These are short vessels connecting ventral and dorsal aortae.
On each side they run within branchial i.e pharyngeal arches are based gradually the 4th and 5th week, in 6 pairs in total the first,
second and fifth pairs are developmental in perspective and they soon disappear.
1st aortic arch:
It disappears into a small portion persists, It also forms a piece of the maxillary artery.
2nd aortic arch:
It disappears into small portions of this arch contributing to the hyoid and stapedial arteries
3rd aortic arch:
It commonly carotid and initial segments of internal carotid artery.
4th aortic arch:
It has ultimate fate different on the right and left side on the left.
1. LEFT, both the proximal and distal segments are retained they are incorporated into the descending arch of the aorta.
2. RIGHT, the proximal segment of the right dorsal aorta persists and they are incorporated into the R subclavian artery
whereas the distal segment regresses.
5th aortic arch -
It is transient and soon obliterates.
6th aortic arch - pulmonary arch
1. RIGHT arch: this proximal segment is incorporated into the R pulmonary artery and the distal segment regresses.
2. LEFT arch: this proximal segment is incorporated into the L pulmonary artery and the distal segment persists as the ductus arteriosus.
- Works on Cyclo-oxygenase (AA -> thromboxane)
- Low dose (80-160 mg/day) irreversibly inhibits plt COX, and they can’t make new COX b/c they have no nucleus
- Some inhibition of endothelial COX but not much, therefore prostacyclin (anti-coag) synthesis isn’t affected much
- Benefit is greater after thrombolysis
- SE is bleeding
- Prophylaxis for MI or TIA (80mg/day), higher doses for post-MI/TIA (160-325mg/day)
- Contraindications (bleeding risk): Vit. K def., Hemophilia, Hypoprothombinemia, pregnancy & childbirth
- ADP antagonist
- Competes with ADP for P2Y receptor (prevents lowering of cAMP)
- Less incidence of neutropenia/thrombocytopenia
- Used in combo with ASA
- ADP antagonist, prodrug
- Often used in combo with ASA (synergistic)
- May cause severe neutropenia (1%)
- phosphodiesterase inhibitor (prevents cAMP breakdown)
- Eptifibatide, Abciximab, Tirofiban
- Block the receptor for fibrinogen blocking plt Aggregation
Heparin (& derivatives)
- Stimulates natural anticoags (antithrombin)
- Monitor using aPTT (add negative charges)
- Negatively charged, therefore cannot cross membranes (given IM, IV, parentally)
- Good for pregnancy
- Eliminated by RES & macrophages
- Potentiates AT III (in the plasma) – inhibits IIa, Xa, IXa and VIIa
- Toxicity – hemorrhage
- Antidote – protamine sulfate (1mg for every 100 units of heparin)
Heparin-Induced Thrombocytopenia (HIT) – occurs 5-10 days after, stop heparin immediately; use alternatives lepirudin/danaparoid
- Good for PE and DVT and during pregnancy
LMWH – better bioavailability, can be given subcut. w/o lab monitoring as outpatient, less risk of bleeding
- More expensive, not good in renal failure, not for pregnancy
- DOES NOT inhibit IIa (but inhibit Xa)
- Good for DVT, PE and UA
Danaparoid – promotes inhibition of Xa by AT (for HIT)
Lepirudin – direct thrombin inhibitor (for HIT)
Coumarin (Oral) anticoags
- Monitored using PT (add tissue factor)
- Inhibit Vit. K Epoxide reductase in liver
-Prevents carboxylation of Vit.K dependent factors
-Takes 4-5 days to get effective (carboxylated fx’s in plasma need to be cleared before inactive ones take over)
-Small volume of distribution, steep dose-response curve (small therapeutic window)
- For DVT and PE, prosthetic heart valves or Afib, MI
-Metabolized by CYP1A and CYP2C9
-Efficacy measured by INR, pt’s PT time divided by PT time in pooled plasma
- INR = (PTpt/PTref)^ISI (target is 2.0 – 3.0)
- Warfarin overdose
- Give Excess Vit.K, goes through a diff enzyme that isn’t inhibited by warfarin (Diaphorase)
Fibrinolytics (lyse formed thrombi)
Streptokinase – turns plasminogen -> plasmin
-Plasmin breaks down fibrin (lysis of formed clot) Dissolves clots post-MI/DVT/PE
- SE – bleeding (systemic plasminogen activation), allergy, hTN, fever
- Streptokinase has an additive effect with ASA
Tissue plasminogen activator (tPA) – acts on fibrin and circulating plasminogen -> plasmin
- Less systemic plasmin
- Same indications as streptokinase
- More expensive
Alport’s Sd (most cases): "hereditary nephritis", type IV collagen deficit, mutation of COL4A5 ("colaas" - alpha-5 chain, type 4 collagen), hearing loss, ocular abnormalities (lens & cornea), hematuria since childhood (gross, micro)
Charcot Marie Tooth: loss of motor & sensory innervation, distal weakness & sensory loss, wasting in the legs, decreased deep tendon reflexes, tremor, foot deformity with a high arch is common (pes cavus), legs look like inverted champagne bottles. Most accurate test: electromyography. No tx.
Focal Dermal Hypoplasia: skin abnormalities and a wide variety of defects in eyes; teeth; and skeletal, urinary, gastrointestinal, cardiovascular, and central nervous systems.
Fragile X Syndrome: CGG trinucleotid repeat, FMR 1 gene mutation, mental retardation, large ears and jaw, post-pubertal macro-orchidism (males), attention deficit disorder (females)
Hypophosphatemic rickets: infants may show growth retardation, widened joint spaces and flaring at the knees at age 1 (> boys), bowing of the weight-bearing long bones, young children-dentition absent or delayed, older children-multiple dental abscesses.
Incontinentia pigmenti: skin abnormalities (blister--> warts--> hyperpigmentation--> hypopigmentation), alopecia, hypodontia, cerebral atrophy, slow motor development, mental retardation, seizures, skeletal & structural anomalies. Letal >males.
Orofaciodigital Sd: OFD1 gene mutation, malformations of face, oral cavity, digits with polycystic kidney disease and variable involvement of the central nervous system.
RETT’s Sd: sporadic mutation of MECP2 gene, onset 2yo, acquired microcephaly, stopped development, motor & speech regression, autism-like behavior, self-mutilating behavior, inconsolable crying/screaming fits, emotional inversion, hypotonia, dystonia, chorea, bruxism, scholiosis, long QT
Alport’s Sd: "hereditary nephritis", type IV collagen deficiency, alternating thickening & thinning of GBM, COL4A5 mutation, hearing loss, ocular abnormalities (lens & cornea), hematuria (gross or micro) since childhood.
Bruton’s Agammaglobulinemia: btk gene defect, no mature B cells or plasma cells, low lymphoid tissue, hepatitis, enterovirus infxs, first 6 months protected by maternal ab (no symptoms)
Becker’s Muscular Dystrophy: altered dystrophin gene, later onset than Duchene's, slow progression, relatively normal life span, less severe, rare cardiac involvement.
Chronic Granulomatose Disease (CGD): NAPDH oxidase deficiency, recurrent catalase (+) infxs, nitroblue tetrazolium test negative (yellow)
Congenital Aqueductus Stenosis: MCC of congenital obstructive hydrocephalus.
Color blindness (red-green): can't distinguish shades of red and green (usually blue-green)
Duchene’s muscular Dystrophy: dystrophin gene mutation (Xp21), absent dystrophyn protein, MC & severe of muscular dystrophies, normal until 5yo, short life span (<30yo), progressive muscle weakness, calf pseudohypertrophy, <3 failure, arrythmias, respiratory insufficiency and infxs (decreased mucociliary clearence). Pneumonias CC of death.
Fabry’s Disease: alpha Galactosidase A, Ceramide trihexose accumulation, angiokeratomas, renal failure, peripheral neuropathy.
Glucose 6-P Dehydrogenase (G6PD) Deficiency: chronic hemolytic anemia, MCC of enzymatic deficiency HA, Heinz bodies, bite cells. Triggers are infections, drugs (antimalarial), fava beans
Hemophilia A & B: factor VIII & IX deficiency respectively. PTT prolongation.
Hunter Disease: iduronate sulfatase deficiency, heparan sulfate accumulation, no corneal clouding, aggressive behaviour.
Inherited Nephrogenic Diabetes Insipidus: V2 receptors in collecting duct don't respond to ADH.
Lesch-Nyhan Sd: HGPRT1 deficiency, spastic cerebral palsy, self-mutilation, hyperuricemia, oral crystals in diapers, early death.
Menkes Disease: ATP7A gene mutation (copper efflux protein), Cu+ is lysil oxidase cofactor, Cu+ accumulates in intestine & kidneys; deficient in other tissues = deficient collagen cross linking; steely 'kinky' hair, MR, arterial tortuosity, hypotonia.
Ornithine Transcarbamoylase Deficiency: urea cycle, orotic aciduria + hyperammonemia (no megaloblastic anemia), orotic acid accumulation, increased glutamine . Cerebral edema, lethargy, vomiting, hyperventilation, convulsions, coma, death.
SCID: IL-receptor, Gamma chain deficiency
Wiskott Aldrich Sd: combined partial B & T immunodeficiency, IgM deficiency, thrombocytopenia, eczema.
a forcep is a metal device that enables gentle rotation and/or traction of the fetal head during vaginal delivery
Kielland: enables rotation and traction of the fetal head
Simpson: only enables traction of the fetal head
Barton: used for occiput transverse position of the fetal head
Piper: used to deliver the fetal head during breech delivery
Outlet: fetal head lies on the pelvic floor
Low: fetal head is below +2 station (not on the pelvic floor)
Mid: fetal head is below 0 station (not at +2 station)
High: fetal head is not engaged
Prolonged second stage of labor
Nonreassuring fetal heart rate
To avoid/assist maternal pushing efforts
Clinically adequate pelvic dimensions (see “Mechanics of childbirth”)
Full cervical dilation
Engagement of the fetal head
Knowledge of exact position and attitude of the fetal head
Emptied maternal bladder
No suspicion of fetal bleeding or bone mineralization disorders
Scalp injuries are less common
Cannot undergo decompression and “pop off”
Maternal: obstetric lacerations (cervix, vagina, uterus)
Fetal: head or soft-tissue trauma (e.g., scalp lacerations, injured ears), facial nerve palsy
Tissue conduction velocity (m/s)
SA node - 0.05
Atrial pathways - 1
AV node - 0.02- 0.05
Bundle of His - 1
Purkinje system - 4
Ventricular muscles -1
Abetalipoproteinemia: decrease ApoB-48, Apo B-100; pigmentary degeneration of retina, acanthocytes, steatorrhea, cerebellar ataxia.
Acute Fatty Liver of Pregnancy: microvesicular steatosis in the liver, mitochondrial dysfunction in the oxidation of fatty acids leading to an accumulation in hepatocytes
Alkaptonuria: homogentisate oxidase deficiency, increase homogenistic acid, ochronosis, dark blue urine.
AcylCoA Dehydrogenase deficiency (MCAD): fasting hypoglycemia, no ketone bodies, dicarboxilic acidemia.
Bernard Soulier Sd: gp1b deficiency, prolonged bleeding time
Bloom Sd: chromosome 15, Ashkenazi Jews, BLM gene.
Carpenter Sd: craniosynostosis, acrocephaly, craniofacial asymmetry, increased ICP, cutaneous syndactyly, polydactily, mild-profound MR.
Chediak Higashi Sd: Lyst gene mutation, microtubule polymerization defect, no phagolysosome formation, albinism.
Chondrodystrophy: normal-sized trunk and abnormally short limbs and extremities (dwarfism)
Congenital Adrenal Hyperplasia: 17alpha or 21beta or 11 beta hydroxylase deficiency; enlargemente od adrenal glands due to increase ACTH
Congenital Hepatic Fibrosis: hepatic (periporta) fibrosis, irregularly shaped proliferating bile duct, portal hypertension, renal cystic disease.
Cystic Fibrosis: CFTR gene, Phe508, defective Chloride channel, chromosome 7.
Dubin-Johnson Sd: direct hyperBbnemia, cMOAT deficiency, black liver
Endocardial Fibroelastosis: restrictive/infiltrative cardiomyopathy, thick fibroelastic tissue in endocardium of young children, <2yo
Familial Mediterranean Fever: chromosome 16, recurrent autoinflammatory disease, characterized by F°, PMN disfx, sudden attacks pain/inflammation (7 types of attacks (abdominal, joints, chest, scrotal, myalgias, erysipeloid, fever). Complication: AA-amyloidosis
Fanconi Anemia: genetic loss of DNA crosslink repair, often progresses to AML, short stature, ↑incidence of tumors/leukemia, aplastic anemia
Friedreich’s Ataxia: GAA triplet repeat, chromosome 9, neuronal degeneration, progressive gait & limb ataxia, arreflexia, hypertrophic cardiomyopathy, axonal sensory neuropathy, kyphoscoliosis, dysarthria, hand clumsiness, loss of sense of position, impaired vibratory sensation.
Gaucher’s disease: glucocerebrosidase deficiency, glucocerebroside accumulation, femur necrosis, crumpled paper inclusions in macrophages.
Ganzman’s thromboasthenia: gpIIbIIIa deficiency, deficient platelet aggregation.
Hartnup Disease: tryptophan deficiency, leads to niacin deficiency, pellagra-like dermatosis
Hemochromatosis: HFE gene, C282Y MC mutation, chromosome 6, unrestricted reabsorption of Fe+ in SI, iron deposits in organs, bronze diabetes, DM1, malabsorption, cardiomyopathy, joint degeneration, increased iron, ferritin, TIBC. Complications: liver cirrhosis, hepatocelullar carcinoma
Homocystinuria: due to B6 deficiency (defective Cystathionine synthase) or due to B9,B12 deficiency (defective Homocysteine Methyltrasnferase), dislocated lenses (in & down), DVT, stroke, atherosclerosis, MR.
Krabbe's Disease: Galactocerebrosidase deficiency, galactocerebroside accumulation, gobloid cells, optic atrophy, peripheral neuropathy.
Leukocyte Adhesion Defect (LAD): CD-18+ deficiency, omphalitis in newborns, chronic recurrent bacterial infxs, increase WBC count, no abscess or pus formation.
Metachromic Leukodystrophy: Aryl-sulfatase A deficiency, sulfatides accumulation, Demyelination (central & peripheral), Ataxia, Demantia (DAD)
Niemann-Pick Disease: sphingomyelinase deficiency, sphingomyelin accumulation, HSM, cherry-red macula, foam cells.
Phenylketonuria (PKU): phenylalanine hydroxylase deficiency, Phe accumulation, MR, microcephaly, diet low in Phe!!! also in pregnancy, avoid aspartame, musty odor.
Polycystic Kidney Disease (children): ARPKD, rogressive & fatal renal failure, multiple enlarged cysts perpendicualr to renal capsule, association with liver cysts. Bilateral palpable mass.
Rotor Sd: direct hyperBbnemia, cMOAT deficiency, no black liver
Shwaman Diamond Sd: exocrine pancreatic insufficiency (2°MCC in children after CF), bone marrow dysfunction, skeletal abnormalities, short stature.
Situs inversus: assoc w/ Kartagener sd
Sicke Cell Disease and Trait: Hb S, beta globin chain, chromosome 11, position 6, nucleotide codon change (glutamic acid --> valine), vaso-occlusive crisis (pain), autosplenectomy, acute chest pain sd, priapism, hand-foot sd, leg ulcers, aplastic crisis, drepanocytes & Howell-Jolly bodies, hemolytic anemia, jaundice, bone marrow hyperplasia
Tay-Sachs Disease: Hexoaminidase A deficiency, GM2 accumulation, cherry-red macula, onion skin lysosomes.
Thalasemia: alpha (chromosome 16, gene deletion), beta (chromosome 11, point mutation)
Werner Disease: adult progeria
Wilson’s Disease: Chromosome 13, WD gene, ATP7B gene (encondes for Copper transporting ATPase), copper accumulation in liver, brain (putamen), eyes (Descemet membrane - Kayser-Fleischer ring), decreased ceruloplasmin.
Xeroderma Pigmentosa: defective excision endonuclease, no repair of thymine dymers caused by UV radiation, excessive freckling, multiple skin cancers.
- Abnormal synchronous APs of groups of neurons in various parts of brain
- Many casues (infection, fever, tumors, injury, lyte imbalance, etc)
- Therapy aimed to reduce excitability of neurons
Benzodiazepines (Clonazepam, Diazepam) - Diazepam used for status epilepticus
Barbiturates (Phenobarbital)- Benzos and Barbituates increase GABA channel - hyperpolarization of neurons
Gabapentin - Increases gaba release
Valproic acid - Increases GABA, also blocks Na+ and Ca2+ channels, and increase K+ conductance
2.Alter transmembrane flow of ions
Phenytoin- Blocks Na+ channels
Carbamazepine - Blocks Na+ channels and potentiates postsynaptic effect of GABA
Ethosuximde - Blocks Ca2+ channels
Iamotrigine - Blocks Na+ channels
3. Decrease glutamate excitatory tone
Glutamate antagonists have too many side effects and none are on the market as anticonvulstants yet
Most Common Site of Primary Bone Tumors
- Chondroblastoma (before physeal closure)
- Osteoclastom/Giant cell tumor (after physeal closure in adults)
- Articular osteochondroma
- Bone cyst
- Osteoclastoma (in children)
- Osteomyelitis mostly starts in metaphysis
- Round cell lesions: Ewing’s sarcoma/Multiple myeloma /Reticulum cell sarcoma
- Osteoid osteoma
- It include nitroglycerin (glyceryl trinitrate) or pentaerythritol tetranitrate, isosorbide dinitrate and isosorbide mononitrate.
- Liberation of NO
- Cause venodilation, decrease VR and ventricular filling pressure and wall tension; therefore decrease O2 consumption
- Problem with Tolerance – fix with intermittent administration (patch 12hrs on 12hrs off)
- Often offered sublingually or transdermally
- It include either cardioselectives such as acebutolol or metoprolol, or non-cardioselectives such as oxprenolol or sotalol.
- Reduce myocardial O2 demand by decreasing HR and contractility; blocking B1
- Contraindicated in variant angina, good for chronic prophylaxis of stable angina
Calcium Channel Blockers
-It include Class I agents (e.g., verapamil), Class II agents (e.g., amlodipine, nifedipine), or the Class III agent diltiazem.
- All existing CCBs block L-Type channels
- 1st Generation; 3 Classes: - Phenylalkalamines (ex: Verapamil) , - Benzothiazepinones (ex: Diltiazem) , - Dihydropyridines (ex: nifedipime)
- Less depressant activity on heart than the other
- Associated with reflex-tachycardia from baroreceptors
- Problem in pts with angina
Nifedipine is more a potent vasodilator and more effective in angina. It is in the class of dihydropyridines and does not affect refrectory period on SA node conduction.