Motivation

Hippocampus -> Fornix -> Septal
Striatum -> Thalamus -> Mammillary
Cingulate -> Hypothalamus -> Pituitary

Sickle Cell Disease (SCD)

Hemoglobin
2 Mutant Beta-Globulins (2 Wild Type Alpha-Gb)
11q6 SNP A to T; glutamate to valine

Alpha-1 Anti-Atrypsin Deficiency (A1AT)

Lungs/Liver/Etc.
Uninhibited Tissue Breakdown
14q32.1

Colon Adenocarcinoma

Colon
Polyp [ACP] -> Large [K-ras] -> Malignant [p53/DCC]
Chronic Inflammatory Stress

HNPCC

Colon, Extra-intestinal, Etc.
DNA Mismatch Repair Gene
3p21:MLH1, 2p.21:MSH2, MSH6

Hydrocephalus Ex Vacuo

Cerebrum
Atrophy -> Non-Pressure Communicating H'dro
Alzheimers, Etc.

Carpel Tunnel Syndrome

Carpal bones -[Transverse Carpal Ligament]- Flexor Retinaculum
Median Nerve Compression
Joint (Movement, Arthritis), Deposits (Dialysis, Amyloid), Edema

Acute Lymphoblastic Leukemia

Mediastinum (Thymus)
Pre-B Cells: CD 2-10+, CD 19-20+/SVC Obstruction
cryptic t(12,21), etc.

Huntington's Disease (HD)

GABAnergic Striatal Neurons
Dementia + Choreaform movements + Lat.Ventricular Dilation
4p16.3 = Huntingtin (HTT) gene: -(CAG)- repeats

Romano-Ward Syndrome

Myocarium
K+ Channels -> Q-T length
ANK2, KCN(E1, E2, H2 Q1), SCN5A AD Gene Mutations

Amyotrophic Lateral Sclerosis (ALS)

Anterior Horn + Corticospinal Tracts
LMN + UML -> Denervation Atrophy (Amyotrophy)
SOC1 Gene: Codes for Copper-Zinc Superoxide Dismutase

Hodgkins Disease

Lymph Nodes
B-cell -> B-symptoms -> Reed-Sternberg Cells
Somatic Mutation -> loss of NF-kB inhibition

Duchene Muscular Dystrophy

Muscle
Proximal Atrophy, Compensatory Distal Pseudohypertophy
Xp21 = Dystrophin gene mutation

Pituitary Adenoma

Adenohypophysis
Inhibition of H<-P->O axis
???

Burkitt's lymphoma

Jaw/Abdomen
C-MYC t(8,14) + Immortalization
EBV

Dermititis Herpetiformis/Celiac Disease

Skin/Duodenam
IgA + Neutrophils + Fibrin
HLA-DQ2/DQ8 + Gluten Diet (Wheat, Rye, Barley)

Sydenham Chorea

Caudate/Subthalamic Nuclei
Anti-neural antibody
Autoimmune/Beta-hemolytic Strep

Hereditary Breast/Ovarian Cancer

Tubules/Glands
DNA Repair -> Adenocarcinoma
BRCA1/BRCA2

Gastric (Upper GIT*) Metastasis

L+ Supraclavicular, Umbilicus, Ovary
Virchow's, Sr. Mary Joseph, Krukenburg tmr || CEA,CA19.9,CA125
H. pylori, etc.

Chron's Disease

Full GIT Length
Poor 'Phage Fx-> Chronic Infla -> Th17 -> NF-kB
CARD15, ATG16L1

Thyroid Cancer

Thyroid
Neoplasia
RET (Medullary-Est?), RAS (Follicular-And?), p53 (Anaplastic-Phr?)

Arnold Chiari Malformation I & II

Foramen Magnum
Small Posterior Fossa
I(Cbll Hernia), II(I+Pons+M'cele), III(II+Enc'cele), IV(III+ Cbll atrophy)

Lobar Pneumonia

Lobe
Congestion -> [Hepatization: Red -> Gray] -> Resolution
S. Pneumonea

Breast Cancer + Ovarian Cancer

Specialized "Glandular" Tissue (Breast, Ovary, Lymph Node)
Epidermal Growth Factor Receptor Family Over-expression
HER2/neu oncogene

Bronchiolitis Obliterans (BO)

Bronchioloes
Granulation Tissue Plugs
Chronic Graft Rejection, etc.

Epidural Hematoma

Sub-periosteal
Fracture + Laceration of MMA
A-D Injury

Cystinuria

Renal Tubules/Intestinal Lumen
Dibasic (++) a.a's (COAL)Trans/Hexagonal Cystine Crystals
SLC3A1/SLC7A9

Plasma Cell Myeloma/Multiple Myeloma (MM)

B-Plasma Cells
IL-6 -> RANK-L -> Amyloidosis + CRAB
t(4,14), t(14,16): 14q32=Ig -> oncogene e.g. 16

Ankylosing Spondylitis

Sacroiliac + Apophyseal jxt of spine, Costovertebral/Sternal jxt, etc.
Enthesopathies
HLA B27 (RF absent)

Guillain Barre Syndrome (Maladie de Charcot)

PNS Gangliosides (unlike CNS -> MS & ANS -> ALS)
Autoimmune Acute Demyelination
C. jejuni, Influenza vaccine* (o-i-m)

Diabetes Insipidus (DI)

Renal Collecting Ducts
Supraoptic+Paravent Nuclei (Central DI)/Nephrogenic ADH Resistance
Vaso [ADH+V1] & Tubular [ADH+(G-V2)+Aq2]

Vitamin E Deficiency

Neuronal/Retina/Erythrocyte Membranes
Oxidative Stress -> Spinocerebellar & Dorsal Column Tracts
Abetalipoproteinemia (Pancreatic insufficiency of CS -> ADE++K def.)

Waterhouse-Friderichsen Syndrome (WFS)

Adrenals
Hemorrhagic Meningococcal Septicemia
Caps (N.M, P.P., S.A., H.I) & CMV*/ C def./ Splenic (SCD) atrophy

Polycytic Kidney Disease (PCKD)

Collagen + Matrix
Hemorrhage: Polycystin-1 protein -> Cilial Proteins in Embryo
16/4: PKD1-2 autosomal dominant genes, etc.

Trigeminal Neuralgia (Tic Douloureux)

Face
Demyelination of CN. V
Posterior Cerebella Artery Occlussion

Primary Pulmonary Hypertension (PPH)

Pulmonary Artery Branches
Medial (SM) Hype of /Intimal (End) fibrosis/Luminal Stenosis
M apoptosis (-)/ I ?/ L ? ... No Adventicial prob-> vasovasora

Anti-Psychotics

Trad-D2/Pot+++/Expy+++, Tradi-D2/Pot+/Expy+, Atyp-D2/Potency+++
[Hal, Fluphenazine, Pimozide], [CPZ, Thioridazine], [CROQ)]
Agranulocytosis=Clon; ???=Risperidone: !!!=Olanzapine/Quetiapine

Body Fat Redistribution Syndrome (Dyslipidemia)

Hematological
Apolipoprotein B degredation (--)/Hepatic Uptake
19p13.1-13.3, LDL, [??? PI's]

Adrenal Insufficiency/Crisis

HPA-axis
ZG (-) <- ZF (---) -> ZR (++)
HPA event

Essential Tremor

Cerebellothalamocortical circuits
Lewy bodies in Purkinje cell
Familial & Heterogenous

Von Willebrand Disease

Hemopoietic
vWF
12p.13.2: vWF gene: autosomal dominant (1,2) or recessive (3)

Eisenmenger Syndrome

ASD/VSD/PDA
Conversion of L->R to R-> Shunt
Pulmonary Hypertension

HIV-1 Infection

Lymphopoetic
CD4+ Depletion
CCR5-D32, APOBEC3B

Hepatocellular Carcinoma

Hepatocyte
INF-3
IL28B gene, HBeAg, p53 G-to-T SNP, etc.

Subacute Combined Myelopathy

Dorsal Columns, Lateral Tracts & Peripheral Nerves
Position/Vibration, Spastic Paresis & Paraesthesia
Vitamin B12 Deficiency

Giant Cell (Temporal) Arteritis (Horton's Disease)*

Medium-Large Cranial Vessels
GCA coexists with Polymyalgia Rheumatica (PMR)
ER-alpha receptor upregulation e.g. in Menopause

Acute Rheumatic Carditis (Fever)

Myocardium (and Joints)
Aschoff's (plump m'phages)/Anitschow cells (slender chromatin)
Type-II HS: GpA Strep mimicry->APC->Th2->B-cell->

Polycytic Ovarian Syndrome (PCOS)

HPO Axis
Insulin resistance + Aromatase -> T + E -||-> HPO Axis
CYP19A1 (Aromatase) gene mutation + Adiposity

Bronchiolitis

Small Airways
Obstruction
Respiratory Synctial Virus (RSV) Replication

Paget's Disease (Osteitis Deformans)

Osteoclasts
18q22.1 RANK-L (& M-CSF)
Paramyxovirus

Achondroplasia

Epiphyseal Growth Plate
Short Appendicular Bones (Normal axial bones)
Fibroblast Growth Factor Receptor-3 Mutation

Pancoast Syndrome

Lung Apex (Superior Sulcus)
Extensive Local Spread
Cumulative DNA Changes

Central Neurofibromatosis

Cerebella-Pontine Angle
Bilateral Acoustic Neuromas; Merlin
22: NF-2 Autosomal Dominant Tumor suppressor

Diabetes Mellitus Type-I

Beta-Islets
Lymphocytic Infiltration
HLA-DQ/DR

Diabetes Mellitus Type-II

GLUT expressing cells
Insulin Resistance -> Islet Stress -> Insulin + Amylin (IAPP)
Systemic Adiposity +++

Goodpasture Syndrome

Glomerus/Alveoli
Anti-GBM IgG/C3 to Alpha-3 Chain of Collagen Type IV/Fibrin Deposits
Type II Hypersensitivity to Goodpasture's Ag/HLA-DR2

Syringomyelia (Syringohydromyelia)

Ventral White Commissure of Cervical Spine
Pain & Temperature Sensory Loss (not Proprioception & Vibration)
Syrinx (CSF in white matter) + Hydromyelia (CSF++ in Canal)

Petit Mal Seizure

Thalamic Neurones
Thalamo-cortical T-Type Ca++ Channels
Various Local Insults Restricted to Childhood

Prinzmetal's (Variant) Angina

Coronary Vessels (Associated with Migraine headache)
Nocturnal Spasms -> Temporary Transmural MI
Ergonovine (Diagnostic)

Chronic Constrictive Pericarditis

Pericardial Space
Thick Fibrous Shell Replacement
Tuberculous Caseous Pericarditis

Wolff-Parkinson-White Syndrome* (PSVT)

CVS
AV-conduction: PR-int short, +delta wave, ++QRS
Accessory Pathway

Normal Pressure Hydrocephalus (NPH)

Cerebrum
Diminished Arachnoid Villi
Atrophy

Friedreich Ataxia

Neural Tracts & Peripheral Nerves
Mitochondrial Function
9: Autosomal Recessive mutation for Frataxin gene

Tardive Dyskinesia

Perioral + Axis
Extrapyramidal Cells
Atypicals (Risperidone+++, Clozapine+)

MAO Tyramine Crisis

CVS (Hypertensive Cx)
MAO inhibitor (Bipolar Rx)
Tyramine (Cheese, Wine, Sausage)

Lyme's Disease (Borreliosis)

Bite -> Systemic -> {Varied+CNS}
Molecular Mimicry -> Autoimmunity -> {IL-6/TNF-alpha}
Borrelia Burgdorferi (Tick-borne)

Hyperestrinism

Reproductive Glands
Liver Failure
Hepatitis (e.g. Viral, Alcoholic, etc.)

Chronic Myeloid Leukemia

B-Lymphocytes
bcr-abl fusion protein
t(9,22) = Philadelphia Chromosome

Paroxysmal Nocturnal Hemoglobinuria

Complement (C3-convertase & C9-MAC)
CD55 & CD59 Deficiency
X-linked Phosphatidyl Inositol Glycol A (PIGA) gene polymorphism

Liver Injury*

Serum Albumin + Prothrombin Time*
AST + ALT
Alcohol or Hep-(A,B,C)-Virus

Emphysema

Alveoli
Alpha-1 Anti-trypsin [Functional or Actual] Deficiency
Toxins (e.g. Cigarette) or PiSS, PiMZ or PiSZ Phenotypes

Carcinoid Syndrome

Neuroendocrine
Serotonine (5-HT), et al. Vasoactive substances (e.g. Kallikrein)
Tumors expressing Somatostatin receptors

Colorectal Carcinoma

Colonic Mucosa
Adenoma-to-Carcinoma
APC gene mutation

Hashimoto's Thyroiditis

Thryoid Parenchyma
Antithryoid Peroxidase
HLA

Wegener's Granulomatosis

Vascular (small/medium)
c-ANCA's -> Neutrophil Proteinase 3
HLA

Esophageal Adenocarcinoma

Esophagus
Barret Esophagus
GERD

Pemphigus Vulgaris

Desmogleins (3,1)
Autoantibodies
HLA

Scleroderma

Systemic
TGF-beta receptor over-expression
TGF-b1 & COL1A2 polymorphisms

CREST Syndrome

Localized
Anti-Centromere/Anti DNA Topoisomerase (Scl-70)
HLA

Infectious Mononucleosis (IM, Mono)

Nasopharynx/Lymphoreticular
Gen Lymphadenopathy // Lymphoma/Nasopharyngeal Carcinoma
EBV (ddx & dx: CMV)

Multiple Sclerosis (MS)

PNS
IgG in CSF
HLA type

Tetanus

Muscular
Inhibition of Glycine & GABA
Tetanospasmin (Exotoxin of C.tetani)

Ecthyma Gangrenosum

Skin
Vascular Necrosis
Pseudomonas Aeruginosa exotoxin

Leucocyte Adhesion Deficiency

Skin
Integrin Deficiency
Autosomal Recessive Absence of CD18 Ag

Rheumatoid Arthritis

Joints
IgM (RF) -> Fc of IgG
Autoimmune

Systemic Lupus Erythematosus (SLE)

Vascular
Immune Complex Depositions
Anti-dsDNA

Henoch-Schonlein Purpura (HSP)

Systemic Leukocytoclastic Vasculitis
IgA-containing Immune Complexes
Proteolysis Resistance IgA1 molecule

Huntington's Disease

CNS
Histone methylation
Autosomal Dominant HD-gene

Mitochondrial Encephalopathy (MELAS)

CNS
Neuronal damage
mtDNA mutation

Alzheimer's Disease

Hypocampus vasculature+Basal Nucleus of Meynert
A beta-amyloid deposition
APP gene on Ch.21

Follicular Lymphoma (a NHL)

B-Lymphocyte
BCL-2 overexpression
t(14,18)

AML

Hemopoeietic/Lymphopoietic
Myeloblast differentiation inhibited
t(15,17) = New PML/RAR-alpha chimeric gene

Fragile X Chromosome

Somatic/Sexual/Neurological Development
Macrosmia/Macrochidism/Mental Retardation
CGG repeats in the FMR-1 gene

Klinefelter's Syndrome

Seminiferous tubules
Hyalin deposition
XXY

Caudal Regression Syndromme

Fetal Sacral Spine
Aplasia
Uncontrolled Diabetes

Craniopharyngoma

Suprasella region
Cystic Mass
Rathke's Pouch

Potter's Syndrome

Fetus
Oligohydramnios
Bilateral Renal Agenesis

Hirschsprung Disease

Colorectal Submucosal/Myenteric
Meissner's/Auerbach's Plexi
Migration of Neurocrest cells

Multiple Endocrine Neoplasia (MEN)

1. Endocrine
2. MEN: 1, 2A & 2B
3. Germ line mutation of RET proto-oncogene

Merkel's Diverticulum

2-2-2 Ileocecal junction
Ectopic gastric mucosa+submucosa+muscularis
Partial obliteration of omphalomesentric duct

Ehlers Danlos Syndrome

Connective Tissue
Collagen Metabolism
Autosomal Dominant

Marple Syrup Disease (MSUD)

Mitochondria
Branched Chain Alpha-Ketone Dehydrogenase
Autosomal recessive mutations

Medium Chain Acyl CoA Deficiency (MCAD)

Mitochondria
Acyl-CoA Dehydrogenase
Autosomal recessive ACADM mutation

Methylmalonyl aciduria

Mitochondria
Methylmalonyl CoA Isomerase
Varying MMA autosomal recessive mutations

Alkaptonuria

Connecive tissues
Homogentisic acid 1,2-dioxygenase
Autosomal recessive HGD-gene

Xeroderma Pigmentosum (XP)

Skin
Lesions on exposure to light
Autosomal recessive mutation (8 kinds)

Marfan's Syndrome

Connective Tissues
Defective Fibrillin
Autosomal dominant FBN-1 gene

Narcolepsy

CNS
Acute REM phenomena
Orexin (hypocretin)

Conversion Disorder

Neurological
None
Unconscious motive

Wilson's Disease (Hepatolenticular degeneration)

Connective Tissue
Ceruloplasmin Deficiency
13q:14.3: ATP7B Protein Mutation

Hyperacusis

Ear
Paralysis of Stapedius
Facial (VII) Nerve injury

Lacuna infarctions (LACI)

Basal ganglia
Penetrating microvascular lipohyalinosis/atherosclerosis
Hypertension/Diabetes Mellitus

von Recklinghausen's disease

CNS/PNS
Oligodendrocyte/Schwann cells: Neurofibromin
17: Autosomal dominant NF-1 gene defect in Tumor Suppressor

Broca's (motor, non-fluent) aphasia

Cells in Broca's area
Apoptosis
G.E.E.

Pneumoconiosis

Terminal bronchioles and alveolar ducts
Chronic Macrophagocytosis & Fibroblastosis
Tiny Dust particles (2 micromills and less)

Myasthenia Gravis

Post-synaptic terminal of muscle endplate
ACh receptors
Autoimmune destruction

Paroxysmal Supraventricular Tachycardia

AV node
Re-entry circuit
Sympathetic tone

Obstructive Sleep Apnea

CVS
Hypertension (Systemic & Pulmonary), Right heart failure
Reflexive Vascular constriction and Cardiac stimulation

Osteoporosis

Osteoclasts
RANK receptor/RANK ligand interaction
Hypoestrogenemia

Cystic Fibrosis

Epithelial cells
Cystic Fibrosis Transmembrane Regular
7: CFTR gene variant

Autism

CNS
Neural connections during embryologic development
Sematophorin 5A variant

Hepatic Encephalopathy

CNS
GABA receptor stimulation
Hyper ammonemia

Zollinger-Ellison Syndrome

Gastric mucosa
Enlargement/Excessive Acid Secretion
Gastrinoma=DNA-methylation

Takayusi's Arteritis

Vascular
Inflammation
idiopathic

Hemolytic Uremic Syndrome

Kidney
Failure
Toxin ("Shiga")

Familial Hypercholestrolemia

Liver
LDL receptors
Gene Mutation

Therapy

Demographic Bias
1. Internal Medicine
2. Obstetrics & Gynecology
3. Pediatrics

Philosophical Bias
1. Preventive Medicine
2. Psychiatry
3. Surgery

Prognosis

Where?
What?
Why?

Why ?

Genome
1. DNA
2. Transcription
3. Translation

Epigenome
4. Methylation
5. Conjugation
6. Lysis

Environment
7. Physical/Energy/Distruption
8. Chemical/Toxin/Medications
9. Biological/Deficiency/Excess

What ?

1. behavior
2. anatomy/histology
3. biochemistry

4. physiology
5. pathology
6. microbiology/immunology

7. pharmacology
8. nutrition
9. genetics/ageing

Where ?

Diffusely 'localized'
1. Hematopoetic/lymphopoetic
2. Nervous/Special Sense
3. Musckuloskeletal

Thoraco-abdominal 'localization'
1. Cardiovascular
2. Pulmonary
3. Gastrointestinal

Pelvic 'localization'
1. Renal
2. Reproductive
3. Endocrine

Diagnosis

Where?
What?
Why?