1st Semester Quick Review

Jonathan AbesamisRoss University School of Medicine

August 11, 2010

Connective Tissue Sheaths of Peripheral Nerves

• Epineurium – Dense C.T.• Perineurium – Flattened Epithelium– Blood Nerve Barrier– No Basement Membrane

• Endoneurium – Reticular Fibers

Myelin

• Major Dense Line: Fused Inner Leaflet• Intraperiod Line: Fused Outer Leaflet

Multiple Sclerosis

• Episodes of random, multifocal inflammation, edema, and subsequent demyelination of axons in CNS.

• Each episode may become malignant.

Astrocytes

• Think “End Feet”• Scavenges Ions & Metabolic Remnants• Glial Fibrillar Acidic Protein (GFAP)– Unique to Astrocytes

Neuron / Nissel Bodies

• No Nissel Bodies in Axon• Transportation Along Axon:– Slow Protein, Actin– Intermediate Mitochondria– Fast Synaptic Vessicles

Gastroschisis

• Newborn Infant with an abdominal wall defect.

Neural Tube Defects

• Think “Failure to Close”• Cranial = Anencephaly• Cervical/Sacral = Spina Bifida

Ectopic Pregnancy

• Implantation outside uterus.– 90% are tubal pregnancies.– Eventually hemorrhage results.

• Implantation in abdominal cavity & ovary are rare.

Placenta Previa

• Implantation in lower segment of uterus.• Placenta covers opening.• Leads to severe bleeding.

Lymphocyte

• The only leukocyte that can re-enter the bloodstream after entering the connective tissue.

Cell Motility / Wound

• 1st on Site = Neutrophils• 2nd on Site = Fibroblasts

Integrins

• Actin Integrins ECM• Heterodimers of α and β subunits.• Different combinations of different α and β

recognize different ligands.

Lamellipodium

• Actin rearrangements inside the cell to move the cell body.

• Integrins to attach the cell to the substratum.

Epistasis

• Patient has a certain genotype but the expressed phenotype is partially controlled by another gene.– Patient could be AB, but also has hh gene for

Fructose Transferase Oh

Hemolytic Disease of the Newborn

• IgG will attack newborn.• 2nd Child or Later– At Birth of Rh+ Baby– At Abortion of Rh+ Fetus– By Transfusion– By Amniocentesis/Chorion Villi Sampling

Amylase

• Indicative of Acute Pancreatitis

γ-Glutamyltransferase (γ-GT)

• Indicative of Liver Disease

Aspartate Transaminase (AST)

• Indicative of Cardiac M.I.• Indicative of Liver Trouble

Alanine Transaminase (ALT)

• Indicative of Acute Viral Hepatitis• Indicative of Cirrhosis• Indicative of Cholestatic Jaundice

Lactate Dehydrogenase (LDH)

• LDH 1 & 2 = Acute M.I.• LDH 5 = Acute Hepatitis

Therapeutic Plasma Preparations

• Fresh Frozen Plasma = Liver Cirrhosis• Cryoprecipitate = Clotting Disorders• Factor VIII Concentrate = Hemophelia A• Albumin 5% = Hypovolemic Shock• Albumin 25% = Cerebral Edema• Immune Serum Globulin = Immune Deficiency

Tetanus

Electrophoresis: Nephrotic Syndrome

• Albumin ↑• α2 ↑↑• γ↓

Electrophoresis: Liver Cirrhosis

• Albumin ↑• α2 ↑• γ (IgA) ↑↑• Think “Over Production”

Electrophoresis: Immediate Response

• Albumin ↓• α2 ↑

Electrophoresis: Delayed Response

• Albumin ↓• α2 ↑• γ ↑

Blood in Urine

• Haptoglobin & Hemopexin– Prevent loss of hemoglobin & heme groups.

• Low Plasma Haptoglobin (Hemoglobinuria)• Normal Plasma Haptoglobin

Acute Phase Proteins

• Synthesized in Bulk in Response to Infection• α1-Antiprotease = Cells Are Dying

• α2-Antiprotease = Death of Hepatocytes

• β2-Microglobin = Renal Disease• Ceruloplasm = Wilson’s Disease

Hyperalbuminemia

• Dehydration• Excessive Stasis During Venepuncture– (a.k.a. “Fake Condition”

Hypoalbuminemia

• Think “vasodilation”• Albumin↓• α2↑• Proteins in Urine• Burns, Renal Disease, G.I. Loss, Hemorrhage

Plasma Protein Production

• With the exception of immunoglobulins (B-lymphocytes) all plasma proteins are synthesized in the liver.

Serum vs. Plasma

• Plasma contains Fibrinogen– Allowed to Coagulate

Pyruvate Kinase Deficiency

• Hemolytic Anemia– Enlarged Spleen– Abnormal RBS Shape– 2,3-BPG ↑– ATP ↓

Wrist: Radiocarpal Joint

• Radius– *No Ulna

• Carpals– Scaphoid (RE: Pollex)– Lunate– Triquetrum– *No Pisiform

Posterior Dislocation of Elbow

• May tear Ulnar Collateral Ligament– Anterior (Think “diagonal”)– Posterior– Oblique

• May damage Ulnar Nerve

Glenoid Labrum

• Fibrocartilage• Inferior Aspect of Shoulder Cuff

Acromioclavicular Joint

• Acromioclavicular• Coracoacromial• Coracoclavicular Ligament– Trapezoid– Conoid

Joints of the Hand

• Thumb = Saddle– Trapezium

• Metacarpal Phalangeal = Condyloid• Palm = Planar• Fingers = Hinge

Sternoclavicular Joint

• Interclavicular• Anterior Sternoclavicular• Costoclavicular

Cartilagenous Joints

• Hyaline = Neck of Femur• Fibrocartilage = Intervertebral Discs

Hilton’s Law

• Nerves that supply a joint also supply the muscles moving that joint and the skin overlying their distal attachments.

Clara Cells

• Only in Bronchioles• 3 Functions– CCSP (Surfactant) & GAGs (Reduce Adhesion)• Decrease Inflammatory Response

– Cytochrome P450– Differentiate into Epithelial Tissue

Thymoma

• Can compress the Right Cephalic Vein

Bronichal Veins

• Venous Drainage of Lungs– Bronical Veins• Azygous Vein

– Superior Vena Cava

• Accesory Hemiazygous/Left Superior Intercostal Vein

– Pulmonary Veins

Bronichial Arteries

• Blood Supply for Lungs– Root of Lung– Supporting Tissues– Visceral Pleura

Thoracocenthesis

• Remove fluid/pus/blood• Location:– 9th Intercostal Space– Superior to Rib• Think “VAN”

– Midaxillary Line

Lymph Drainage of Thorax

• Superior to Clavical– Inferior jugular Lymph Nodes

• Inferior to Clavical– Axillary Lymph Nodes

Layers of Thorax

• Skin• Superficial Fascia– External Intercostal Muscles– Internal Intercostal Muscles– Innermost Intercostal Muscles

• Endothoracic Fascia• Parietal Pleura

Embryology: Umbilical Veins

• Left: Persists; Brings 02 From Mother• Right: Obliterated 2nd Month of Development

Embryology: Vitelline Veins

• Left: Regresses• Right: Forms Hepatic Portion of IVC

Embryology: 6 Aortic Arches

• 1st: Maxillary• 2nd: Stapedial• 3rd: Common/Internal Right & Left Carotid• 4th: Aortic Arch & Right Subclavian• 6th: Pulmonary Arteries– Ductus Arteriosus

• Think “Head, Head, Neck, Heart, Lungs”

Fragile X Syndrome

• Female: Premutation, 20% Risk for Premature Ovarian Failure

• Male: Premutation, Unmethylated Risk for FXTAS

X-linked Diseases

• Fragile X• Hemophelia• Duchenne Muscular Dystrophy– Becker’s Muscular Dystrophy (15%)

• Hypophosphatemia– Think “PHEX”

DMD Testing

• CK Levels• Stain for Dystrophin Protein• PCR & Linkage Analysis

Osteogenesis Imperfecta

• Glycine Substitution– Collagen Packs Tightly

• C Terminus worse than N Terminus• In Type I: α1 worse than α2

– More α1 expressed

Embryology: Ductus Arteriosus

• Ductus Arteriosus Ligamentum Arteriosum– Think “Left Recurrent Laryngeal N.”

Ankylosing Spondylitis

• Chronic Inflammatory Disease– Axial Skeleton

• Presents as Back Pain• Treatment: Supportive/Preventative

Tetrology of Fallot

• VSD• Overriding Aorta• Pulmonary Stenosis• Hypertrophy of RV

Hypophosphatemia

• X-linked– ↓PHEX = ↑PTN ↓NPT2 = ↓Phosphate

• Autosomal Dominant– ↑FGF3 ↓NPT2 = ↓Phosphate

• Autosomal Recessive– ↓NPT2 = ↓Phosphate

Hamartomas

• Altering Tumor Supressors• No stimulation; only lack of inhibitor.• TSC1 vs. TSC2– TSC2 is more common.– Think “HemarTWOmas”

Polycystic Kidney Disease

• Kidney Failure• PKD1 vs. PKD2– PKD1 is more common.

Autosomal Recessive Diseases

• Hereditary Hemachromatosis• EDS VI & VII• Hypophosphatemia (Think “NPT2”)• Recessive Dystrophic EB– Carcinomas

Lung Branching

• 23 Branch Generations– 1-16: Anatomical Dead Space– 17-23: Respiratory Zone

Familial Hypertrophic Cardiomyopathy

• MYH7 = β Myosin Heavy Chain• TNNT2 = cTnT• ??? = Myosin Binding Protein

Partitioning of Outflow Tract

• Aortico Pulmonary Septum– Divides;

• Truncus Arteriosus & Conus Cordis– Into;

• Aorta & Pulmonary Trunk

Differentiation of Heart Tube

• Think “ABC”– Truncus Arteriosus– Bulbus Cordis• Conus Cordis

– Primitive Ventricle– Primitive Atrium– Sinus Venosus

Primitive Inflow to Heart

• Vitteline Veins– Deoxy from Yolk Sac

• Cardinal Veins– Deoxy from Fetus

• Umbilical Veins– Oxy from Placenta• (a.k.a. “mom”)

5 Nerves of Skin

• Free Nerve Endings (Epidermis)– Pain

• Merkel (Stratum Basale)– Touch

• Meissner’s (Dermal Papilae)– Touch

• Pacinian – Pressure

• Ruffini’s– Strech

Effect of NO in Smooth Muscle

• NO Relax Increase Blood Flow• Arterioles & Metarterioles

Marfan Syndrome / Endocarditis

• Effects Fibrous Skeleton– Causes;

• Mitral/Aortic Valve Prolapse– Which leads to;

• Regurgitation

Valve Heart Sounds

• Think “All Physicians Take Money”

Internal Right Atrium

• Sinus Venarum– Smooth

• Crista Terminalis– Ridge Inbetween

• Pectinate Muscles– Rough

Typical Intercostal Nerves

• 3rd – 6th

• Endothoracic Fascia– Near the Angle of the Rib;

• Between Internal/Innermost Muscles– At the Angle of the Rib;

• Collateral Branches

Thoracic Splanchnic Nerves

• Supply Viscera Inferior to Diaphragm• Greater = T5-T9– Think “Heart”

• Lesser = T10-T11• Least = T12

5 Layers of Skin

• Stratum Corneum• Stratum Lucidum– Only in Thick Skin

• Stratum Granulosum– Water Proof– Contains Lamellar Granules

• Stratum Spinosum– Last Layer with Mitotic Activity

• Stratum Basale

Selectins in Diapedesis

• Endothelial Cells– P-selectins– E-selectins

• Lymphocytes– L-selectins

Blood Flow Control

• Arterioles– Smooth Muscle

• Capillaries– Pericytes

Fenestrated Capillaries

• Rapid Exchange• Kidney, Intestine, and Endocrine Glands– No Diaphragm in Renal Glomerulus

Metarterioles

• Discontinuous Smooth Muscle• If any smooth muscle Metarteriole; not

capillary

Asthma

• Constriction of Bronchioles– Dyspnea

• β2 Agonist Relax

BALT

• Bronchus Associated Lymphoid Tissue• Protects Against Infection

Steps of Smell

• Odorant & Receptors• Mitral Cells/Glomeruli– If Enough;

• Signal Sent

Olfactory Epithelium

• Pseudostratified Columnar Epithelium• Olfactory Receptor Cells• Sustentacular Cells– Supporting Cells

• Basal Cells

Brody Jenner Syndrome

• Cilia & Flagella Affected– Males Infertile

• Lack of Dynein

Respiratory Epithelium

• Ciliated Columnar• Goblet Cells• Brush Cells– Sensory Receptors

• Basal Cells• Granular Cells– Secrete Bombasin & Seratonin

Nasal Cavity

• Vestibule– Stratified Squamous / Vibrissae

• Respiratory Segment• Olfactory Segment

Sympathetic Trunk

• Inside of the Mediastinum• Outside of the Pleural Cavity

Lung Volume / Respiratory Disease

• Obstructive– Emphysema, Chronic Bronchitis– ↓TLC, ↑↑RV, ↑RV/TLC%

• Restrictive– Pulmonary Fibrosis– ↓TLC, ↓RV, (normal) RV/TLC%

Right Vagus Nerve

• Right Vagus Nerve– Anterior to Subclavian Artery;

• Right Recurrent Laryngeal Nerve– Posterior to Hilum

• Right Pulmonary Plexus & Esophageal Plexus• *Left Vagus passes over arch of aorta.

Muscle Fascia

• Epimysium– Entire Muscle

• Perimysium– Bundle

• Endomysium• Myofibril– Individual Fiber

Classification of Skeletal Muscle

• Red: Type I– Slow Repetitive– Posture

• White: Type IIB– Fast Twitch– Fingers & Eyes

• Intermediate: Type IIA

Hind Brain

• Voluntary Movement– Cerebellum• Initiate

– Pons• Regulate

– Medulla– 4th Ventricle

Nerve Regeneration

• Repaired by proliferation of astrocytes.• Astrocytic Scar = Gliosis– Anterograde Degeneration– Only PNS– Only if soma is intact.

Layers of Cerebral Cortex

• Molecular Layer• Purkinje Layer• Granular Cell Layer

Blood Brain Barrier

• Endothelial Cells and Tight Junctions• Pass Freely: O2, H2O, CO2

• Active Transport: Glucose, aa, vitamins• Cannot Pass: Macromolecules

SNPs

• Single Nucleotide Polymorphism– Used to create haplotypes to differentiate

between maternal/paternal chromosomes.

Purines / Pyrimidines

• Think “GATTACA”• Purines– Guanine– Adenine

• Pyrimidines– Thymine– Cytocine

Camptothecin

• Chemotherapeutic Agent• Topoisomerase I Inhibitor• Used to Treat Cancer

Ciprofloxacin

• Antibiotic• Inhibits Gyrase Activity in Bacteria– Think “Topoisomerase II”

Doxorubicin / Etoposide

• Chemotherapeutic Agent• Inhibits Topoisomerase Type II• Used to Treat Cancer

Topoisomerase II / Gyrase

• 2 Cuts• Induces Negative Supercoils– Opening DNA instills positive supercoils.

Exonuclease vs. Endonuclease

• Exonuclease– Removes nucleotides from a 3’ end of DNA strand.– Think “Proofread”

• Endonuclease– Cut inside of a DNA strand to produce single

stranded nicks.• These nicked ends can be used by Exonucleases

Replication

• Eukaryotes replicate their DNA only in S-phase– Think “G1, S, G2, M”

Bacteria vs. Eukaryotes

• SSB / RPA• Primase / Pol α• Pol III Polymerase / Pol δ and ε• β2 Sliding Clamp (subunit of Pol III) / PCNA• 3’ Exonuclease of Pol I / RNaseH and/or FEN1• γ subunit of Pol III / RFC

Oligomycin

• Inhibition of ATP Synthase

Km

• The concentration of substrate at which ½ of the active sites are filled.

Inhibitors

• Competitive Inhibitors• Noncompetitive Inhibitors• Irreversible Inhibition– Covalent Bond– Most are toxins

Werner’s Syndrome

• Advanced Aging• Telomeres Shorter Than Normal

RNA vs. DNA Synthesis

• NTPs Instead of dNTPs• No Primers• No Proofreading• U instead of T• RNA pol

Rifampicin

• Inhibits RNA polymerase in bacterial cells by binding to β-subunit of RNA polymerase (the essential polymerase enzyme).

• Used to treat TB, Leprosy, MRSA, and bacterial meningitis due to lipophic nature and uniqueness.

• Adverse effects include hepatotoxicity.

Promoters

• Prokaryotic– TATAAT -10 bp

• Eukaryotic– TATA Box -25 bp– CAT Box -50 to -100

Ribosome Structure

• Prokaryotes (70S)– 50S (23S & 5S)– 30S

• Eurakyotes (80S)– 60S (28S, 5.8S, & 5S)– 40S