GENERAL PATHOLOGY

University of the East

College of Dentistry
 BASIC PATHOLOGIC PROCESSES
Cellular Adaptation
Inflammation
Hypersensitivity
Thrombosis
Hypovolemic conditions
Neoplasia
 SPECIFIC DISEASE STATES
Genetic abnormalities
Infectious Diseases
Gastrointestinal Diseases
Cardiovascular Diseases
Pulmonary Diseases
CNS Diseases
 The Concept of HOMEOSTASIS
The body is able to handle normal physiologic
demands, maintaining a steady state called
homeostasis.

More severe physiologic stresses and some

pathologic stimuli may bring about a number of
physiologic and morphologic cellular adaptations,
during which new but altered steady states are
achieved, preserving the viability of the cell and
modulating its function as it responds to such
stimuli.
General Pathology

CELLULAR ADAPTATION
CELLULAR ADAPTATION
HYPER- vs. HYPOPLASIA
NUMBER OF CELLS
 HYPERTROPHY
INCREASE IN THE SIZE OF CELLS
 ATROPHY
SHRINKAGE - DEREASE IN THE SIZE OF CELLS
 METAPLASIA
CHANGE IN CELL TYPE
 CELL DEATH
APOPTOSIS
(normal death)

NECROSIS
(premature or
untimely death due
to particular causes)
 CAUSES OF CELL INJURY
HYPOXIA oxygen deficiency
ISCHEMIA loss of blood supply due to impeded
blood flow.
CHEMICAL INJURY
INFECTIOUS AGENTS
IMMUNOLOGIC REACTIONS
GENETIC DEFECTS
NUTRITIONAL IMBALANCES
PHYSICAL AGENTS
AGING
EFFECTS OF FREE RADICALS
 TYPES OF CELLULAR INJURY
REVERSIBLE
Cellular swelling
HYDROPIC CHANGE or VACUOLAR
DEGENERATION (the presence of small,
clear vacoules in the cytoplasm which
are pinched off segments othe ER)
FATTY CHANGE (appearance of lipid
vacoules in the cytoplasm)
IRREVERSIBLE
NECROSIS
Increased EOSINOPHILIA
Dead cells are replaced by MYELINE
FIGURES (whorled phospholipid masses
from destroyed cell membranes)
CALCIFICATION OF DEAD CELLS
Nuclear changes:
KARYOLYSIS (basophilia of chromatin)
PYKNOSIS (nuclear shrinkage in increased
basophilia)
KARYORRHEXIS (fragmentation of the
pyknoytic nucleus)
 PATTERNS OF NECROSIS
Coagulative (Heart, Kidney, any solid organ
except the brain)
Liquefactive (Brain)
Gangrenous (Extremities, Bowel, non-specific)
WET
DRY
Fibrinoid (Rheumatoid)
Caseous (Tuberculosis)
Fat (Pancreas, Breast, any fat)
COAGULATIVE NECROSIS,
heart
LIQUEFACTIVE NECROSIS,
BRAIN
CASEOUS NECROSIS, TB
FIBRINOID NECROSIS
WET GANGRENE
DRY GANGRENE
FAT NECROSIS,
Pancreas
General Pathology

INFLAMMATION
 ACUTE INFLAMMATION
PROTECTIVE RESPONSE
NON-specific
ACUTE INFLAMMATION
VASCULAR EVENTS
CELLULAR EVENTS (PMN or
PolyMorphonuclear Neutrophil)
The involvement of MEDIATORS
 ACUTE
INFLAMMATION
Neutrophil
Polymorphonuclear
Leukocyte, PMN, PML
Granulocyte, Neutrophilic
granulocyte
Poly-
Polymorph
HISTORICAL HIGHLIGHTS
Rubor
Calor
Tumor
Dolor
5th (functio laesa)
 STIMULI
for acute inflammation
INFECTIOUS
PHYSICAL
CHEMICAL
Tissue Necrosis
Foreign Bodies (FBs)
Immune responses, or complexes
 Vascular Changes
Changes in Vascular Flow and
Caliber

Increased Vascular Permeability

 INCREASED PERMEABILITY
DILATATION
Endothelial gaps
Direct Injury
Leukocyte Injury
Transocytosis
New Vessels
LEAKAGE OF PROTEINACEOUS
EXUDATE, NOT
FLUID (
TRANSUDATE)
 EXTRAVASATION of PMNs
MARGINATION (PMNs
go toward wall)

ROLLING (tumbling and

HEAPING)

ADHESION

TRANSMIGRATION
(DIAPEDESIS)
 CHEMOTAXIS
PMNs going to the site of
injury AFTER transmigration
 LEUKOCYTE
ACTIVATION
triggered by the offending stimuli for PMNs to:
1) Produce eicosanoids (arachidonic acid
derivatives)
Prostaglandin (and thromboxanes)
Leukotrienes
Lipoxins
2) Undergo DEGRANULATION
3) Secrete CYTOKINES
 PHAGOCYTOSIS
RECOGNITION

ENGULFMENT

KILLING
(DEGRADATION
/DIGESTION)
 OUTCOMES OF
ACUTE INFLAMMATION

1) 100% complete RESOLUTION

2) SCAR

3)CHRONIC inflammation
 Morphologic PATTERNS
of Acute INFLAMMATION
Serous (watery)
Fibrinous (hemorrhagic, rich
in FIBRIN)
Suppurative (PUS)
Ulcerative
BLISTER, Watery, i.e., SEROUS
FIBRINOUS
 PUS
=
PURULENT

ABSCESS
=
POCKET
OF
PUS
=
NEUTROPHILS
ULCERATIVE
 SEQUENCE OF EVENTS
NORMAL HISTOLOGY
VASODILATATION
INCREASED VASCULAR PERMEABILITY
LEAKAGE OF EXUDATE
MARGINATION, ROLLING, ADHESION
TRANSMIGRATION (DIAPEDESIS)
CHEMOTAXIS
PMN ACTIVATION
PHAGOCYTOSIS: Recognition, Attachment,
Engulfment, Killing (degradation or digestion)
TERMINATION
100% RESOLUTION, SCAR, or CHRONIC inflammation
CHRONIC INFLAMMATION

LYMPHOCYTE MONOCYTE
MACROPHAGE
HISTIOCYTE
 CAUSES of
CHRONIC INFLAMMATION
1) PERSISTENCE of Infection
2) PROLONGED EXPOSURE to
insult
3) AUTO-IMMUNITY
 MORPHOLOGY
INFILTRATION
TISSUE DESTRUCTION
HEALING
 GRANULOMAS
GRANULOMATOUS INFLAMMATION
General Pathology

WOUND HEALING
CELL CYCLE
G0
Quiescent (not a very long
or dominant phase)
G1
PRE-synthetic, but cell
GROWTH taking place
S
DNA synthesis
G2
PRE-mitotic
M (Mitotic:, P,M,A,T)
 CELL TYPES
Labile: bone marrow, GI
Quiescent: liver, kidney
NON-mitotic: neuron, striated
muscle
 HEALING
FOLLOWS INFLAMMATION
PROLIFERATION and MIGRATION of connective
tissue cells
ANGIOGENESIS (Neovascularization)
Collagen, other ECM protein synthesis
Tissue Remodeling
Wound contraction
Increase in wound strength (scar = fibrosis)
 ANGIOGENESIS
(NEOVASCULARIZATION)
From endothelial precursor cells
From PRE-existing vessels
Stimulated/Regulated by GFs,
especially VEGF
Also regulated by ECM proteins
 WOUND HEALING
1st INTENTION 2nd INTENTION

Edges lined up Edges NOT lined up

Ergo.
More granulation
More epithelialization
MORE FIBROSIS
HEALTHY Granulation Tissue
 FIBROSIS/SCARRING
DEPOSITION OF COLLAGEN by
FIBROBLASTS
With time (weeks, months, years?)
the collagen becomes more dense,
ergo, the tissue becomes
STRONGER
General Pathology

HYPERSENSITIVITY
 HYPERSENSITIVITY
HYPERSENSITIVITY REACTIONS
TYPE I Immediate hypersensitivity
Anaphylactic type hypersensitivity
IgE mediated hypersensitivity

TYPE II Cytotoxic reactions

TYPE III Immune complex deposition
TYPE IV Delayed hypersensitivity
Cell-mediated hypersensitivity
Tuberculoid type hypersensitivity
 Type I
IMMEDIATE HYPERSENSITIVITY
Immediate means seconds to minutes
Immediate Allergic Reactions, which may lead to
anaphylaxis, shock, edema, dyspnea death
1) Allergen exposure
2) IMMEDIATE phase: MAST cell DEgranulation,
vasodilatation, vascular leakage, smooth muscle
(broncho)-spasm
3) LATE phase (hours, days): Eosinophils, PMNs,
T-Cells
Type I - Urticaria
Type I - Angiodema
 TYPE II HYPERSENSITIVITY
ANTIBODY MEDIATED IMMUNITY
ABs attach to cell surfaces
OPSONIZATION (basting the turkey)
PHAGOCYTOSIS
COMPLEMENT CASCADE
LYSIS (destruction of cells by rupturing or
breaking of the cell membrane)
 TYPE III HYPERSENSITIVITY
IMMUNE COMPLEX MEDIATED
Antigen/Antibody Complexes
Where do they go?
Kidney (Glomerular Basement Membrane)
Blood Vessels
Skin
Joints (synovium)
Common Type III Diseases- SLE (Lupus),
Poly(Peri)arteritis Nodosa, Poststreptococcal
Glomerulonephritis, Arthus reaction (hrs), Serum
sickness (days)
Type III Systemic Lupus
Erythematosus
TYPE III Arthus reaction
 TYPE IV HYPERSENSITIVITY
CELL-MEDIATED (T-CELL)
DELAYED HYPERSENSITIVITY
Tuberculin Skin Reaction

DIRECT ANTIGENCELL CONTACT

GRANULOMA FORMATION
CONTACT DERMATITIS
Type IV Tuberculin skin reaction
General Pathology

HEMODYNAMIC DISORDERS
 Edema (increased fluid in the ECF)
Hyperemia (INCREASED flow)
Congestion (INCREASED backup)
Hemorrhage (extravasation of blood)
Thrombosis (clot formation)
Embolism (downstream travel of a
dislodged thrombus)
Infarction (death of tissues w/o blood)
Shock (circulatory failure/collapse)
 EDEMA
ONLY 4 POSSIBLE CAUSES
Increased Hydrostatic Pressure
Reduced Oncotic Pressure
Lymphatic Obstruction
Sodium/Water Retention
 WATER
60% of body
2/3 of body water is INTRA-cellular
The rest is INTERSTITIAL
Only 5% is INTRA-vascular

EDEMA is SHIFT to the INTERSTITIAL SPACE

HYDRO-
-THORAX, -PERICARDIUM, -PERITONEAL
EFFUSIONS, ASCITES, ANASARCA
INCREASED HYDROSTATIC PRESSURE
Impaired venous return
Congestive heart failure
Constrictive pericarditis
Ascites (liver cirrhosis)
Venous obstruction or compression
Thrombosis
External pressure (e.g., mass)
Lower extremity inactivity with prolonged dependency
Arteriolar dilation
Heat
Neurohumoral dysregulation
 REDUCED PLASMA ONCOTIC
PRESSURE (HYPOPROTEINEMIA)
Protein-losing glomerulopathies (nephrotic
syndrome)
Liver cirrhosis (ascites)
Malnutrition
Protein-losing gastroenteropathy
 LYMPHATIC OBSTRUCTION
(LYMPHEDEMA)
Inflammatory
Neoplastic
Postsurgical
Postirradiation
 Na+ RETENTION
Excessive salt intake with renal
insufficiency
Increased tubular reabsorption of sodium

Renal hypoperfusion Increased

renin-angiotensin-aldosterone
secretion
 CONGESTIVE HEART
FAILURE EDEMA
INCREASED VENOUS PRESSURE DUE TO
FAILURE

DECREASED RENAL PERFUSION,

triggering of RENIN-ANGIOTENSION-
ALDOSTERONE complex, resulting
ultimately in SODIUM RETENTION
 HEPATIC ASCITES

PORTAL HYPERTENSION

HYPOALBUMINEMIA
ASCITES
 RENAL EDEMA
SODIUM RETENTION

PROTEIN LOSING
GLOMERULOPATHIES (NEPHROTIC
SYNDROME)
 EDEMA
SUBCUTANEOUS (PITTING)
DEPENDENT
ANASARCA
LEFT vs RIGHT HEART
PERIORBITAL
PULMONARY
CEREBRAL (closed cavity, no expansion)
HERNIATION of cerebellar tonsils
HERNIATION of hippocampal uncus over tentorium
HERNIATION, subfalcine
Pitting Edema
 Transudate vs Exudate
Transudate
results from disturbance of Starling forces
specific gravity < 1.012
protein content < 3 g/dl, LDH LOW
Exudate
results from damage to the capillary wall
specific gravity > 1.012
protein content > 3 g/dl, LDH HIGH
HYPEREMIA/CONGESTION
HYPEREMIA
Active Process

CONGESTION
Passive Process
Acute or Chronic
Kerley B

Air
Bronch-
ogram
 CHRONIC PASSIVE
HYPEREMIA/CONGESTION, LUNG
Acute Passive Congestion, Liver
 CHRONIC PASSIVE
HYPEREMIA/CONGESTION, LIVER
 HEMOSTASIS
OPPOSITE of THROMBOSIS
PRESERVE LIQUIDITY OF BLOOD
PLUG sites of vascular injury
THREE COMPONENTS
VASCULAR WALL, i.e., endoth/ECM
PLATELETS
COAGULATION CASCADE
 SEQUENCE of EVENTS
following VASCULAR INJURY
ARTERIOLAR VASOCONSTRICTION
Reflex Neurogenic
Endothelin, from endothelial cells
THROMBOGENIC ECM at injury site
Adhere and activate platelets

Platelet aggregation (1 HEMOSTASIS)

TISSUE FACTOR released by endothelium, plats.
Activates coagulation cascadethrombinfibrin (2
HEMOSTASIS)
FIBRIN polymerizes, TPA limits plug
 ENDOTHELIUM
NORMALLY
ANTIPLATELET PROPERTIES
ANTICOAGULANT PROPERTIES
FIBRINOLYTIC PROPERTIES
IN INJURY
PRO-COAGULANT PROPERTIES
 ENDOTHELIUM
ANTI-Platelet PROPERTIES
Protection from the subendothelial ECM
Degrades ADP (inhib. Aggregation)
ANTI-Coagulant PROPERTIES
Membrane HEPARIN-like molecules
Makes THROMBOMODULIN Protein-C
TISSUE FACTOR PATHWAY INHIBITOR
FIBRINOLYTIC PROPERTIES (TPA)
 ENDOTHELIUM
PROTHROMBOTIC PROPERTIES
Makes vWF, which binds PlatsColl
Makes TISSUE FACTOR (with plats)
Makes Plasminogen inhibitors
 ENDOTHELIUM
ACTIVATED by INFECTIOUS AGENTS
ACTIVATED by HEMODYNAMICS
ACTIVATED by PLASMA
ACTIVATED by ANYTHING which disrupts it
 PLATELET PHASES
ADHESION
SECRETION (i.e., release or
activation or
degranulation)
AGGREGATION
 PLATELET ADHESION
Primarily to the subendothelial
ECM
Regulated by vWF, which
bridges platelet surface
receptors to ECM collagen
 PLATELET AGGREGATION
ADP
TxA2 (Thromboxane A2)
THROMBIN from coagulation
cascade also
FIBRIN further strengthens and
hardens and contracts the platelet
plug
 PLATELET EVENTS
ADHERENCE to ECM
SECRETION of ADP and TxA2
EXPOSE phospholipid complexes
Express TISSUE FACTOR
PRIMARYSECONDARY PLUG
STRENGTHENED by FIBRIN
 COAGULATION CASCADE

INTRINSIC(contact)/EXTRINSIC(TissFac)
ProenzymesEnzymes
Prothrombin(II)Thrombin(IIa)
Fibrinogen(I)Fibrin(Ia)
Cofactors
Ca++
Phospholipid (from platelet membranes)
Vit-K dep. factors: II, VII, IX, X, Prot. S, C, Z
 HEMORRHAGE
EXTRAVASATION beyond vessel

PETECHIAE (1-2mm) (PLATELETS)

PURPURA <1cm
ECCHYMOSES >1cm (BRUISE)
HEMATOMA (implies MASS effect)

HEMO-: -thorax, -pericardium, -peritoneum, HEMARTHROSIS

 EVOLUTION of HEMORRHAGE

ACUTE CHRONIC
PURPLE GREEN BROWN
HGB BILIRUBIN HEMOSIDERIN
 THROMBOSIS
Virchows TRIANGLE
ENDOTHELIAL
INJURY

ABNORMAL FLOW HYPER-

(NON-LAMINAR) COAGULATION
 ABNORMAL FLOW
NON-LAMINAR FLOW
TURBULENCE
STASIS
DISRUPTED ENDOTHELIUM
ALL of these factors may bring platelets into
contact with endothelium and/or ECF
 HYPERCOAGULABILITY
Prolonged bed rest or immobilization
Myocardial infarction
Atrial fibrillation
Tissue damage (surgery, fracture, burns)
Cancer
Prosthetic cardiac valves
Disseminated intravascular coagulation
Heparin-induced thrombocytopenia
Antiphospholipid antibody syndrome (lupus anticoagulant syndrome)
Lower risk for thrombosis:
Cardiomyopathy
Nephrotic syndrome
Hyperestrogenic states (pregnancy)
Oral contraceptive use
Smoking, Obesity
 FATE of THROMBI
PROPAGATION (Downstream)
EMBOLIZATION
DISSOLUTION
ORGANIZATION
RECANALIZATION
 ATHEROEMBOLI
CHOLESTEROL clefts are components
of atherosclerotic arterial plaques, NOT
venous thrombi!!!
 EMBOLISM
Pulmonary
Systemic (Mural Thrombi and
Aneurysms)
Fat
Air
Amniotic Fluid
 D.V.T.
D. (CALF, THIGH, PELVIC) V.T.
CHF a huge factor
INACTIVITY!!!
Trauma
Surgery
Burns
Injury to vessels,
Procoagulant substances from tissues
Reduced t-PA activity
 PULMONARY EMBOLISM
USUALLY SILENT, USUALLY SILENT
CHEST PAIN, LOW PO2, S.O.B.
Sudden OCCLUSION of >60% of pulmonary
vasculature, presents a HIGH risk for sudden
death, i.e., acute cor pulmonale, ACUTE right
heart failure
SADDLE embolism often/usually fatal
PRE vs. POST mortem blood clot:
PRE: Friable, adherent, lines of ZAHN
POST: Currant jelly or chicken fat
SADDLE EMBOLISM
 SYSTEMIC EMBOLI
PARADOXICAL EMBOLI
80% cardiac/20% aortic
Embolization lodging site is proportional
to the degree of flow (cardiac output)
that area or organ gets, i.e., brain (15%),
kidneys (~25%), legs, splanchnic (~25%),
liver (~25%)
 INFARCTION
Defined as an area of necrosis*
secondary to decreased blood flow
HEMORRHAGIC vs. ANEMIC
RED vs. WHITE
END ARTERIES vs. DUAL ARTERY SUPPLY
ACUTEORGANIZATIONFIBROSIS
 SHOCK
Pathogenesis
Cardiac
Septic
Hypovolemic
Morphology
Clinical Course
 SHOCK
Definition: CARDIOVASCULAR COLLAPSE

Common pathophysiologic features:

INADEQUATE CARDIAC OUTPUT and/or
INADEQUATE BLOOD VOLUME
 GENERAL RESULTS
INADEQUATE TISSUE PERFUSION
CELLULAR HYPOXIA
If UN-corrected, a FATAL outcome
 TYPES of SHOCK
CARDIOGENIC: (Acute, Chronic Heart Failure)
HYPOVOLEMIC: (Hemorrhage or Leakage)
SEPTIC: (ENDOTOXIC shock, #1 killer in ICU)
NEUROGENIC: (loss of vascular tone)
ANAPHYLACTIC: (IgE mediated systemic
vasodilation and increased vascular
permeability)
 CARDIOGENIC shock
MI
VENTRICULAR RUPTURE
ARRHYTHMIA
CARDIAC TAMPONADE
PULMONARY EMBOLISM (acute RIGHT heart
failure or cor pulmonale)
 HYPOVOLEMIC shock
HEMORRHAGE, Vasc. compartmentH2O
VOMITING, Vasc. compartmentH2O
DIARRHEA, Vasc. compartmentH2O
BURNS, Vasc. compartmentH2O
 SEPTIC shock
OVERWHELMING INFECTION
ENDOTOXINS, i.e., LPS (Usually Gm-)
Gm+
FUNGAL
General Pathology

NEOPLASIA
 Nomenclature Benign Tumors
-oma = benign neoplasm (NOT carcin-, sarc-, lymph-, or
melan-)
Mesenchymal tumors (mesodermal derived)
chrondroma: cartilaginous tumor
fibroma: fibrous tumor
osteoma: bone tumor
Epithelial tumor (ecto- or endo- derived)
adenoma: tumor forming glands
papilloma: tumor with finger like projections
papillary cystadenoma: papillary and cystic tumor forming
glands
polyp: a tumor that projects above a mucosal surface
Nomenclature Malignant Tumors
Sarcomas: mesenchymal tumor
chrondrosarcoma: cartilaginous tumor
fibrosarcoma: fibrous tumor
osteosarcoma: bone tumor
Carcinomas: epithelial tumors
adenocarcinoma: gland forming tumor
squamous cell carcinoma: squamous differentiation
undifferentiated carcinoma: no differentiation
note: carcinomas can arise from ectoderm,
endoderm, or less likely, mesoderm
 Tumors with mixed differentiation
mixed tumors: e.g. pleomorphic adenoma of salivary gland
carcinosarcoma
Teratoma
tumor comprised of cells from more than one germ layer
arise from totipotent cells (usually gonads)
benign cystic teratoma of ovary is the most common
teratoma
Aberrant differentiation (not true neoplasms)
Hamartoma: disorganized mass of tissue whose cell types are
indigenous to the site of the lesion, e.g., lung
Choriostoma: ectopic focus of normal tissue (heterotopia),
e.g., pancreas, perhaps endometriosis too
Misnomers
hepatoma: malignant liver tumor
melanoma: malignant skin tumor
seminoma: malignant testicular tumor
lymphoma: malignant tumor of lymphocytes
Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 28 July 2005 03:41 PM)
2005 Elsevier
Natural History Of Malignant Tumors

1. Malignant change in the target

cell, referred to as
transformation
2. Growth of the transformed cells
3.Local invasion
4. Distant metastases.
 Differentiation
Well differentiated neoplasm
Resembles mature cells of tissue of origin
Poorly differentiated neoplasm
Composed of primitive cells with little
differentiation
Undifferentiated or anaplastic tumor
Correlation with biologic behavior
Benign tumors are well differentiated
Poorly differentiated malignant tumors usually
have worse prognosis than well differentiated
malignant tumors.
 Dysplasia
Literally means abnormal growth
Malignant transformation is a multistep process
In dysplasia some but not all of the features of malignancy
are present, microscopically
Dysplasia may develop into malignancy
Uterine cervix
Colon polyps
Graded as low-grade or high-grade, often prompting
different clinical decisions
Dysplasia may NOT develop into malignancy
HIGH grade dysplasia often classified with CIS
 Tumor Growth Rate
Doubling time of tumor cells
Lengthens as tumor grows
30 doublings (109 cells) = 1 g
10 more doublings (1 kg) = lethal burden
Fraction of tumor cells in replicative pool
May be only 20% even in rapidly growing tumors
Tumor stem cells
Rate at which tumor cells are shed or lost
Apoptosis
Maturation
 Features of Malignant Tumors

Cellular features

Local invasion
Capsule
Basement membrane
Metastasis
Unequivocal sign of malignancy
Seeding of body cavities
Lymphatic
Hematogenous
 Benign vs Malignant Features
Feature Benign Malignant

Rate of growth Progressive but Variable. Mitoses

slow. Mitoses few more frequent and
and normal may be abnormal

Differentiation Well differentiated Some degree of

anaplasia
Cohesive growth. Poorly cohesive
LOCAL Capsule & BM not and
INVASION breached
infiltrative!
Metastasis Absent May occur
Geographic & Environmental Factors

Sun exposure
Smoking and alcohol abuse
Body mass
Overweight = 50% increase in cancer
Viral exposure
Human papilloma virus (HPV) and cervical cancer
Hepatitis B virus (HBV) and liver cancer (Africa, Asia)
Epstein-Barr Virus (EBV) and lymphoma
HIV (Kaposi Sarcoma)
 Predisposing Factors for Cancer
Age
Most cancers occur in persons 55 years
Childhood cancers
Leukemias & CNS neoplasms
Bone tumors
Genetic predispostion
Familial cancer syndromes
Early age at onset
Two or more primary relatives with the cancer (soil theory)
Multiple or bilateral tumors
Polymorphisms that metabolize procarcinogens, e.g., nitrites
Nonhereditary predisposing conditions
Chronic inflammation?
Precancerous conditions
Chronic ulcerative colitis
Atrophic gastritis of pernicious anemia
Leukoplakia of mucous membranes
Immune collapse?
 MOLECULAR BASIS
of CANCER
NON-lethal genetic damage
A tumor is formed by the clonal
expansion of a single precursor cell
(monoclonal)
Four classes of normal regulatory genes
PROTO-oncogenes
Oncogenes Oncoproteins
DNA repair genes
Apoptosis genes
Carcinogenesis is a multistep process
 Normal CELL CYCLE Phases

INHIBITORS: Cip/Kip, INK4/ARF

Tumor (really growth) suppressor genes: p53
 ONCOGENES
Are MUTATIONS of NORMAL genes
(PROTO-oncogenes)
Growth Factors
Growth Factor Receptors
Signal Transduction Proteins (RAS)
Nuclear Regulatory Proteins
Cell Cycle Regulators
Oncogenes code for Oncoproteins
 PROTO- Mode of Associated Human
Category Oncogene Activation Tumor
GFs
PDGF- chain SIS Overexpression Astrocytoma

Osteosarcoma
Fibroblast HST-1 Overexpression Stomach cancer
growth factors
INT-2 Amplification Bladder cancer

Breast cancer
Melanoma
TGF TGF Overexpression Astrocytomas

Hepatocellular
carcinomas
HGF HGF Overexpression Thyroid cancer
 PROTO- Mode of Associated Human
Category Oncogene Activation Tumor

GF
Receptors
EGF-receptor ERB-B1 Overexpression Squamous cell carcinomas of
family (ECFR) lung, gliomas
ERB-B2 Amplification Breast and ovarian cancers

CSF-1 receptor FMS Point mutation Leukemia

Receptor for RET Point mutation Multiple endocrine neoplasia 2A

neurotrophic and B, familial medullary thyroid
factors carcinomas
PDGF receptor PDGF-R Overexpression Gliomas
Receptor for stem KIT Point mutation Gastrointestinal stromal tumors
cell (steel) factor and other soft tissue tumors
 PROTO- Mode of Associated Human
Category Oncogene Activation Tumor
Signal
Transduction
Proteins
GTP-binding K-RAS Point mutation Colon, lung, and pancreatic
tumors
H-RAS Point mutation Bladder and kidney tumors
N-RAS Point mutation Melanomas, hematologic
malignancies
Nonreceptor ABL Translocation Chronic myeloid leukemia
tyrosine kinase
Acute lymphoblastic leukemia
RAS signal BRAF Point mutation Melanomas
transduction
WNT signal -catenin Point mutation Hepatoblastomas,
transduction hepatocellular carcinoma
 Mode of
PROTO- Activation Associated Human
Category Oncogene Tumor
Nuclear
Regulatory
Proteins
Transcrip. C-MYC Translocation Burkitt lymphoma
activators
N-MYC Amplification Neuroblastoma,
small cell
carcinoma of lung
L-MYC Amplification Small cell
carcinoma of lung
 MYC
Encodes for transcription factors
Also involved with apoptosis
 P53 and RAS
p53 RAS
Activates DNA repair H, N, K, etc., varieties
proteins Single most common
Sentinel of G1/S abnormality of
transition dominant oncogenes in
Initiates apoptosis human tumors
Mutated in more than Present in about 1/3 of
50% of all human all human cancers
cancers
 LIMITLESS REPLICATIVE POTENTIAL

TELOMERES determine the limited

number of duplications a cell will
have, like a cat with nine lives.
TELOMERASE, present in >90% of
human cancers, changes telomeres so
they will have UNLIMITED replicative
potential
 TUMOR ANGIOGENESIS
Activation of VEGF and FGF-b

Tumor size is regulated (allowed) by

angiogenesis/anti-angiogenesis balance
TRANSFORMATION
GROWTH
BM INVASION
ANGIOGENESIS
INTRAVASATION
EMBOLIZATION
ADHESION
EXTRAVASATION
METASTATIC GROWTH
 Invasion Factors
Detachment ("loosening up") of the
tumor cells from each other
Attachment to matrix components
Degradation of ECM, e.g.,
collagenase, etc.
Migration of tumor cells
 CHEMICAL CARCINOGENS:
INITIATORS
DIRECT PROCARCINOGENS
-Propiolactone Polycyclic and Heterocyclic
Dimeth. sulfate Aromatic Hydrocarbons
Diepoxybutane Aromatic Amines, Amides,
Azo Dyes
Anticancer drugs
(cyclophosphamide, Natural Plant and Microbial
chlorambucil, nitrosoureas, Products
and others) Aflatoxin B1 Hepatomas
Griseofulvin Antifungal
Acylating Agents
Cycasin from cycads
1-Acetyl-imidazole
Safrole from sassafras
Dimethylcarbamyl chloride
Betel nuts Oral SCC
 CHEMICAL CARCINOGENS:
PROMOTORS

HORMONES
PHORBOL ESTERS (TPA), activate kinase C
PHENOLS
 RADIATION CARCINOGENS
UV
IONIZING: photons and particulate
Hematopoetic and Thyroid (90%/15yrs) tumors in
fallout victims
 VIRAL CARCINOGENESIS
HPV SCC
EBV Burkitt Lymphoma
HBV HepatoCellular Carcinoma (Hepatoma)
HIV Kaposi Sarcoma
 H. pylori CARCINOGENESIS

100% of gastric lymphomas

General Pathology

GENETIC ABNORMALITIES
COMMON CYTOGENETIC DISEASES
AUTOSOMES
TRISOMY-21 (DOWN SYNDROME)
8, 9, 13 (Patau), 18 (Edwards)
SEX CHROMOSOMES
KLINEFELTER: XXY, XXXY, etc.
TURNER: XO
TRISOMY-21
 TRISOMY-21
#1 cause of mental retardation
Maternal age related
Congenital Heart Defects, risk for acute
leukemias, GI atresias
SEX CHROMOSOME DISORDERS
Problems related to sexual development and
fertility
Discovered at time of puberty
Retardation related to the number of X
chromosomes
If you have at least ONE Y chromosome,
you are male
 KLINEFELTER (XXY, XXXY, etc.)

Hypogonadism found at puberty

#1 cause of male infertility
NO mental retardation unless more Xs
XXY 82% of the time
L----O----N----G legs, atrophic testes,
small penis
 TURNER (XO)
NECK WEBBING
EDEMA of HAND DORSUM
CONGENITAL HEART DEFECTS
 HERMAPHRODITES

GENETIC SEX is determined by the PRESENCE or ABSENCE
of a Y chromosome, but there is also, GONADAL
(phenotypic), and DUCTAL sex
TRUE HERMAPHRODITE: OVARIES AND TESTES, often on
opposite sides (VERY RARE)

PSEUDO-HERMAPHRODITE:
MALE: TESTES with female characteristics (Y-)
FEMALE: OVARIES with male characteristics (XX)
General Pathology

RESPIRATORY DISEASES
 OBSTRUCTION (cOPD)
EMPHYSEMA (almost always chronic)
CHRONIC BRONCHITIS
ASTHMA
BRONCHIECTASIS
COPD
 EMPHYSEMA
A form of COPD
Centri-acinar, Pan-acinar, Paraseptal, Irregular

(PROGRESSIVE) EXPIRATORY AIR TRAPPING, i.e.,

WHEEZING

Associated with Alpha1-antitrypsin deficiency

INcreased crepitance, BULLAE (BLEBS)

1) HYPER-expansion 2) flattened diaphragms (blunted),
3) bullae 4) increased lucency* (why?)
 CHRONIC BRONCHITIS
INHALANTS, POLLUTION, CIGARETTES
CHRONIC COUGH

MUCUS hypersecretion, early, i.e. goblet cell

increase
CHRONIC bronchial inflammatory infiltrate
 ASTHMA
Similar to chronic bronchitis but:
Wheezing is hallmark (bronchospasm, i.e. wheezing)
STRONG allergic role, i.e., eosinophils, IgE, allergens
Often starting in CHILDHOOD
ATOPIC (allergic) or NON-ATOPIC (infection)
Chronic small airway obstruction and infection
 PATHOPHYSIOLOGY of ASTHMA
When the airways come into
contact with one of these
triggers, the tissue inside the
bronchi and bronchioles
becomes inflamed
(inflammation). At the same
time, the muscles on the
outside of the airways tighten
up (constriction), causing them
to narrow. Then the
fluid/mucus is released into the
bronchioles, which also
become swollen (edema). The
breathing passages are
narrowed still more
(remodelling), and breathing
becomes very difficult
 BRONCHIECTASIS
DILATATION of the BRONCHUS, associated with,
often, necrotizing inflammation
CONGENITAL

TB, other bacteria, many viruses

BRONCHIAL OBSTRUCTION (i.e., LARGE AIRWAY, NOT
SMALL AIRWAY)
Rheumatoid Arthritis, SLE, IBD (Inflammatory Bowel
Disease)
BRONCHIECTASIS
 PNEUMOCONIOSES
OCCUPATIONAL
COAL MINERS LUNG
DUST OR CHEMICALS OR ORGANIC MATERIALS
Coal (anthracosis)
Silica
Asbestos
Be, FeO, BaSO4
HAY, FLAX, BAGASSE, INSECTICIDES, etc.
PNEUMONIA
 Classifications of PNEUMONIAS
COMMUNITY ACQUIRED
COMMUNITY ACQUIRED, ATYPICAL
NOSOCOMIAL
ASPIRATION
CHRONIC
NECROTIZING/ABSCESS FORMATION
PNEUMONIAS in IMMUNOCOMPROMISED
HOSTS*
 COMMUNITY ACQUIRED
STREPTOCOCCUS PNEUMONIAE (i.e.,
diplococcus)
HAEMOPHILUS INFLUENZAE (H-Flu)
MORAXELLA
STAPHYLOCOCCUS (STAPH)
KLEBSIELLA PNEUMONIAE
PSEUDOMONAS AERUGINOSA
LEGIONELLA PNEUMOPHILIA
 STREPTOCOCCUS
PNEUMONIAE
The classic LOBAR pneumonia
Normal flora in 20% of adults
Only 20% of victims have + blood cultures
Vaccines are often 100% preventive
 HAEMOPHILUS PNEUMONIA
Commonest in CHILDREN <2, with otitis, URI,
meningitis, cellulitis, osteomyelitis
PNEUMONIAS in CHILDREN <2 are often
thought of as being H Flu until proven
otherwise, otitis, meningitis too
Most common pneumonia from COPD in
adults
 KLEBSIELLA PNEUMONIAE
DEBILITATED MALNOURISHED
PEOPLE
ALCOHOLICS with pneumonia
are often thought of as having
Klebsiella until proven otherwise
 PSEUDOMONAS Aeruginosa
Usually NOT community acquired but
nosocomial
CYSTIC FIBROSIS patients with
pneumonia are presumed to have
PSEUDOMONAS until proven otherwise
COMMUNITY ACQUIRED, (atypical)
VIRAL (INFLUENZA)
MYCOPLASMAL (MYCOPLASMA
PNEUMONIAE (obligate intracellular))

NOT BACTERIAL
CULTURES NOT HELPFUL
 VIRAL PNEUMONIAS
Frequently interstitial, NOT alveolar
 SARS
(Severe Acute Respiratory Syndrome)
CORONA-VIRUS
2002 China outbreak
Spread CHIEFLY in Asia
Like most other NON-bacterial
pneumonias confirmed by PCR
Like most viral pneumonias, interstitium
infiltrated, some giant cells often present
S
A
R
S
 NOSOCOMIAL
Acquired in HOSPITALS, also called hospital acquired, versus
community acquired pneumonias.
DEBILITATION
CATHETERS, VENTILATORS
ENTEROBACTER, PSEUDOMONAS
STAPH (MRSA)

MRSA (MR=Methicillin Resistant)

OTHER Common causes of Noso. Pneum.
P. aeruginosa
Klebsiella
E. coli
S. pneumoniae
H. influenzae
 ASPIRATION PNEUMONIAS
UNCONSCIOUS PATIENTS
PATIENTS IN PROLONGED BEDREST
LACK OF ABILITY TO SWALLOW OR GAG
USUALLY CAUSED BY ASPIRATION OF GASTRIC
CONTENTS
POSTERIOR LOBES (gravity dependent) MOST
COMMONLY INVOLVED, ESPECIALLY THE SUPERIOR
SEGMENTS of the LOWER LOBES
Often lead to ABSCESSES
 LUNG ABSCESSES
ASPIRATION
SEPTIC EMBOLIZATION
NEOPLASIA
From NEIGHBORING structures:
ESOPHAGUS
SPINE
PLEURA
DIAPHRAGM
ANY pneumonia which is severe and destructive,
and UN-treated enough
 CHRONIC Pneumonias
USUALLY NOT persistences of the community or
nosocomial bacterial infections, but CAN BE, at
least histologically
Often SYNONYMOUS with the 4 classic systemic
fungal or granulomatous pulmonary
infections infections, i.e., TB, Histo-, Blasto-,
Coccidio-
If you see pulmonary granulomas, think of a
CHRONIC process, often years
 CHRONIC Pneumonias
TB
HISTO-PLASMOSIS
BLASTO-MYCOSIS

COCCIDIO-MYCOSIS
Mycobacterium tuberculosis
TRANSMISSION
PATHOPHYSIOLOGY
OF PULMONARY
TUBERCULOSIS
PRIMARY COMPLEX
 COMPROMISED HOSTS
PNEUMOCYSTIS CARINII*
CYTOMEGALOVIRUS (CMV)
FUNGI
GRANULOMA
 LUNG TUMORS
Benign, malignant, epithelial, mesenchymal, but
90% are CARCINOMAS
BIGGEST USA killer. Why? Ans: Prevalence not as
high as prostate or breast but mortality higher.
Only 15% 5 year survival.
TOBACCO has polycyclic aromatic
hydrocarbons, such as benzopyrene, anthracenes,
radioactive isotopes
Radiation, asbestos, radon
C-MYC, K-RAS, EGFR, HER-2/neu
 PATHOGENESIS
NORMAL BRONCHIAL MUCOSA
METAPLASTIC/DYSPLASTIC MUCOSA
CARCINOMA-IN-SITU (squamous,
adeno)
INFILTRATING (i.e., INVASIVE)
cancer
 TWO TYPES
NON-SMALL CELL
SQUAMOUS CELL CARCINOMA
ADENOCARCINOMA
LARGE CELL CARCINOMA

SMALL CELL CARCINOMA

OTHER TUMORS
 TNM, Lung
T1 Tumor <3 cm without pleural or main stem bronchus involvement
T2 Tumor >3 cm or involvement of main stem bronchus 2 cm from carina,
visceral pleural involvement, or lobar atelectasis
T3 Tumor with involvement of chest wall (including superior sulcus tumors),
diaphragm, mediastinal pleura, pericardium, main stem bronchus 2 cm from
carina, or entire lung atelectasis

T4 Tumor with invasion of mediastinum, heart, great vessels, trachea,

esophagus, vertebral body, or carina or with a malignant pleural
effusion
N0 No demonstrable metastasis to regional lymph nodes
N1 Ipsi-lateral hilar or peribronchial nodal involvement
N2 Metastasis to ipsilateral mediastinal or subcarinal lymph nodes
N3 Metastasis to contra-lateral mediastinal or hilar lymph nodes, ipsilateral
or contralateral scalene, or supraclavicular lymph nodes
M0 No (known) distant metastasis
M1 Distant metastasis present
 METASTATIC TUMORS
LUNG is the MOST COMMON site
for all metastatic tumors, regardless
of site of origin
It is the site of FIRST CHOICE for
metastatic sarcomas for purely
anatomic reasons!
 PLEURA
PLEURITIS (pleurisy)
PNEUMOTHORAX
EFFUSIONS
HYDRO-THORAX (Peric-, Perito-)
HEMO-THORAX (Peric-, Perito-)
CHYLO-THORAX (Peric-, Perito-)
MESOTHELIOMAS
 PLEURITIS
Usual bacteria, viruses, etc.
Infarcts
Lung abscesses, empyema
TB
Collagen diseases, e.g., RA, SLE
Uremia
Metastatic
 PNEUMOTHORAX
SPONTANEOUS, TRAUMATIC,
THERAPEUTIC
OPEN or CLOSED
TENSION pneumothorax, valvular
effect
Bleb (bulla) rupture
Perforating injuries
Post needle biopsy
 EFFUSIONS
TRANSUDATE (HYDROTHORAX)
EXUDATE (HYDROTHORAX)
BLOOD (HEMOTHORAX)
LYMPH (CHYLOTHORAX)
General Pathology

GASTROINTESTINAL DISEASES
 PEPTIC ULCER
An ulcer is defined as disruption of the mucosal
integrity of the stomach and/or duodenum
leading to a local defect or excavation due to
active inflammation.

It is the net result of a lack of homeostasis

between factors within the gastrointestinal tract
responsible for the breakdown of food (e.g.,
gastric acid and pepsin) and factors that promote
epithelial defense and repair (e.g., bicarbonate,
mucus secretion, and prostaglandins).
 ETIOLOGY OF PEPTIC ULCER DISEASE

Peptic ulcers are most commonly caused by one of

three etiologies:
H. pylori infection
95% or more of duodenal ulcers and 80 85% of gastric ulcers are
associated with H. pylori.
Use of NSAIDs
NSAID-related peptic ulcers usually occur in the stomach; duodenal
ulcers are much less common.
Stress-related mucosal damage (SRMD)
most frequently in critically ill patients and is thought to be caused
by factors such as compromised mesenteric perfusion rather than
HP or NSAIDs.
Helicobacter pylori
 Helicobacter pylori
H. pylori is an S-shaped, Gram-negative rods with lophotrichous
flagellation.
Cultures from stomach biopsies are grown on enriched mediums and
selective mediums under microaerobic conditions (90% N2, 5% CO2,
and 5% O2) for three to four days.
Identification is based on detection of oxidase, catalase, and urease.

H. pylori occurs only in humans and is transmitted by the fecal-oral

pathway. The pathogen colonizes and infects the stomach mucosa.

A number of host and pathogenic factors contribute to the ability of

HP to cause gastroduodenal mucosal injury including:
direct mucosal damage
alterations to host inflammatory responses
hypergastrinemia leading to a state of elevated acid secretion.
Pathophysiology of Helicobacter pylori-
induced ulcer
Once the pathogen has infected the stomach tissues an
acute gastritis results, the course of which may or may
not involve overt symptoms. Potential sequelae include:

Mild chronic gastritis that may persist for years or even

decades and is often asymptomatic.
Duodenal ulceration, sometimes gastric ulceration as
well.
Chronic atrophic gastritis from which a gastric
adenocarcinoma sometimes develops.
Rarely, B cell lymphomas of the gastric mucosa
(MALTomas).
INFLAMMATORY BOWEL DISEASE
CROHNS DISEASE Cobblestone pattern
 Extra-intestinal manifestation of IBD

pyoderma gangrenosum
(involving papules and vesicles that develop into painful
ulcerations)
Extra-intestinal manifestation of IBD

erythema nodosum
(red nodules of varying size typically found on the lower
extremities)
Extra-intestinal manifestation of IBD

Ocular involvement with episcleritis, uveitis, or

iritis may manifest as blurred vision, eye pain, and
photophobia.
Extra-intestinal manifestation of IBD
 ULCERATIVE COLITIS
formation of crypt abscesses within the
mucosal layers of the GI tract
Severe inflammation may also result in areas
of hypertrophied GI mucosa, which may
manifest as pseudopolyps within the colon
General Pathology

CARDIOVASCULAR DISEASES
 RHEUMATIC Heart Disease
Follows a group A strep infection, a few
weeks later

PANCARDITIS: 1) Endocarditis,
2) Myocarditis, 3) Pericarditis
ACUTE:
-Inflammation
-Aschoff body/ nodule
-Anitschkow cells
-Pancarditis
-Vegetations on
chordae tendinae at
leaflet junction

CHRONIC:
THICKENED VALVES
COMMISURAL FUSION
THICK, SHORT,
CHORDAE TENDINAE
 INFECTIOUS ENDOCARDITIS
Microbes

Usually strep viridans

Often Staph aureus in IVD users
Enterococci

HACEK (normal oral flora, gram - , in children)

Hemophilus influenzae
Actinobacillus
Cardiobacterium
Eikenella
Kingella
Fungi, rickettsiae, chlamydia
Splinter
hemorrhages,
Janeway lesions
(palms, soles),
Oslers nodes
(raised),
Roths spots (eye).
 PERICARDIUM
Normally 30-50 ml clear serous fluid
Visceral (epicardium)
Parietal (fibrous pericardium)

PERICARDIAL EFFUSIONS TAMPONADE

Ruptured MI
Traumatic perforation
Ruptured aortic dissection
 PERICARDITIS
SEROUS: Rheum. Fever (RF), SLE, scleroderma,
tumors, uremia
FIBRINOUS: MI (Dressler), uremia, radiation, RF,
SLE, s/p open heart surgery
PURULENT: infective, bacterial
HEMORRHAGIC: Malignancy, TB
CASEOUS: TB
CHRONIC: (ADHESIVE, CONSTRICTIVE)
 TUMORS
90% benign mesenchymal, i.e., stromal
MYXOMAS (LEFT ATRIUM MOST
COMMON)
FIBROMAS
LIPOMAS
FIBROELASTOMAS (valvular, usually papillary)
RHABDOMYOMA (Most common cardiac tumor in children)
10% SARCOMAS
MYXOMA
General Pathology

CNS DISEASES
 CNS
Normal
Neurons
Glia
Astrocytes
Oligodendrocytes
Ependymal Cells
Microglia
 CEREBRAL EDEMA
EDEMA AND HERNIATION
Subfalcine (SUPRA-tentorial)
Cingulate (TENTORIAL)
Cerebellar tonsilar (SUB-tentorial,
or INFRA-tentorial)
HYDROCEPHALUS
 HYDROCEPHALUS
Impaired RESORPTION
Increased PRODUCTION

OBSTRUCTION
COMMUNICATING (entire)
NON-COMMUNICATING (part)
HIGH Pressure
NORMAL Pressure
NEURAL TUBE DEFECTS
 SUBARACHNOID
HEMORRHAGE
Rupture of large intracerebral arteries
which are the primary branches of the
anatomical circle (of Willis)

Congenital (berry aneurysms)

Atherosclerotic (atherosclerotic
aneurysms, or direct wall rupture)
 CNS INFECTIONS
Meningitis (generally* bacterial)
E. coli, Strep B (neonates)
H. influenzae (children)
Neisseria meningitidis (adults)
Strep. pneumoniae, Listeria (elderly)
PMNs in CSF, INCREASED protein, REDUCED glucose
Encephalitis (generally viral)
Arboviruses, HSV, CMV, V/Z, polio, rabies, HIV
Lymphs and macrophages in perivascular Virchow-Robbins
spaces
Meningoencephalitis
 PRION DISEASES
Transmissible spongiform encephalopathies
Creutzfeldt-Jakob Disease (CJD)
Gerstmann-Straussler-Scheinker syn. (GSS)
Fatal familial insomnia
Kuru, human variety (cannibalism)
Scrapie (sheep and goats)
Mink transmissible encephalopathy
Chronic wasting disease (deer and elk)
Bovine Spongiform Encephalopathy (BSE)
 PRION DISEASES:
common features
Infectious agents with apparently no
DNA
DEMENTIA
Prion Protein (PrP) accumulation
SPONGIFORM changes in neurons and
glia
TRANSMISSIBLE, FATAL
PRION PROTEIN
Normally found in
humans
Exact structure
known, 208 amino
acids
Specific
chromosome, #20,
specific genes also
known
Requires a
conformational
change to
accumulate and do
damage
CNS DEGENERATIVE DISEASES
CORTEX (dementias)
BASAL GANGLIA and BRAIN STEM
(parkinsonian)
SPINOCEREBELLAR (ataxias)
MOTOR NEURONS (muscle atrophy)
 ALZHEIMERs DISEASE
Most common cause of dementias (majority)
Sporadic, 5-10% familial
CORTICAL (grey matter) ATROPHY
NEURITIC PLAQUES* (extraneuronal)
NEUROFIBRILLARY TANGLES
(intraneuronal)
AMYLOID!!! (i.e., BETA amyloid)
 PARKINSONs DISEASE
PALLOR of the
SUBSTANTIA NIGRA (and LOCUS
COERULEUS)

LEWY BODIES (alpha-synuclein protein)

Lewy bodies are commonly regarded as diagnostic of
Parkinsons disease also. The main substance of the
eosinophilic inclusion is alpha-synuclein.
 PARKINSON DISEASE
Parkinsonism symptoms, i.e.,
cogwheel rigidity
intention tremor
Progressive
Hallucinations
Dementia
Symptomatic response to L-DOPA
 Amyotrophic Lateral Sclerosis
Unknown etiology
Progressive muscle atrophy due to motor neuron
loss (lower, upper)
5-10% familial
Lou Gehrig had it, so does Steven Hawking
Hand weakness diaphragm
Anterior horn cells reduced and gliotic
 A.L.S., DEMYELINATION IN
CORTICOSPINAL TRACTS

ALS, pathologic changes in anterior horn cells

 ACQUIRED TOXIC/METABOLIC
CNS DISEASES
Vitamin B1 deficiency (Wernicke-Korsakoff)
Vitamin B12 deficiency (vibratory sense)
Diabetes Increased/Decreased GLUCOSE
Hepatic Failure (NH4+)
CO (Cortex, hippocampus, Purkinje cells)
CH3-OH, Methanol (Retinal ganglion cells)
 CNS TUMORS
GLIOMAS (do not metastasize out of the CNS)
Astrocytes
Oligodendroglioma
Ependymoma
NEURONAL (neuroblastoma)
POORLY DIFFERENTIATED (medulloblastoma)
MENINGIOMAS
LYMPHOMAS
METASTATIC
 MENINGIOMAS
Occur where dura is
Very vascular
BENIGN
Can invade skull, etc.
Only invade (displace) brain
in areas adjacent to dura, i.e.,
parasagittal, falx, tentorium,
venous sinuses
Small, firm, and well defined
like a SUPERBALL
Often have
PSAMMOMA bodies
END