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Pathology & Pathophysiology - Pathologie - Patologia

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REFERENCES

TOC
OVERVIEW
DIAGNOSTIC
TESTS

GENERAL PATHOLOGY
CELL & MOLECULAR BIOLOGY
CELL INJURY, CELL DEATH & ADAPTATIONS - AGING
INFLAMMATION (ACUTE & CHRONIC) & REPAIR (REGENERATION & HEALING)
WATER, ELECTROLYTE & ACID-BASE DISORDERS
HEMODYNAMIC DISORDERS, THROMBOEMBOLIC DISEASE & SHOCK
GENETIC DISORDERS
IMMUNE SYSTEM - AMYLOIDOSIS
NEOPLASIA
INFECTIOUS DISEASES
ENVIRONMENTAL & NUTRITIONAL DISEASES
ENVIRONMENT
NUTRITION
INFANCY & CHILDHOOD

SYSTEMIC PATHOLOGY : DISEASES OF ORGAN SYSTEMS
BLOOD VESSELS
HEART
WHITE BLOOD CELLS, LYMPH NODES, SPLEEN, & THYMUS
RED BLOOD CELL & BLEEDING DISORDERS
LUNG
HEAD & NECK, ORAL CAVITY & SALIVARY GLANDS - ENT
GASTROINTESTINAL TRACT
LIVER & GALLBLADDER & BILIARY TRACT
PANCREAS
KIDNEY
LOWER URINARY TRACT & MALE GENITAL SYSTEM
FEMALE GENITAL TRACT
BREAST
METABOLIC DISORDERS
ENDOCRINE SYSTEM
SKIN
BONES, JOINTS & SOFT TISSUE TUMORS
PERIPHERAL NERVES & SKELETAL MUSCLES - MYOPATHIES & NEUROPATHIES
CENTRAL NERVOUS SYSTEM
EYE
EAR

REFERENCES

MAPS

OVERVIEW

CONTENTS
(Schneider) V1 PDF
(Robbins PBD 2014) V1 PDF
(Robbins BP 2012) V1 PDF

HISTORY EVOLUTION

DIAGNOSTIC
(Gattuso) V1 PDF
Light microscopy
Histologic stains
Fluorescence microscopy
Electron microscopy
Immunohistochemistry
Flow cytometry
Cytogenetic Analysis
Molecular
Exfoliative Cytology
Interventional Cytology

TOC
TESTS

PURPOSES OF LABORATORY TESTS
Screen for disease
Confirm disease
Monitor disease status

OPERATING CHARACTERISTICS OF LABORATORY TESTS
Terms for test results for people with a specific disease
Terms for test results for people without disease
Sensitivity of a test
Specificity of a test
Comments on using tests with high sensitivity and specificity
Use of multiple tests to improve sensitivity or specificity of a test
“Gold standard” test
Examples of sensitivity and specificity of common tests

PREDICTIVE VALUE OF POSITIVE AND NEGATIVE TEST RESULTS LIKELIHOOD RATIO
Predictive value of a negative test result (PV−)
Predictive value of a positive test result (PV+)
Effect of prevalence on PV− and PV+
Likelihood ratio (LR)

PRECISION AND ACCURACY OF TEST RESULTS
Precision
Accuracy

NORMAL RANGE OF A TEST
Establishing the normal range (reference interval) of a test using a Gaussian distribution
General methods of reporting laboratory test results

CREATING HIGHLY SENSITIVE AND SPECIFIC TESTS
Ideal test
Establishing a test with 100% sensitivity and 100% PV−
Establishing a test with 100% specificity and PV+
Critical values (“panic or “alert” values) for a test

VARIABLES AFFECTING SELECTED LABORATORY TESTS (PREANALYTIC VARIABLES)
Age
Pregnancy
Diet
Other variables

TOC
GENERAL PATHOLOGY

TOC
MOLECULAR CELL BIOLOGY
(Robbins Summary) V2 PDF

THE GENOME
Noncoding DNA
Histone Organization
Micro-RNA and Long Noncoding RNA
Gene Editing

CELLULAR HOUSEKEEPING
Plasma Membrane: Protection and Nutrient Acquisition
Cytoskeleton
Cell-Cell Interactions
Biosynthetic Machinery: Endoplasmic Reticulum and Golgi
Waste Disposal: Lysosomes and Proteasomes  

CELLULAR METABOLISM AND MITOCHONDRIAL FUNCTION

CELLULAR ACTIVATION
Cell Signaling
Signal Transduction Pathways
Modular Signaling Proteins, Hubs, and Nodes
Transcription Factors

GROWTH FACTORS AND RECEPTORS

EXTRACELLULAR MATRIX
Components of the Extracellular Matrix

MAINTAINING CELL POPULATIONS
Proliferation and the Cell Cycle
Stem Cells
Regenerative Medicine

TOC
CELLULAR INJURY
(Sattar) V1 PDF
(Schneider) V1 PDF
(Robbins Summary) V2 PDF

INTRODUCTION TO PATHOLOGY

OVERVIEW OF CELLULAR RESPONSES TO STRESS & NOXIOUS STIMULI
Causes of Cell Injury
Aging
Oxygen Deprivation  : Anoxia (complete lack of oxygen), Hypoxia (inadequate oxygen)
Physical Agents
Chemical Agents & Drugs
Free radicals
Infectious Agents Microbes
Immunologic Reactions
Genetic Abnormalities Genetic & metabolic disorders
Inflammation & immune reactions
Nutritional Imbalances Nutritional deficiencies
Intracellular accumulations

The Progression of Cell Injury and Death

Injury to Cellular Organelles

REVERSIBLE CELL INJURY
Reversible cell injury
Irreversible cell injury

CELL DEATH
Cell death occurs when cells or tissues are unable to adapt to injury

NECROSIS
dystrophic calcification
Causes
Ischemia/hypoxia
Ischemia/reperfusion injury
Chemical/toxic injury
Morphology
Myelin figures

PATTERNS OF TISSUE NECROSIS - TYPES OF NECROSIS
Coagulat-ive -ion necrosis > white red infarct
Definition
Mechanism
Microscopic features
Infarction
Liquefactive
Definition
Mechanism
Examples
Caseous necrosis
Definition
Mechanism
Microscopic features of caseous necrosis in a granuloma
Gummatous necrosis
Definition
Mechanism
Locations for gummas
Gross and microscopic appearance of gummas
Enzymatic Fat necrosis > saponification
Definition
Mechanism in pancreas
Traumatic fat necrosis
Fibrinoid necrosis
Gangrenous necrosis

Ischemia
Types of infarcts
Red infarct
Pale infarct

Free radical injury

Ionizing radiation toxicity

APOPTOSIS
Causes of Apoptosis
physiologic
pathologically
Morphologic & Biochemical Changes in Apoptosis
Mechanisms of Apoptosis
Intrinsic (mitochondrial) pathway
Extrinsic (death receptor) pathway  Autoimmune lymphoproliferative syndrome

OTHER MECHANISMS OF CELL DEATH
Pyroptosis

Enzyme markers of cell death

AUTOPHAGY

MECHANISMS OF CELL INJURY
General Mechanisms of Cell Injury & Intracellular Targets of Injurious Stimuli
Mitochondrial Damage
Membrane Damage
Damage to DNA
Oxidative Stress: Accumulation of Oxygen-Derived Free Radicals
Generation of Free Radicals
Removal of Free Radicals
Pathologic Effects of Free Radicals
Disturbance in Calcium Homeostasis
Endoplasmic Reticulum Stress: the Unfolded Protein Response

CLINICOPATHOLOGIC CORRELATIONS : SELECTED EXAMPLES OF CELL INJURY & DEATH
Hypoxia & Ischemia
Mechanisms of Ischemic Cell Injury
Ischemia-Reperfusion Injury
Chemical (Toxic) Injury

TISSUE HYPOXIA
Hypoxia
Definition: Hypoxia is inadequate oxygenation of tissue
Factors contributing to the total amount of O2 carried in blood
In hypoxia, there is decreased synthesis of adenosine triphosphate (ATP)
Clinical findings
Causes of tissue hypoxia
Ischemia
Hypoxemia
Hemoglobin (Hb)-related abnormalities
Mitochondrial causes of ATP depletion
Enzyme inhibition of oxidative phosphorylation
Uncoupling of oxidative phosphorylation
Tissues susceptible to hypoxia
Watershed areas between terminal branches of major arterial blood supplies are susceptible to hypoxic injury
Hepatocytes located around the central venules
Subendocardial tissue
Renal cortex and medulla
Neurons in the CNS
Consequences of hypoxic cell injury
Reversible changes in the cells
Irreversible changes in the cell

FREE RADICAL CELL INJURY
Overview of free radicals (FRs)
Definition
Radicals attack a molecule and “steal” its electron, causing that molecule to become an FR,the net result of which is a chain of reactions that ultimately leads to cell death
Biologic FRs are generated predominantly from oxygen metabolism
FRs primarily target nucleic acids and cell membranes (CMs)
FR damage is cumulative and is part of the normal aging process
FRs are important in microbial killing by neutrophils and monocytes
FRs are important in the reperfusion injury associated with fibrinolytic therapy in an acute myocardial infarction
Production and types of FRs
Reactive oxygen species
Other examples of FRs
Neutralization of FRs
Clinical examples of FR injury

INJURY TO CELLULAR ORGANELLES
Mitochondria
Smooth endoplasmic reticulum (SER)
Lysosomes
Cytoskeleton

ADAPTATIONS OF CELLULAR GROWTH & DIFFERENTIATION  - CELLULAR ADAPTATIONS - ADAPTATION TO CELL INJURY: GROWTH ALTERATIONS
Hypertrophy
Mechanisms of Hypertrophy
Definition
Hypertrophy in muscle tissue is caused by increased workload
Surgical removal of one kidney produces compensatory hypertrophy
Cell enlargement occurs in cytomegalovirus infections
Hyperplasia
Definition
Causes
Mechanisms of Hyperplasia
Increased risk for progressing into cancer, in some types of hyperplasia
Atrophy
Mechanisms of Atrophy
Definition
Causes
Cellular and metabolic changes
Metaplasia
Definition
Types of metaplasia
Mechanisms of Metaplasia
Dysplasia
Definition
Risk factors
Microscopic features of dysplasia

INTRACELLULAR ACCUMULATIONS
Types of accumulations
Lipids
Steatosis (Fatty Change)
Cholesterol and Cholesterol Esters
Iron accumulation
Ferritin
Hemosiderin
Proteins
Hyaline Change
Glycogen
Pigments
Exogenous Pigments
Endogenous Pigments
Lipofuscin
 
PATHOLOGIC CALCIFICATION
Dystrophic Calcification
Metastatic Calcification

(CELLULAR) AGING - NORMAL AGING
Theories of aging
Stochastic (random error) theories
Programmed cell death theory
Age-dependent changes
Age-related changes
Changes with aging and clinical consequences
Progeria

TOC
INFLAMMATION
(Le FA 1) Cellular Injury & Inflammation V1 PDF
(Sattar) V1 PDF
(Schneider) V1 PDF
(Robbins Summary) V2 PDF

OVERVIEW OF INFLAMMATION: DEFINITIONS AND GENERAL FEATURES
Historical Highlights
Causes of Inflammation
Recognition of Microbes & Damaged Cells
Cardinal signs
1 Rubor & Calor
2 Tumor
3 Dolor
Functio laesa

Exudate vs Transudate

ACUTE INFLAMMATION
STIMULI OF AI
Infections
Other stimuli
MEDIATORS OF AI
Inflammasome
COMPONENTS : VASCULAR & CELLULAR
Reactions of Blood Vessels -  Vascular Reaction - Sequential
1 Vasoconstriction of arterioles
Changes in Vascular Flow and Caliber - 2 Vasodilation of arterioles
Increased Vascular Permeability (Vascular Leakage) - 3 Increased permeability of venules
4 Swelling of tissue
5  Reduced blood flow eventually occurs
Responses of Lymphatic Vessels and Lymph Nodes
Stasis >
Leukocyte Recruitment to Sites of Inflammation - Cellular Reaction - Sequential
complement component 5a extravasation
Neutrophils 1° leukocytes AI
1 Margination &
2 Rolling
3 Tight binding - Leukocyte (Firm) Adhesion to Endothelium
4 Diapedesis - Leukocyte Trans-Migration Through Endothelium  Migration
5 Migration - Chemotaxis of Leukocytes
6 Neutrophil phagocytosis & killing of bacteria
Phagocytosis & Clearance of the Offending Agent
Phagocytosis
Intracellular Destruction of Microbes and Debris
Neutrophil Extracellular Traps
Leukocyte-Mediated Tissue Injury
Other Functional Responses of Activated Leukocytes
TERMINATION OF AI RESPONSE
Mediators short half-life
Lipoxins Inhibit transmigration/chemotaxis Enhance apoptosis
Resolvins Inhibit recruitment inflammatory cells
Mediators of Inflammation - Local & Systemic effects Mediators have diverse functions
Vasoactive Amines: Histamine and Serotonin
Arachidonic Acid Metabolites
Cytokines and Chemokines
Complement System
Other Mediators of Inflammation

MORPHOLOGIC PATTERNS OF AI - TYPES OF AI
Location, cause, and duration of inflammation determine the morphology of an inflammatory reaction
Serous
Definition
Examples
Fibrinous
Definition
Common locations
Clinical signs
Purulent (Suppurative) & Abscess
Definition
Staphylococcus aureus
Cellulitis
Definition
Group A streptococcus
Signs
Symptoms
Pseudomembranous
Ulcers Ulcerative

OUTCOMES OF ACUTE INFLAMMATION - CONSEQUENCES OF AI
Persistent acute inflammation (IL-8)
1 Resolution Complete resolution AI Resolution & healing (IL-10, TGF-β) 1st-degree burn, bee sting
2 Tissue destruction, scarring formation 3rd-degree burn, acute myocardial infarction Fibrosis
3 Abscess (acute inflammation walled off by fibrosis) Collection liquefied material (pus); lung abscess
4 Fistula formation Open lumen connecting two hollow spaces
5 Progression to Chronic inflammation (antigen presentation by macrophages and other APCs activation of CD4+ Th cells)

Leukocyte extravasation
Extravasation predominantly occurs at postcapillary venules

CLINICAL FINDINGS IN AI

CHRONIC INFLAMMATION
DEFINITION OF CI
Prolonged inflammation; persistence injury-causing agent
Causes of Chronic Inflammation - Stimuli
Persistent microbial & viral infection MCC, TB, leprosy
Prolonged exposure to a toxic agent
Autoimmune diseases SLE, RA
Inflammatory reaction to sterile agents; Silicosis, gout, silicone breast implants, suture material
Morphologic Features
Cells & Mediators of Chronic Inflammation - Cell types that define CI
Role of Macrophages - Monocytes and/or macrophages are the key cells
Role of Lymphocytes
Other Cells in CI
Loss parenchyma → lossfunctional tissue → repair by fibrosis
Formation of granulation tissue
Vascular tissue composed blood vessels/fibroblasts
Fibronectin
Comparison of Acute and Chronic Inflammation
Granulomatous Inflammation
Specialized CI forming granulomas
Histology
Mechanism
Etiologies Infectious Noninfectious - Causes
Morphology
Outcomes of CI

SYSTEMIC EFFECTS OF INFLAMMATION - Systemic manifestations (acute-phase reaction)
Fever
Leukocytosis
Augment plasma acute-phase reactants

PATHOGENESIS & ROLE OF FEVER IN AI
Pathogenesis of fever
Beneficial effects of fever
Fever in children
Fever in adults
Fever in hospitalized patients
Fever in travelers recently in the tropics
Fever of unknown origin (FUO)

ACUTE PHASE REACTANTS APRs
1 Acute phase reactants are proteins whose serum concentrations either increase or decrease by at least 25% during an inflammatory state
All APRs are synthesized by the liver
2 IL-6 major inducer APRs
3 Positive (upregulated)
C-reactive protein
Ferritin
Fibrinogen
Haptoglobin
Hepcidin
Procalcitonin
Serum amyloid A
4 Negative (downregulated)
Albumin
Transferrin
Transthyretin
5 Cachexia (wasting), anorexia, impaired growth in children

Erythrocyte Sedimentation Rate

TISSUE REPAIR
Overview of Tissue Repair - Parenchymal cell regeneration/repair by fibrosis
Cell & Tissue Regeneration - Parenchymal cell regeneration
Cell Proliferation: Signals and Control
Mechanisms
Mechanisms of Tissue Regeneration
Repair by Connective Tissue Deposition - Repair by connective tissue (fibrosis)
Steps in Scar Formation
Angiogenesis
Deposition of Connective Tissue
Remodeling of Connective Tissue
Factors That Influence Tissue Repair - Factors that impair wound healing
Examples of Tissue Repair & Fibrosis
Healing of Skin Wounds
Fibrosis in Parenchymal Organs
Repair in other tissues
Liver
Lung
Brain
Peripheral nerve transection
Heart
Skeletal muscle after exercise
Abnormalities in Tissue Repair
Defects in Healing: Chronic Wounds
Excessive Scarring

Wound healing
Tissue mediators
Inflammatory (up to 3 days after wound)
Proliferative (day 3–weeks after wound)
Remodeling (1 week–6+ months after wound)

Scar formation
Hypertrophic scar
Keloid scar

LABORATORY FINDINGS ASSOCIATED WITH INFLAMMATION
Leukocyte and plasma alterations
AI (e.g., bacterial infection)
Chronic inflammation (CI; e.g., TB, RA)
Peripheral blood findings associated with corticosteroid therapy
C-reactive protein (CRP)
Definition
Measurement of serum CRP is clinically useful
Erythrocyte sedimentation rate
Serum protein electrophoresis in inflammation
AI
CI

TOC
WATER, ELECTROLYTE & ACID-BASE DISORDERS

WATER & ELECTROLYTE DISORDERS

BODY FLUID COMPARTMENTS
Definition ≈60% body weight kg
TBW distribution
Na+ ECF cation, Cl− ECF anion
K+ ICF cation, PO4 3− ICF anion
POsm
POsm: number osmoles in plasma mOsm/kg
Three different tonicity states may be present in a person
POsm = 2 (serum Na+) + serum glucose/18 + serum BUN/2.8 = 275–295 mOsm/ kg
Osmotic gradient: ↓/↑ Na+ concentration; ↑glucose
Hyponatremia: ↓serum Na+/POsm
Osmotic gradient: H2O moves from ECF to ICF (always expanded)
H2O moves from ICF (contracted) to ECF

HYPOTONIC, ISOTONIC & HYPERTONIC DISORDERS
Serum Na+ ≈ TBNa+/TBW
Hypotonic disorders: clinical findings that correlate with a decrease in TBNa+
Isotonic fluid disorders
Isotonic loss of fluid
Isotonic gain of fluid
Hypotonic fluid disorders
Hyponatremia, ↓POsm
Hyponatremia caused by a hypertonic loss of Na+
Gain of pure water
Hypotonic gain of Na+ and water
Child: seizures commonly occur
Pseudohyponatremia
Hypertonic fluid disorders
Hypernatremia/hyperglycemia
Increase in POsm is most often due to hypernatremia or hyperglycemia, the latter being more common due to the high incidence of diabetes mellitus
Hypotonic loss of Na+
Loss of pure water
Hypertonic gain of Na+
Hypertonic state due to hyperglycemia

VOLUME CONTROL
Effective Arterial Blood Volume
Baroreceptors and the Renin-Angiotensin-Aldosterone System
Renal Mechanisms in Volume Regulation

OVERVIEW OF FUNCTIONS OF THE MAJOR NEPHRON SEGMENTS
Proximal renal tubule
Thick ascending limb (TAL; medullary segment)
Na+-Cl− symporter in the early distal tubule
Aldosterone-enhanced Na+ and K+ epithelial channels in the late distal tubule and collecting ducts
Aldosterone-enhanced H+/K+-ATPase pump
Electrolyte changes in Addison disease
Primary aldosteronism

CLINICAL CONDITIONS ASSOCIATED WITH DILUTION ABNORMALITIES
Overview of normal dilution of urine
Diabetes insipidus

CLINICAL CONDITIONS ASSOCIATED WITH CONCENTRATION ABNORMALITIES
Overview of normal concentration of urine
Syndrome of inappropriate antidiuretic hormone (SIADH)

POTASSIUM (K+) DISORDERS
Functions of potassium include regulation of the following
Potassium handling by the kidneys
Control of potassium
Hypokalemia
Hyperkalemia

ACID-BASE DISORDERS

PRIMARY ALTERATIONS IN ARTERIAL Pco2 (NORMAL RANGE OF Paco2 = 33–45 mm Hg)
Respiratory acidosis
Respiratory alkalosis

PRIMARY ALTERATIONS IN HCO3− (22–28 mEq/L)
Metabolic acidosis
Metabolic alkalosis

MIXED ACID-BASE DISORDERS

SCHEMATIC OF ACID-BASE DISORDERS

SELECTED ELECTROLYTE PROFILES

SELECTED ARTERIAL BLOOD GAS PROFILES

FORMULAS FOR CALCULATIONS OF ACID-BASE DISORDERS

TOC
HEMODYNAMIC  HOMEOSTASIS
(Schneider) V1 PDF
(Robbins Summary) V2 PDF

EDEMA & EFFUSIONS
Definition of edema
Types of edema
Transudate
Exudate
Lymphedema
Myxedema
Pathophysiology of edema
Transudate: alteration in Starling forces
Increased vascular permeability in venules
Lymphatic Obstruction
Increased Hydrostatic Pressure
Reduced Plasma Osmotic Pressure
Sodium & Water Retention
Myxedema is produced when there is increased synthesis of extracellular matrix components
Clinically important forms of localized edema

HYPEREMIA & CONGESTION

HEMOSTASIS, HEMORRHAGIC DISORDERS, & THROMBOSIS
Normal Hemostasis
Platelets
Coagulation Cascade
Endothelium
Hemorrhagic Disorders

THROMBOSIS
Definition
Pathogenesis
Endothelial Injury
Alterations in Normal Blood Flow - Stasis of blood flow
Hypercoagulability
Types
Definition
Venous thrombus
Arterial thrombus
Postmortem clot
Fate of the Thrombus

DISSEMINATED INTRAVASCULAR COAGULATION (DIC)

EMBOLISM
Detached mass → blood → distant site
Pulmonary (thrombo) Embolism (PE)
Sites of origin of an embolus
Clinical findings
Paradoxical embolism
Systemic (Thrombo)embolism
Embolus in arterial system
Causes
Target sites for systemic embolization
Complications of systemic embolization
Fat Embolism
Microglobules fat post traumatic fracture
Epidemiology
Clinical findings
Laboratory findings
Air Embolism
Amniotic Fluid Embolism
Tears placental membranes; rupture uterine veins postpartum
Epidemiology
Clinical findings
Laboratory findings
Decompression sickness
Gas embolism; scuba diving, deep sea diving
Epidemiology; pathogenesis
Clinical findings
Recompression in high pressure chamber followed by slow decompression

INFARCTION

SHOCK
Reduced perfusion to tissue → impaired oxygenation
Types of shock
Hypovolemic shock
Cardiogenic shock
Septic Shock
Pathogenesis of Septic Shock
Stages of Shock

TOC
GENETIC & DEVELOPMENTAL DISORDERS
(Schneider) V1 PDF
(Robbins Summary) V2 PDF

GENES & HUMAN DISEASES

MUTATIONS
Permanent change in DNA
Point mutations
Frameshift mutation
Trinucleotide repeat disorder

MENDELIAN DISORDERS

OVERVIEW OF MENDELIAN DISORDERS

TRANSMISSION PATTERNS OF SINGLE-GENE DISORDERS
Autosomal Dominant Disorders
Inheritance pattern characteristics
Autosomal dominant protein defects
Other autosomal dominant disorders include von Willebrand disease (vWD; MC autosomal dominant disorder), Huntington disease, osteogenesis imperfecta, achondroplasia, tuberous sclerosis, hereditary spherocytosis, myotonic dystrophy, and familial hypercholesterolemia
Autosomal Recessive Disorders
Inheritance pattern characteristics of autosomal recessive disorders
Autosomal recessive protein defects
Selected inborn errors of metabolism
Other autosomal recessive disorders include hemochromatosis (MC), 21-hydroxylase deficiency, Wilson disease, and thalassemia
X-Linked Disorders
X-linked recessive (XR) disorders
Inheritance pattern characteristics
Sex-linked recessive protein defects
Fragile X syndrome (FXS)
Lesch-Nyhan syndrome
Other XR disorders include androgen insensitivity syndrome (AIS), chronic granulomatous disease (CGD), Bruton agammaglobulinemia (BAG), and glucose-6- phosphate dehydrogenase (G6PD) deficiency
X-linked dominant (XD) disorders
Inheritance pattern characteristics
Vitamin D–resistant rickets

Biochemical & Molecular Basis of Single-Gene (Mendelian) Disorders
Enzyme Defects and Their Consequences
Defects in Receptors and Transport Systems
Alterations in Structure, Function, or Quantity of Nonenzyme Proteins
Genetically Determined Adverse Reactions to Drugs
Disorders Associated With Defects in Structural Proteins
Marfan Syndrome
Ehlers-Danlos Syndromes (EDSs)
Disorders Associated With Defects in Receptor Proteins
Familial Hypercholesterolemia
Disorders Associated With Enzyme Defects
Lysosomal Storage Diseases
Glycogen Storage Diseases
(Glycogenoses)
Disorders Associated With Defects in
Proteins That Regulate Cell Growth

COMPLEX MULTIGENIC DISORDERS

CHROMOSOMAL DISORDERS

GENERAL CONSIDERATIONS IN CHROMOSOMAL DISORDERS
NORMAL KARYOTYPE

STRUCTURAL ABNORMALITIES OF CHROMOSOMES
CHROMOSOMAL ALTERATIONS
Numeric/structuralabnormalities → autosomes  or sex chromosomes
Nondisjunction
Mosaicism
Translocation
Deletion

CYTOGENETIC DISORDERS INVOLVING AUTOSOMES
Trisomy 21 (Down Syndrome)
Trisomy 18: Edwards syndrome
Patau syndrome
Other Trisomies
Chromosome 22q11.2 Deletion Syndrome

CYTOGENETIC DISORDERS INVOLVING SEX CHROMOSOMES
Klinefelter Syndrome
Turner Syndrome
XYY syndrome
Hermaphroditism and Pseudohermaphroditism

SINGLE-GENE DISORDERS WITH NONCLASSIC INHERITANCE - OTHER PATTERNS OF INHERITANCE
Multifactorial (complex) inheritance
Diseases Caused by Trinucleotide-Repeat Mutations
Fragile X Syndrome (FXS)
Fragile X–Associated Tremor/Ataxia Syndrome
and Fragile X–Associated Primary Ovarian
Failure
Mutations in Mitochondrial Genes—Leber Hereditary Optic - Mitochondrial DNA (mtDNA) disorders
Neuropathy
Genomic Imprinting
Prader-Willi Syndrome and Angelman
Syndrome
Gonadal Mosaicism

DISORDERS OF SEX DIFFERENTIATION
Normal sex differentiation
True hermaphrodite
Pseudohermaphrodite
Androgen insensitivity syndrome (AIS; testicular feminization)

CONGENITAL ANOMALIES
Defect recognized only at birth
Epidemiology
Pathogenesis of congenital anomalies

PERINATAL AND INFANT DISORDERS
Stillbirth
Spontaneous abortion (miscarriage)
Sudden infant death syndrome (SIDS)
Prematurity and intrauterine growth impairment
Neonatal period

MOLECULAR GENETIC DIAGNOSIS - AND DEVELOPMENTAL DISORDERS
Invasive testing
Amniocentesis
Chorionic villus sampling
Noninvasive testing
Ultrasonography
Maternal triple marker screening
Genetic analysis
Karyotyping; ID numeric/structural abnormalities
DNA molecular assays: PCR, FISH
Diagnostic Methods & Indications for Testing
Laboratory Considerations
Indications for Analysis of Inherited Genetic Alterations
Indications for Analysis of Acquired Genetic Alterations
PCR & Detection of DNA Sequence Alterations
Molecular Analysis of Genomic Alterations
Fluorescence In Situ Hybridization (FISH)
Cytogenomic Array Technology
Polymorphic Markers and Molecular Diagnosis
Epigenetic Alterations
RNA Analysis
Next-Generation Sequencing (NGS)
Bioinformatics
Clinical Applications of Next-Generation DNA Sequencing
Future Applications

TOC
IMMUNE & AMYLOIDOSIS
(Schneider) V1 PDF
(Robbins Summary) V2 PDF

THE NORMAL IMMUNE RESPONSE

INNATE IMMUNITY
Nonadaptive immune response microbial/nonmicrobial pathogens
Components of Innate Immunity
Anatomic barriers, phagocytes, complement, APRs
Recognizes microbial structures
Effector Cells
Phagocytic, NK/DCs
Microglial/Kupffer cells
Eosinophils, mast cells
Mucosal, endothelial cells
Cellular Receptors for Microbes, Products of Damaged Cells, & Foreign Substances
Toll-like receptors (TLRs)
Nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs)
Natural Killer Cells
Reactions of Innate Immunity
Examples of noncellular innate immunity responses to infections
Human diseases: mutations/dysfunction TLRs

ADAPTIVE IMMUNITY - ACQUIRED
B/T cell protection from antigens produced by microbial pathogens
Cells of the Adaptive Immune System
B lymphocytes produce antibodies (i.e., humoral immune response)
B cells → antibodies
B cells → eliminate extracellular microbial pathogens
Naïve B cells produce IgM/IgD at birth
Antigen-stimulated B cells → IgM, isotype switching (IgG, IgE, IgA)
Isotype switching changes heavy chain locus in constant region of gene
CD4 TH cells → isotype switching
T cells are primarily involved in cell-mediated immunity (CMI)
CD4 TH/CD8 T cells → CMI
Activated T cells → eliminate intracellular microbial pathogens
Tissues of the Immune System

MAJOR HISTOCOMPATIBILITY COMPLEX MOLECULES MHC : THE PEPTIDE DISPLAY SYSTEM OF ADAPTIVE IMMUNITY
Overview of the MHC
Mark all body cells as “self”
Important in transplantation
Human leukocyte antigens
(HLAs)
Leukocytes; all nucleated cells except nucleated RBCs
Parents to children
Unique to each individual
Identical twins same set
HLA genes
HLA-A, HLA-B, HLA-C gene loci
Interact with CD8 T/NK cells
Altered antigens → destroyed by CD8 T cells/NK cells
CD8 T cells recognize class I molecules (8 × 1 = 8)
Encoded in HLA-D region (DP-DQ-DR subregions)
Class II proteins → CD4 TH cells
APCs: B cells, macrophages,DCs
Rule of 8: CD4 TH cells recognize class II molecules (4 × 2 = 8)
Class III molecules
Code for complement, HSP, TNF
HLA associations with disease
Applications of HLA testing
Transplantation workup
Disease risk
Developing antibodies against HLA antigens
Pregnancy
Fetal-maternal hemorrhage → maternal anti-HLA antibodies
Blow to abdomen, MVA, abruptio placenta, amniocentesis
Mother develops anti-HLA antibodies against fetal HLA antigens on leukocytes/platelets
Recipient develops antibodies against foreign HLA antigens in donor leukocytes/platelets
Recipient develops antibodies against foreign HLA antigens in donor organ

CYTOKINES : MESSENGER MOLECULES OF THE IMMUNE SYSTEM

OVERVIEW OF LYMPHOCYTE ACTIVATION & IMMUNE RESPONSES
Display and Recognition of Antigens
Cell-Mediated Immunity: Activation of T
Lymphocytes and Elimination of Intracellular Microbes
Humoral Immunity: Activation of B Lymphocytes and Elimination of Extracellular Microbes
Decline of Immune Responses and Immunologic Memory

HYPERSENSITIVITY : IMMUNOLOGICALLY MEDIATED TISSUE INJURY
CLASSIFICATION OF HYPERSENSITIVITY REACTIONS HSR

IMMEDIATE (TYPE I) HYPERSENSITIVITY
Definition
IgE activation mast cells/ basophils (effector cells)
Activation of Th2 Cells & Production of IgE Antibody - (sensitization)
Sensitization & Activation of Mast Cells - (re-exposure to allergen)
Mediators of Immediate Hypersensitivity
Late-Phase Reaction
Development of Allergies
Systemic Anaphylaxis
Local Immediate Hypersensitivity Reactions
Laboratory tests for type I hypersensitivity
Clinical examples

ANTIBODY-MEDIATED (TYPE II) HYPERSENSITIVITY - CYTOTOXIC
Definition
IgM/G/E antibodies directed against cell surface/ECM antigens
Complement-dependent reactions
Complement-independent reactions
Opsonization & Phagocytosis
Inflammation
Cellular Dysfunction
Tests used to evaluate type II hypersensitivity disease

IMMUNE COMPLEX–MEDIATED (TYPE III) HYPERSENSITIVITY
Definition
Circulating antigen-antibody complexes damage tissue
IC formation and their mechanism of tissue damage
Arthus reaction
Other clinical examples
Systemic Immune Complex Disease
Local Immune Complex Disease
Immunofluorescent staining of tissue biopsies identifies IC deposition

T CELL–MEDIATED (TYPE IV) HYPERSENSITIVITY
Definition
Antibody-independent T-cell CMI
Antigen activation CD4 and/or CD8 T cells
Delayed reaction hypersensitivity
Functions of CMI
Types of cell-mediated immunity
CD4+ T Cell–Mediated Inflammation
CD8+ T Cell–Mediated Cytotoxicity
Tests used to evaluate type IV hypersensitivity disorders
Additional clinical examples of CMI

AUTOIMMUNE DISEASES

DEFINITION
Loss self-tolerance; host tissue considered foreign
Self-antigens: class I/II MHC, nuclear/cytoplasmic

IMMUNOLOGIC TOLERANCE
Central Tolerance
Peripheral Tolerance

MECHANISMS OF AUTOIMMUNITY: GENERAL PRINCIPLES
Role of Susceptibility Genes
Role of Infections and Other Environmental Factors
General Features of Autoimmune Diseases

MARKERS OF AUTOIMMUNE DISEASE

CLASSIFICATION OF AUTOIMMUNE DISORDERS

LABORATORY EVALUATION OF AUTOIMMUNE DISEASE

SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)
Spectrum of Autoantibodies in Systemic Lupus
Erythematosus
Chronic Discoid Lupus Erythematosus
Subacute Cutaneous Lupus Erythematosus
Drug-Induced Lupus Erythematosus

RHEUMATOID ARTHRITIS

SJÖGREN SYNDROME

SYSTEMIC SCLEROSIS (SCLERODERMA)

INFLAMMATORY MYOPATHIES - NON INFECTIOUS

MIXED CONNECTIVE TISSUE DISEASE

POLYARTERITIS NODOSA AND OTHER VASCULITIDES

IGG4-RELATED DISEASE

REJECTION OF TISSUE TRANSPLANTS - TRANSPLANTATION IMMUNOLOGY
Factors that enhance graft viability
Must be ABO blood group compatibility between recipients and donors
Must be an absence of preformed anti-HLA cytotoxic antibodies in graft recipients
Must be close matches of HLA-A, HLA-B, HLA-C (minor importance), and HLA-DR loci between recipients and donors
Types of grafts
Mechanisms of Recognition & Rejection of Allografts
Recognition of Graft Alloantigens by T and B Lymphocytes
Patterns & Mechanisms of Graft Rejection
Methods of Increasing Graft Survival
Graft-versus-host (GVH) reaction
Transplantation of Hematopoietic Stem Cells (HSCs)

IMMUNODEFICIENCY DISEASES
Definition
Primary or secondary
Risk factors
Prematurity, autoimmune disease, lymphoproliferative disorders
Infections; immunosuppressive drugs
B-cell tests
T-cell tests

PRIMARY IMMUNODEFICIENCIES
Defects in Innate Immunity
Defects in Adaptive Immunity
Immunodeficiencies Associated With Systemic
Diseases

SECONDARY IMMUNODEFICIENCIES

ACQUIRED IMMUNODEFICIENCY SYNDROME (AIDS)
Epidemiology
Etiology: the Properties of HIV
Pathogenesis of HIV Infection and
AIDS
Natural History of HIV Infection
Clinical Features of AIDS

COMPLEMENT SYSTEM DISORDERS

AMYLOIDOSIS
Properties of Amyloid Proteins
Pathogenesis and Classification of Amyloidosis
SYSTEMIC
Primary amyloidosis
Secondary amyloidosis
Dialysis-related amyloidosis
LOCALIZED
Alzheimer disease
Type 2 diabetes mellitus
Medullary thyroid cancer
Isolated atrial amyloidosis
Systemic senile (age-related) amyloidosis
HEREDITARY
Familial amyloid cardiomyopathy
Familial amyloid polyneuropathies

TOC
NEOPLASIA
(Le FA 1) V1 PDF
(Sattar) V1 PDF
(Schneider) V1 PDF
(Robbins Summary) V2 PDF

NOMENCLATURE
Benign Tumors
Unregulated benign proliferation epithelial/connective tissue
Derivation of benign tumors of epithelial origin
Benign tumors of connective tissue origin
Unusual tumors that are usually benign : mixed, teratomas
Malignant Tumors (cancer)
Unregulated proliferation; invasion; possible spread
Carcinomas
Sarcomas
Tumor-like conditions
Hamartoma
Choristoma (heterotopic rest)
Mixed Tumors
Prefix
Suffix, benign
Suffix, malignant
Exception

PROPERTIES OF BENIGN & MALIGNANT TUMORS
COMPONENTS OF BENIGN & MALIGNANT TUMORS
Parenchyma
Neoplastic component
Stroma
Nonneoplastic (supportive)
Infiltrating cancer: desmoplasia
DIFFERENTIATION IN BENIGN AND MALIGNANT TUMORS
Benign tumors
Well-differentiated; no metastasis
Malignant tumors
Well-differentiated (low-grade)
Poorly differentiated, high-grade, or anaplastic cancer
Moderately well-differentiated (intermediate-grade) cancer
CELL ORGANELLES IN MALIGNANT VERSUS NORMAL CELLS
Organelles in the cytoplasm when compared to a normal cell
Nuclear features when compared to a normal cell
BIOCHEMICAL CHANGES IN MALIGNANT CELLS
Anaerobic glycolysis ↑Lactic acid in neoplastic cells
↑Uptake of glucose analog PET scan Diagnosis, staging, monitoring therapy
Store glycogen in cytosol
β-oxidation fatty acids or anaerobic glycolysis for energy
GROWTH RATE IN BENIGN AND MALIGNANT TUMORS
Benign: usually low growth rate
Malignant: variable growth rate
Correlates with degree of differentiation
High-grade cancer: ↑growth rate
Clinically detectable: 30 population doublings to produce 109 cells (1 g tissue)
↑Growth rate: use cell cycle–specific chemo
MTX inhibits S phase; vincristine inhibits M phase
Malignant cells killed: other cells enter cycle
MONOCLONALITY IN BENIGN & MALIGNANT TUMORS
Nonneoplastic tumors polyclonal
Benign/malignant cells: from single precursor cell
TELOMERASE ACTIVITY IN BENIGN & MALIGNANT TUMORS
Telomere complexes
Benign tumors have normal telomerase activity
Malignant tumors: upregulation telomerase activity; prevents apoptosis
UPREGULATION OF DECAY ACCELERATING FACTOR (DAF) BY MALIGNANT CELLS
DAF: normally degrades C3/C5 convertase
Upregulation DAF prevents MAC formation
LOCAL INVASION & METASTASIS
Benign tumors do not invade
Malignant tumors
TYPES OF METASTASIS
Benign tumors do not metastasize
Malignant tumors metastasize (exception: basal cell carcinoma [BCC] of skin)
Pathways of dissemination
Bone metastasis
Metastasis is more common than a primary cancer in the following sites
COMPARISON BETWEEN BENIGN & MALIGNANT TUMORS

DEFINITIONS
Hyperplasia
Metaplasia
Dysplasia
Anaplasia

CELL TYPES

NEOPLASIA & NEOPLASTIC PROGRESSION
Normal cells
Dysplasia
Carcinoma in situ/preinvasive
Invasive carcinoma
Metastasis

CHARACTERISTICS OF NEOPLASTIC CELLS

METASTASIS Common metastases
Metastasis to Liver
Metastasis to Brain
Metastasis to Bone
Direct (Local) Effects of Tumor Growth
infiltration
Obstruction

CARCINOGENESIS
OVERVIEW OF CARCINOGENESIS
Mutations, telomerase activation, angiogenesis, invasion, metastasis
TYPES OF GENE MUTATIONS PRODUCING CANCER
Point mutations (MC)
Balanced translocation
Insertional mutagenesis
Deletion, amplification, overexpression
GENES INVOLVED IN CANCER
Mutations involving proto-oncogenes
Mutations involving suppressor genes (antioncogenes)
Mutations involving antiapoptosis genes; BCL2 family of genes
Mutations involving DNA repair genes

CARCINOGENIC AGENTS
CHEMICAL CARCINOGENS
Polycyclic aromatic hydrocarbons (PAHs) in tobacco smoke
Mechanism of action of chemical carcinogens
Direct-acting carcinogens
Indirect-acting carcinogens
Sequence of chemical carcinogenesis
Initiation Initiators
Promotion Promoters
Progression
CARCINOGENIC MICROBIAL AGENTS Viruses & microbes oncogenic microbes
Oncogenic viruses
Oncogenic bacteria
Oncogenic parasites
Order of importance of microbial agents causing cancer: viruses > bacteria > parasites
RADIATION
Ultraviolet (UV) rays
UVB light–induced cancers
Ionizing radiation–induced cancers
PHYSICAL INJURY

TUMOR IMMUNITY Serum tumor markers
TSAs
TAAs

CHARACTERISTICS OF BENIGN & MALIGNANT NEOPLASMS
Differentiation and Anaplasia
Metaplasia, Dysplasia, and Carcinoma In Situ
Local Invasion
Metastasis
Pathways of Spread

EPIDEMIOLOGY OF CANCER
The Global Impact of Cancer
Environmental Factors
Age
Acquired Predisposing Conditions
Genetic Predisposition and Interactions
Between Environmental & Inherited Factors
Common cancers Cancer incidence
Males
Females
Highest mortality rate Cancer mortality
Males
Females
GENERAL EPIDEMIOLOGY OF CANCER
Second most common cause of death in the United States
Causes
Age is an important risk factor for cancer
Racial and ethnic differences affect cancer incidence
CANCER INCIDENCE BY AGE & SEX
Cancers in children
Top three noncutaneous cancer sites in men, in decreasing order, are prostate, lung/bronchus, and colorecta
Top three noncutaneous cancer sites in women, in decreasing order, are breast, lung/bronchus, and colorectal
Top three sites for gynecologic cancers, in decreasing order, are ovary, uterine corpus (endometrium), and cervix
SITES FOR CANCER-RELATED DEATHS
CANCER AND HEREDITY
CANCER AND GEOGRAPHY
ACQUIRED PRENEOPLASTIC DISORDERS
PREVENTION MODALITIES IN CANCER
Modify lifestyle
Immunization
Screening procedures to detect cancer
Treatment of conditions that predispose to cancer decreases the risk for cancer

MOLECULAR BASIS OF CANCER : ROLE OF GENETIC & EPIGENETIC ALTERATIONS

CELLULAR & MOLECULAR HALLMARKS OF CANCER
Self-Sufficiency in Growth Signals: Oncogenes - Growth signal self-sufficiency
Oncoproteins and Cell Growth
Insensitivity to Growth Inhibition: Tumor Suppressor Genes -  Anti-growth signal insensitivity
Growth-Promoting Metabolic Alterations : The Warburg Effect
Evasion of Cell Death - Evasion of apoptosis
Limitless Replicative Potential : The Stem Cell–Like Properties of Cancer Cells
Sustained Angiogenesis
Invasion & Metastasis
Invasion of Extracellular Matrix
Vascular Dissemination, Homing, and Colonization
Evasion of Immune Surveillance
Tumor Antigens
Antitumor Effector Mechanisms
Mechanisms of Immune Evasion by Cancers

Immune checkpoint interactions

Genomic Instability
Cancer-Enabling Inflammation
Dysregulation of Cancer-Associated Genes
Chromosomal Changes
Epigenetic Changes
Noncoding RNAs and Cancer
Molecular Basis of Multistep Carcinogenesis

CARCINOGENIC AGENTS & THEIR CELLULAR INTERACTIONS
Chemical Carcinogenesis
Direct-Acting Carcinogens
Indirect-Acting Carcinogens
Radiation Carcinogenesis
Ultraviolet Rays
Ionizing Radiation
Microbial Carcinogenesis
Oncogenic RNA Viruses
Oncogenic DNA Viruses
Helicobacter pylori

CLINICAL ASPECTS OF NEOPLASIA - CLINICAL ONCOLOGY
Clinical Manifestations
HOST DEFENSES AGAINST CANCER
Humoral immunity: antibodies, complement
CMI most effective
Cytotoxic CD8 T cells most effective defense
NK cells kill cell directly (type IV HSR)/indirectly via type II HSR
Macrophages kill cancer cells
GRADING & STAGING OF CANCER TUMORS
Grading criteria for cancer
Staging criteria
CANCER EFFECTS ON THE HOST
Cachexia (wasting disease)
Anemia in cancer
Hemostasis abnormalities
Fever in malignancy
Paraneoplastic syndromes
TUMOR MARKERS (BIOMARKERS) IN CANCER
Biological markers of cancer include hormones, enzymes, oncofetal antigens, immunoglobulins, and glycoproteins
Pathologists use special stains and techniques that help define the origin of different types of cancer
Tumor markers are used to diagnose cancer, estimate tumor burden, detect recurrences, and predict the tumor response to treatment

PARANEOPLASTIC SYNDROMES - EFFECTS
Definition
Epidemiology of paraneoplastic syndromes
Musculoskeletal and cutaneous
Dermatomyositis
Acanthosis nigricans
Sign of Leser-Trélat
Hypertrophic osteoarthropathy
Endocrine
Hypercalcemia
Cushing syndrome
Hyponatremia (SIADH)
Hematologic
Polycythemia
Pure red cell aplasia
Good syndrome
Trousseau syndrome
Nonbacterial thrombotic endocarditis
Neuromuscular
Anti-NMDA receptor encephalitis
Opsoclonus-myoclonus ataxia syndrome
Paraneoplastic cerebellar degeneration
Paraneoplastic encephalomyelitis
Lambert-Eaton myasthenic syndrome
Myasthenia gravis

Laboratory Diagnosis of Cancer
Molecular Profiles of Tumors : The Future of Cancer Diagnostics
Tumor Markers

Important immunohistochemical stains
Chromogranin and synaptophysin
Cytokeratin
Desmin
GFAP
Neurofilament
Neurofilament
S-100
TRAP
Vimentin

P-glycoprotein

Psammoma bodies

TOC
INFECTIOUS

GENERAL PRINCIPLES OF MICROBIAL PATHOGENESIS
How Microorganisms Cause Disease
Routes of Entry of Microbes
Spread and Dissemination of Microbes Within the Body
Release From the Body and Transmission of Microbes
Host-Pathogen Interactions
Immune Evasion by Microbes
Injurious Effects of Host Immunity
Infections in People With Immunodeficiencies
Host Damage by Microbes
Mechanisms of Viral Injury
Mechanisms of Bacterial Injury
Spectrum of Inflammatory Responses to Infection
Suppurative (Purulent) Inflammation
Mononuclear and Granulomatous Inflammation
Cytopathic-Cytoproliferative Reaction
Tissue Necrosis
Chronic Inflammation and Scarring

VIRAL INFECTIONS
Acute (Transient) Infections
Measles
Mumps
Poliomyelitis
West Nile Virus Infections
Viral Hemorrhagic Fever
Zika Virus Infections
Dengue
Novel Coronavirus SARS-CoV-2 (COVID-19)
Latent Infections (Herpesvirus Infections)
Herpes Simplex Virus (HSV) Infections
Varicella-Zoster Virus (VZV) Infections
Cytomegalovirus (CMV) Infections
Chronic Productive Infections
Transforming Viral Infections
Epstein-Barr Virus (EBV) Infections

BACTERIAL INFECTIONS
Gram-Positive Bacterial Infections
Staphylococcal Infections
Streptococcal and Enterococcal
Infections
Diphtheria
Listeriosis
Anthrax
Nocardial Infections
Gram-Negative Bacterial Infections
Neisserial Infections
Pertussis
Pseudomonal Infections
Plague
Chancroid (Soft Chancre)
Granuloma Inguinale
Mycobacterial Infections
Tuberculosis
Nontuberculous Mycobacterial Infections
Leprosy
Spirochete Infections
Syphilis
Lyme Disease
Anaerobic Bacterial Infections
Abscesses
Clostridial Infections
Obligate Intracellular Bacterial Infections
Chlamydial Infections
Infections Caused by Other Intracellular Bacteria

FUNGAL INFECTIONS
Yeast Infections
Candidiasis
Cryptococcosis
Pneumocystis Infections
Mold Infections
Aspergillosis
Mucormycosis (Zygomycosis)

PARASITIC INFECTIONS
Protozoal Infections
Malaria
Babesiosis
Leishmaniasis
African Trypanosomiasis
Chagas Disease
Toxoplasmosis
Metazoal Infections
Strongyloidiasis
Cysticercosis and Hydatid Disease (Tapeworm
Infections)
Trichinosis
Schistosomiasis
Lymphatic Filariasis
Onchocerciasis

SEXUALLY TRANSMITTED INFECTIONS

EMERGING INFECTIOUS DISEASES

SPECIAL TECHNIQUES FOR DIAGNOSING INFECTIOUS AGENTS

TOC
ENVIRONMENTAL & NUTRITIONAL DISEASES

TOC
ENVIRONMENT TOC
(Schneider) V1 PDF

HEALTH EFFECTS OF CLIMATE CHANGE

TOXICITY OF CHEMICAL & PHYSICAL AGENTS

ENVIRONMENTAL (CHEMICALS) POLLUTION
Air pollution
Outdoor Air Pollution
Indoor Air Pollution
Metals as Environmental Pollutants
Lead
Mercury
Arsenic
Cadmium

INJURIES CAUSED BY ARTHROPODS AND REPTILES

OCCUPATIONAL HEALTH RISKS: INDUSTRIAL & AGRICULTURAL EXPOSURES
 
EFFECTS OF TOBACCO - USE
Epidemiology
Systemic effects
Beneficial effects of smoking cessation

EFFECTS OF ALCOHOL - USE DISORDER
Definition
Epidemiology
Alcohol absorption and metabolism
Systemic effects
Laboratory findings

INJURY BY THERAPEUTIC DRUGS & (OTHER) DRUGS OF ABUSE
Sedatives, stimulants, and hallucinogens
Central nervous system (CNS) effects of long-term drug abuse
Complications of intravenous drug use (IVDU)

INJURY BY THERAPEUTIC DRUGS (ADVERSE (EFFECTS) DRUG REACTIONS) 
Anticoagulants
Menopausal Hormone Therapy
Oral Contraceptives
Acetaminophen
Aspirin (Acetylsalicylic Acid)
Disorders associated with exogenous estrogen without progestin (unopposed estrogen)
Disorders associated with oral contraceptive pills (OCPs; estrogen + progestin)

INJURY BY NONTHERAPEUTIC AGENTS (DRUG ABUSE)
Cocaine
Opioids and Opiates
Amphetamines and Related Drugs
Marijuana
Other Drugs

INJURY BY PHYSICAL AGENTS

MECHANICAL TRAUMA - INJURY
Types of skin wounds
Gunshot wounds
Motor vehicle accidents (MVAs)
Shaken baby syndrome

THERMAL INJURY
Thermal Burns
Hyperthermia
Minor heat syndromes
Major heat syndrome: classic heatstroke (CHS)
Major heat syndrome: exertional heatstroke (EHS)
Hypothermia
Frostbite and related cold injuries

ELECTRICAL INJURY
Epidemiology
Pathophysiology
Lightning injury

DROWNING

HIGH-ALTITUDE INJURY

INJURY PRODUCED BY IONIZING RADIATION

IONIZING RADIATION INJURY

NONIONIZING RADIATION INJURY

TOC
NUTRITIONAL DISEASES
(Schneider) V1 PDF

NUTRIENT & ENERGY REQUIREMENTS IN HUMANS
Recommended dietary allowance (RDA)
Daily energy expenditure

DIETARY FUELS
Carbohydrates
Glucose
Enzymatic digestion of carbohydrates
Proteins
Amino acids (AAs) are substrates for gluconeogenesis
Digestion of protein
Complete oxidation of protein produces 4 kcal/g
Fats
Triglyceride (TG)
Essential FAs
Digestion of dietary TG

PROTEIN-ENERGY MALNUTRITION (PEM)
Overview of PEM
Kwashiorkor
Marasmus
Secondary PEM

Dietary Insufficiency

Severe Acute Malnutrition

EATING DISORDERS & OBESITY
Anorexia Nervosa
Some other important causes of weight loss
Bulimia nervosa

Obesity
Clinical Consequences of Obesity
Obesity and Cancer

Vitamin Deficiencies

FAT-SOLUBLE VITAMINS
Overview of fat- and water-soluble vitamins
Vitamin A
Vitamin D
Vitamin E
Vitamin K

WATER-SOLUBLE VITAMINS
Thiamine (vitamin B1)
Riboflavin (vitamin B2)
Niacin (vitamin B3, nicotinic acid)
Pyridoxine (vitamin B6)
Vitamin B12 (cobalamin)
Folic acid
Biotin
Ascorbic acid (vitamin C)

TRACE ELEMENTS
Definition
Zinc
Copper
Iodine
Chromium
Selenium
Fluoride

MINERAL AND ELECTROLYTE DEFICIENCY AND EXCESS

DIETARY FIBER

SPECIAL DIETS
Sodium-restricted diets; nonpharmacologic treatment for
Protein-restricted diets

Diet and Cancer
Diet and Systemic Diseases

TOC
INFANCY & CHILDHOOD
(Robbins. Tumors and Tumorlike Lesions of Infancy and Childhood. Summary) V1 PDF

CONGENITAL ANOMALIES
Definitions
Causes of Anomalies
PREMATURITY AND FETAL GROWTH RESTRICTION
Fetal Growth Restriction
Maternal Abnormalities
Fetal Abnormalities
Placental Abnormalities
Neonatal Respiratory Distress Syndrome
Necrotizing Enterocolitis
PERINATAL INFECTIONS
Transcervical (Ascending) Infections
Transplacental (Hematologic) Infections
Sepsis
FETAL HYDROPS
Immune Hydrops
Nonimmune Hydrops
INBORN ERRORS OF METABOLISM AND OTHER GENETIC DISORDERS
Phenylketonuria
Galactosemia
Cystic Fibrosis (Mucoviscidosis)
Cystic Fibrosis Gene: Normal Structure and
Function
Cystic Fibrosis Gene: Mutational Spectrum
and Genotype-Phenotype Correlation
Genetic and Environmental Modifiers
SUDDEN INFANT DEATH SYNDROME
TUMORS AND TUMORLIKE LESIONS OF INFANCY AND CHILDHOOD
Benign Tumors and Tumorlike Lesions
Hemangioma
Fibrous Tumors
Teratomas
Malignant Tumors
Neuroblastic Tumors
Wilms Tumor

TOC
SYSTEMIC PATHOLOGY : DISEASES OF ORGAN SYSTEMS

TOC
BLOOD VESSELS & LYMPHATICS
(Schneider) V1 PDF
(Robbins Summary) V1 PDF

LIPOPROTEIN DISORDERS
LIPOPROTEINS
Definition
Structure
Overview
Chylomicron formation (exogenous cycle)
VLDL
Causes of increased plasma turbidity
LDL
High-density lipoprotein (HDL)
LIPOPROTEIN DISORDERS

VASCULAR STRUCTURE & FUNCTION

VASCULAR ANOMALIES

VASCULAR WALL RESPONSE TO INJURY
Intimal Thickening: A Stereotyped Response to Vascular Injury

HYPERTENSIVE VASCULAR DISEASE - HYPERTENSION HTN
Blood Pressure Regulation
Vascular Pathology in Hypertension
DEFINITION
EPIDEMIOLOGY
PATHOPHYSIOLOGY
Systolic blood pressure (SBP)
Diastolic blood pressure (DBP)
Role of sodium in HTN
PRIMARY HTN
SECONDARY HYPERTENSION
COMPLICATIONS OF HTN

A-RTERIO-SCLEROSIS
Medial calcification
Atherosclerosis
Arteriolosclerosis
DEFINITION
Thickening arterial wall; loss elasticity
MEDIAL CALCIFICATION
Dystrophic calcification muscular arteries
Calcification uterine/radial arteries
No clinical significance except atherosclerosis
A-THERO-SCLEROSIS
Definition
Epidemiology
Prevalence
Risk factors
Risk Factors
Constitutional Risk Factors
Modifiable Major Risk Factors
Additional Risk Factors
Pathogenesis
Sites of atherosclerosis include
Consequences of Atherosclerotic Disease - Complications of atherosclerosis
A-RTERIOLO-SCLEROSIS
Definition
Arteriole occlusion
Hyaline arteriolosclerosis
Arteriole occlusion by protein in vessel wall
Hyaline arteriolosclerosis:DM
NEG: glucose + proteins in basement membrane arterioles
Leaky basement membranes permeable to plasma protein
HTN: Hyaline arteriolosclerosis
HTN: ↑intraluminal pressure
Hyaline arteriolosclerosis causes: DM, HTN
Hyaline arteriolosclerosis: vessel rigidity, ↓luminal size → ↓blood flow → tissue atrophy
Hyperplastic arteriolosclerosis
Hyperplastic arteriolosclerosis: Rapid ↑BP → basement membrane duplication → SMC hyperplasia
Hyperplastic arteriolosclerosis: involves afferent/efferent arterioles; malignant HTN
Malignant HTN: renal failure, cerebral edema
Malignant HTN: “onion skinning” renal arterioles

VESSEL ANEURYSMS & DISSECTION
DEFINITION
ABDOMINAL AORTIC ANEURYSM (AAA)
Definition
Epidemiology
Pathogenesis
Clinical findings
Diagnosis
THORACIC AORTIC ANEURYSM
POPLITEAL ARTERY ANEURYSM
Male dominant
MC peripheral artery aneurysm
MYCOTIC ANEURYSM
Definition
Epidemiology
Clinical findings
BERRY (SACCULAR) ANEURYSM OF CEREBRAL ARTERIES
Definition
Epidemiology
Pathogenesis
Clinical findings
Complications of a ruptured berry aneurysm
Diagnosis
SYPHILITIC ANEURYSM
Definition
Epidemiology
Clinical findings
Linear calcifications (dystrophic calcification)
AORTIC DISSECTION
Definition
Epidemiology
Pathogenesis
Clinical findings

VASCULITIS - VASCULITIC DISORDERS
DEFINITION OF VASCULITIS
PATHOGENESIS
CLINICAL FINDINGS
Small vessel vasculitis
Medium-sized vessel vasculitis
Large vessel vasculitis
Noninfectious Vasculitis
Immune Complex–Associated Vasculitis
Antineutrophil Cytoplasmic Antibodies
Anti–Endothelial Cell Antibodies
Giant Cell (Temporal) Arteritis
Takayasu Arteritis
Polyarteritis Nodosa (PAN)
Kawasaki Disease
Microscopic Polyangiitis
Granulomatosis With Polyangiitis (GPA)
Churg-Strauss Syndrome
Thromboangiitis Obliterans (Buerger Disease)
Vasculitis Associated With Other Noninfectious Disorders
Infectious Vasculitis

DISORDERS OF BLOOD VESSEL HYPERREACTIVITY
Raynaud Phenomenon
Myocardial Vessel Vasospasm

VEINS - VENOUS SYSTEM DISORDERS
SAPHENOUS VENOUS SYSTEM
VARICOSE VEINS
Definition
Epidemiology
VENOUS THROMBOSES
Definition
Causes
Locations
DVT in the calf
SUPERFICIAL THROMBOPHLEBITIS
Definition
Epidemiology
Clinical findings
Thrombophlebitis & Phlebothrombosis
SUPERIOR VENA CAVA (SVC) SYNDROME
Superior & Inferior Vena Caval Syndromes
THORACIC OUTLET SYNDROME (TOS)

LYMPHATIC DISORDERS
STRUCTURE OF LYMPHATIC VESSELS
ACUTE LYMPHANGITIS
NODULAR LYMPHANGITIS
LYMPHEDEMA

VASCULAR TUMORS & TUMOR-LIKE CONDITIONS
Benign Tumors and Tumor-Like Conditions
Intermediate-Grade (Borderline) Tumors
Malignant Tumors

PATHOLOGY OF VASCULAR INTERVENTION
Endovascular Stenting
Vascular Replacement

TOC
HEART
(Schneider) V1 PDF
(Robbins Summary) V1 PDF

CARDIAC STRUCTURE & SPECIALIZATIONS
Myocardium
Valves
Conduction System
Blood Supply
Cardiac Regeneration
Effects of Aging on the Heart

CARDIAC PHYSICAL DIAGNOSIS

OVERVIEW OF NORMAL ANATOMY

OVERVIEW OF CARDIAC PATHOPHYSIOLOGY

VENTRICULAR HYPERTROPHY
DEFINITION OF VENTRICULAR HYPERTROPHY
Compensatory change pressure/volume changes
PATHOGENESIS OF LEFT VENTRICULAR HYPERTROPHY (LVH) & RIGHT VENTRICULAR HYPERTROPHY (RVH)
↑Pressure ↑wall stress
Wall stress ↑sarcomere duplication
Contractile element muscle
Changes occur in wall stress when there is an increase in afterload
Changes occur in wall stress when there is an increase in preload
CONSEQUENCES OF VENTRICULAR HYPERTROPHY
Left- and right-sided heart failure (LHF, RHF)
Angina pectoris (AP; chest pain) with exercise (only a complication of LVH)
Pathologic S4 heart sound is commonly present in either LVH and/or RVH
Pathologic S3 heart sound is commonly present in either left- or right-sided eccentric hypertrophy

Cardiac Hypertrophy : Pathophysiology & Progression to Heart Failure

(CONGESTIVE) HEART FAILURE (CHF)
DEFINITION
Heart fails if unable to eject blood from venous system
EPIDEMIOLOGY
MCC hospital admission persons >65 years old
Types
LHF MC
RHF
LHF + RHF
HOF least common
Blood builds up behind failed ventricle
LHF: blood backs up into lungs
RHF: blood backs up into venous system
LFH - LEFT-SIDED HEART FAILURE
Definition
Pathogenesis of LHF
Gross and microscopic findings in LHF
Clinical and laboratory findings in LHF include
RHF - RIGHT-SIDED HEART FAILURE
Definition
Pathogenesis
Clinical and laboratory findings
HIGH OUTPUT FAILURE (HOF)
Definition
Pathogenesis

CARDIAC DEVELOPMENT
FETAL CIRCULATION

CONGENITAL HEART DISEASE (CHD)
Definition
Epidemiology
Sao2 findings that help distinguish cyanotic from noncyanotic shunts
LEFT SIDED - TO - RIGHT SIDED SHUNTS
Causes volume overload in the right side of the heart
Ventricular Septal Defect VSD
Atrial Septal Defect ASD
Patent Ductus Arteriosus PDA
Patent Foramen Ovale
RIGHT-TO-LEFT SHUNTS
These shunts come under the heading of cyanotic CHD.
Complications of cyanotic CHD were discussed earlier.
ToF Tetralogy of Fallot
(Complete) transposition of the great arteries
Other less common types of cyanotic CHD include
Total anomalous pulmonary venous return
Truncus arteriosus
TV atresia Tricuspid Atresia
OBSTRUCTIVE LESIONS
Coarctation of the Aorta
Pulmonary Stenosis & Atresia
Aortic Stenosis & Atresia

ISCHEMIC HEART DISEASE (IHD)
Definition
Coronary artery (CA) blood flow
Epidemiology of IHD
Angina pectoris (AP)
Chronic ischemic heart disease (CIHD)
Acute myocardial infarction (AMI)
Sudden cardiac death (SCD)
DEFINITION
IHD: imbalance in demand of O2 and supply
CORONARY ARTERY (CA) BLOOD FLOW
CAs provide O2 to cardiac muscle
CAs fill in diastole
Tachycardia ↓ diastole → ↓ filling CAs
Left anterior descending (LAD) CA
Right coronary artery (RCA)
Left circumflex coronary artery (LCCA)
Reduction CA blood flow → collateral circulation Collateral circulation protective against AMI
EPIDEMIOLOGY OF IHD
IHD is the major COD in the United States
Types of IHD include angina pectoris (AP; MC type), chronic ischemic heart disease (CIHD), sudden cardiac death (SCD), and AMI
Risk factors
ANGINA PECTORIS (AP)
Definition of AP
Epidemiology
Chronic (stable) AP (chronic CAD)
Prinzmetal variant angina
Unstable angina (UA)
Diagnostic tests for AP include
CHRONIC ISCHEMIC HEART DISEASE (CIHD)
Definition
Pathogenesis
Clinical findings include
ACUTE MYOCARDIAL INFARCTION (AMI)
Definition
Epidemiology
Pathogenesis
Less common causes AMI include
Types of AMI include
Ischemia/reperfusion injury in AMI
Gross and microscopic (GM) findings in an AMI
Clinical findings of an AMI
Complications of STEMI AMIs
Laboratory diagnosis of AMI
Correlation of ECG changes with pathologic changes
Classic ECG patterns in AMI
SUDDEN CARDIAC DEATH (SCD)
Definition
Epidemiology
Pathogenesis of SCD in adults

ARRHYTHMIAS
Sudden Cardiac Death
Hypertensive Heart Disease
Systemic (Left-Sided) Hypertensive Hear Disease
Pulmonary (Right-Sided) Hypertensive Heart Disease (Cor Pulmonale)

VALVULAR HEART DISEASE - ACQUIRED VALVULAR HEART DISEASE
RHEUMATIC FEVER (RF) & RHEUMATIC HEART DISEASE
Definition
Epidemiology
Pathogenesis of RF
Clinical findings
Diagnosis of RF (revised Jones criteria)
Clinical features of acute RF are summarized
MITRAL VALVE STENOSIS
Definition
Epidemiology
Clinical findings
Diagnosis of MV stenosis is confirmed by ECHO
Treatment of MV stenosis is replacement of the valve
MITRAL VALVE REGURGITATION
Definition
Epidemiology
Clinical findings in MV regurgitation include
Diagnosis is confirmed by echocardiography (ECHO)
MITRAL VALVE PROLAPSE (MVP) (MYXOMATOUS DEGENERATION)
Definition
Epidemiology
Clinical findings
Diagnosis of MVP is confirmed by ECHO
AORTIC VALVE (AV) STENOSIS
Definition
Epidemiology
Clinical findings
Diagnosis of AV stenosis is confirmed by ECHO
AV sclerosis
AORTIC VALVE (AV) REGURGITATION
Definition
Epidemiology
Clinical findings
Diagnosis of AV regurgitation is confirmed by ECHO
TV REGURGITATION
Definition
Epidemiology
Clinical findings
Diagnosis of TV regurgitation is confirmed by ECHO
PV STENOSIS
Definition
Epidemiology
Clinical findings
Diagnosis of PV stenosis is confirmed by ECHO
PV REGURGITATION
Definition
Epidemiology
Clinical findings
Diagnosis of PV regurgitation is confirmed by ECHO
CARCINOID HEART DISEASE
Definition
Epidemiology
INFECTIVE ENDOCARDITIS (IE)
Definition
Epidemiology
Clinical findings
Laboratory findings
Diagnosis
NONINFECTED VEGETATIONS :
LIBMAN-SACKS ENDOCARDITIS Endocarditis of Systemic Lupus Erythematosus
Definition
Occurs in 30% to 50% of patients with SLE
Sterile vegetations are located over the MV surface and chordae; produces valve deformity and MV regurgitation
NONBACTERIAL THROMBOTIC ENDOCARDITIS (NBTE; MARANTIC ENDOCARDITIS)
Definition
Epidemiology
Complications include embolization of vegetation material to distant sites and secondary infection of the vegetations
COMPLICATIONS OF PROSTHETIC VALVES

Calcific Valvular Degeneration
Calcific Aortic Stenosis
Calcific Stenosis of Congenitally Bicuspid Aortic Valve
Mitral Annular Calcification

CARDIOMYOPATHIES
Definition and epidemiology of cardiomyopathy
Dilated Cardiomyopathy (DCM) (nonischemic cardiomyopathy)
Arrhythmogenic Cardiomyopathy
Hypertrophic Cardiomyopathy (HCM)
Restrictive Cardiomyopathy
Amyloidosis

MYOCARDITIS
Definition
Epidemiology
Clinical findings
Diagnosis of myocarditis by ECHO and cardiac catheterization
Laboratory findings
Approximately 50% of patients die within 5 years

OTHER CAUSES OF MYOCARDIAL DISEASE
Cardiotoxic Drugs
Radiation

PERICARDIAL DISEASE
Pericardial Effusion & Hemopericardium

PERICARDITIS
Definition
Epidemiology
Clinical findings
Diagnosis of pericardial effusion
Constrictive pericarditis
Acute Pericarditis
Chronic or Healed Pericarditis

TUMORS OF THE HEART
Epidemiology of tumors of the heart
Cardiac myxoma
Rhabdomyoma
Primary Cardiac Tumors
Metastatic Neoplasms

CARDIAC TRANSPLANTATION

CARDIAC DEVICES
Ventricular Assist Devices

TOC
WHITE BLOOD CELLS, LYMPH NODES, SPLEEN, & THYMUS
(Schneider Neoplastic & Proliferative of Hematopoietic & Lymphoid ) V1 PDF
(Moi. Thymus. Tumors) V1 PDF
(Robbins. Summary. WBC. Summary) V1 PDF
(Robbins. Thymus. Summary) V1 PDF

NORMAL HEMATOPOIESIS

DISORDERS OF WHITE CELLS

BENIGN QUALITATIVE WHITE BLOOD CELL (WBC) DISORDERS
Definition
Pathogenesis
Clinical findings include
Unusual benign leukocyte reactions

BENIGN QUANTITATIVE WHITE BLOOD CELL DISORDERS
Disorders involving neutrophils
Disorders involving eosinophils
Disorders involving basophils; basophilia
Disorders involving lymphocytes
Disorders involving monocytes; monocytosis

LEUKOPENIA
Neutropenia, Agranulocytosis

LYMPHOID TISSUE
Locations of lymphoid tissue
Lymphadenopathy
Types of reactive lymphadenitis

REACTIVE PROLIFERATIONS OF WHITE CELLS & LYMPH NODES 
Leukocytosis
Lymphadenitis
Acute Nonspecific Lymphadenitis
Chronic Nonspecific Lymphadenitis
Hemophagocytic Lymphohistiocytosis

NEOPLASTIC PROLIFERATIONS OF WHITE CELLS: OVERVIEW 
Etiologic and Pathogenetic Factors in White Cell Neoplasia

NON-HODGKIN’S LYMPHOMA (NHL)
DEFINITION
EPIDEMIOLOGY
PATHOGENESIS
B-CELL LYMPHOMAS
T-CELL LYMPHOMAS
TUMOR LYSIS SYNDROME
SURVIVAL STATISTICS FOR NHL

LYMPHOID NEOPLASMS 
Definitions and Classifications
Precursor B- and T-Cell Neoplasms
Acute Lymphoblastic Leukemia/
Lymphoma
Peripheral B-Cell Neoplasms
Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Follicular Lymphoma
Diffuse Large B-Cell Lymphoma
Burkitt Lymphoma
Mantle Cell Lymphoma
Marginal Zone Lymphomas
Hairy Cell Leukemia
Peripheral T- and NK-Cell Neoplasms
Peripheral T-Cell Lymphoma, Unspecified
Anaplastic Large-Cell Lymphoma (ALK Positive)
Adult T-Cell Leukemia/Lymphoma
Mycosis Fungoides/Sézary Syndrome
Large Granular Lymphocytic Leukemia
Extranodal NK/T-Cell Lymphoma
Plasma Cell Neoplasms & Related Disorders
Multiple Myeloma
Smoldering Myeloma
Solitary Osseous Plasmacytoma
Lymphoplasmacytic Lymphoma

HODGKIN LYMPHOMA (HL)
DEFINITION
EPIDEMIOLOGY
PATHOGENESIS
PATHOLOGIC FINDINGS
CLINICAL FINDINGS AND PROGNOSIS
PROGNOSIS AND TREATMENT

HISTIOCYTOSIS SYNDROMES (LANGERHANS’ CELL HISTIOCYTOSIS [LCH])

MAST CELL DISORDERS (MASTOCYTOSIS)

PLASMA CELL DYSCRASIAS (MONOCLONAL GAMMOPATHIES [MGS])

ACUTE & CHRONIC LEUKEMIAS
Definition
Epidemiology
Pathogenesis
Clinical findings in acute leukemia
Laboratory findings in acute leukemia include
Clinical findings in chronic leukemia
Laboratory findings in chronic leukemia

MYELOID NEOPLASMS - NEOPLASTIC MYELOID DISORDERS
Overview of neoplastic myeloid disorders
Chronic myeloproliferative disorders
Myelodysplastic syndromes (MDS)
Acute myelogenous leukemia (AML)
Acute Myeloid Leukemia
Myelodysplastic Syndrome
Myeloproliferative Neoplasms
Chronic Myeloid Leukemia
Polycythemia Vera
Essential Thrombocytosis
Primary Myelofibrosis
Langerhans Cell Histiocytosis

LYMPHOID LEUKEMIAS
Acute lymphoblastic leukemia (ALL)
Adult T-cell leukemia
Chronic lymphoblastic leukemia (CLL)
Hairy cell leukemia (HCL)
Summary table of the lymphoid leukemias

SPLEEN DISORDERS
Clinical anatomy and physiology
Splenomegaly
Nonspecific Acute Splenitis
Congestive Splenomegaly
Splenic Infarcts
Spleen in portal hypertension (PH); increased portal vein pressure
Hypersplenism
Splenic dysfunction and splenectomy
Neoplasms
Congenital Anomalies
Rupture

THYMUS
Developmental Disorders
Thymic Hyperplasia
Thymoma

TOC
RED BLOOD CELL & BLEEDING DISORDERS
(Schneider Anemia) V1 PDF
(Schneider Hemorrhagic) V1 PDF
(Robbins. Summary. RBC. Summary) V1 PDF

ERYTHROPOIESIS
Erythropoiesis & erythropoietin
Reticulocytes & the reticulocyte count
Extramedullary hematopoiesis (EMH)

COMPLETE BLOOD CELL COUNT & OTHER STUDIES
Components of a complete blood cell (CBC) count
Hb, Hct, and RBC counts
RBC indices
Characteristics of mature RBCs
WBC count and differential
Platelet count
Iron studies
Hb electrophoresis

ANEMIAS

MICROCYTIC ANEMIAS
Types of microcytic anemia include
Iron deficiency (most common).
ACD
Thalassemia (thal; α and β)
Sideroblastic anemias (least common)
Pathogenesis
Iron metabolism
Anemia of chronic disease (ACD)
Thalassemia (thal)
Sideroblastic anemia

MACROCYTIC ANEMIAS
Overview
subdivided into
megaloblastic anemias (enlarged hematopoietic cells caused by folic acid and/or vitamin B12 deficiency) and
nonmegaloblastic anemia (e.g., macrocytosis related to alcohol intoxication)
Vitamin B12 (cobalamin) metabolism
Causes of vitamin B12 deficiency
Folic acid metabolism
Causes of folic acid deficiency
Pathogenesis of macrocytic anemia in folic acid and vitamin B12 deficiency
Vitamin B12 and folic acid in conversion of homocysteine to methionine and in DNA synthesis
Vitamin B12 in odd-chain fatty acid metabolism
Clinical findings in vitamin B12 deficiency
Laboratory findings
Clinical findings in folic acid deficiency
Laboratory findings in folic acid deficiency
Comparison table of vitamin B12 and folic acid deficiency
Nonmegaloblastic macrocytosis
Definition
Epidemiology

NORMOCYTIC ANEMIAS : CORRECTED RETICULOCYTE COUNT OR INDEX <2%
Acute blood loss
Early iron deficiency or ACD
Aplastic anemia
Anemia in chronic renal failure (CRF)
Malignancy; causes of anemia include

NORMOCYTIC ANEMIAS : CORRECTED RETICULOCYTE COUNT >2%
Definition
Pathogenesis of hemolytic anemias
Hereditary spherocytosis (HS)
Hereditary elliptocytosis
Paroxysmal nocturnal hemoglobinuria (PNH)
Paroxysmal cold hemoglobinuria (PCH)
Sickle cell disease
Glucose 6-phosphate dehydrogenase deficiency (G6PD)
Pyruvate kinase (PK) deficiency
Immune hemolytic anemia (IHA)
Microangiopathic and macroangiopathic hemolytic anemias (MHAs)
Malaria
Morphology of Anemias
Summary table of normocytic anemias

ANEMIAS OF BLOOD LOSS
Acute Blood Loss
Chronic Blood Loss

HEMOLYTIC ANEMIAS
Hereditary Spherocytosis
Hemolytic Disease Due to Red Cell Enzyme Defects: Glucose-6-Phosphate Dehydrogenase Deficiency
Sickle Cell Disease
Thalassemia
Paroxysmal Nocturnal Hemoglobinuria
Immunohemolytic Anemia
Hemolytic Anemia Resulting From Trauma to Red Cells

ANEMIAS OF DIMINISHED ERYTHROPOIESIS
Megaloblastic Anemia
Anemia of Folate Deficiency
Iron Deficiency Anemia
Anemia of Chronic Inflammation
Aplastic Anemia
Pure Red Cell Aplasia
Other Forms of Marrow Failure

POLYCYTHEMIA

HEMOSTASIS DISORDERS

NORMAL HEMOSTASIS & HEMOSTASIS TESTING
DEFINITION
FACTORS PREVENTING THROMBUS FORMATION IN SMALL BLOOD VESSELS
Small blood vessels include capillaries, venules, and arterioles
Thrombus formation is prevented by heparin-like molecules
Prostaglandin (PG) I2 (prostacyclin)
Proteins C and S
Tissue plasminogen activator (tPA)
FACTORS ENHANCING THROMBUS FORMATION IN SMALL-VESSEL INJURY
Thromboxane A2 (TXA2)
von Willebrand factor (vWF)
Tissue thromboplastin (TT; factor III)
Extrinsic and intrinsic coagulation systems
PLATELET STRUCTURE & FUNCTION
Derivation of platelets
Locations of platelets
Platelet receptors
Platelet factor 3 (PF3)
Platelet structure
Platelet functions
COAGULATION SYSTEM
The coagulation cascade consists of the extrinsic system (factor VII) and the intrinsic system (factors VIII, IX, XI, and XII)
Extrinsic coagulation system
Intrinsic coagulation system
Final common pathway
Vitamin K–dependent factors include
Some of the coagulation factors are consumed in the formation of a fibrin clot
FIBRINOLYTIC SYSTEM
Activation of the fibrinolytic system
Functions of plasmin
SMALL-VESSEL HEMOSTASIS RESPONSE TO INJURY
Hemostasis is a balance between natural anticoagulants (proteins C/S, ATIII, fibrinolytic factors) and coagulation factors, platelets, and fibrinolysis inhibitors
Sequence of small-vessel hemostasis includes vascular, platelet, coagulation, and fibrinolytic phases, in that order
Vascular phase of small-vessel hemostasis (vessel injury)
Platelet phase of small-vessel hemostasis
Coagulation phase of small-vessel hemostasis
Fibrinolytic phase of small-vessel hemostasis
PLATELET TESTS
Platelet count
BT
Platelet aggregation tests (functional tests)
Tests for vWF: vWF mediates platelet adhesion to CG at sites of small-vessel injury
COAGULATION TESTS
Coagulation pathways
Prothrombin time (PT)
Activated partial thromboplastin time (aPTT)
FIBRINOLYTIC SYSTEM TESTS
Definition
d-Dimer assay

BLEEDING DISORDERS: HEMORRHAGIC DIATHESES

BLEEDING DISORDERS CAUSED BY VESSEL WALL ABNORMALITIES

PLATELET DISORDERS
CLASSIFICATION OF PLATELET DISORDERS
Thrombocytopenia (↓number)
Thrombocytosis (↑ number)
Functional disorders regardless of numbers
PATHOGENESIS OF PLATELET DISORDERS
Thrombocytopenia
Thrombocytosis
Qualitative platelet disorders
CLINICAL FINDINGS ASSOCIATED WITH PLATELET DYSFUNCTION
Epistaxis
Petechiae and multiple small ecchymoses (purpura) are most commonly caused by thrombocytopenia
Bleeding from superficial scratches
Other findings in platelet dysfunction include menorrhagia (excessive menstrual blood loss), hematuria (loss of RBCs in urine), bleeding from tooth extraction sites, easy bruising, and gastrointestinal (GI) and intracranial bleeding

COAGULATION DISORDERS
CLASSIFICATION OF COAGULATION DISORDERS
Acquired coagulation disorders. Single or multiple coagulation factor deficiencies may occur
Hereditary coagulation disorders (e.g., hemophilia A): usually involve a single coagulation factor deficiency
PATHOGENESIS
Decreased production of coagulation factors. Examples: hemophilia A and cirrhosis (decreased synthesis of coagulation factors)
Pathologic inhibition of coagulation factors. Example: acquired circulating antibodies (inhibitors) against one or more coagulation factors
Excessive consumption of coagulation factors. Example: DIC
CLINICAL FINDINGS
Late rebleeding after surgery or tooth extraction
Findings in severe coagulation factor deficiencies include
Clinical findings in coagulation factor deficiency that also occur in qualitative platelet disorders or thrombocytopenia include ecchymoses, epistaxis, menorrhagia, hematuria, bleeding from tooth extraction sites, easy bruising, and GI and intracranial bleeding
HEMOPHILIA A
CLASSIC vWD
CIRCULATING ANTICOAGULANTS (INHIBITORS)
Definition: Circulating antibodies that destroy specific coagulation factors
VITAMIN K DEFICIENCY
HEMOSTASIS DISORDERS IN CIRRHOSIS
DISSEMINATED INTRAVASCULAR COAGULATION (DIC)

FIBRINOLYTIC DISORDERS
PRIMARY FIBRINOLYSIS
SECONDARY FIBRINOLYSIS

SUMMARY OF LABORATORY TEST RESULTS IN HEMOSTASIS DISORDERS

THROMBOSIS SYNDROMES
ACQUIRED THROMBOSIS SYNDROMES
Antiphospholipid syndrome (APLS)
Other acquired causes of thrombosis include
HEREDITARY THROMBOSIS SYNDROMES
Epidemiology
Factor V Leiden
Antithrombin III (ATIII) deficiency
Proteins C and S deficiency

BLEEDING RELATED TO REDUCED PLATELET NUMBER : THROMBOCYTOPENIA
Chronic Immune Thrombocytopenic Purpura
Acute Immune Thrombocytopenic Purpura
Drug-Induced Thrombocytopenia
HIV-Associated Thrombocytopenia
Thrombotic Microangiopathies: Thrombotic Thrombocytopenic Purpura (TTP) and Hemolytic Uremic Syndrome (HUS)

BLEEDING DISORDERS RELATED TO DEFECTIVE PLATELET FUNCTION

HEMORRHAGIC DIATHESES RELATED TO ABNORMALITIES IN CLOTTING FACTORS
Factor VIII–vWF Complex
Von Willebrand Disease
Hemophilia A (Factor VIII Deficiency)
Hemophilia B (Christmas Disease, Factor IX Deficiency)

DISSEMINATED INTRAVASCULAR COAGULATION (DIC)

IMMUNOHEMATOLOGY DISORDERS

ABO BLOOD GROUP ANTIGENS
Definition of ABO blood group antigens
Blood group O characteristics
Blood group A characteristics
Blood group B characteristics
Blood group AB characteristics
Newborns (NBs)
Older adults
Paternity issues in newborns
Determining an individual’s ABO group in the laboratory
RH AND NON-RH ANTIGEN SYSTEMS
Rh antigen system
Alloimmunization
Clinically important non-Rh antigens
BLOOD TRANSFUSION THERAPY
Blood donors
Patient crossmatch (CX) for a blood transfusion
Blood component therapy
Blood transfusion reactions
HEMOLYTIC DISEASE OF THE NEWBORN
Definition of HDN
ABO HDN
Rh HDN
Blue fluorescent light or sunlight
 
COMPLICATIONS OF TRANSFUSION
Allergic Reactions
Hemolytic Reactions
Transfusion-Related Acute Lung Injury
Infectious Complications

TOC
LUNG - UPPER AND LOWER RESPIRATORY DISORDERS
(Finlayson) V1 PDF
(Schneider) V1 PDF
(Robbins Upper Airways Summary )  V1 PDF
(Finlayson Lung Tumors) V1 PDF
(Robbins Lung Tumors Summary) V1 PDF Summary V1 PDF
(Moi Lung Tumors) V1 PDF
(Moi Larynx Tumors) V1 PDF
(Robbins Lung) V1 PDF

OVERVIEW OF THE RESPIRATORY SYSTEM

SYMPTOMS & SIGNS OF RESPIRATORY DISEASE

UPPER AIRWAY DISORDERS
CHOANAL ATRESIA
NASAL POLYPS
OBSTRUCTIVE SLEEP APNEA (OSA)
RHINOSCLEROMA
RHINOSPORIDIOSIS
SINUSITIS
NASOPHARYNGEAL (NP) CARCINOMA
LARYNGEAL CARCINOMA
Nose
Inflammatory Lesions
Necrotizing Lesions of the Nose and Upper Airways
Nasopharynx
Inflammatory Lesions
Tumors of the Nose, Sinuses, and Nasopharynx
Larynx
Inflammatory Lesions
Reactive Nodules (Vocal Cord Nodules and Polyps)
Squamous Papilloma and Papillomatosis
Carcinoma of the Larynx

CONGENITAL ANOMALIES

ATELECTASIS (COLLAPSE)
Definition of atelectasis
Resorption atelectasis
Compression atelectasis
Atelectasis caused by collapse (spontaneous pneumothorax)
Respiratory distress syndromes
Surfactant
Respiratory distress syndrome (RDS) in newborns

ALI
PULMONARY EDEMA
Hemodynamic Pulmonary Edema
Edema Caused by Microvascular (Alveolar) Injury - ARDS
Respiratory Failure in Children

ACUTE LUNG INJURY & ACUTE RESPIRATORY DISTRESS SYNDROME (DIFFUSE ALVEOLAR DAMAGE)

OBSTRUCTIVE & RESTRICTIVE LUNG DISEASES

OBSTRUCTIVE LUNG DISEASES
CHRONIC OBSTRUCTIVE PULMONARY DISEASE - (COPD)
Definition
Epidemiology
Emphysema
Chronic Bronchitis
ASTHMA
BRONCHIECTASIS

CHRONIC DIFFUSE INTERSTITIAL (RESTRICTIVE) DISEASES - (RLDs)
Spirometry
Definition and epidemiology of RLD
FIBROSING DISEASES
Idiopathic Pulmonary Fibrosis (IPF)
Nonspecific Interstitial Pneumonia
Cryptogenic Organizing Pneumonia
Pulmonary Involvement in Autoimmune Diseases
Pneumoconioses
Complications of Therapies
GRANULOMATOUS DISEASES
Sarcoidosis
Hypersensitivity Pneumonitis
Idiopathic Pulmonary Fibrosis (IPF)

Collagen vascular diseases
Drugs associated with interstitial fibrosis include
Radiation-induced lung disease

Pulmonary Eosinophilia
Smoking-Related Interstitial Diseases
Desquamative Interstitial Pneumonia
Respiratory Bronchiolitis–Associated Interstitial Lung Disease
Pulmonary Langerhans Cell Histiocytosis
Pulmonary Alveolar Proteinosis
Surfactant Dysfunction Disorders

DISEASES OF VASCULAR ORIGIN - VASCULAR LUNG LESIONS
Pulmonary Embolism & Infarction (PE)
Pulmonary Hypertension (PAH)
Diffuse Pulmonary Hemorrhage Syndromes
Idiopathic Pulmonary Hemosiderosis
Goodpasture Syndrome (Anti–Glomerular Basement Membrane Antibody Disease With Pulmonary Involvement)
Polyangiitis With Granulomatosis

PULMONARY INFECTIONS
Gram stain characteristics
Pneumonia
Definition
Epidemiology
CAP
Epidemiology
Pathogenesis
Bronchopneumonia
Lobar pneumonia
Chest radiography is the gold standard screen
Laboratory findings in pneumonia
Interstitial types of pneumonia (old term, atypical pneumonia)
Definition
Epidemiology
Pathogenesis: contracted by inhalation (droplet infection)
Histologic findings
Clinical findings include
Nosocomial pneumonia
Pneumonia is commonly seen in immunocompromised patients
important respiratory microbial pathogens except tuberculosis
Tuberculosis
Mycobacterium avium–intracellulare complex (MAC)
Systemic fungal infections
Community-Acquired Bacterial Pneumonias
Streptococcus pneumoniae
Haemophilus influenzae
Moraxella catarrhalis
Staphylococcus aureus
Klebsiella pneumoniae
Pseudomonas aeruginosa
Legionella pneumophila
Mycoplasma pneumoniae
Community-Acquired Viral Pneumonia
Influenza
Human Metapneumovirus
Human Coronaviruses
Health Care–Associated Pneumonia
Hospital-Acquired Pneumonia
Aspiration Pneumonia
Lung Abscess
Chronic Pneumonia
Histoplasmosis
Blastomycosis
Coccidioidomycosis
Pneumonia in the Immunocompromised Host
Pulmonary Disease in Human
Immunodeficiency Virus Infection

LUNG TRANSPLANTATION

TUMORS
EPIDEMIOLOGY
TUMORS & TUMOR-LIKE DISORDERS
Carcinomas
Neuroendocrine Proliferations and Tumors
Miscellaneous Tumors
Metastatic Tumors - Cancer
CLINICAL FINDINGS FOR PRIMARY LUNG CANCER INCLUDE
DIAGNOSIS OF LUNG CANCER
PROGNOSIS FOR LUNG CANCER

PLEURA - MEDIASTINUM
Mediastinal masses
Epidemiology
Thymoma
Mediastinitis
Diagnosis of mediastinitis
Pleural Effusions
Inflammatory Pleural Effusions
Noninflammatory Pleural Effusions
Pleuritis
Pleural diseases
Pneumothorax
Spontaneous pneumothorax
Tension pneumothorax
Pleural Tumors
Solitary Fibrous Tumor
Malignant Mesothelioma

TOC
HEAD & NECK ORAL CAVITY & SALIVARY GLANDS

ORAL CAVITY
Diseases of Teeth and Supporting Structures
Caries (Tooth Decay)
Gingivitis
Periodontitis
Inflammatory/Reactive Lesions
Aphthous Ulcers (Canker Sores)
Fibrous Proliferative Lesions
Infections
Herpes Simplex Virus Infections
Oral Candidiasis (Thrush)
Deep Fungal Infections
Oral Manifestations of Systemic Disease
Hairy Leukoplakia
Precancerous and Cancerous Lesions
Leukoplakia and Erythroplakia
Squamous Cell Carcinoma
Odontogenic Cysts and Tumors

EARS
Inflammatory Lesions
Otosclerosis
Tumors

NECK
Branchial Cyst (Cervical
Lymphoepithelial Cyst)
Thyroglossal Duct Cyst
Paraganglioma (Carotid Body Tumor)

SALIVARY GLANDS
Xerostomia
Inflammation (Sialadenitis)
Neoplasms
Pleomorphic Adenoma
Warthin Tumor (Papillary Cystadenoma Lymphomatosum)
Mucoepidermoid Carcinoma
Other Salivary Gland Tumors

TOC
GASTROINTESTINAL DISORDERS
(Schneider) V1 PDF
(Moi Colon Tumors) V1 PDF
(Moi Appendix Tumors) V1 PDF
(Robbins Chapter Contents)
V1 PDF (And Key Concepts)
Summary
V1 PDF (From Congenital to Sigmoid Diverticular)
V2 PDF

OVERVIEW OF THE GASTROINTESTINAL (GI) SYSTEM

ORAL CAVITY, SALIVARY GLAND, & NECK DISORDERS
Cleft lip and palate
Common infections in the oral cavity
Oral manifestation of human immunodeficiency (HIV) include
Dental caries
Noninfectious ulcerations in the oral cavity
Pigmentation abnormalities in the oral cavity
Tooth discoloration
Macroglossia (enlarged tongue); causes include
Glossitis (inflammation of tongue)
Mucoceles
Pyogenic granuloma
Temporomandibular Joint (TMJ) Dysfunction
Leukoplakia and erythroplakia
Lichen planus
Dentigerous cyst
Benign tumors of the oral cavity (excluding salivary glands)
Malignant tumors of the oral cavity (excluding salivary glands); epidemiology
Salivary gland disorders
Neck disorders (excluding thyroid gland)

CONGENITAL ABNORMALITIES
Atresia, Fistulae, and Duplications
Diaphragmatic Hernia, Omphalocele, and Gastroschisis
Ectopia
Meckel Diverticulum
Pyloric Stenosis
Hirschsprung Disease

ESOPHAGUS
Overview of Anatomy
Physiology of Swallowing
Signs and symptoms of esophageal disease include
Overview of Common Esophageal Disorders
Tracheoesophageal (TE) Fistula
Plummer-Vinson syndrome
Esophageal diverticulum
Hernias at the hiatus
Gastroesophageal reflux disease (GERD)
Esophageal Obstruction
Achalasia
Esophagitis & Related Disorders
Lacerations
Chemical and Infectious Esophagitis
Reflux Esophagitis
Eosinophilic Esophagitis
Esophageal Varices
Barrett Esophagus
Barrett Esophagus
Infectious Esophagitis
Corrosive esophagitis
Esophageal varices
Mallory-Weiss syndrome
Boerhaave syndrome
Motor disorders of the esophagus
SS (90% esophageal involvement) and CREST syndrome
Achalasia
Diffuse esophageal spasm
Nutcracker esophagus (hypertensive peristalsis; “jackhammer” esophagus)
Esophageal Tumors
Leiomyoma
Incidence of esophageal cancer has plateaued
Adenocarcinoma of distal esophagus
Squamous Cell Carcinoma

STOMACH
Overview of stomach anatomy and physiology
Signs and symptoms of stomach disease include
Hypertrophic pyloric stenosis (HPS)
Gastric acid secretion overview
Gastroparesis
Gastropathy & Acute Gastritis
Stress-Related Mucosal Disease
Chronic Gastritis & Its Complications
Helicobacter pylori Gastritis
Autoimmune Atrophic Gastritis
Uncommon Forms of Gastritis
Peptic Ulcer Disease
Other Complications of Chronic Gastritis
Mucosal Atrophy and Intestinal Metaplasia
Dysplasia
Gastritis Cystica
Other types of gastritis
Lymphocytic gastritis
Granulomatous gastritis
Eosinophilic gastritis
Hypertrophic Gastropathies
Ménétrier Disease (hypertrophic lymphocytic gastritis)
Zollinger-Ellison Syndrome
Peptic ulcer disease (PUD)
GASTRIC POLYPS & TUMORS 
Gastric polyps
Leiomyoma
Primary gastric adenocarcinomas
Causes of upper GI bleeding

Inflammatory and Hyperplastic Polyps
Fundic Gland Polyps
Gastric Adenoma
Gastric Adenocarcinoma
Lymphoma
Neuroendocrine Neoplasms
Gastrointestinal Stromal Tumor

SMALL INTESTINE & COLON
Signs and symptoms of small bowel disease (SBD)
Signs and symptoms of large bowel disease
Diarrheal diseases (excluding malabsorption)
Overview of digestion of carbohydrates, protein, and fat
Malabsorption
Intestinal Obstruction
Hernias
Adhesions
Volvulus
Intussusception
Hernias
Vascular Disorders in the Bowel
Ischemic Bowel Disease
Small bowel diverticula
Angiodysplasia
Malabsorption and Diarrhea
Cystic Fibrosis
Celiac Disease
Environmental Enteric Dysfunction
Autoimmune Enteropathy
Lactase (Disaccharidase) Deficiency
Microvillus Inclusion Disease
Abetalipoproteinemia
Infectious Enterocolitis
Cholera
Campylobacter Enterocolitis
Shigellosis
Salmonella
Typhoid Fever
Yersinia
Escherichia coli
Pseudomembranous Colitis
Whipple Disease
Viral Gastroenteritis
Parasitic Enterocolitis
Irritable Bowel Syndrome
Inflammatory Bowel Disease (IBD)
Crohn Disease
Ulcerative Colitis
Indeterminate Colitis
Colitis-Associated Neoplasia
Necrotizing enterocolitis (NEC)
Other Causes of Chronic Colitis
Diversion Colitis
Microscopic Colitis
Graft-Versus-Host Disease
Sigmoid colon Diverticular Disease
Pneumatosis cystoides intestinalis
Small bowel malignancy
Small and large bowel polyps
Polyps
Hyperplastic Polyps
Inflammatory Polyps
Hamartomatous Polyps
Juvenile Polyps
Peutz-Jeghers Syndrome
Neoplastic Polyps
Familial Adenomatous Polyposis
Hereditary Non-Polyposis
Colorectal Cancer (HNPCC)
Adenocarcinoma
Tumors of the Anal Canal
Hemorrhoids
Acute Appendicitis
Tumors of the Appendix

ANORECTAL DISORDERS
Signs and symptoms of anorectal disease include
Anorectal Disorders

PERITONEAL CAVITY
Peritonitis
Inflammatory Disease
Peritoneal Infection
Sclerosing Retroperitonitis
Tumors

TOC
LIVER, GALLBLADDER, BILIARY TRACT & EXOCRINE PANCREAS
(Schneider) V1 PDF
(Robbins Liver Gallbladder Summary) V1 PDF

OVERVIEW OF THE LIVER & BILIARY SYSTEM

LABORATORY EVALUATION OF LIVER CELL INJURY
Bilirubin metabolism and jaundice
Summary of liver function tests
Summary of laboratory findings in selective liver disorders

THE LIVER & BILE DUCTS

GENERAL FEATURES OF LIVER DISEASE

MECHANISMS OF INJURY & REPAIR 
Hepatocyte and Parenchymal Responses
Scar Formation and Regression

LIVER FAILURE
Acute Liver Failure
Chronic Liver Failure and Cirrhosis
Portal Hypertension
Acute-on-Chronic Liver Failure

CIRRHOSIS
Definition: Irreversible diffuse fibrosis of the liver with the formation of regenerative nodules (non-neoplastic nodules without sinusoids or portal triads)
Regenerative nodules in cirrhosis
Causes of cirrhosis include
Complications associated with cirrhosis
Postnecrotic cirrhosis
Primary biliary cirrhosis (PBC)
Secondary biliary cirrhosis
Hereditary hemochromatosis (HHC)
Wilson’s disease (hepatolenticular degeneration)
Alpha1-antitrypsin (AAT) deficiency (PiZZ)
Laboratory test abnormalities in cirrhosis include

INFECTIOUS DISORDERS

VIRAL HEPATITIS
Phases of acute viral hepatitis
Microscopic findings in acute viral hepatitis
Epidemiology and clinical findings of viral hepatitis (A, B, C, D, E)
Serologic studies in viral hepatitis (A, B, C, D, E)
Other laboratory test findings in viral hepatitis
Hepatitis A Virus
Hepatitis B Virus
Hepatitis C Virus
Hepatitis D Virus
Hepatitis E Virus
Clinicopathologic Syndromes of Viral Hepatitis

OTHER INFLAMMATORY LIVER DISORDERS
Summary of important infectious diseases
Autoimmune hepatitis
Neonatal hepatitis
Reye syndrome
Acute fatty liver of pregnancy; epidemiology and clinical
Preeclampsia
Fulminant hepatic failure (FHF)

BACTERIAL, FUNGAL, & PARASITIC INFECTIONS

AUTOIMMUNE HEPATITIS

DRUG- & TOXIN-INDUCED LIVER INJURY - ALCOHOL-RELATED & DRUG- & CHEMICAL-INDUCED

ALCOHOL-RELATED DISORDERS; EPIDEMIOLOGY

CHEMICAL- AND DRUG-INDUCED LIVER DISEASES

FATTY LIVER DISEASE
Alcoholic Liver Disease
Nonalcoholic Fatty Liver Disease (NAFLD)

INHERITED LIVER DISEASE
Hemochromatosis
Wilson Disease
α1-Antitrypsin Deficiency

CHOLESTATIC DISEASE - OBSTRUCTIVE (CHOLESTATIC) LIVER DISEASE
Types of cholestatic liver disease
Gross and microscopic findings include
Clinical findings include
Laboratory findings include
Benign intrahepatic cholestasis of pregnancy
Extrahepatic biliary atresia (EHBA)
Primary sclerosing cholangitis (PSC)

Bile Formation and Secretion
Pathophysiology of Hyperbilirubinemia
Physiologic Jaundice of the Newborn
Hereditary Hyperbilirubinemia
Large Bile Duct Obstruction
Cholestasis of Sepsis
Primary Hepatolithiasis
Neonatal Cholestasis
Extrahepatic Biliary Atresia
Nonobstructive Neonatal Cholestasis
Autoimmune Cholangiopathies
Primary Biliary Cholangitis (PBC)
Primary Sclerosing Cholangitis (PSC)

STRUCTURAL ANOMALIES OF THE BILIARY TREE
Choledochal Cyst
Fibropolycystic Disease

CIRCULATORY DISORDERS
Impaired Blood Flow Into the Liver -  Prehepatic obstruction to blood flow
Hepatic Artery Compromise
Portal Vein Obstruction and Thrombosis
Impaired Blood Flow Through the Liver - Intrahepatic obstruction to blood flow
Hepatic Venous Outflow Obstruction - Posthepatic obstruction to blood flow
Hepatic Vein Thrombosis
Sinusoidal Obstruction Syndrome
Passive Congestion and Centrilobular Necrosis
Hematobilia

HEPATIC DISEASE ASSOCIATED WITH PREGNANCY
Preeclampsia and Eclampsia
Acute Fatty Liver of Pregnancy
Intrahepatic Cholestasis of Pregnancy

NODULES AND TUMORS - LIVER TUMORS AND TUMOR-LIKE DISORDERS
NON-NEOPLASTIC MASS LESIONS
Focal Nodular Hyperplasia (FNH)
Other Non-Neoplastic Mass Lesions
Cysts and abscesses
BENIGN NEOPLASMS
Cavernous Hemangioma
Hepatocellular Adenoma - Liver (hepatic) cell adenoma
PRIMARY MALIGNANT NEOPLASMS 
Hepatoblastoma
Hepatocellular Carcinoma (HCC)
Fibrolamellar variant of HCC
Angiosarcoma
Malignant Biliary Tumors
Other Primary Hepatic Malignant Tumors
Metastasis

GALLBLADDER - GALLBLADDER & BILIARY TRACT DISEASE

CYSTIC DISEASES OF THE BILIARY TRACT INCLUDE

CHOLANGIOCARCINOMA

CHOLESTEROLOSIS

HYDROPS OF THE GALLBLADDER

CONGENITAL ANOMALIES

CHOLELITHIASIS (GALLSTONES) - GALLSTONES

CHOLECYSTITIS

ACUTE CHOLECYSTITIS

CHRONIC CHOLECYSTITIS

GALLBLADDER CARCINOMA - CANCER

TOC
PANCREAS
(Robbins Exocrine Pancreas Summary) V1 PDF

OVERVIEW OF ANATOMY AND PHYSIOLOGY OF THE PANCREAS

RELATIVE IMPORTANCE OF MOST COMMON PANCREATIC DISEASES

EMBRYOLOGIC ABNORMALITIES OF THE PANCREAS
CONGENITAL ANOMALIES

PANCREATITIS
ACUTE PANCREATITIS
CHRONIC PANCREATITIS

NONNEOPLASTIC CYSTS
Congenital Cysts
Pseudocysts

NEOPLASMS - EXOCRINE CANCER
Cystic Neoplasms
Pancreatic Carcinoma
Precursors to Pancreatic Cancer
Acinar Cell Carcinoma
Pancreatoblastoma

TOC
KIDNEY & URINARY TRACT
(Schneider) V1 PDF
Moi Kidney Tumors
Moi LUT Tumors
Robbins Summary V1 PDF
Robbins Neoplasms of the Kidney Summary V1 PDF

OVERVIEW OF THE KIDNEY

RENAL FUNCTION OVERVIEW
Excretes harmful waste products
Maintains acid–base homeostasis
Reabsorbs essential substances
Regulates water and sodium metabolism
Maintains vascular tone
Produces erythropoietin
Maintains calcium homeostasis

IMPORTANT LABORATORY FINDINGS IN RENAL DISEASE
Hematuria
Proteinuria

RENAL FUNCTION TESTS
Serum blood urea nitrogen (BUN)
Serum creatinine (Cr)
Creatinine clearance (CCr)
Serum BUN/Cr (Cr) ratio
Urinalysis

CLINICAL ANATOMY OF THE KIDNEY
Blood supply of the kidney
Structure of the glomerulus

CLINICAL MANIFESTATIONS OF RENAL DISEASES

GLOMERULAR DISEASES 
Terminology of glomerular disease
Routine studies on biopsy specimens
Mechanisms producing glomerular disease
ICs
Antibodies (abs) are directed against GBM antigens
T-cell production of cytokines
Clinical manifestations of glomerular diseases
Nephritic syndrome
Nephrotic syndrome
Chronic GN

STRUCTURE OF THE GLOMERULUS 

PATHOLOGIC RESPONSES OF THE GLOMERULUS TO INJURY 
Hypercellularity 
Basement Membrane Thickening 
Hyalinosis & Sclerosis 

PATHOGENESIS OF GLOMERULAR INJURY 
Diseases Caused by in Situ Formation of Immune Complexes 
Disease Caused by Antibodies Directed Against Normal Components of the Glomerular Basement Membrane 
Glomerulonephritis Resulting From Deposition of Circulating Immune Complexes 
Mechanisms of Glomerular Injury Following Immune Complex Formation 
Cell-Mediated Immunity in Glomerulonephritis 
Activation of Alternative Complement Pathway 
Mediators of Glomerular Injury 
Epithelial Cell Injury 
Mechanisms of Progression in Glomerular Diseases 
Tubular Injury and Interstitial Fibrosis 

NEPHRITIC SYNDROME 
Definition
Clinical and laboratory findings
Primarily nephritic types of glomerular disease
IgA glomerulopathy (Berger disease)
Poststreptococcal
Diffuse proliferative glomerulonephritis (SLE)
Pauci-immune necrotizing crescentic glomerulonephritis
Acute Proliferative (Postinfectious and Infection-Associated) Glomerulonephritis 
Crescentic (Rapidly Progressive) Glomerulonephritis 

NEPHROTIC SYNDROME 
Definition
Clinical and laboratory findings
Primarily nephrotic types of glomerular disease
Membranous Nephropathy 
Minimal Change Disease 
Focal Segmental Glomerulosclerosis 
Diffuse membranous glomerulopathy
Type I MPGN
Type II MPGN
HIV-Associated Nephropathy 
Membranoproliferative Glomerulonephritis 
Secondary Membranoproliferative Glomerulonephritis 
Dense Deposit Disease 
Fibrillary Glomerulonephritis 

SYSTEMIC DISEASES WITH NEPHROTIC SYNDROME
Diabetic glomerulopathy (nephropathy)
Renal amyloidosis associated with primary and secondary amyloidosis

HEREDITARY GLOMERULAR DISEASES
Alport syndrome
Thin basement membrane disease (“benign familial hematuria”)

OTHER GLOMERULAR DISEASES 
IgA Nephropathy (Berger Disease) 
Hereditary Nephritis 
Alport Syndrome 
Thin Basement Membrane Nephropathy (Benign Familial Hematuria) 

GLOMERULAR LESIONS ASSOCIATED WITH SYSTEMIC DISEASES 
Lupus Nephritis 
Henoch-Schönlein Purpura 
Diabetic Nephropathy 
Other Systemic Disorders

CHRONIC GLOMERULONEPHRITIS
Causes in descending order of incidence include
Rapidly progressive glomerulonephritis (RPGN)
Focal segmental glomerulosclerosistype I membranoproliferative glomerulonephritis (MPGN)
Membranous glomerulopathy
Type IV diffuse proliferative GN in SLE
IgA glomerulopathy
Gross and microscopic findings in chronic GN include
Shrunken kidneys
Glomerular sclerosis and tubular atrophy
 
TUBULAR & INTERSTITIAL DISEASES 

ACUTE RENAL FAILURE (ARF)
Definition
Epidemiology

ACUTE TUBULAR INJURY/NECROSIS  (ATN)
Definition
Ischemic ATN
Nephrotoxic type of ATN
Clinical and laboratory findings

TUBULOINTERSTITIAL NEPHRITIS (TIN)
Definition
Epidemiology
Acute pyelonephritis (APN)
Chronic pyelonephritis (CPN)
Acute drug-induced TIN
Contrast media nephropathy
Analgesic nephropathy
Urate nephropathy
Chronic lead (Pb) poisoning
Multiple myeloma; mechanisms for renal disease include

PYELONEPHRITIS & URINARY TRACT INFECTION 
Acute Pyelonephritis 
Chronic Pyelonephritis and Reflux Nephropathy 

TUBULOINTERSTITIAL NEPHRITIS INDUCED BY DRUGS & TOXINS 
Acute Drug-Induced Interstitial Nephritis 

OTHER TUBULOINTERSTITIAL DISEASES 
Urate Nephropathy
Hypercalcemia and Nephrocalcinosis 
Autosomal Dominant Tubulointerstitial Kidney Disease 
Light-Chain Cast Nephropathy (“Myeloma Kidney”) 
Bile Cast Nephropathy 

CHRONIC RENAL FAILURE
Definition
Epidemiology
Clinical findings in CRF
Overview of clinical findings in chronic renal failure
Laboratory findings in CRF
Dialysis kidney

VASCULAR DISEASES 

NEPHROSCLEROSIS - BENIGN NEPHROSCLEROSIS (BNS)
MALIGNANT HYPERTENSION
RENAL INFARCTION

RENAL ARTERY STENOSIS 

THROMBOTIC MICROANGIOPATHIES 
Typical (Epidemic, Classic, Diarrhea-Positive)
Hemolytic Uremic Syndrome 
Atypical (Non-Epidemic, Diarrhea-Negative)
Hemolytic Uremic Syndrome 
Thrombotic Thrombocytopenic Purpura 

OTHER VASCULAR DISORDERS 
Atherosclerotic Ischemic Renal Disease 
Atheroembolic Renal Disease 

Sickle Cell Nephropathy 

Renal Infarcts

DIFFUSE CORTICAL NECROSIS
 
CONGENITAL & DEVELOPMENTAL ANOMALIES
CONGENITAL DISORDERS & CYSTIC DISEASES OF THE KIDNEYS
Horseshoe kidney

CYSTIC DISEASES OF THE KIDNEY 
AUTOSOMAL DOMINANT (ADULT) POLYCYSTIC KIDNEY DISEASE 
AUTOSOMAL RECESSIVE (CHILDHOOD)
POLYCYSTIC KIDNEY DISEASE 
CYSTIC DISEASES OF THE RENAL MEDULLA 
Medullary sponge kidney 
Nephronophthisis 
MULTICYSTIC RENAL DYSPLASIA 
ACQUIRED CYSTIC DISEASE 
SIMPLE CYSTS 

URINARY TRACT OBSTRUCTION (OBSTRUCTIVE UROPATHY)
Overview of causes of urinary tract obstruction
Hydronephrosis
UROLITHIASIS (RENAL CALCULI STONES) 

NEOPLASMS OF THE KIDNEY  AND RENAL PELVIS
Overview of neoplasms of the urinary tract
BENIGN NEOPLASMS 
Renal Papillary Adenoma 
Angiomyolipoma 
Oncocytoma 
MALIGNANT NEOPLASMS 
Renal Cell Carcinoma  RCC
Urothelial Carcinoma of the Renal Pelvis

Wilms tumor

TOC
LOWER URINARY TRACT, MALE & PROSTATE - URETER
(Schneider) V1 PDF

OVERVIEW
The lower urinary tract (LUT) refer to the urinary bladder, prostate, and urethra

THE LOWER URINARY TRACT

URETERS
Primary obstructed nonrefluxing megaureter
Ureteritis cystica
Ureteral stones
Retroperitoneal Fibrosis
Congenital Anomalies
Tumors & Tumor-Like Lesions
Obstructive Lesions
Sclerosing Retroperitoneal Fibrosis

URINARY BLADDER
CONGENITAL ANOMALIES
Exstrophy
Urachal cyst remnants
INFLAMMATION
Acute & Chronic Cystitis
Special Forms of Cystitis
ACUTE CYSTITIS
Definition
Epidemiology; risk factors for LUT infections
Epidemiology; pathogens causing acute cystitis
Other types of cystitis
Chronic cystitis: recurrent cystitis usually in women
Interstitial cystitis (Hunner cystitis)
Eosinophilic cystitis
Emphysematous cystitis
Clinical findings in LUT infections
Laboratory findings
Asymptomatic bacteriuria in women
Sterile pyuria
Malakoplakia
MISCELLANEOUS DISEASES OF THE URINARY BLADDER

METAPLASTIC LESIONS

NEOPLASMS
Bladder papilloma: very uncommon benign papillary tumor
UC (old term, transitional cell carcinoma)
Squamous cell carcinoma (SCC) of the urinary bladder
Adenocarcinoma of urinary bladder
Embryonal rhabdomyosarcoma (sarcoma botryoides)
Cancers that invade the bladder include cervical cancer and prostate cancer

Urothelial Neoplasms
Other Epithelial Bladder Tumors
Mesenchymal Tumors
Secondary Tumors

OBSTRUCTION

URETHRA
Segments of the urethra in the male
Comparison between male and female urethras
Infections of the urethra
Urethral caruncle
Urethral diverticulum in females
Posterior urethral valve (PUV) and anterior urethral valve (AUV)
SCC of the urethra; epidemiology
Inflammation
Tumors and Tumor-Like Lesions

THE MALE GENITAL TRACT

PENIS
Overview of infections of the male reproductive tract
Homologues in Urogenital Development
Congenital Anomalies - Malformations of the urethral groove of the penis
Hypospadias and Epispadias
Phimosis
Balanoposthitis
Inflammation
Miscellaneous disorders of the penis
Peyronie disease
Priapism
Balanitis xerotica obliterans (BXO)
TUMORS
Benign Tumors and Tumor-Like Conditions
Carcinoma in situ (CIS) of the penis
Bowen disease
Erythroplasia of Queyrat
Bowenoid papulosis
Malignant Tumors
Squamous cell carcinoma (SCC) of the penis

TESTIS AND EPIDIDYMIS SCROTAL SAC
Overview of testis
Congenital Anomalies
Cryptorchidism
Regressive Changes
Atrophy and Decreased Fertility
Inflammation and Infections
Nonspecific Epididymitis & Orchitis
Granulomatous (Autoimmune) Orchitis
Infections
Vascular Disorders
Varicocele
Torsion
Testicular torsion
Hydrocele
Spermatic Cord & Paratesticular Tumors
TESTICULAR TUMORS
Epidemiology
Most common clinical finding in testicular cancer is a unilateral, painless enlargement of the testis
Tumor markers
Most frequent sites of metastasis for seminomas and nonseminomatous germ cell tumors are paraaortic lymph nodes at the level of the renal vessels (MC) followed in descending order by the lung, liver, brain, bone, and kidney
Most common secondary tumor of the testis is a malignant lymphoma, which causes diffuse enlargement of both testes
The most common metastatic tumors to the testis are prostate, lung, gastrointestinal tract, kidney, and malignant melanoma
The most common mesenchymal tumors (derive from mesoderm) are fibromas, angiomas, leiomyomas, and neurofibromas
Diagnosis: US, computed tomography (CT) scan, or MRI of the pelvis and abdomen
Germ Cell Tumors
Tumors of Sex Cord–Gonadal Stroma
Gonadoblastoma
Testicular Lymphoma

Lesions of Tunica Vaginalis

PROSTATE
Clinical anatomy of the prostate

INFLAMMATION
Acute and chronic prostatitis

BENIGN ENLARGEMENT
Benign Prostatic Hyperplasia - Prostate hyperplasia (PH) (old term, benign prostate hyperplasia)

NEOPLASMS
Adenocarcinoma
Miscellaneous Tumors

MALE HYPOGONADISM
Normal male reproductive physiology
Pathogenesis of male hypogonadism
Causes of male hypogonadism
Clinical findings for male hypogonadism
Summary of causes of male hypogonadism

MALE INFERTILITY
Definition
Epidemiology and pathogenesis
Laboratory tests for infertility

ERECTILE DYSFUNCTION (IMPOTENCE)
Definition
Causes

TOC
FEMALE
(Robbins Contents) V1 JPG
(Robbins Summary) V1 PDF
(Schneider BRS) V1 PDF

OVERVIEW OF FEMALE REPRODUCTIVE ORGANS

INFECTIONS - SEXUALLY TRANSMITTED DISEASES (STDS) AND OTHER GENITAL INFECTIONS
INFECTIONS OF THE LOWER GENITAL TRACT
Herpes Simplex Virus
Other Lower Female Genital Tract Infections
INFECTIONS INVOLVING THE LOWER AND UPPER GENITAL TRACT
Pelvic Inflammatory Disease (PID)

VULVA
VULVA ANATOMY
BARTHOLIN GLAND CYST
BARTHOLIN GLAND ABCESS
NON-NEOPLASTIC EPITHELIAL DISORDERS - DERMATOSES
Lichen Sclerosus
Psoriasis
Squamous Cell Hyperplasia
BENIGN & MALIGNANT TUMORS
Malignant melanoma
BENIGN EXOPHYTIC LESIONS
Condyloma Acuminatum
SQUAMOUS NEOPLASTIC LESIONS
Vulvar Intraepithelial Neoplasia VIN &
Vulvar Carcinoma (SCC)
GLANDULAR NEOPLASTIC LESIONS
Papillary Hidradenoma (hidradenoma papilliferum)
Extramammary Paget Disease

VAGINA
DEVELOPMENTAL ANOMALIES
Imperforate hymen
Rokitansky-Küster-Hauser (RKH) syndrome
Gartner duct cyst of the vagina
BENIGN AND MALIGNANT TUMORS OF THE VAGINA
Rhabdomyoma
Clear cell adenocarcinoma of the vagina
PREMALIGNANT & MALIGNANT NEOPLASMS OF THE VAGINA
Vaginal Intraepithelial Neoplasia & Squamous Cell Carcinoma (SCC)
Embryonal Rhabdomyosarcoma

CERVIX
CLINICAL ANATOMY AND HISTOLOGY
INFLAMMATIONS
Acute & Chronic Cervicitis
Follicular cervicitis
CERVICAL PAP SMEAR
ENDOCERVICAL (EC) POLYPS
PREMALIGNANT & MALIGNANT NEOPLASMS OF THE CERVIX
Cervical Intraepithelial Neoplasia (CIN) (Squamous Intraepithelial Lesions)
Cervical Carcinoma
CERVICAL CANCER SCREENING AND PREVENTION

REPRODUCTIVE PHYSIOLOGY & SELECTED HORMONE DISORDERS
SEQUENCE TO MENARCHE
SYNTHESIS OF SEX HORMONES IN THECAL CELLS OF THE OVARY
DEVELOPMENT OF THE DOMINANT FOLLICLE (OOCYTE) IN THE OVARY IN THE MENSTRUAL CYCLE
PHASES OF THE MENSTRUAL CYCLE
ORAL CONTRACEPTIVE PILLS (OCPS)
SOURCES AND TYPES OF E
SOURCES AND TYPES OF ANDROGENS
SEX HORMONE–BINDING GLOBULIN (SHBG)
MENOPAUSE
HIRSUTISM AND VIRILIZATION IN FEMALES
MENSTRUAL DYSFUNCTION
AMENORRHEA

BODY OF UTERUS & ENDOMETRIUM
ENDOMETRIAL HISTOLOGY IN THE MENSTRUAL CYCLE
FUNCTIONAL ENDOMETRIAL DISORDERS (DYSFUNCTIONAL UTERINE BLEEDING)
Anovulatory Cycle
UTERINE (PELVIC ORGAN) PROLAPSE
INFLAMMATORY DISORDERS
ENDOMETRITIS
Acute Endometritis
Chronic Endometritis
ENDOMETRIOSIS &
ADENOMYOSIS
Endometrial Polyps
ENDOMETRIAL HYPERPLASIA
MALIGNANT TUMORS OF THE ENDOMETRIUM
Carcinoma of the Endometrium
Endometrioid Endometrial Carcinoma
Serous Endometrial Carcinoma
Carcinosarcoma (Malignant Mixed Müllerian Tumors)
TUMORS OF ENDOMETRIAL STROMA
Adenosarcoma
Stromal Tumors
TUMORS OF THE MYOMETRIUM
Leiomyoma (fibroids)
Leiomyosarcoma
FALLOPIAN TUBES
Hydatid cysts of Morgagni
Pelvic inflammatory disease (PID)
Salpingitis isthmica nodosa (SIN)
Ectopic pregnancy
Inflammations
TUMORS & CYSTS

DIFFERENTIAL DIAGNOSIS OF ADNEXAL MASSES

OVARIES
NON-NEOPLASTIC & FUNCTIONAL CYSTS
Follicle & Luteal Cysts
Polycystic Ovaries and Stromal
Oophoritis
Stromal Hyperthecosis
Ovarian torsion
OVARIAN TUMORS
Definition
Epidemiology
Classification of ovarian tumors
EPITHELIAL TUMORS - SURFACE-DERIVED TUMORS
Serous Tumors
Mucinous Tumors
Endometrioid Ovarian Tumors
Clear Cell Carcinoma
Cystadenofibroma
Transitional Cell Tumors
Clinical Course, Detection, & Prevention of Ovarian Epithelial Tumors
GERM CELL TUMORS
Teratoma
Dysgerminoma
Yolk Sac Tumors
Choriocarcinoma
Other Germ Cell Tumors
SEX CORD–STROMAL TUMORS
Granulosa Cell Tumors
Fibromas, Thecomas, and Fibrothecomas
Sertoli-Leydig Cell Tumors
Other Sex Cord–Stromal Tumors
Metastatic Tumors
TUMOR MARKERS

GESTATIONAL & PLACENTAL DISORDERS

PLACENTAL ANATOMY

PLACENTAL INFECTIONS
Epidemiology
Funisitis and placentitis
Chorioamnionitis

SELECTED PLACENTAL ABNORMALITIES
Placenta previa
Abruptio placenta
Placenta accreta, increta, and percreta
Velamentous insertion
Succenturiate placenta
Marginal cord insertion (battledore placenta)
Placentomegaly
Twin placentas

PREECLAMPSIA & ECLAMPSIA (TOXEMIA OF PREGNANCY)
Definition of preeclampsia
Definition of eclampsia
Epidemiology of preeclampsia
Clinical and laboratory findings in preeclampsia

GESTATIONAL TROPHOBLASTIC NEOPLASMS
Hydatidiform mole
Choriocarcinoma

AMNIOTIC FLUID (AF)

Α-FETOPROTEIN (AFP) IN PREGNANCY

URINE ESTRIOL IN PREGNANCY

DISORDERS OF EARLY PREGNANCY
Spontaneous Abortion
Ectopic Pregnancy
DISORDERS OF LATE PREGNANCY
Twin Placentas
Abnormalities of Placental Implantation
Placental Infections
Preeclampsia & Eclampsia
GESTATIONAL TROPHOBLASTIC DISEASE
HYDATIDIFORM MOLE
Complete Mole
Partial Mole
Invasive Mole
CHORIOCARCINOMA
PLACENTAL SITE TROPHOBLASTIC TUMORS

TOC
BREAST

CLINICAL ANATOMY
Overview of anatomy
Hormone effects during menstrual cycle
Hormone effects in lactation
Lymph nodes

DISORDERS OF DEVELOPMENT
Milk Line Remnants
Accessory Axillary Breast Tissue
Congenital Nipple Inversion

CLINICAL PRESENTATIONS OF BREAST DISEASE
LOCATIONS OF BREAST LESIONS
NIPPLE DISCHARGES
Galactorrhea (excessive production of milk)
Bloody nipple discharge
Purulent nipple discharge
Greenish brown nipple discharge
BREAST PAIN (MASTALGIA)
EXAMPLES OF BENIGN TYPES OF MICROCALCIFICATIONS IN MAMMOGRAMS

INFLAMMATORY DISORDERS - INFLAMMATION
Acute Mastitis
Squamous Metaplasia of Lactiferous Ducts
Duct Ectasia (plasma cell mastitis)
Fat Necrosis Traumatic
Lymphocytic Mastopathy (Sclerosing Lymphocytic Lobulitis)
Granulomatous Mastitis
Silicone breast implant

BENIGN EPITHELIAL LESIONS
NONPROLIFERATIVE BREAST CHANGES (FIBROCYSTIC CHANGES) (FCC)
SCLEROSING ADENOSIS
PROLIFERATIVE BREAST DISEASE WITHOUT ATYPIA
Gynecomastia
PROLIFERATIVE BREAST DISEASE WITH ATYPIA
CLINICAL SIGNIFICANCE OF BENIGN EPITHELIAL CHANGES

BENIGN BREAST TUMORS
Fibroadenoma
Phyllodes tumor
Intraductal papilloma

GYNECOMASTIA
Definition
Physiologic gynecomastia
Pathologic gynecomastia

BREAST CANCER IN MEN; EPIDEMIOLOGY

CARCINOMA OF THE BREAST - BREAST CANCER
Definition
Incidence & Epidemiology
Risk Factors
Family history and genetics
Prolonged E stimulation; causes include
Ductal carcinoma in situ (DCIS) and lobular carcinoma in situ (LCIS), both of which can become invasive cancers
Other risk factors
Factors that decrease the risk for breast cancer
Clinical findings
Mammography
Molecular Classification and Pathogenesis
TYPES OF BREAST CARCINOMA
Carcinoma in Situ
Invasive (Infiltrating) Carcinoma
Special Histologic Types of Invasive Carcinoma
Natural history and prognosis of breast cancer
Prognostic and Predictive Factors for Invasive Carcinoma
Male Breast Cancer

STROMAL TUMORS
Fibroadenoma
Phyllodes Tumor
Lesions of Interlobular Stroma
Malignant Tumors of Interlobular Stroma

OTHER MALIGNANT TUMORS OF THE BREAST

TOC
METABOLIC DISORDERS

OVERVIEW
AMINO ACIDS
CARBOHYDRATES
LIPIDOSES
ABNORMALITIES OF LIPOPROTEIN METABOLISM
GOUT
HEMOCHROMATOSIS
WILSON’S DISEASE
HEME SYNTHESIS, PORPHYRIAS

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ENDOCRINE
(Schneider) V1 PDF
Thyroid Tumors

OVERVIEW OF ENDOCRINE DISEASE
Clinical significance of various endocrine diseases
Location of endocrine glands
Hormones in the endocrine system
Examples of cell-to-cell signaling
Endocrine axis and feedback mechanisms
Negative feedback loops
Positive feedback loops
Stimulation tests evaluate hypofunctioning disorders
Suppression tests

HYPOTHALAMUS DISORDERS
TUMORS OR TUMOR-LIKE CONDITIONS ALTERING HYPOTHALAMIC FUNCTION
INFLAMMATORY DISORDERS ALTERING HYPOTHALAMIC FUNCTION
CLINICAL FINDINGS OF HYPOTHALAMIC DYSFUNCTION

PINEAL GLAND DISORDERS
CLINICAL ANATOMY OF THE PINEAL GLAND
PINEAL GLAND DISORDERS
Pinealoma
CLINICAL FINDINGS IN PINEAL GLAND TUMORS

PITUITARY GLAND

PITUITARY GLAND HORMONES
OVERVIEW OF SIGNS AND SYMPTOMS OF PITUITARY SELLA DISORDERS
Clinical syndromes of excess hormone production (hyperfunction; e.g., acromegaly, pituitary Cushing disease, galactorrhea or secondary amenorrhea from prolactinoma)
Clinical syndromes caused by hypofunction of the pituitary (e.g., secondary hypothyroidism, hypocortisolism, infertility)
Compression syndromes (hydrocephalus, frontal headaches, visual disturbances [bitemporal hemianopsia])
ANTERIOR PITUITARY HYPOFUNCTION
Definition
Epidemiology
Causes of hypopituitarism
Nonfunctioning (null) pituitary adenoma
Craniopharyngioma
Sheehan postpartum necrosis
Pituitary apoplexy
Sickle cell anemia
Lymphocytic hypophysitis
Empty sella syndrome
Clinical & laboratory findings in anterior pituitary hypofunction
Diagnosis of anterior pituitary hypofunction
POSTERIOR PITUITARY HYPOFUNCTION
Normal function of the posterior pituitary
Diabetes insipidus
PITUITARY HYPERFUNCTION DISORDERS
Thirty percent of pituitary adenomas are nonfunctioning
Prolactinoma
Growth hormone adenoma
Pituitary adenoma secreting ACTH 7% of adenomas
Syndrome of inappropriate antidiuretic hormone

CLINICAL MANIFESTATIONS OF PITUITARY DISEASE
PITUITARY ADENOMAS & HYPERPITUITARISM
Lactotroph Adenoma
Somatotroph Adenoma
Corticotroph Adenoma
Other Anterior Pituitary Tumors
HYPOPITUITARISM
POSTERIOR PITUITARY SYNDROMES
HYPOTHALAMIC SUPRASELLAR TUMORS

THYROID GLAND

OVERVIEW OF THYROID GLAND

STEPS IN THYROID HORMONE SYNTHESIS

FUNCTIONS OF THYROID HORMONE

THYROID FUNCTION TESTS
Total serum T4
Serum thyroid stimulating hormone (TSH)
123I (radioactive) uptake
Serum thyroglobulin is used as a marker for thyroid cancer

THYROIDITIS
Acute thyroiditis
Subacute Lymphocytic (Painless) Thyroiditis
Hashimoto Thyroiditis
Riedel thyroiditis
Subacute painless lymphocytic thyroiditis (SPLT)
Granulomatous Thyroiditis

HYPOTHYROIDISM
Definition
Epidemiology
Causes of hypothyroidism
Hashimoto thyroiditis (90% of cases)
Subacute painless lymphocytic thyroiditis ; Reidel thyroiditis
Hypopituitarism, hypothalamic dysfunction
Iodine deficiency, enzyme deficiency, congenital
Drugs, including amiodarone, lithium, sulfonamides, and phenylbutazone
Congenital hypothyroidism
Clinical findings in adult hypothyroidism
Overview of clinical findings in hypothyroidism
Laboratory findings in hypothyroidism
Myxedema coma
Cretinism
Myxedema

THYROID HORMONE EXCESS
Classification
Thyrotoxicosis :Thyroid hormone excess regardless of cause (e.g., Graves disease, thyroiditis, increased intake of thyroid hormone)
Hyperthyroidism : Thyroid hormone excess caused by increased synthesis of the hormone. Examples: Graves disease and toxic nodular goiter
Patients are hypermetabolic because there is an increase in the BMR
GRAVES DISEASE
Definition
Epidemiology
Clinical and laboratory features unique to Graves disease and not found in other causes of thyrotoxicosis
Clinical findings in Graves disease in the elderly
Toxic multinodular goiter (Plummer disease)
Clinical signs in all causes of thyrotoxicosis
Laboratory findings in thyrotoxicosis
Comparison of hyperthyroidism with hypothyroidism
Thyroid storm
Euthyroid sick syndrome (ESS)

SUMMARY OF LABORATORY FINDINGS IN THYROID DISORDERS Serum t4 Free t4 Serum TSH 123I uptake
Graves disease
Patient taking excess hormone
Initial phase of thyroiditis
Primary hypothyroidism
Secondary hypothyroidism (hypopituitarism)
Increased TBG (e.g., excess estrogen)
Decreased TBG (e.g., anabolic steroids)

NONTOXIC GOITER
Definition
Goiter: thyroid enlargement from excess colloid
Thyroid enlargement ; excess colloid (thyroglobulin)
Epidemiology
Types of goiter
Pathogenesis
Complications associated with goiters

OVERVIEW OF PALPABLE THYROID NODULES
Occur in ~6% of population
Malignancy ~10% thyroid nodules
Incidence ↑with age; women > men

SOLITARY THYROID NODULE
Definition
Epidemiology
Diagnosis

DIFFUSE & MULTINODULAR GOITER
Diffuse Nontoxic (Simple) Goiter
Multinodular Goiter

NEOPLASMS OF THE THYROID - BENIGN AND MALIGNANT TUMORS OF THE THYROID
Comparison of a benign versus a malignant tumor of the thyroid
THYROID ADENOMAS
Follicular adenoma
THYROID CARCINOMAS
Papillary Adeno-Carcinoma and Follicular Variants, Including Invasive Encapsulated Follicular Variant of PTC & Noninvasive Follicular Thyroid Neoplasm With Papillary-like Nuclear Features
Follicular Carcinoma
Poorly Differentiated & Anaplastic (Undifferentiated) Carcinoma
Medullary Carcinoma
Primary B-cell malignant lymphoma
Anaplastic thyroid cancer

CONGENITAL ANOMALIES

PARATHYROID GLANDS

CLINICAL ANATOMY & PHYSIOLOGY
Superior and inferior parathyroid gland
PTH functions
Role of vitamin D (D) in Ca metabolism
Total serum Ca

HYPOPARATHYROIDISM
Hypofunction parathyroid glands
Causes
Clinical findings
Laboratory findings
Other causes hypocalcemia
Pseudohypoparathyroidism

HYPERPARATHYROIDISM
PRIMARY HYPERPARATHYROIDISM (HPTH)
Excessive production/secretion PTH
Epidemiology
Clinical findings
Laboratory findings and metabolic consequences
Localization of a parathyroid adenoma is made using a technetium-99m-sestamibi radionuclide scan
Other causes of hypercalcemia
SECONDARY HYPERPARATHYROIDISM (HPTH)
Compensation for hypocalcemia hyperphosphatemia,↓serum calcitriol/calcium
Epidemiology
SCHEMATIC SUMMARIZING SERUM PTH AND CA RELATIONSHIPS
PHOSPHOROUS (PH) DISORDERS
The causes of hypophosphatemia
Clinical findings
Causes of hyperphosphatemia
Clinical findings
SUMMARY TABLE INTEGRATING CA, PH, AND PTH IN CA AND PH DISORDERS

THE ENDOCRINE PANCREAS

DIABETES MELLITUS
DEFINITION
FUNCTIONS OF INSULIN
Anabolic functions of insulin
Anticatabolic functions of insulin
The functions of insulin in the fed state and the fasting state
The actions of insulin on target tissues
EPIDEMIOLOGY
CLASSIFICATION OF DIABETES MELLITUS
Types 1 and type 2 DM
Secondary causes of DM
Impaired glucose tolerance (IGT)
Gestational diabetes mellitus (GDM)
MODY
Metabolic syndrome
PATHOLOGIC PROCESSES & COMPLICATIONS IN DM
Poor glycemic control
Nonenzymatic glycosylation (NEG)
Osmotic damage
Diabetic microangiopathy
CLINICAL FINDINGS IN DM
Insulin-induced hypoglycemia
Diabetic ketoacidosis (DKA)
Hyperosmolar hyperglycemic state (HHS)
OVERVIEW OF COMPLICATIONS OF DM
LABORATORY DIAGNOSIS OF DM
IMPAIRED GLUCOSE TOLERANCE (IGT)
GESTATIONAL DIABETES MELLITUS (GBS)

GLUCOSE HOMEOSTASIS
Regulation of Insulin Release
Insulin Action and Insulin-Signaling Pathways

PATHOGENESIS OF TYPE 1 DIABETES
Genetic Susceptibility
Environmental Factors
Mechanisms of β-Cell Destruction

PATHOGENESIS OF TYPE 2 DIABETES
Genetic Factors
Environmental Factors
Metabolic defects in type 2 diabetes

MONOGENIC FORMS OF DIABETES
Genetic Defects in β-Cell Function
Genetic Defects That Impair Tissue Response to Insulin

DIABETES AND PREGNANCY

CLINICAL FEATURES OF DIABETES
The Classic Triad of Diabetes
Acute Metabolic Complications of Diabetes
Chronic Complications of Diabetes
Morphology of Chronic Complications of Diabetes
Clinical Manifestations of Chronic Diabetes

PANCREATIC NEUROENDOCRINE TUMORS - ISLET CELL TUMORS
Glucagonoma
Hyperinsulinism (Insulinoma)
Somatostatinoma
VIPoma (pancreatic cholera)
Zollinger-Ellison Syndrome (Gastrinoma)
Other Rare Pancreatic Endocrine Neoplasms

HYPOGLYCEMIA
DEFINITION
FED STATE HYPOGLYCEMIA
FASTING TYPE OF HYPOGLYCEMIA

ADRENAL GLANDS
REGULATION OF CORTISOL SECRETION
OVERVIEW OF ADRENAL CORTEX HORMONES
OVERVIEW OF ADRENAL MEDULLA HORMONES

ADRENAL CORTEX
ADRENOCORTICAL HYPERFUNCTION (HYPERADRENALISM)
Hypercortisolism (Cushing Syndrome)
Clinical abnormalities that occur caused by excess production of cortisol
Epidemiology; causes
Clinical findings
Laboratory findings
Nelson syndrome
Hyperaldosteronism
Primary Hyperaldosteronism (Conn syndrome)
Secondary aldosteronism
Adrenogenital Syndromes
ADRENOCORTICAL INSUFFICIENCY - ADRENOCORTICAL HYPOFUNCTION (PRIMARY HYPOCORTISOLISM)
Primary Acute Adrenocortical Insufficiency
A sudden lack of production of glucocorticoids or mineralocorticoids by the adrenal cortex
Epidemiology and causes
Waterhouse-Friderichsen Syndrome (WFS)
Primary Chronic Adrenocortical Insufficiency (Addison Disease)
↓Production glucocorticoids/ mineralocorticoids → ↑ACTH
Epidemiology and causes
Clinical findings
Laboratory findings
Adrenogenital syndrome (congenital adrenal hyperplasia)
Cortex enzyme deficiency(ies) → ↓cortisol → ↑ACTH
Epidemiology/clinical
Classic 21-hydroxylase (21-OHase) deficiency ; epidemiology
Nonclassical 21-OHase deficiency; epidemiology
11-Hydroxylase deficiency (11-OHase
Diagnosis of adrenogenital syndrome (congenital adrenal hyperplasia)
Summary of adrenogenital syndrome
Secondary Adrenocortical Insufficiency
ADRENOCORTICAL NEOPLASMS
OTHER ADRENAL LESIONS

ADRENAL MEDULLA
ADRENAL MEDULLA HYPERFUNCTION
Increased production of catecholamines resulting in hypertension
Pheochromocytoma
Neuroblastoma

MULTIPLE ENDOCRINE NEOPLASIA SYNDROMES - POLYGLANDULAR DEFICIENCY SYNDROMES
Multiple Endocrine Neoplasia, Type 1
Multiple Endocrine Neoplasia, Type 2

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SKIN
(Schneider) V1 PDF

THE SKIN: MORE THAN A MECHANICAL BARRIER
SKIN HISTOLOGY AND TERMINOLOGY
NORMAL SKIN HISTOLOGY
Epidermis layers
Dermis
Histology of sweat gland, apocrine gland, and hair follicle with sebaceous glands
Melanocytes
Age-related skin changes
COMMON TERMS USED IN DERMATOLOGY

DISORDERS OF PIGMENTATION & MELANOCYTES -  MELANOCYTIC DISORDERS
Overview of pigmented lesions
Solar lentigo (“liver spots”)
Vitiligo
Melasma
Freckle (Ephelis)
Lentigo
Melanocytic Nevus (Pigmented Nevus,Mole) Nevocellular nevus (mole)
Dysplastic Nevi
Melanoma Cutaneous malignant

BENIGN EPITHELIAL TUMORS
Seborrheic Keratosis
Acanthosis Nigricans AN
Keratoacanthoma (KA)
Fibroepithelial Polyp (skin tag)
Syringoma
Epithelial or Follicular Inclusion Cyst (Wen)

ADNEXAL (APPENDAGE) TUMORS

PREMALIGNANT AND MALIGNANT EPIDERMAL TUMORS
Actinic Keratosis (solar)
Squamous Cell Carcinoma SCC
Basal Cell Carcinoma BCC

SELECTED SKIN DISORDERS
Ichthyosis vulgaris
Xerosis
Polymorphous light eruption (PML)
Eczema
Autoimmune skin disorders
Lichen planus (LP)
Psoriasis
Pityriasis rosea
Erythema multiforme (EM)
Erythema nodosum
Granuloma annulare
Porphyria cutanea tarda (PCT)
Urticaria
Cherry angiomas
Rosacea
Pyoderma gangrenosum
Necrotizing fasciitis

TUMORS OF THE DERMIS - DERMAL AND SUBCUTANEOUS GROWTHS
Benign Fibrous Histiocytoma (Dermatofibroma)
Dermatofibrosarcoma Protuberans
Epidermal inclusion cyst (sebaceous cyst)
Pilar cysts (wen)

TUMORS OF CELLULAR MIGRANTS TO THE SKIN
Mycosis Fungoides (Cutaneous T-Cell Lymphoma)
Mastocytosis

DISORDERS OF EPIDERMAL MATURATION
Ichthyosis

ACUTE INFLAMMATORY DERMATOSES
Urticaria
Acute Eczematous Dermatitis
Erythema Multiforme

CHRONIC INFLAMMATORY DERMATOSES
Psoriasis
Seborrheic Dermatitis
Lichen Planus

BLISTERING (BULLOUS) DISEASES
INFLAMMATORY BLISTERING DISORDERS
Pemphigus
Bullous Pemphigoid
Dermatitis Herpetiformis
NONINFLAMMATORY BLISTERING DISORDERS
Epidermolysis Bullosa and Porphyria

DISORDERS OF EPIDERMAL APPENDAGES
Acne Vulgaris
Rosacea

PANNICULITIS
Erythema Nodosum and Erythema Induratum
Other Types of Panniculitis

INFECTION

SELECTED VIRAL DISORDERS
Verrucae (Warts) Common wart
Molluscum Contagiosum
Rubeola (regular measles)
Rubella (German measles)
Erythema infectiosum (fifth disease)
Roseola infantum (exanthem subitum)
Disorders caused by varicella-zoster virus (VZV)
Herpes simplex virus (HSV)-1
Hand-foot-and-mouth (HFM) disease

SELECTED BACTERIAL DISORDERS
Staphylococcus aureus skin infections Impetigo
S. pyogenes skin infections
Leprosy
Acne vulgaris

SELECTED FUNGAL DISORDERS Superficial Fungal Infections
Superficial mycoses (dermatophytoses)
Sporotrichosis
Fusarium spp. infection

SELECTED PARASITIC AND ARTHROPOD DISORDERS
Cutaneous larva migrans
Cutaneous leishmaniasis
Arthropod disorders: chiggers
Arthropod disorders: scabies
Arthropod disorders: lice
Arthropod disorders: bedbug
Arthropod: tick
Arthropod: fire ants

SELECTED SKIN DISORDERS IN NEWBORNS
Sites of common dermatoses in infants and children
Erythema toxicum neonatorum (ETN)
Sebaceous hyperplasia
Milia
Miliaria
Salmon patch
Irritant contact dermatitis; diaper rash
Seborrheic dermatitis of the scalp (cradle cap)
Congenital dermal melanocytosis (Mongolian spots)
Cutis marmorata

SELECTED HAIR AND NAIL DISORDERS
Phases of hair growth in succession
Massive hair loss; causes
Alopecia areata
Nail disorders

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BONES, JOINTS & SOFT TISSUE TUMORS
(Schneider) V1 PDF
Osteosarcoma
Soft Tissues Tumors

BONE

BASIC STRUCTURE AND FUNCTION OF BONE
Matrix
Cells
Development
Homeostasis and Remodeling

DEVELOPMENTAL DISORDERS OF BONE & CARTILAGE
Defects in Nuclear Proteins and Transcription Factors
Defects in Hormones and Signal Transduction Proteins
Defects in Extracellular Structural Proteins
Type 1 Collagen Diseases (Osteogenesis Imperfecta) (brittle bone disease)
Defects in Metabolic Pathways (Enzymes, Ion Channels, and Transporters)
Osteopetrosis (marble bone disease)
Diseases Associated With Defects in Degradation of Macromolecules
Mucopolysaccharidoses

Achondroplasia
Osgood-Schlatter disease (OSD)

METABOLIC DISEASES OF BONE
Osteopenia & Osteoporosis
Osteomalacia and Rickets
Hyperparathyroidism
Renal Osteodystrophy
Paget Disease (Osteitis Deformans)

Fibrous dysplasia

FRACTURES
Healing of Fractures

OSTEONECROSIS (AVASCULAR NECROSIS) AVN
Osteochondritis dissecans

OSTEOMYELITIS
Pyogenic Osteomyelitis
Mycobacterial Osteomyelitis
Skeletal Syphilis

BONE TUMORS & TUMOR-LIKE LESIONS
EPIDEMIOLOGY
Metastasis: MC bone malignancy; breast cancer MCC
Multiple myeloma, osteosarcoma, chondrosarcoma, and Ewing sarcoma
Osteochondroma: MC benign bone tumor
BONE-FORMING TUMORS
Osteoid Osteoma and Osteoblastoma
Osteosarcoma
CARTILAGE-FORMING TUMORS
Osteochondroma
Chondroma
Chondrosarcoma
TUMORS OF UNKNOWN ORIGIN
Ewing Sarcoma
Giant Cell Tumor
Aneurysmal Bone Cyst
LESIONS SIMULATING PRIMARY NEOPLASMS
Fibrous Cortical Defect and Nonossifying
Fibroma
Fibrous Dysplasia
Metastatic Tumors

JOINTS
SYNOVIAL FLUID ANALYSIS
Routine studies performed on synovial fluid include WBC count and differential, crystal analysis, culture, and Gram stain
Crystal identification
CLASSIFICATION OF JOINT DISORDERS
Group I Noninflammatory joint disease
Examples: OA, neuropathic joint
Group II Inflammatory joint disease
Examples: rheumatoid arthritis (RA), gout
Group III Septic joint disease
Examples: Lyme disease (LD), disseminated gonococcemia (GC)
Group IV Hemorrhagic joint disease
Examples: trauma, hemophilia A and B
SIGNS AND SYMPTOMS OF JOINT DISEASE
Arthralgia
Arthritis
Morning stiffness
Abnormal joint mobility
Swelling of the joint (effusion)
Redness (rubor) and warmth (calor; “hot joint”) of the join
Joint crepitus with motion

ARTHRITIS
Osteoarthritis OA
Rheumatoid Arthritis RA
Juvenile Idiopathic Arthritis JIA
Seronegative Spondyloarthropathies
Ankylosing Spondylitis
Reactive Arthritis
Infectious Arthritis
Suppurative Arthritis
Mycobacterial Arthritis
Viral Arthritis
Lyme Arthritis
Crystal-Induced Arthritis
Gout Gouty arthritis
Calcium Pyrophosphate dihydrate Crystal Deposition Disease (Pseudogout) (CPPD)

Neuropathic arthropathy (Charcot joint)
Sjögren syndrome (SS)
Septic arthritis

JOINT TUMORS AND TUMOR-LIKE CONDITIONS
Ganglion and Synovial Cysts
Tenosynovial Giant Cell Tumor

Miscellaneous joint disease Bunion

SOFT TISSUE DISORDERS
Fibromyalgia
Fibromatosis

SOFT TISSUE TUMORS

TUMORS OF ADIPOSE TISSUE
Lipoma
Liposarcoma
FIBROUS TUMORS
Nodular Fasciitis
Fibromatoses
Superficial Fibromatosis
Deep Fibromatosis (Desmoid Tumors)
SKELETAL MUSCLE TUMORS
Rhabdomyosarcoma
SMOOTH MUSCLE TUMORS
Leiomyoma
Leiomyosarcoma
TUMORS OF UNCERTAIN ORIGIN
Synovial Sarcoma
Undifferentiated Pleomorphic Sarcoma

SELECTED ORTHOPEDIC DISORDERS

TOC
PERIPHERAL NERVES & SKELETAL MUSCLES

DISEASES OF PERIPHERAL NERVES

GENERAL TYPES OF PERIPHERAL NERVE INJURY
Axonal Neuropathies
Demyelinating Neuropathies
Neuronopathies

ANATOMIC PATTERNS OF PERIPHERAL NEUROPATHIES

PERIPHERAL NEUROPATHIES
Definition
Epidemiology
Charcot-Marie-Tooth (CMT) disease
Guillan-Barre syndrome (GBS)
Diabetes mellitus (DM); epidemiology
Toxin-associated neuropathies: alcohol, heavy metals, and diphtheria
Idiopathic Bell palsy
Drugs producing peripheral neuropathy
Vitamin deficiencies producing peripheral neuropathy

Inflammatory Neuropathies
Infectious Neuropathies
Metabolic, Hormonal, and Nutritional Neuropathies
Toxic Neuropathies
Neuropathies Associated With Malignancy
Neuropathies Caused by Physical Forces
Inherited Peripheral Neuropathies

SELECTED NERVE INJURIES

DISEASES OF THE NEUROMUSCULAR JUNCTION
ANTIBODY-MEDIATED DISEASES OF THE NEUROMUSCULAR JUNCTION
Myasthenia Gravis
Lambert-Eaton Myasthenic Syndrome
CONGENITAL MYASTHENIC SYNDROMES
DISORDERS CAUSED BY TOXINS

MUSCLE FIBERS
DISEASES OF SKELETAL MUSCLE
Pathogenesis of muscle weakness
Abnormality in motor neuron pathways. Example: poliomyelitis
Abnormality in neuromuscular synapse. Example: myasthenia gravis (MG)
Abnormality in muscle. Example: muscular dystrophy (MD)
Trichinella spiralis infection (called trichinosis)
Invasive infections caused by group A streptococcus
Clostridium tetani: tetanus
Clostridium perfringens
SKELETAL MUSCLE ATROPHY
Neurogenic
NEUROGENIC AND MYOPATHIC CHANGES IN SKELETAL MUSCLE
INFLAMMATORY MYOPATHIES
Dermatomyositis
Immune-Mediated Necrotizing Myopathy (IMNM)
Polymyositis
Inclusion Body Myositis
TOXIC MYOPATHIES
INHERITED DISEASES OF SKELETAL MUSCLE
Muscular Dystrophies
Duchenne muscular dystrophy (DMD)
Myotonic dystrophy
Diseases of Lipid or Glycogen Metabolism
Mitochondrial Myopathies
Spinal Muscular Atrophy and Differential Diagnosis of a Hypotonic Infant
Ion Channel Myopathies (Channelopathies)
Congenital myopathies

PERIPHERAL NERVE SHEATH TUMORS
SCHWANNOMAS (neurilemoma)
NEUROFIBROMAS
MALIGNANT PERIPHERAL NERVE SHEATH TUMORS
NEUROFIBROMATOSIS TYPE 1 AND TYPE 2
Neurofibromatosis Type 1
Neurofibromatosis Type 2

TOC
CENTRAL NERVOUS SYSTEM
(Schneider) V1 PDF

OVERVIEW OF CENTRAL NERVOUS SYSTEM

CEREBROSPINAL FLUID ANALYSIS

OVERVIEW OF CSF
CSF choroid plexus ventricles
Enters SAD space
Cushions brain/spinal cord
Autoregulation blood flow
Circulates nutrients/chemicals
Removes waste products
Reabsorbed by arachnoid granulations
Drained into dural venous sinuses

CSF ANALYSIS
Lumbar puncture; L4 to L5
Three tubes for CSF analysis are usually collected
Gross appearance
CSF protein
CSF glucose
CSF WBC count
Detection of microbial pathogens in CSF

CELLULAR PATHOLOGY OF THE CENTRAL NERVOUS SYSTEM
Reactions of Neurons to Injury
Reactions of Astrocytes to Injury
Reactions of Microglia to Injury
Reactions of Other Glial Cells to Injury

CEREBRAL EDEMA, HYDROCEPHALUS, RAISED INTRACRANIAL PRESSURE, IDIOPATHIC INTRACRANIAL HYPERTENSION, & HERNIATION

CEREBRAL EDEMA
Definition
Epidemiology
Clinical findings in cerebral edema are related to intracranial pressure (intracranial hypertension [ICH]

RAISED INTRACRANIAL PRESSURE & HERNIATION
IDIOPATHIC ICH (PSEUDOTUMOR CEREBRI)
Definition
Epidemiology
Diagnosis of idiopathic ICH

CEREBRAL HERNIATION
Definition
Epidemiology; pathogenesis
Subfalcine herniation
Uncal (uncinate) herniation
Tonsillar herniation

HYDROCEPHALUS
Normal ventricle anatomy and flow of CSF
Definition
Communicating (nonobstructive) hydrocephalus
Noncommunicating (obstructive) hydrocephalus
In NBs with hydrocephalus
In adults with hydrocephalus
Hydrocephalus ex vacuo
Normal pressure hydrocephalus

MALFORMATIONS AND DEVELOPMENTAL DISORDERS
NEURAL TUBE DEFECTS (NTDs)
Definition
Epidemiology and pathogenesis
Anencephaly
Spina bifida occulta (SBO)
Meningocele
Meningomyelocele
Encephalocele
ARNOLD-CHIARI MALFORMATION
DANDY-WALKER MALFORMATION
SYRINGOMYELIA
PHAKOMATOSES (NEUROCUTANEOUS SYNDROMES)
Definition
Epidemiology
Neurofibromatosis
Tuberous sclerosis (TS)
Sturge-Weber syndrome (SWS)
FOREBRAIN ANOMALIES
POSTERIOR FOSSA ANOMALIES
SYRINGOMYELIA & HYDROMYELIA

PERINATAL BRAIN INJURY

TRAUMA HEAD

CEREBRAL CONTUSION
Definition
Permanent damage small BVs
Epidemiology
Acceleration-deceleration injury
Coup: site of impact
Contrecoup: opposite site of impact; tips frontal/temporal lobes

CEREBRAL PALSY (CP)
Definition
Static motor/posture disorder; cerebral or cerebellar origin
Epidemiology and clinical
Defects motor planning/control
Clinical manifestations change over time
Motor function correlates with part or brain injure
Causes : Cerebral malformations, metabolic/genetic, stroke, hypoxia-ischemia, trauma
Brain lesions seen on MRI
Levine (POSTER) criteria for the diagnosis of CP
Types of cerebral palsy

SKULL FRACTURES

PARENCHYMAL INJURIES
Concussion
Direct Parenchymal Injury
Diffuse Axonal Injury

TRAUMATIC VASCULAR INJURY

(ACUTE) EPIDURAL (EXTRADURAL) HEMATOMA
Definition
Arterial blood between surface of skull and dura
Epidemiology
1% to 4% head injuries
Pathogenesis Temporoparietal skull fracture Hammer, baseball bat, focused blow to head Severance middle meningeal artery
Clinical findings in epidural hematoma
Lucid interval → neurologic deterioration
↑Intracranial pressure → cerebral herniation → death
Diagnosis of epidural hematoma Dx
CT scan: imaging test of choice
Hematoma rarely crosses suture line

SUBDURAL HEMATOMA
Definition
Venous blood between dura and arachnoid membranes
Epidemiology
Acute/chronic Acute all age groups Chronic: elderly 8th decade; males > females
Pathogenesis Tear bridging veins between brain and dural sinuses Slow enlarging blood clot
Causes Blunt trauma Car accident, baseball bat Anticoagulation Hemophilia, child abuse Shaken baby syndrome Spontaneous bleed Major risk factor brain atrophy Elderly, chronic alcoholics Loss brain mass → traction on bridging veins
Clinical findings
Fluctuating consciousness
Herniation leads to death
Chronic subdural hematoma cause of dementia
Dx
CT scan: imaging test of choice

CEPHALHEMATOMA
Definition
Hemorrhage between bone/periosteum in NBs
Epidemiology and clinical
Mass overlying skull confined by cranial sutures
↑Size after birth
Dystrophic calcification may occur
Unilateral over parietal bone
Associated with forceps delivery
Blood loss not life-threatening
Underlying fracture 10% to 25%

SUBGALEAL HEMORRHAGE
Definition
Hemorrhage beneath aponeurosis covering scalp
Epidemiology and clinical
Blood may extend into posterior neck
Fluctuant mass that increases in size
Serious, life-threatening injury
Vacuum extraction
Linear skull fracture, suture diastasis, parietal bone fragmentation
Subaponeurotic space: reservoir for blood → hypovolemic shock
Caput: swelling (edema) NB scalp after delivery

SUMMARY OF SITES FOR EXTRACRANIAL & EXTRADURAL HEMORRHAGES (INCLUDES NBS)

SEQUELAE OF BRAIN TRAUMA

SPINAL CORD INJURY

CEREBROVASCULAR DISEASE

OVERVIEW OF CEREBROVASCULAR DISEASES (CVDS)
Thrombosis Infarction Hemorrhage
↓Blood supply, hypoxia, ischemia, infarction
Sites: parenchyma, subarachnoid/subdural space

GLOBAL HYPOXIC INJURY
Causes
Cardiogenic shock
Hypovolemic shock
Septic shock
CO poisoning
Process of neuronal ischemia and infarction
Hypoglycemia: similar effect on brain as global hypoxia
Complications
Cerebral atrophy
Watershed infarcts
Stroke

STROKE
Definition
Epidemiology and clinical
Transient ischemic attack (TIA)
Summary of stroke syndromes
Ischemic stroke
Embolic (hemorrhagic) stroke
Lacunar strokes
Intracerebral hemorrhage
Subarachnoid hemorrhage (SAH)
Superior sagittal venous thrombosis (SSVT)
Diagnosis of strokes

HYPOXIA & ISCHEMIA
Focal Cerebral Ischemia
Lacunar Infarcts
Global Cerebral Hypoxia/Ischemia

INTRACRANIAL HEMORRHAGE
Intraparenchymal Hemorrhage
Subarachnoid Hemorrhage & Ruptured Saccular Aneurysm
Vascular Malformations

VASCULAR DEMENTIA

INFECTIONS
DEFINITION
PATHOGENESIS
MENINGITIS
ENCEPHALITIS
CEREBRAL ABSCESS
VIRAL CNS INFECTIONS AND SPONGIFORM ENCEPHALOPATHY
BACTERIAL CNS INFECTIONS
FUNGAL AND PARASITIC CNS INFECTIONS

ACUTE MENINGITIS
Acute Pyogenic (Bacterial) Meningitis
Acute Aseptic (Viral) Meningitis

ACUTE FOCAL SUPPURATIVE INFECTIONS
Brain Abscess
Subdural Empyema
Extradural Abscess

CHRONIC BACTERIAL MENINGOENCEPHALITIS
Tuberculosis
Neurosyphilis
Neuroborreliosis (Lyme Disease)

VIRAL MENINGOENCEPHALITIS
Arthropod-Borne Viral Encephalitis
Herpes Simplex Virus Type 1
Herpes Simplex Virus Type 2
Varicella-Zoster Virus
Cytomegalovirus
Poliomyelitis
Rabies
Human Immunodeficiency Virus
Progressive Multifocal Leukoencephalopathy

FUNGAL MENINGOENCEPHALITIS

OTHER INFECTIOUS DISEASES OF THE NERVOUS SYSTEM

DEMYELINATING DISEASES

DEFINITION OF A DEMYELINATING DISORDER
Group of disorders characterized by the breakdown of myelin derived from Schwan cells (SCs) and oligodendrocytes (ODC)
White matter contains myelinated axons (myelinated processes are white in color)
Gray matter mostly contains nerve cell bodies and has a gray color (lack of myelin)

EPIDEMIOLOGY OF DEMYELINATING DISORDERS; PATHOGENESIS
Destruction of normal myelin. Example: multiple sclerosis
Production of abnormal myelin. Example: leukodystrophy
Destruction of oligodendrocytes. Examples: Multiple sclerosis, slow virus infections (SVIs)
Destruction of Schwann cells in the peripheral nervous system (PNS). Example: GBS

ACQUIRED DEMYELINATING DISORDERS
Multiple Sclerosis (MS)
Central Pontine Myelinolysis CPM

HEREDITARY DEMYELINATING DISORDERS; LEUKODYSTROPHIES
Definition
Adrenoleukodystrophy
Metachromatic leukodystrophy
Krabbe disease

Neuromyelitis Optica
Acute Disseminated Encephalomyelitis and Acute Necrotizing Hemorrhagic Encephalomyelitis
 
NEURODEGENERATIVE DISEASES

DEFINITION OF DEGENERATIVE DISORDERS
Diseases with progressive deterioration of neurons

PRION DISEASES
Creutzfeldt-Jakob Disease (CJD)
Variant Creutzfeldt-Jakob Disease

ALZHEIMER DISEASE (AD)
Definition
Epidemiology
Role of β-amyloid (Aβ) protein in causing Alzheimer disease
Role of tau protein in Alzheimer disease
Gross and microscopic findings
Clinical findings in Alzheimer disease
A presumptive diagnosis of Alzheimer disease is made with mental status testing, which tests for orientation (e.g., place and time), attention (selective awareness), verbal recall (recall information which was received verbally), and visual-spatial skills (e.g., complete a jigsaw puzzle
Positron emission tomography (PET) is useful for the differential diagnosis of dementia. Florbetapir-PET imaging of the brain correlates with the presence and density of Aβ

FRONTOTEMPORAL LOBAR DEGENERATIONS (FTLDS)
FTLD-tau
FTLD-TDP

PARKINSONISM
DEFINITION
EPIDEMIOLOGY

IDIOPATHIC PARKINSON DISEASE
PARKINSON DISEASE (PD)
Dementia With Lewy Bodies

ATYPICAL PARKINSONIAN SYNDROMES
Progressive Supranuclear Palsy (PSP)
Corticobasal Degeneration (CBD)
Multiple System Atrophy (MSA)

HUNTINGTON DISEASE (HD)

SPINOCEREBELLAR DEGENERATIONS
Spinocerebellar Ataxias (SCA)
Friedreich Ataxia
Ataxia-Telangiectasia

AMYOTROPHIC LATERAL SCLEROSIS (ALS)

OTHER MOTOR NEURON DISEASES
Spinal and Bulbar Muscular Atrophy (Kennedy Disease)
Spinal Muscular Atrophy (SMA)

FRIEDREICH ATAXIA
LOU GEHRIG DISEASE (ALS)
WERDNIG-HOFFMANN DISEASE (WHD)

TOXIC AND METABOLIC DISORDERS
WILSON DISEASE
ACUTE INTERMITTENT PORPHYRIA
VITAMIN B12 DEFICIENCY; NEUROLOGIC FINDINGS INCLUDE
CNS FINDINGS ASSOCIATED WITH ALCOHOL ABUSE

GENETIC METABOLIC DISEASES
Neuronal Storage Diseases
Leukodystrophies
Mitochondrial Encephalomyopathies

TOXIC & ACQUIRED METABOLIC DISEASES
VITAMIN DEFICIENCIES
Thiamine (Vitamin B1) Deficiency
Vitamin B12 Deficiency
NEUROLOGIC SEQUELAE OF METABOLIC DISTURBANCES
Hypoglycemia
Hyperglycemia
Hepatic Encephalopathy
TOXIC DISORDERS
Carbon Monoxide
Ethanol
Radiation

TUMORS

DEFINITION
EPIDEMIOLOGY
LOCATIONS OF INTRACRANIAL TUMORS

ASTROCYTOMA
MENINGIOMA
EPENDYMOMA
MEDULLOBLASTOMA
OLIGODENDROGLIOMA
CNS MALIGNANT LYMPHOMA
METASTASIS TO THE CNS; EPIDEMIOLOGY

GLIOMAS
Astrocytoma
Oligodendroglioma
Ependymoma

CHOROID PLEXUS TUMORS

NEURONAL & GLIONEURONAL TUMORS

EMBRYONAL NEOPLASMS
Medulloblastoma

PRIMARY CNS LYMPHOMA

MENINGIOMAS

METASTATIC TUMORS

PARANEOPLASTIC SYNDROMES

FAMILIAL TUMOR SYNDROMES
Neurofibromatoses and Schwannomatosis
Tuberous Sclerosis Complex
Von Hippel-Lindau Disease

TOC
EYE 

ORBIT
BONES
Sphenoid
Maxillary
Ethmoid
Lacrimal
Zygoma
Palatine
Frontal
OSTEOLOGY
POSTERIOR CONTENTS
The ANNULUS OF ZINN is the tendon- ring that encircles the ON and acts  as an origin for the muscles
ANTERIOR BOUNDARY
The ORBITAL SEPTUM is the anterior fascial boundary to the orbit
FUNCTIONAL ANATOMY & PROPTOSIS
Thyroid Ophthalmopathy (Graves Disease) Orbitopathy
Autoimmune condition, triggered by TSH-R Antibodies, with lymphocytic infiltration, FIBROSIS, and ENLARGEMENT of extraocular muscles
Proptosis, strabismus/muscle-restriction, exposure problems (dry-eye), and compressive optic neuropathy
Treated with steroids, radiation therapy, or surgical decompression (opening the orbital walls into the sinuses)
Other Orbital Inflammatory Conditions / Infections
Orbital Cellulits frequently extends from adjacent sinus infections, or periocular trauma.
A life and sight threatening emergency!  Can extend into the cavernous sinus, and brain
“Pre-Septal” vs. “Post-Septal” can be distinguished by involvement of intraorbital structures
NEOPLASMS
Wide variety of lacrimal, lymphoid, neural, vascular, meningeal origin tumors, & metastatic tumors
Children
rhabdomyosarcoma is the most common primary malignancy of orbit.
neuroblastoma is most common metastatic tumor
TRAUMA
“Blow–out”  fractures occur when blunt trauma to the eye causes the orbit to rupture
Orbital Floor fractures can cause restricted upgaze if there is muscle entrapment

EYELID
FUNCTIONAL ANATOMY
LAYERS:
Skin
Orbicularis
Tarsal plate
Meibomian glands
Palpebral conjunctiva
NEOPLASMS
Malignant
Basal cell carcinoma - most common
Squamous
Melanoma
Sebaceous cell carcinoma
Benign
Chalazion a cyst of the meibomian gland vs. Hordeolum an inflammed cyst of the MG (foreign body granuloma)
Papillomas/Verrucae
Epidermal inclusion cysts
Many others…

CONJUNCTIVA
FUNCTIONAL ANATOMY
Thin, non-keratinized skin covering the sclera (bulbar) or the inner surface of the lid (palpebral)
Rich in goblet cells, which secret the mucinous components of the tear film
The bulbar layer is continous with the palpebral layer
CONJUNCTIVITIS (“pink-eye”)
is an inflammation of the conjunctiva due to a viral (Adenovirus), bacterial, or allergic cause
CONJUNCTIVAL SCARRING
PINGUECULA & PTERYGIUM  Degenerative conditions
Pinguecula – on the conj only
Pterygium – encroaching onto cornea
Histologically identical
Both involve “elastotic degeneration” of the conjunctiva, usually due to chronic ultraviolet exposure
NEOPLASMS
Conjunctival intraepithelial neoplasia (CIN) HPV 16/18
Squamous Cell
Melanoma
Lymphoid - arising from mucosa-associated lymphoid tissue (MALT)

SCLERA

CORNEA
FUNCTIONAL ANATOMY
The cornea is a unique transparent and  avascular tissue that is the most important refractive structure of the eye
5 Layers:
Epithelium – Continuous with conj, richly innervated by CN-V1
Bowman’s Membrane
Stroma – The thickest central portion (90%).  This is where LASIK/Refractive surgery happens!  Primarily made up of Type 1 Collagen in uniformly-spaced lamellar bundles.
Descemet’s membrane
Endothelium – pumps the water out of the cornea and keeps it clear
The uniform spacing of the stromal collagen bundles at a distance of approx ¼ wavelength light allows transparency
Excimer Laser is applied to the stromal bed, underneath a reflected corneal flap (LASIK)
The tissue is ablated precisely to counteract the refractive error of the eye
KERATITIS & ULCERS
Keratitis – inflammation of cornea
Bacterial ulcer – Frequent in contact lens users, Pseudomonas most common
Epithelial defect, infiltrate of white cells into the cornea, and a layered leukocyte collection in the AC (Hypopyon)
Viral – Herpes (HSV) is a frequent etiology
Epithelial “dendritic” Keratitis
Stromal Keratits (note the vessels and clouding)
Autoimmune, Syphilis, Fungal, ameobic, and many other types
CORNEAL DEGENERATIONS & DYSTROPHIES
Band Keratopathies
Keratoconus
Fuchs Endothelial Dystrophy
Sromal Dystrophy
Dystrophy – a heritable disorder resulting in abnormal tissue morphology, function, or abnormal depositions of material into the cornea
MANY types, affecting each specific layer
Ectasia
Progressive deformation of cornea is an ectasia.  Keratoconus is the most common ectatic dystrophy.  Ectasia can also be a complication of refractive surgery…

ANTERIOR SEGMENT
FUNCTIONAL ANATOMY
LENS
A transparent, avascular structure consisting of concentric cellular fibers
Highest protein content of the body (Crystallins), which account for a high refractive index
Interaction of the ciliary body muscle, through the zonular fibers, cause dynamic shape changes.
In concert with the cornea, helps to focus light on the retina
Entire structure encapsulated
Lens cells migrate and elongate into fibers
The deepest fibers are the oldest ones
The lens continues to fatten throughout life
Central fibers become sclerotic and opaque with time
CATARACT
Opacities  of the lens develop with time, or insult
UV light, steroids, and inflammation are pathogenic factors
Surgery
A opening into the lens capsule is made
The cataract is emulsified with ultrasound energy, and aspirated out of the eye
The dense, cloudy crystalline lens is removed, and replaced with an optical implant
ANTERIOR SEGMENT & GLAUCOMA
ENDOPHTHALMITIS & PANOPHTHALMITIS

UVEA
"The uvea” is:
The Iris
The Ciliary body
The Choroid
Each has a function
Iris is a diaphragm for light
Ciliary body suspends and “flexes” the lens, and makes the aqueous humor
The choroid helps nourish the outer retina
The “angle” is a special region of the uvea where the iris meets the cornea
Regulates the outflow of Aqueous humor through the Canal of Schlem
Determines the Intraocular pressure (Important in Glaucoma)
UVEITIS
“Uveitis” is inflamation of any combination of the iris, ciliary body, or choroid.
Many etiologies (autoimmune, syphilis, sacrcoid, TB, HLA-B27, infectious, idiopathic, etc…)
Many names (iritis, anterior uveitis, iridocylitis, choroiditis, etc…) depending on the location
Sometimes associated with SERIOUS systemic inflamatory diseases (eg. arthritic diseases), inflamatory bowel disease, and vasculitis
Anterior Uveitis
Posterior Uveitis
NEOPLASMS
Uveal Nevi and Melanomas
The Choroid is a highly perfused vascular “net” feeding the outer retina
It is a potential target site for metastasis for carcinoma, such as breast and lung
The uvea (especially choroid) is also richly pigmented, and primary melanocytic tumors are common.
Nevi and malignant melanomas are both relatively common, and can be difficult to distinguish, clinically.
Tumors with “spindle-B” or epithelioid histologic patterns are malignant

RETINA & VITREOUS
FUNCTIONAL ANATOMY
RETINA
Cell types (overview)
Photoreceptors (detect light signal)
Bipolars transmit/modulate signal to ganglion cells
Ganglion cells send signal by long axons through optic nerve and into visual pathways of the brain
Other cell types…
Layers (inside to out):
Inner limiting membrane
Nerve Fiber Layer
Ganglion Cell Layer
Inner plexiform layer
Inner nuclear layer
Outer plexiform layer
Outer nuclear layer
Photoreceptor segments
Retinal Pigment Epithelium
Bruch’s Membrane
(Choroid)
(Sclera)
RETINAL DETACHMENT
Retinal detachment: Separation between RPE and photoreceptor segments
Retinal tears are the most frequent causes of detachment (rhegmatogenous RD)
RETINAL VASCULAR DISEASE / ISCHEMIC
Microvascular (small vessel disease)
Diabetes
Sickle Cell
Radiation
Macrovascular (large vessel occlusions)
Central retinal vein occlusion (CRVO)
Branch retinal vein occlusion (BRVO)
Central retinal artery occlusion (CRAO)
Branch retinal artery occlusion (BRAO)
Hypertension
Diabetes Mellitus Microvascular
Microvascular dysfunction leads to tissue ischemia
Thickened and Leaky Capillary basement membranes
Loss of pericytes
Microaneurysms
Nonperfusion
Ischemia leads to vascular endothelial growth factor (VEGF) production from injured tissues
Promotes Neovascularization (abnormal blood vessel growth) of the retina, optic nerve, or iris.
Abnormal vessels can cause edema or tractional retinal detachments
VEGF implicated in other ischemic eye diseases, like Retinopathy of Prematurity
MACROvascular Disease
CRVO/BRVO – variety of anatomical  prothrombotic predispositions
CRAO/BRAO – watch out for carotid/cardiac embolic disease, or vasculitis
Vascular occlusion (Vein occlusion/Arterial Occlusion)
RETINOPATHY OF PREMATURITY (RETROLENTAL FIBROPLASIA)
Sickle Retinopathy, Retinal Vasculitis, and Radiation Retinopathy
Retinal Artery and Vein Occlusions
AGE-RELATED MACULAR DEGENERATION (AMD)
Macular degeneration: Bruch’s membrane damaged by deposition of drusen, allowing leaky choroidal vessels to grow into retina (exudative type)
OTHER RETINAL DEGENERATIONS
Retinitis Pigmentosa
RETINITIS
RETINAL NEOPLASMS
Retinoblastoma
Classic pediatric tumor of retina
Hereditary or Sporadic
Requires two gene mutations (Knudsen’s “two-hit” hypothesis)
Classic histologic features of Flexner-Wintersteiner Rosettes, and fleurettes
RETINAL LYMPHOMA

OPTIC NERVE
Ischemic Neuropathy – due to arteritic (Giant Cell Arteritis) or non-arteritic causes.
Optic Neuritis –Many causes, but demyelinating (Multiple Sclerosis) causes are most important
Papilledema – swelling due to increased intracranial pressure
ANTERIOR ISCHEMIC OPTIC
NEUROPATHY
PAPILLEDEMA
GLAUCOMATOUS OPTIC NERVE DAMAGE
Pathologic conditions of…
Glaucoma – progressive injury of optic nerve, frequently associated with elevated intraocular pressure
Characteristic “cupping” of nerve
Loss of retinal nerve fiber layer
Advancing peripheral visual field loss
Loss of rim correlates to loss of axons from ganglion cells in retina (Nerve fiber layer).
Regions of lost ganglion cells/axons cause visual field loss
OTHER OPTIC NEUROPATHIES
OPTIC NEURITIS

THE END-STAGE EYE: PHTHISIS BULBI

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REFERENCES

AUTHORS

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Silbernagl. Atlas of Pathophysiology. 3e. 2016. [ Download ]

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Le. First Aid Basic Sciences General Principles. Pathology. 3e. 2017.
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Alfrey. Rapid Review Pathology. 7e. 2023. [ 416 pages ]
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Robbins.
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Kumar. Pathologic Basis of Disease. 10e. 2020. 9e. 2014. [ 1392 pages ] [ Download ]
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Kumar. Robbins Essential Pathology. 1e. 2020. [ 352 pages ]

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mohan-practical-pathology-5th-edition-pdf-free-download
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TOPICS

Molecular Pathology Methods
http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/InVitroDiagnostics/ucm330711.htm
http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/InVitroDiagnostics/ucm301431.htm
https://www.dnalc.org/
https://www.dnalc.org/resources/animations/
http://www.bio.davidson.edu/courses/Immunology/Flash/RT_PCR.html
https://www.biosearchtech.com/products/qpcr-and-snp-genotyping

Cell and molecular biology
Genetics and Epigenetics
Authors : Thomas Cech - http://cechlab.colorado.edu/

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