tremor Type Frequency Cause Treatment
  • Resting 4 6 Hz Parkinsons Dopaminergics
  • Action 3 4 Hz Cerebellar None
  • Postural
  • Exaggerated 10 12 Hz Catechols Treat cause
  • physiologic ßblockers
  • Essential 4 10 Hz Unknown ßblockers,
  • primidone

135
Chorea
  • Definition
  • Irregular, unpredictable, random, rapid, jerky
  • Pathophysiology
  • Dopamine excess in striatum
  • Estrogen effect (mild)
  • Etiology
  • Huntingtons disease (and misc. hereditary forms)
  • Sydenhams chorea (acute rheumatic fever)
  • Cerebral palsy
  • Pregnancy, OCPs
  • Treatment
  • Dopamine antagonists

136
Huntingtons Disease
  • Etiology
  • Autosomal dominant progressive chorea and
    dementia
  • Defective huntingtin protein (chromosome 4)
  • Degeneration of cholinergic and GABAergic cells
    in BG
  • Relative excess dopamine
  • Manifestations
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