DermIn psoriasis: Neutrophils may form spongiotic clusters in the superficial dermis and the parakeratotic stratum corneum (munro microabscesses) Melanoma commonly mets to the brain, GI tract, bone, liver and lungs. The most common metastatic tumors to the brain are lung cancer, renal cancer, and melanoma. Disinfectants: Agent Alcohols (isopropanol, ethanol) Chlorhexidine Hydrogen peroxide Iodine Mechanism Disruption of cell membranes; denaturation of proteins Disruption of cell membranes; coagulation of cytoplasm Produces destructive free radicals that oxidize cellular components Halogenation of proteins and nucleic acids Sporicidal No N Yes Yes Xeroderma pigmentosum is AR. It is DNA excision repair – can’t repair DNA following UV light damage. An IgE independent urticarial can develop after exposure to substances that directly stimulate mast cell degranulation (opiates, ABX, radiographic contrast media). Erythema migrans is the classic skin lesion of lyme disease. Mycobacterium scrofulaceum is commonly found in and around environmental water sources. It is the etiologic agents of scrofula, a disease characterized by lymphadenitis (cervical) that occurs most often in children. Rocky mountain spotted fever risk factors include frequent contact with dogs and exposure to wooded areas or grassy fields. Most common organisms that cause otitis media are: strep pneumo, h. influenza, and moraxella. Recurrent infections with these organisms suggests humoral immunodeficiency. Pneumocystitis and chronic candidiasis suggests T-cell deficiency. The key cells involved in cell mediated immunity are macrophages, CD4+ helper T cells, CD8 cytotoxic t cells and NK cells. Failure to generate a response to a skin test testing for type IV HS is called anergy. Post-herpetic neuralgia (MC complication of VZV) is described as stabbing pain. RPR for syphilis (rapid plasma reagin). The patients serum is mixed with a solution of cardiolipin, cholesterol, and lecithin. Aggregation or flocculation of the sample demonstrates the presence of cardiolipin antibodies int eh pts serum. This test detects antibodies to human cellular lipids released into the bloodstream after cell destruction by T. pallidum. RPR is positive in all illnesses caused by T. pallidum and subspecies (syphilis, yaws, pinta, bejel). Common medical conditions influenced by multiple genes: Androgenetic alopecia, epilepsy, ischemic heart disease, schizophrenia, glaucoma, HTN, malignancy, type II DM Koplik spots are grains of sand on an erythematous base next to the 2 nd molar. Tuberculoid leprosy spots are hypopigmented and anesthetized due to superifical nerve involvement. Skin test for tuberculoid leprosy is the lepromin skin test. It will be positive because of the strong CD4 Th1 cell-mediated immune response. Lepromatous leprosy is is characterized by a weak cell mediated response. The lepromin skin test is usually nonreactive in these pts. Remember: tuberculosis itself involves a strong cellmediated response (resulting in caseating necrosis). This should help remember it. Plane xanthomas are linear lesions in skin folds that are strongly associated with primary biliary cirrhosis. Xanthelasma is a cutaneous lesion (commonly found on th eyelid) that contains lipid-laden histiocytes (foam cells). Classically, these are associated with primary or secondary hyperlipidemia. Chronic cholestatic processes including obstructive biliary lesions and primary biliary cirrhosis result in subsequent hypercholesterolemia, leading to the formation of xanthelasmas. VZV mainfests with a burning sensation and/or pain unilaterally in a dermatomal distribution. In 2-3 days, an erythematous maculopapular rash develops in the affected dermatome. The papules transform into the vesicles that later coalesce. Rupture of the vesicles produces ulcers that crust in a few weeks. The pt is contagious until the lesions are dry. Tzanck – intranuclear invlsuions in keratinocytes and multinucleated giant cells are seen In bacterial vaginosis, alterations in the normal vaginal flora (specifically loss of lactobacilli and overgrowth of mixed anaerobic organisms) produce a gray discharge and a fishy odor that becomes more prominent with addition of KOH (the whiff test). Class Anti-pseudomonal pencillins Cephalosporins Aminoglycosides Flouroquinolones Monobactams Carbapenems Drugs Ticarcillin, piperacillin Ceftazidime (3rd generation), cefepime (4th generation) Amikacin, gentamycin, tobramycin Ciprofloxacin, levofloxacin Azteronam Imipenem, meropenem Lymphangiosarcoma (pg. 295) is also called Stewart-Treves syndrome. In breast carcinoma, nipple inversion is observed when the tumor invades the central region of the breast, and skin retraction is identified when the cancer infiltrates the suspensory Cooper ligaments. Granulomas associated with TB develop a central zone of necrosis due to hypoxia and free-radical injury. This appears grossly as a granular and cheesy material. Bacillary angiomatosis is from bartonella henselae (cat scratch disease, which can also cause culture-negative endocarditis). Cat scratch disease is characterized by low fever, lymphadenopathy, and self limited course. BA can be fatal if left untreated though. PABA esters are sunscreens for UVB only (290-320). UVA is 320-400. A number of topical and systemic therapies are available for treating psoriasis. Topical vitamin D analogs are frequently used and include calcipotriene, calcitriol, tacalcitol. These medications bind to and activate the vit D receptor, a nuclear transcription factor that causes inhibition of keratinocyte proliferation and stimulation of keratinocyte differentiation. Treatment with vit D analogs has also been shown to inhibit T cell proliferation and other inflammatory mediators. Nafcillin is often used to treat skin and soft tissue infectinos for which S. aureus is a common cause (folliculitis, abscess). Acyclovir, its prodrug valacyclovir, famiciclovir, and ganciclovir are all nucleoside analogues that require both herpes viral and cellular kinases for conversion to their active nucleoside triphosphate form. Cidofovir is a nucleoside monophosphate that requires only cellular kinases for activation. Local cutaneous adverse effects of chronic topical corticosteroid administration including atrophy/thinning of the dermis that is assoacited with loss of dermal collagen, drying, cracking, and/or tightening of the skin, telangiectasias, and ecchymoses. Musculoskeletal Caudal regression syndrome is a rare condition. Patients are born with agenesis of the sacrum and occasionally lumbar spine and experience resultant flaccid paralysis of the legs, dorsiflexed contractures of the feet, and urinary incontinence. Caudal regression syndrome can range in severity from isolated anal atresia to sirenomelia. It is frequently related to poorly controlled maternal diabetes, though this is certainly not the only etiologic factor considering the frequency of diabetes and the relative rarity of caudal regression syndrome. Glenohumeral joint is the most commonly dislocated joint int eh body owing to the shallow articulation between the humeral head and the glenoid fossa of the scapula. In rotator cuff syndrome, the most commonly injured tendon is the supraspinatous because this tendon is prone to repeated impingement trauma between the humeral head and the acromion. Female athlete triad: eating disorder, amenorrhea, osteoporosis. All injections into the gluteal region should target the superloateral quadrant, to avoid damage to the gluteal nerves and sciatic nerve. This pt is exhibiting the classic “gluteus medius gait” – hip dips downwards when the ipsilateral foot is lefted off of the ground. This is observed when there is injury to the superior gluteal nerve or to the gluteus medius muscle itself. The superior gluteal nerve leaves the pelvis through the greater sciatic foramen above the level of the piriformis. Injection in the superomedial quandrant of the buttock is liekyl to injure this nerve. Sciatic nerve is in the inferomedial quadrant of the buttock. Large fluid collection in the retroperitoneum laying anterior to the psoas muscle with isodense fluid is consistent with a spontaneous retroperitoneal hematoma, likely secondary to warfarin use. The femoral nerve descends through the fibers of the psoas muscle, and then runs beneath the inguinal ligament into the thigh. Femoral nerve mononeuropathy can occur due to pelvic fracture, compression from a hematoma or abscess, stretch injury, or ischemia. Femoral nerve injury – knee buckles, patellar reflex is diminished, sensory loss over the anterior thigh. Several muscles insert of the clavicle including the pectoralis major on the inferior medial aspect, the deltoid on the inferior lateral aspect, the subclavius on the interior lateral aspect, the trapezius on the superior lateral aspect, and the SCM on the superior medial aspect. SCM is innervated by CN XI. Radial head subluxation (nursemaid’s elbow) is the MC elbow injury in children. It occurs most frequently between the ages of 1-4 yo. The injury often results from a sarp pull on the hand while the forarm is pronated and the elbow is extended. This traction causes the annular ligament to tear form its periosteal attachement at the neck of the radius. It then becomes trapped in the radiohumeral joint. Kids with this injury present with the injured arm held close to the body with the elbow extended (or slightly flexed) and the forearm pronated. The child is typically in little distress until attempts are made to move the elbow. The inferior gluteal nerve exits the pelvis through the greater sciatic foramen below the piriformis. Housemaid’s knee – prepatellar bursitis – chornic trauma from repeated kneeling. Also common in roofers, plumbers,a nd carpet layers. Dysthymic disorder is a chronic, low-intensity mood disorder (at least 2 years) that responds well to antidepressant medications. Major depression is diagnosed when at least 5 of the following symptoms are present for at least 2 weeks: depressed mood, sleep disorder, anhedonia, guilt (worthless, hopelessness, regret), energy deficit, concentration deficit, appetite disorder, psychomotor retardation or agitation, suicidality (SAGECAP). The median nerve courses with the brachial artery in the groove bewteween the biceps brachii and the brachialis muscles. It gains access to the forearm in the medial aspect of the antecubital fossa and immediately courses between the humeral and ulnar heads of the pronator teres muscle. It then courses between the flexor digitorum superficialis and the flexor digitorum profundus muscles before netering the wrist and hand within the flexor retinaculum. The musculocutaneous nerve courses directly between the biceps brachii and the coracobrachialis muscles. Injury to this nerve leads to paralysis of the biceps and the brachialis, which results in an inability to flex the forearm. Treatment for paroxysmal supraventricular tachycardia can be with vagal stimulation, such as carotid sinus massage or the valsalva maneuver. Maneuvers that increase vagal tone increase the refractory period in the AV node and help prevent a reentrant circuit from conducting. If valsalva fails, the IV adenosine is used. Serum sickness is a type III HS reaction which generally produces fever, urticarial, arthralgias, glomerulonephritis, and lymphadenopathy 5-10 days after exposure to an antigen. It can have vasculitis with vessel wall fibrinoid necrosis and neutrophil infiltration can be features of systemic despotition of circulating Salmonella possesses a special capsule called the vi antigen (Vi stands for virulence) which protects the bacterium from opsonization and phagocytosis. and lactic acidosis suggest mitochondrial encephalomyopathy. In MPO defiencicy. Serum sickness is a type III HS reaction characterized by desposition of circulating. Neuromuslcular lesions. Give pneumovax for S. Strep pneumo. and the meningitis polysaccharide capsular vaccine for N. Absence of these inhibitor NTs causes sutained muscle contraction. Heteroplasmy describes the condition of having different organellar genomes (mutated and wild type) within a single cell. There is often hypocomplimentemia. Hot tub folliculitis is a superficial and self-limited P. Also assoacited is synovitis. hib for h. influenza. In CGD the absence of NADPH oxidase causes an inability to form hydrogen peroxide. influenza type B. including a decreased serum C3 level. hot tub folliculitis. Mitochondria make ATP via oxidative phsophorylation. ragged red skeletal muscle fibers. pneumo. pts with more severe disease are those with a higher proportion of defective mitochondrial genomes within their cells. so both catalase positive and catalase negative organisms will survive with pahgocytes. Strep pyogenes is pyrrolidonyl arylamidase (PYR) positive. muscular tissue). or tetanus. thereby helping to regulate bony remodeling. which is why mitochondrial problems often lead to lactic acidosis and primarily affect tissues with the highest metabolic rates (neural tissue. and facial muscle spasm (risus sardonicus). lymphadenopathy. opisthotonos. urticarial. Osteocytes in bone communicate via gap junctions to send signals and exchange nutreints and waste products. Homocysteinuria is characterized by ectopic lentis. An Interesting Zoo Must Have Mammals (Actin in the I-band attaches at the Z-line. and congenital heart defects. Congenital hypothyroid: also associated with muscle hypotonia. H. The tetanospasmin heavy chain binds ganlioside receptors on the neuronal membranes and the light chain inhibits release of glycine and GABA from inhibitor interneurons. marfanoid habitus. mental retardation. complement fixing immune complexes and resulting vasculitis. In goodpastures. E. and a low serum C3 level 5-10 days after intravascular exposure to antigen. All medically important fungi may be divided into a few groups according to the area of involvement: . This vasccination elecitis humoral immunity for tetanus toxin (antitoxin antibodies – active immunity). prolonged jaundice. and keratoderma blennorrhagicum. Tetanus is inhibited by tetanus toxoid (inactived tetanus toxin) vaccination. coli is second MCC of osteomyelitis after salmonella in SS> Sacroiliitis occurs in 20% of reactive arthritis cases. the enzyme MPO is absent. Myosine in the H-band attaches at the M line) Many infections of P. Myeloperoxidase deficiency is an immune deficiency not unlike the caused by CGD. burn wound). aeruginosa often begin with exposure to a water course of creation of a moist environment (swimmers ear.immune complexes in arteries and arterioles. Neisseria. aeruginosa infection of the hair follicles. poor feeding. autoantibodies are formed against the noncollagenous domain of the alpha-3 chain of collagen IV (anti-GBM antibodies). Tetanospasmin is a protein toxin produces by C. Prominent signs and symptoms include: masseter muscle spasm (lockjaw). and salmonella are encapsulated (increased risk in asplenics and SS pts). Osteocytes can stress mechanical stresses and send signals to modulate the activity of surface osteoblasts. mouth ulcerations. balanitis circinata. glomerulonephritis. Sulfonamides can provoke this condition. meningitidis. hoarse cry. enthesitis. and therefore the enzyme MPO has no susbtrate (hydrogen peroxide) to metabolize into reactive oxygen species (oxygen free radicals) used to kill microorganisms. Associated findings include fever. and osteoporosis in addition to vascular problems. arthralgias. tetani that can travel by retrograde axonal transport into the CNS. The difference between these 2 illnesses lies in the fact that in CGD some phagocytosed organisms can be killed because these organisms produce their own H2O2 which MPO then uses to produce free radicals. For mitochondrial diseases. dysphagia. conjunctivitis. When a specific ion channel opens. There are 2 different types of bones in the body. blacks fracture less often. with heat. Hydroxyproline is also released into blood when osteoclasts resorb bone. or thymectomy. PTH stimulates the secretion of monocyte colony stimulating factor and RANK-L by osteobalsts. Postmenopausal osteoporosisi typically involves cancellous bone. rhizopus) C. Tx of MG involves cholinesterase inhibitors. Overexpression of RANK receptors in hypoestrogenic states causes increased bone resorption due to increased osteoclastic activity. Without the hydroxylation. B. thus stimulating osteoclastic precursor to become mature osteoclasts. and urinary deoxypyridinoline reflect osteoclastic activity. Tartrate resistant acid phosphatase. Even at same bone density. other chronic lung dz assoacited with hypoxia. TB. these cross-links are the most commonly used method in assessing osteoclastic activity. the respective ions will flow across the membrane in a direction that brings the resting membrane potential closer to that ion’s equilibrium potential (question ID: 1381) Bone specific alkaline phosphatase is easily denatured by heat (bone will boil!). Skeletal muscle is nicotinic cholinergic receptors. urinary hydroxyproline. malaborption Elevated levels of PGE2 and PDGF and VEGF causing fibrovascular proliferation is associated with clubbing. C. Pyridinoline covalently corss-links collagen fibers. Vit C is required. The capsule is unique in that it contains D-glutamate instead of polysaccharide. gut is muscarinic. Iron deficiency: spoon shaped nails Subperiosteal thinning: hyperparathyroid (from FA: renal osetodystrophy) Osteoclasts in Paget’s dz are typically very large and can have up to 100 nuclei. empyema. anthracis produces an antiphagocytic capsule that is required for pathogenicity. UC). urinary deoxypyridinoline is the most reliable. cross linking is greatly reduced and strength is worse. perfrigens causes late onset food poisoning. perfingens makes gas gangrene by rapidly metabolizing carbohydrates. cyanotic congenital heart dz (especially tet) and bacterial endocarditis. Genetic factors are responsible for up to 80% of the variation in peak bone mass among invididvuals. blastomycoses) Opportunistic mycoses (candida. mucor. are histoplasmosis. . In skeletal muscle. pulmonary HTN. Clubbing: lung cancer (large cell carcinoma especially). Bone density increases with increasing BMI. and it acts as a decoy receptor.- Cutaneous mycoses (dermatophytoses and tinea versicolor) Subcutnaeous mycoses (sporotrichosis) Mycoses with systemic involvement (most often lungs. bronchiectasis. Black females have high bone density than whites. converts to D3 (must still be activated in kidney though). The interaction of RANk with its ligand is decreased by another protein secreted by the osteoblast – osteoprotegerin (OPG). which is preodiminantly present in the vertebral column. distal radius. The cortical or compact bone makes up the shafts of long bones and outer envelopes of all bones. UV-B light is necessary for activation of pro-vit D3 into pre-vitD3 which then. hip. aspergillus. and neck of femur. Bone turnover increases when RANK-L is high and OPG is low. but meat products also increase hydroxyproline. animmunosuppresive agent. Prolyl and lysyl hydroxylase hydrolate proline and lysine residues of pro-collagen. coccioidoses. IBD (crohns. hyperthyroidism. one T-tubule contacts 2 terminal cisterns forming a triad at the junction of the A-band and the I-band. CF. which is coverted to UMP by the action of nucleoside kinases and then UMP inhibits carbamoyl phosphate synthetase 2. Pain is exacerbated by movements that cause the psoas to be stretched or extended (such as extension fo the hip – this is the psoas sign). sinusoidal vasculature that is conducive to microbial passage. Subdural hematoma and bilateral retinal hemorrhages = shaken baby syndrome Spiral fractures = child abuse. The Ib fibers then synapse on inhibitory interneurons in the spinal cord that stop the alpha motor fibers. Hemolysis causes haptoglobin levels to decrease by binding to free haptoglobin and the complex is cleared hepatically. inguinal mass. This is a problem in pyramidine base synthesis only (not purines). (are actin containing fibrobalsts myofibroblasts??) LEMS = proximal uscle weakness. In ankylosing spondylitis there are enthesitis (inflammation where tendons insert into bone). IN contrast. Myofibroblasts initiate wound contraction during healing by second inteitn. Type I muscles = postural muscles (low-level sustained force). causing sudden muscle relaxation. knee and ankle joints. it can start decreasing in number as well. You can also get osteoporosis of disuse (with bone resorption). and condensation rxns. (ID 8266) Ia and II muscle fibers from the intrafusal muscle fibers from muscle psindles are responsible for the stretch reflex. parvovirus can cause arthritis involving the PIP. skeletal muscle fibers in his leg will decrease in size. They also encourage myofibroblast accumulation at the wound edges and scar tissue remodeling. the GTOs inhibit contraction of the muscle. GTOs are relatively insensitive to changes in muscle length because the lengthening that occurs when a muscle is passively stretched takes place primarily in the muscle fibers and not in the tendon. If it is more prolonged. and difficulty woalking. When a muscle exerts too much force. These pts have hip flexion and lumbar lordosis to inhibit hip flexion. MMPs are important in wound healing. If a leg is immobilized for a while. decarboxylation. Osteomyelitis affects young boys.Signs and symptoms of psoas abscess include fever. the increase in tension is transitted through the tendon activated the GTO in the process. When a muscle actively contracts against resistance. Iti usually affects the metaphysis because this region contains slow flowing. unmineraliezzd spongiosa in the medullary canals” Fever/malaise followed by bright red rash on cheeks 5-7 days later: B19 parvovirus. . Blephorospasm is second most common focal dystonia. The golgi tendon circuit is a negative feedback system that regulates and maintains muscle tension. Golgi tendon organs are sensory receptors located at the junction of the muscle and tendon that are innervated by group Ib sensory axons. Biochemistry Orotic aciduria enzymes messed up are orotate phosphoribosyl transferase and OMP decarboxylase. GTOs are connected in series with the contracting extrafusal skeletal muscle fibers. back or flank pain. It orotic aciduria. thus attenuating orotic acid production. Eye stuff (ID 862). They degrade collagen and remodel. sWriter’s cramp is another common dystonia. deamination. it can progress to chronic suppurative osteomyelitis. IN adults. Without treatment. MCP. This way. Osteopetrosis is characterized by the “peristance of primary. Spasmodic torticollis: focal dystonia where the neck is stuck in 1 position. B6 (pyridoxine) is a coafactor in transamination. Symptoms generally resolve spontaneously. If it happens at the costovertebral and costosternal junctions there will be pain limiting chest wall expansion leading to hypoventilation. These turn orotic acid into UMP. give uridine. Contracture may occur when unusually pronounced MMP activity results in excessive wound contraction. This makes sense. This is called methylmalonic aciduria. An enzyme in converting PRPP to IMP is PRPP amidotransferase. This last step is an isomerization using methylmalonyl CoA mutase and vit B12. result in disorders of the urea cycle. This results in dystonia and poor feeding. The common problem resulting . With a vit B12 defcieincy. the pt will have an isomerization problem at this step. vomiting. threonine. It acts similar to PKU if phenylalanine hydroxylase was out (like in moral PKU). cholesterol. However. (ID 1369) Catabolims of isoleucine. leading to inability to degrade branched chain amino acids beyond their deaminated alpha-keto acid state. disulfide bonds) Beta pleated sheets are less soluble than alpha helix and therefore aggregate (alzheimers). Atypical or malignant PKU – BH4 reductase is out. Propionyl coA to to methylmelanyl coA. dehydration. we can’t get BH4. GMP requires ATP and AMP requires GTP so that purine synthesis favors the nucleotide that is deficient. (ID 1341. such as valine. including therapeutic and palliative radiation therapy. induced DNA damage through DNA ds fractures and the formation of oxygen free radicals. This accounts for elastin’s resilient properties. Therefore. RNA pol I makes all ribosomal RNA except the 5S rRNA. This enzyme causes nicks at damaged sites that are later excised yb the 5’ to 3’ exonuclease activity of DNA polymerase. Propionic acid is the intermediate in the catabolism of branched chain AAs. hypotonia. in BH4 reductase problem we also can’t make tyrosine into DOPA. pg 98) Arginase deficiency = spasticity Thymine (pyrimidine) dimers can be removed by the action of UV specific endonucleases. which in turn will make DA. which is then converted to methylmalonic acid by biotin dependent carboxylation.Amino groups are funneled into glutamate during protein catabolism. DNA damage from exposure to UV radiation leads to the formation of pyrimidine-pyrimidien dimers (thymine dimers). as propionyl CoA accumulates. Side chains of some of the lysine residues in elastin are covalently bound to form a dessmosine crosslink. which also synthesis new DNA in the place of the damaged DNA. When PRPP is high. Most common CF mutation is a deletion of the phenylalanine at position 508 in the CFTR protein. PRPP is created by PRPP synthetase in the first step of de novo purine synthesis. lethargy. between all residues of antiparallel strands in beta pleated sheets). (citrulline argininosuccinate arginine ornithine is in the cytoplasm. and odd chian FAs leads to the formation of propionic acid. methionine. which requires PRPP. If you can’t get ornithine from the cytosol to the mitochondria. Exposure to radiation. and is not produced during the catabolism of other amino acids listed. leasd to a development of propionic academia. allowing it to stretch and bend in any direction on applying force only to recoil to its original size when the stretching force is withdrawn. valine. it will be shuttled into more IMP formation and ultimately more GMP and AMP (purine) formation. the enzyme responsible for the conversion of propionyl coA to methylmalonyl coA. Propionic academia is clinically characterized by poor feeding. we will have to make more. Defects in any of the urea cycle steps. and an anion gap acidosis. Primary structure: AA linked by peptide bonds Secondary structure: alpha-Helix and beta pleated hseet heald together by hydrogen bonds (every 4 in alpha helix. Maple syrup urine is caused by a defect in alpha keto acid dehydrogenase. a DNA-dependent RNA polymerase which forms RNA primers. hydrophobic interactions. you can’t finish the urea cycle. Tertiary structure: complex folding (many forces icnludign ionic bonds. Ornithine citrulline is in the mitochondria). H-bonds. Isomerization of methylmalonyl CoA forms succinyl coA. so this enyme will be up also. which is made by RNA pol III. A congenital deficiency of propianyl CoA carboxylase. because without purine salvage. and then methylmelanyl coA becomes succinyl coA. which then enters the TCA cycle. PRPP is a substrate used by HGPRT during purine salvage and it accumulates when there is deficiency of the enzyme. (1340) DNA polymerase synthesize new NDA strands in 5’ to 3’ direction and require a free 3’-OH group upon which to begin polymerization. This 3’-OH group is provided by the enzyme primase. So PRL is not tonically inhibited and they get hyperprolicatinemia. Zellweger syndrome can’t form myelin properly. . likely due to impaired beta-oxidation. an AR condition characterized by ceramide accumulation within neurons and within granulomas in the skin. acyl-CoA dehydrogenase. ALT (B6) Oxaloacetate Aspartate. and Fanconi anemia are all at risk of acute leukemia. Antibodies to CCP are usually measured by ELISA using a mixture of cyclic citrullinated peptides as the antigen. Since RBCs don’t have mitochondria. 85% of heme is produced by bone marrow erythroid cells for hemoglobin and the remaining 15% is syntheized in the liver. phenytoin. thus alleviating the abdominal pain and neuropschiatric manifestations of acute intermittent porphyria. and recurrent miscarriages. alcohol decrease hepatic concentration of heme by inducing the cytochrome P450 enzyme system. ALA synthase is an enzyme in the heme biosynthesis pathway that functions to condense succinyl coA and lgycin to form delta-ALA (the RLS in the heme synthesis pathway. Pseudotumor cerebri cerebral edema in the setting of benign intracranial HTN Parkin. paradoxical PTT prolongation. Refsum dz build up of phytanic acid (branched chain FA) in the body. leading to CNS system dysfunction. AST (B6) These are transaminations. Glucose and IV heme preparations are good at decreasing ALA synthetase activity and abrogating acute episodes of acute intermittent porphyria. Downs. During prolonged starvation. The transfer of an alkyl group from pyruvate to coA is essential for the function of pyruvate dehydrogenase. Enzyme deficiencies in the early steps of porphyrin synthesis cause neurologic abnormalities without photosensitivity. Very long chain and some branched chain FAs cannot undergo mitochondrial beta oxidation. Fabry is assoacited also with acroparesthesia which is episodic. Antiphospholipid antibodies are found in pts with SLE and antiphospholipid antibody syndrome. Administration of drugs such as phenobarbital. while derangements after condensation of prophobilinogen cause photosensitivity. In prolonged starvation. requires B6). Lipoic acid is involved in the decarboxylation of alpha ketoacids and the transfer of alkyl groups. Restrict lactose which is broken down into glucose and galactose. Treatment of urea cycle disorders is balancing protein intake to output. nose. These undergo special oxidation (beta for VLCFA or alpha for branched cahin FA) in peroxisomes. DJ-1 are assoacited with AR forms of parkinsons dz (<50) and all promote the degradation of misfolded proteins via the Ub-proteosome system. burning neuropathic pain in the extremities. Glucose loading decreases prophyrin synthesis by repressing ALA synthase activity. Neuroaminidase (sialidase) deficiency is the cause of human sialidosis. Antiphospholipid antibody syndrome causes hypercoagulability. Bloom syndrome. Galactose problems show up soon after breastfeeding is begun. Glutamate Alanine. often debilitating. pts with this enzyme deficiency cannot utilize fats for energy or produce ketone bodies. primarily for the cyt p450 detoxification enzyme system. Pataus. the continuous supply of energy that ketone bodies provide is especially important to brain functioning. PINK1. Ketone bodies are converted back into acetyl coA in the mitochondria of peripheral tissue. because the brain has no glycogen or TG stores. Impaired beta-oxidation most commonly results from defects involving the first enzyme in the pathway. griseofulvin. they can’t use ketone bodies. Strict avoidance of chlorophyll in the diet is required. If a pt failes to produce ketones during fasting. which is required to convert acetoacetate into acetoacetyle coA before 2 acetyl CoAs. Alkaptonuria causes orchronosis – blue/black pigmentation that is most evident in the ears.from disorders of the urea cycle is increased blood concentration of ammonia. Found on the surface of influenza virus. Ceramidase deficiency causes Farber dz. and cheeks. The liver also can’t utilize ketone bodies for energy because it lacks the enzyme succinylCoA-acetoacetate coA transferase (thiophorase). Ataxia telangiectasia. cholesterol. The Shine-Delgarno sequence is located 10 bases upstream from the AUG start codon on prokaryotic mRNA. nonpolar R groups. TGs stored in adipose tissue is metabolized to free FAs and glycerol by hormone sensitive lipase. an initator tRNA binds to the AUG start codon. which consist of snRNPs plus proteins. Deficiency of pantothenic acid is rare. . PolyA tail protects mRNA from degradation within the cytoplasm after it exits the nucleus. the periosteum. and the aortic media. Synthesis of snRNP occurs in the nucleus. steroids. steroids. Splicing is performed by spliceosomes. Once the mRNA is bound to the 30S subunit. retinoic acid receptors. Glycine is the smallest AA and it fits into the space when three alpha collagen chain come together to form helix. This inhibits IRS tyrosine phosphorylation by insulin. vit D receptors. Cholesterol and FA synthesis use NADPH as an electorn donor. MR). Glycerol in the liver can also be used for TG synthesis. Marfan’s syndrome is a defect in fibrillin. Then the IRS gets involved. FAs. isoleucine. and intracellular FFAs are suspected of increasing serine kinase activity as well. hypotonia. heme A. macroglossia. the 50S ribosomal subunit joins the complex. C-myc is up in burkitt lymphoma. Posphorylation of serine residues in the beta subunit of the IR also hinders downstream signaling. proteins. D. glucocorticoids. and the protein synthesis begins. DHAP can then be used for glycolysis (ATP) or gluconeogenesis (glucose). methionine. resulting in resistance to the normal actions of insulin. B5 (CoA) is important in oxaloacetate to citrate and then succinyl-CoA. and glucagon can also induce insulin resistance by this same mechanism. but also synthesis of vit A. The insulin receptor is a tetrameric structure consisting of 2 alpha and 2 beta subunits. alanine. Promoters: TATA is 25 nuc upstream.Gluconeogenesis is thus impaired due to lack of energy while glucose consumption is markedly increased. which then result in phosphorylation of the IRS-1 serine residues. N-myc can bind DNA. Pathology shows abnormal accumulation in the lysosomes. Transmembrane domain – 7 alpha helical segments each containing 20 AAs with hydrophobic. Neutrophils are the primary cell responsible for the intense inflammatory response in pts with gout due to the phagocytosis of MSU crystals. Homobox genes typically code for DNA-binding transcription factors which alter the expression of genes involved in morphogenesis. but with hepatomegaly and icnresed risk of cirrhosis (also cardiomegaly. resulting in severe hypoglycemia. phenylalanine. Colchincine stops the chemotaxis of neutrophils. DNA transcription and replication proteins. AAs. These 2 complementary sequences allow the mRNA and the 30s ribosomal subunit to bind in preparation for protein translation. This rRNA within the 30S subunit expresses a sequence complementary to the Sine-Delgarno sequence in all prokaryotic mRNA. catalyzed by RNA pol II. A series of downstream signaling is then triggered. Nonpolar hydrophobic AA: valine. Pompe dz presents not with hypoglycemia. The 16S rRNA strand is the only piece of rRNA found in the prokaryotic 30S ribosomal subunit. and others. CAAT box is 70 nucleotides upstream. The alpha subunits are extracellular and they provide the binding site for insulin. thyroid proteins. G3P is then converted to DHAP. TNFalpha is a proinflammatory cytokine that induces insulin resistance through the activation of serine kinases. though it has been observed in severely malnourished people who complain of paresthesias and dysesthesias (burning feet syndrome) and GI distress. Debranching enzyme deficiency can be differentiated from other glycogen storage dz by demonstrating the accumulation of abnormally short outer dextrin-like structures in the cytosol of hepatocytes with an absence of histopathological fatty infiltration of the liver. an extracellular glycoprotein that is abundant in the zonular fibers of the lens. starting with the autophosphorylation of the IR. Catecholamines. The beta subunits are intracellular and contain tyrosin kinase domains that are activated when insulin attaches to the alpha subunits. Examples of proteins that are able to bind DNA include transcription factors. Glycerol is then transported to the liver where it is phosphorylated to G3P via liver specific glyercol kinase. Cortisol is a cytoplasmic receptor that is bound to HSPs. hyperglycemia. lysine. impaired tissue oxygenation decreases oxidative phosphorylation. IN gluconeogenesis. and the formation of substrates will be favored. There are multiple subtypes of alpha G proteins. If delta G is positive. This is how ppl with essential fructosuria metbaolize dietary fructose – otherwise it is not active in most pts. Diabeics get hyperosomolar hyperglycemia. glutamic acid. leading to the shunting of pyruvate to lactate after glycolysis. ATP is made. there is an increase in lactic acid formation. Hence. TCA cycle happens. the receptors dimerize. A Keq of 0 is not mathematically possible A Keq of 1 would occur in a state where G is 0 A Keq of 1. Anaerobic cause this: peptostreptococcus. Keq will be less than 1. each with different secdonary effects. and go to the nucleus. ATP can also be generated by substrate level phosphorylation. PKA phosphorylates the serine tor threonine residues in some enzymes. AIDS low CD4:CD8. AAs with 3 titratable protons: histidine. leading to actiation or deactivation. When cortisol binds to the carboxyl terminal. The alpha subunit of the inactivated G-protein is bound to GDP. Aspiration pneumonia: superior lower lobe or posterior upper lobe. aspartic acid. Beta cell enters glycolysis. thyroid. Substrate level phosphorylation can occur in botht he cytoplasm and the mitochondrial matrix.ADP ratios within the beta cells results in the closure of KATP channel. Upon activation of the receptor. Lack of histidase. a metabolic derangement often precipitated by infection. This is a rate limiting step in the beta cell. High ATP. fusobacterium. leukocytosis. cysteine. This is MODY. arginine. tachycardia shock Lactic acidosis is an angion-gap metabolic acidosis that results from overproduction and/or impaired clearance of lactic acid. mtDNA has 22 tRNAs and 2 rRNAs Herpsensitivity pneumitis low CD4:CD8. hypotension. GLucokinase is a major glucose sensor in the beta cell. Hepatic hypoperfusion also contributes to buildup of lactic acid. bacteroides. lysosomal. hyperosomoalrty without ketoacidosis. emotional disturbance. and integral membrane proteins. Big in Japan. Mitochondrial GTP can undergo transphosphorylation whereby GTP donates a high energy phosphate to ADP to form ATP. Glucose into beta cell. Fever. retinoids. Subsequent binding of GTP then allows for the dissociation of the alpha subunit from the remainder of the G protein complex. as the liver is the primary site of lactate clearance. In septic shock. Fructose F6P via hexokinase. prevotella Protons dissociate from AAs when the pH exceeds the pKa associated with each given proteon. GTP by succinyl coA synthetase during the conversion of succinyl coA to succinate. tyrosine Histidinemia exists: speech defects. FAs. sarcoidosis high CD4:CD8 Cyanide poisoning is bitter. . ATP is generated from the TCA cycle via oxidative phosphorylation. Nuclear receptors. a process which involves the direct transfer of a phosphate group to ADP from a reactive intermediate. the HSPs liberate. PPAR. psychomotor and retardation. Gs is cAMP then activates PKA. which causes insulin secretion by opening the voltage dependent calcium channels. IN the citric acid cycl. the alpha subunit undergoes a conformation change and GDP is released. Keq will be greater than 1. almond breath. the hydrolysis of GTP is required for the phosphorylation and decarboxylation of oxaloacetate to PEP by PEP carboxykinase. They control gene expression by binding to tDNA at the hromoen-responsive elements in the promoter region of target genes. Cortisol increases PNMT. Chaaracterized by dehydration. and the concentration of products at equilibrium will exceed that of the substrates. If delta G is negative.5 would occur in a state where G is negative Gluconeogenesis: alanine glucose which begins with the transamination of alanine to pyruvate RER is the site of secretory. SOS activates RAS which then actiaves RAF to activate MAP Kinase kinase after GF ligand binds to an autophosphorylating tyroskine kinase. caushing inhibition of the Krebs cycle. the transcription and translation of these bacterial proteins is regulated by a single promoter. Commonly located in the parasagittal region. This then casues vasodilation by decreasing calcium levelsin the smooth muscle cytoplasm via PKG. glutamine. which codes for proteins necessary for lactose metabolism by E. . subsequently increases utilization of lactose for energy. Enteropeptidase is produced in the duodenum and cleaves tryspinogen to trypsin. Bitots spots are seen in Vit A deficiency. resulting ina syndreom known as ataxic hemiparesis. These are CL cerebellar deficitis (cerebellar lesions are ipisilateral deficits) Tumor adjacent to the falx cerebri and compressing the medial surface of the hemisphere. Depletion of cAMP by the presence of glucose decreases the expression of the lac operon structural genes. Leishmaniasis in histiocytes – in Iraq. an excitatory NT. This bidnign causes a conformational change which prevents the attachment of the repressor protein to the operator region. a non-neuroactive compound. a potent apetite stimulatnt. are assoacited with shortened telomeres. Leptin is produced by adipocytes. meaning that one mRNA codes for several proteins. The NO then goes into the smooth muscle cells and activates guanylyl cyclase to make cGMP. tRNA is the only RNA species that contains the nucleoside thymidine. coli. and large fat cells produce more leptin than small ones. Infarcts of anterior pons: CST (contralateral hemiparesis and Babinski) and corticobulbar tract (CL facial palsy and dysarthria). Leptin decreases food intake int eh following important ways: Leptin decreases the production of Neuropeptide Y. and ammonia in a process known as the glutamate-glutamine cycle. Glutamine is then released by astrocytes and taken up by neurons.Within the brain. Glucose decreses the activity of Adenylyl cyclase and leads to a reduction of intracellular cAMP. They are abnormal squamous cell proliferation and keratinization of the conjunctiva. Calcium influx into endothelial cells causes eNOS activation and ultimately arginine NO and citrulline. coli in glucose-containing media with or without lactose represses the expression of the lac operon. and set of regulatory elements. astrocytes and neurons interact to regulate the metabolism of glutamate. such as Blood syndrome. Excess ammonia also depletes glutamate. which. Hyperammonemia in hepatic encephalopathy results in depletion of a-KG. resulting in astrocyte swelling and dysfunction. where it is either converted back to glutamate for use as a NT or transaminated into a-KG for use in the Krebs cycle. Glutamate released by neurons during neurtotranmission is taken up by astrocytes and converted to glutamine. which binds cAMP to form a cAMP-CAP complex which then binds to a region upstream from the promoter region and acts as positive regulator of the lac operon. Tinnitus and unilateral hearing loss = CPA angle tumor such as an acoustic neuroma. and causes accumulation of glutamine. Telomeres add to 3’ end of DNA Syndromes of premature aging. An example is the bacterial lac operon. a-MSH is produced by cleavage of POMC and inhibits food intake Bacterial mRNA can be polycistronic. operator. increses transcription of the lac operon structural genes and. Clutluring E coli in lactose containing media results in the binding of lactose to the repressor protein. desert Neurology Trigem nerve arises from the lateral aspect of the mid-pons at the level of the middle cerebellar peduncle. but can also be found adjacent to the lateral convexity of the hemisphere. Can also cause CL dysmetria and dysdiadochokinesia. in the arcuate nuc of the hypothalamus Leptin stimulates the produdciton of POMC in the arcuate nucleus. in the region of the sphenoid wing and olfactory groove (would present with HA and anosmia). Culturing E. in turn. Typical meningioma location. Serum leptin concentrations are highly correlated with body fat content. High cAMP levels activate a protein called catabolite activator protein (CAP). Sx of catastrophic bleeding include bulging anterior fontanelle. the inner portion fo the tympanic membrane is the IX). lower extremity weakness and hyperreflexia. An aneurysm arising from either the superior cerebellar or posterior cerebral artery can cause third nerve palsy (non pupil sparing) – unilateral HA. irritation by bone spurs. Hyperacusis of from paralysis of the stapedius – CN VII. Intraventicular hemorrhage is a common complication of prematurity that can lead to long term neurodevelopmental impairment. Pseudotumor cerebri – hydrocephalus – a condition that classically occurs in overweight young females and is related to decreased CSF outflow at the arachnoid villi. choreoathetosis. upper extremity weakness and hyporeflexia. tonic-clonic seizures. irregular respirations and ocma. It is lateral to GP and internal capsule. Hydrocephalus in early infancy presents with macrocephaly. eye pain. hypotonia. dilated nonreactive pupil. Sciatica can result from herniations. and forgetfulness. and decreased spontaneous movements.Progressive neurologic dz with cystic degeneration of putamen = Wilsons. Usually occurs within the first 5 postnatal days. Ipsilateral hyperacusis is a common finding in Bell’s palsy. diplopia. . Oxaloacetate forms aspartate while reacting with glutamate. Elevated intracranial pressure with normal CSF content and normal neuro imaging. and irritation by the piriformis. ptosis. Frontal cortex lesions – defecits of higher brain function. Vasovagal syncope is parasympathetic outflow via the vagus nerve leads to decreased heart rate and blood pressure. It cocurs most frequently in infants born before 32 weeks or with <1500g. Chronic loss of upper extremity pain and temperature sensation. Damage to the caudate nucleus is associated with transient hemiparesis as well as frontal lobe symptoms such as inattentiveness. There may also be agitiation. Optic nerve atrophy and blindness are the concern. and social behavior. Can have mural foam cells or fibrinoid necrosis. 3 important DA pathways: Mesolimbic-mesocortical o Regulates behavior schizophrenia Nigrostriatal o Coordination of voluntary movements parkinsons Tuberoinfundibular o Controls PRL secretion hyperprolactinemia Myeres loop is pie in the ski. Internal capsle gets blood from anterior choroidal artery. hypotension. decerebrate posturing. Lacunar infarcts results from occlusion of the small penetrating arteries that supply these structures. The rest of the external auditory canal (including the external portion of the tympanic membrane is the mandibular division fo the trigem. muscle hypertonicity. irritability. IVH in a newborn can be clinically silent or present with an altered level of consciousness. spinal canal stenosis. with ipsilateral eye in a down and out position. creativity. sexual interest. This is transamination with B6 necessary. Posterior external auditory canal – vagus nerve. and other dyskinesias. IVH in preterm infants usually originate form germinal matrix. VII chorda tympani branch of facial supplies taste to ant 2/3 of tongue. CNVII and CNV can also be affected by schwannomas. psychosis. and kyphoscoliosis = syringomelia. most commonly in the setting of chronic uncontrolled HTN or diabetes. altering patterns of spontaneity. and hyperreflexia (caused by stretching of the periventricular pyramidal tracts UMN lesiosn). abulia. poor feeding. Lipohyalinosis and microatheromas are believed to be the primary causes of lacunar infarcts. Manifests as HA and papilledema. a highly cellular and vascularized layer in the subventricular zone from which neurons and glial cells migrate out during brain development. K ion permeance is highest during the repoarlization of the AP. Morphine opens K channels. Morphine tolerance is a common problem in the tx of pain. and an increased incidence of malignancy. Beta endorphin is one endogenous opioid peptide that is derived from POMC. Depolarization results from massive inclux of Na through voltage gated Na channels. paresthesias of the face and extremities. dizziness. weakness. One of the purposes of myelin is to reduce charge dissipation by increasing membrane resistance. the length constant is the distance at which the originating potential decreased to 37% of its original amplitude. repeated sinopulmonary infections. oculocutaneous telangiectasias. The action potential results form changes in the membrane perm to K and Na ions. The DNA of these pts is hypersensitive to ionizing radiation. MG or restrictive lung or chest wall dz would cause a normal diaphgram to fatigue rapidly. and loss of reflexes. Bare lymphocyte syndrome is an immunodeficiency from a defect in expression of HLA class II antigens ont eh surfaces of antigen presenting cells.The concept of a latent period can be applied to both dz pathogenesis and exposure to risk modifiers. Activation of NMDA receptors by glutamate is believed to enhance morphine tolerance by increasing phosphorylation or opioid receptors and increasing NO levels. Paresthesias. DNA is hypersensitive to UV radiation. Ataxia telangeiectasia is an AR disorder resulting from a defect in DNA-repair genes. thus increasing the length constant. Espeically in the setting of college dorms. petechial skin rash from Neisseria induced small vessel vasculitis (especially affecting the palms and soles). block the actions of glutamate and effectively decrease morphine tolerance. which allows efflux of K and hyperpolarization of the neuron terminating the pain transmission. Increased susceptibility to neoplasms is present HNPCC occurs due to a defect in DNA mismatch repair enzymes. Repolarization occurs due to closure of voltage gagted Na channels and opening of voltage gated K channels. chills. It has tetrodotoxin. exposure to risk modifiers may need to be continuous over a certain period of time before influencing the outcome. The exact mechanism of teoelrance is unknown but may involve increased pshophoarylation of opiod receptors. It presents with high fever. Tetanoaspasmin travels upt he motor neuron axon by retrograde transport to the spinal cord and medulla. A decrease in the length constant can result form increased charge dissipation along a nerve axon. Death can occur form respiratory failure and hypotension. The organism itself does not travel but rather remains at the local wound site. Demyelination will decrease the length constant and result in impaired stimulus transmission. diarrhea. Tetrodotoxin binds to voltage gated Na cahnnels in nerve and cardiac tissue. Neisseria meningitidis is a common cause of bacterial meningitis. MHC class II is needed to present foreign antigen to T cells to elicit a cell mediated AND a humoral response (because T cells must first activate B cells to mature and undergo class switching). preventing Na influx and depolarization and AP conduction. increased adenylyl cyclase activity. or increased NO levels. Additionally. Symptoms of tetrodotoxin poisoning occur quickly after ingestion and include dizziness. vomiting. a toxin produced by microorganisms assoacited with the fish. sqcc) Fanconi anemia is caused by HS of DNA to cross linking agents Bloom syndrome is characterized by generalized chromosomal instability. NMDA receptor blockers. Tx with IV ceftriaxone for 2 weeks. It leads to increased susceptibility to colon cancer. POMC is a polypeptide that goes through enzymatic cleavage and modification to produce not only beta-endorphines but also ACTH and MSH. More specifically. Manifestations include cerebellar ataxia. altered mentation. A number of inherited disorders are caused by deficiency DNA-repair enzymes: Ataxia telangiectasia is characterized by DNA HS to ionizing radiation In xerdoerma pigemntosia. weakness. nausea and history of fish consumption strongly suggests food poisoning by pufferfish. The length constant (space constant) is a measure of how far alonga n axon an electrical impulse can propagate. nausea. like ketamine. . The initial steps in pathogenesis and/or exposure to a risk factor sometimes occur years before clinical manifestations of a dz are evident. Myelination causes the length constant to increase and the time constant to decrease – both of which improve conduction speed. and ultimately septic shock. The fact that beta endorphins and ACTH are derived from the same precursor suggests a close physiologic relationship between the stress axis and the opioid system. causing premature skin agin and increased risk of skin cancer (melanoma. CSF culture showing growth on MacConkey agar implies CNS infection with enteric bacteria – specifically. hyalinization. Primary CNS lymphoma occurs in immunocomprosmised pts and is of B lymphocyte origin. Strep pneumo is leading cause of community acquired pneumonia. Strep pneumo is the most common cuase of bacterial meningitis in adults of all ages. It often follows a pulmonary infection or mild upper respiratory infection. Grows in macrophages. Cerebellar dysfunction occurs as the tumor compresses adjacent strucutrs. Tetanus vaccine is a toxoid.Meningococcal sepsis may be associated with DIC and hemorrhagic destruction of the bilateral adrenal glands. Ischemic nerve damage follows. myelin. Accumulating glucose is converted into sorbitol and fructose by aldose reductase. dysphagia. Sorbitol increases cell osmolarity and facilitates water influx into the cell. Toxoplasmosis is acquired in utero – it is transplacental. Or intracellular hypergcymia occurs in peripheral nerves. post exposure prophylaxis is no longer effective. It forms biofilms. and astrocytes form a glial scal along the peripheray. It is an excrecelluar polysaccharide matrix. E coli is a frequent cause of neonatal meningitis. dysphonia Listeriosis occurs exclusively in immunocomrpoised pts. lethargy). The three Ds of botulinum toxin: diplopia. The capsule synthesized by some E coli (K1 antigen) is a virulence factor that allows the bacteria to survive hematogenous spread and to establish meningeal infection. A cystic space replaces the necrosis. N meningitis sepsis does NOT necessarily include meningitis. and those in generally poor health are at greater risk for S. intracranial calcifications. vomiting. The result is osmotic damage to axons and schwann cells. and chorioretinitis are classic triad of toxoplasmosis. Coli. . Microglia move to the area of ischemic infarct in apporxiamtely 3-5 days after the onset of ischemia and phagocytize the fragments of neurons. aslepnic individuals. and necrotic debris. Neisser meningitiidis gains access to the CNS by first colonizing the nasopharynx and subsequently invading the mucosal epithelium and gaining access to the bloodstream. We start it 2 months after birth. Staph is common cause of meningitis in neurosurgical pts. Most important mechanism of the development of diabetic neuropathy is non enzymatic glycosylation of proteins leads to increased thickness. Neisseria is in the nasopharynx. These changes lead to diabetic microangiopathy of endoneural arterioles. Eat contaminated food. vertigo. Its pathogenesis is related to an increased volume and pressure of endolymph in the vestibular apparatus. Menieres dz is characterized by the triad of tinnitus. Medullobalstoma symptoms: increased intracranial pressure (morning Has. Rabies travels retrograde to the DRG and then back to brain. sickle cell pts. E. Alcoholics. and meningitis in adults. and narrowing of the walls of the arteries. pneumonia meningitis. Through the blood. then into bloodstream. second only to GBS. It gets into the peripheral nerve axons by binding to ACh receptors. [968] Painful spasms with swallowing or inspiration are the reason for dysphagia in rabies. Most strains of E. Latent EBV infection is strongly assoacited with AIDS related primary CNS lymphoma. gains access to the CNS through the BBB and intiiates an inflammatory process. it spreads to the choroid plexus. Staph epidermidis is assoacited with foreign bodies (VP shunts included). and sensorineural hearing loss. Enteroviruses are the most common cause of aseptic meningitis. This constellation of findings is known as the waterhouse-friedrichson syndrome. Cryptococcus: Yeast only Thick polysaccharide capsule (virulence factor) Hydrocephalus. At this point. Listeria can resemble corneybacterium but tumbiling motility is unique to listeria. coli causing neonatal meningitis do possess this K1 antigen. otitis media. Tabes dorsalis get severe stabbing pains as well as loss of proprioception and vibration sense. Paraneoplastic syndromes occur due to the tumor cells producing substances that frequently induce an autoimmune rxn and cause damage and degeneration of healyhy organs and tissues. CNS tumors of neuronal origin frequently stain positively for synaptophysin on immunohistology. In bipolar disorder and major depression with psychotic features. since it takes SSRIs 4 weeks to kick in. Epidural – between bone and dura. To dx schizoaffective disorder. Other symptoms are GI distress. Subdural – between dura and arachnoid. Differentiating schizoaffective disorder form bipolar disorder or major depression with psychotic features requires determing the temporal relationship of psychotic sx to mood sx. Triazolam (alprazolam) short duration of action (<6 hr) Lorazepam intermediate duration of action (6-24 hr) Diazepam long duration of action (>24 hr) Flurazepam long duration of action Chlordiazepoxide long duration of action A temporary course of benzodiazepines are sometimes used during SSRI intiation if thre is a significant increase in anxiety-related problems. Oligoclonal bands of antibodies to the measles virus are found in the CSF of patients with SSPE. . anxiety. Opsoclonus-myoclonus is a paraneoplastic syndrome associated with neuroblastoma. Neoplasms of glial origin (astrocytomas. psychosis must occur in the absence of major episdoes. associated with increased number of copies of the N-myc gene. there are no psychotic symptoms. ependymomas. the psychotic sx occur exclusively during manic or depressive episodes. Loss of oligodendrocytes in MS. parinaud syndrome. Tremulousness is commonly the first symptom of alcohol w/d. The hippocampus is the area of the brain demonstrating the greatest degree of atrophy in Alzheimers dz. Schizoaffective disorder: Multiple psychotic episodes with concurrent major depressive or manic symptoms >2 weeks of delusions of hallucination in absence of mood ysmptoms Mood symptoms present for majority of total illness Major depressive or bipolar disorder with psychotic features are psychotic symptoms occur exclusively during mood episodes. neuroendocrine and neuroectodermal cells. Antibodies to the M component of the measles virus are absent. Subarachnoid – between arachnoid and pia. It is non rhythmic conjugate eye movements assoacited with myoclonus. Benzodiazepines. Delerium tremens is the most severe manifestation of alcohol withdrawal and typically begins between 2-3 days after the last drink. but mood symptoms have to be present for most of the illness. Synaptophysin is a protein found in the presynaptic vesicles of neurons. When the pts mood is euthymic. Neurologic paraneoplastic syndromes such as paraneoplsatic cerebellar degeneration are AI. and other autonomic disturbances. This tumor. agitation. and oligodendrogliomas) stain for GFAP.Orientation Comprehension Concentration Short term ememory Long term memeory Language Visual spacial Name location and current date Following multistep commands Reciting months of the year backwards Recalling three unrelated words 5 minutes later Providing the details of signgifiant life events Writing a sensible sentence containing a noun and verb Drawing a clock face Permanent memory loss and confabulation don’t come back from Wernicke korsakoffs. Germinomas are the most common tumor of the pineal gland precocious puberty. is the most common extracranial neoplasm in children. aqueductal compression leading to obstructive hydrocephalus. Fluid resuscitation with normal saline and hypertonic NaHCO3 administration are crucial in these pts. complement fixing immune complexes and resulting vasculitis. Extrapyramidal symptoms assoacited with the antipsychotics are tremor and rigidity (look like parkinsons). The pts antipsychotic dose is often increased rather than decreased. and alcohol all bind to GABAa and facilitate the inhibitor action of GABA in the CNS. especially those with unrecognized bipolar disorder. Emergent treatment of hyperpyrexia should consist of increased body heat loss (cooling) and decreasing the hypothalamic set point (antipyretics). or 1st generation antihistamines. Avoidant personality disorder is a maladaptive pattern of behavior characterized by feelings of inadequacy. rejection sensitivity. GABAa and GABAc are ion channels while GABAb receptor is linked to a GPCR. MAOis are used in atypical depression. leaden fatigue. instead give benztropine and amantadine. Opiod pain releivers are the most common OD death. Don’t use with alcohol. Benzodiazepines. All 3 compounds are active anticonvulsants. The most common side effect of diazepam is sedation so don’t give it with other CNS depressants. Serum sickness is a type III HS reaction characterized by deposition of circulating. glomerulonephritis. Atypical depression: mood reactivity. . But odn’t give DA agonists. Methadone is good for heroin addicts because it’s long half life allows for prolonged effects to suppress withdrawal symptoms in heroin dependent pts. Antidepressants can induce mania in susceptible pts. Anesthetics with high tissue solubility are characterized by large arteriovenous concentration gradients and slower onset of action. The most common cause of death in patients with TCA overdose are refractory hypotension and cardiac arrhythmias. and low serum C3 level 5-10 days after intravascular exposure to antigen. It occurs more commonly in women and often occurs after a significant life stress. arthralgias. Pts treated with antidepressants should be monitored for mood elevation and symptoms suggestive of mania that require emergency treatment. neuroleptics. increased sleep and appetite. If an inhaled anesthetic has low peripheral tissue uptake/solubility. Primidone is metabolized to phenobarbital and phenylehtylmalonamide (PEMA). Akathisia is frequently misdiagnosed because the restlessness is misinterpreted as worsening psychotic agitation. barbs. urticarial.Fantasy is an immature defense mechanism that substitutes an imaginary. Pts must wait 2 weeks after discontinuing MAOis before starting SSRI therapy allowing sufficient time for MAO regeneration. lymphadenopathy. Body temperature over 40C is called hyperpyrexia and may lead to permanent brain damage if left untreated. less disturbing view of the world to avoid awareness of painful feelings. Potent anesthetics have low MACs. Massive aggression is a way of expressing aggression towards others by passively refusing to meet their needs. Another extramyrapidal sign is inner restlessness and an inability to sit of stand in one position. and fear of rejection. The arteriorvenous concentration gradient reflects the overall tissue solubility of an anesthetic. Conversion disorder refers to the unconscious manifestation of neurologic symptoms when pathophysiological explanations for the sx cannot be found. so put in cold blanket. Associated findings include fever. then it will have a rapid onset. Facilitating body heat loss takes precedence because it is effective immediately as opposed to antipyretics which take time. The AV concentration gradient influences the rate of induction. timidity. Inhibition of fast Na channels (anti muscarinic) in cardiac myocytes (and His-Purkinje system) is thought to be the major underlying cellular event. Pralidoxime is the only medication that reverses both muscarinic and nicotinic effects of organophosphates by “restoring” cholinesterase from its bond with these substances. exacerbating the akathisia. not anesthetic potency. barbiturates. People with MG that get an exacerbation get it for 2 reasons: myasthenic crisis in which they are undertreated and they don’t have enough ACh in the synaptic cleft to compete with the autoantibodies. demonstate slower equilibrium with the brain. diaphoresis. Hemodialysis is the most effective way of acutely reducing the blood Li level. This is if the pt has too high dose of cholinesterase inhibitor and excessive ACh in the synaptic cleft. Long acting benzos (chlordiazepoxide. confusion Atropine is indicated for the treatment of rbadycardia as it decreases vagal influence on the SA and AV node. diarrhea. toxins and drugs that lead to increased PT absorption of Na (NSAIDs. The on off phenomenon is not temporary and will not self resolve spontaneously. The “on-off” phenomenon is an unpredictable and dose-independent characteristic of advanced Parkinson disease – there is no clear etiology of this phenomemom. ondansetron. The increased ACh causes excessive stimulation of the skeletal muscles and results in muscle refractory to future impulses. Nicotinic receptor – Na into the cell (and Ca). K out of the cell Lithium is exclusively excreted by the kidneys. tremor. Lorazepam and oxazepam are short acting benzodiazepines preferred in pts with advanced liver dysfunction. It may precipitate acute closed-angle glaucoma in susceptible individuals. hyperthermia. Vitamin B6 increases the pierphal metabolism of L-DOPA. A common side effect is increased intraocular pressure. ACE inhibitors) also increase Li levels and elevate the risk of Li toxicity. which increases NM transmission and provides temporary improvement of symptoms. COMPT inhibitors stop peripheral breakdown of L-DOPA and increase the L-DOPA reaching the brain. so it is best for opioid intoxication. give edrophonium (tensilon test). behavioral changes from levodopa can actually worsen with addition of carbidopa because more DA becomes available to the brain. Depressed pt with hyperreflexia and ankle clonus (with tremulesness. Drugs that cause 5HT syndrome: antidepressants. myoclonus. Adding carbidopa can reduce most of the peripheral side effects of levodopa. . Renal injury. Tryptophan is a precuroser to 5HT – so that is the AA responsible for 5HT syndrome. thiazide diuretics. agitation. rigidity. Naloxone mostly binds mu. diazepam) are generally preferred though to treat DT in alcohol w/d. tachycardia. It is an antagonist. Light microscopy shows massive centrilobular hepatic necrosis. as well as Na and K channels. Valproic acid is the drug of choice for myoclonic seizures. the “wearing off” phenomenon of Parkinson disease is due to progressive destruction of straitoniagral DA neurons over a period of time. Cholinergics bind muscarinics and endothelial cells and cause vasodilation. cramping too) = 5HT syndrome A chronically progressive pre-senile dementia with cortical atrophy but no other radiological or laboratory abnormalities permits a dx of Alzheimers. tramadol. and have longer onset times. triptans 5HT syndrome: hyperreflexia. It occurs due to direct liver injury by halothane metabolites and formation of autoantibodies against liver proteins.Dantrolene blocks ryanodine receptors and prevents release of Ca into the cytoplasm of skeletal muscle fibers. Massive hepatic necrosis is a rare but severe complication of halothane exposure. Drugs with high blood/gas partition coefficients are most soluble in the blood. IIn this case. TCAs have anticholinergic affects and will cause urinary retention. However. with filtration and resorption in the PT following sodium reabsorption. Since the NMJ becomes insensitive to ACh. an infusion of edrophonium produces no improvement. clonus. Clozapine – agranulocytosis – check blood regularly. This drug suppresses abnormal electric activity in the cortex by affecting GABA and NMDA receptors. linezolid. which decreases its effectiveness. Cholinergic crises also present with muscle weakness. ON the other hand. They can also get exacerbation from a cholinergic crisis. microcytic anemia. The Kozak consensus sequence plays a role in the initiation of translation. It helps RBCs deliver oxygen to tissues. Leftward shift of hemoglobin dissociation curve means that oxygen is less available to tissues. The blood partial pressure of O2 is a measure of O2 dissolved in the plasma and is not realted to hemoglobin function. Pyruvate kinase deficiency causes hemolytic anemia due to failure of glycolysis and resultant failure to generate sufficient ATP to maintain erythrocyte structure. Thalamssemia intermedia results in hypochromic. percent saturation is worse in CO posinoing and O2 ceontent is decreased in both CO posinoing and anemia with low Hb. Cyanide binds to . which limits DNA synthesis and promotes megaloblastosis and erythroid precuroser cell apoptosis. cytokine independent activation of STAT transcription factors. JAK2 mutations in chornic myeloproliferative disorders is a constitutively active form. Lysis of erythrocytes in hematomas causes release of hemoglobin intot he soft tissue. To see hemoglobin type. while heme in the bone marrow is generated for hemoglobin use. In CO poisoning. The conversion of 1. In this case. griseofulvin. and consequently. However. Nitrites are oxidizing agetns that are effective in the treatment of cyanide poisoning due to their ability to cause methemoglobinemia. leading to renal hypoxia. increased EPO synthesis. Heme in the liver is synethesized for CYP use.3 DPG. Phenobarbitol.3 bisphosphoglycerate (BPG) via bisphosophoglycerate mutase. Folate deficiency inhibits the formation of dTMP.3 BPG is increased in hypoxia and crhonic anemia. High oxygen affinity hemoglobins have reduced ability to release oxygen within the peripheral tissues. and compensatory erythrocytosis. Methemoglobinemia contains ferric rather than ferrous iron. If a hemoglobin molecule is dissociated. Methhemoglobinemia cuases dusky discoloration to the skin (similar to cyanosis). it can reduce erythroid precursor cell apoptosis. splenic hypertrophy results form increased work of splenic parenchyma. It is bade from 1.Hematology/Oncology Valine – non polar Glutamic acid – charged Sickling occurs under conditions of anoxia. a state of functional anemia is induced. and the heme molecule is ultaimtely degraded to bilirubin. phenytoin all can lead to acute porphyria. Signal - transduction systems: MAP-kinase pathway PI3K/Akt (PKB)/mTOR pathway Inositol phospholipid pathway cAMP pathway JAK/STAT pathway High oxygen affinity hemoglobins have a decreased P50 that is represented by a leftward shift of the oxygendissociation curve. Nitrites induce methemoglobinemia. A mutation 3 bases upstream from the start codon (AUG) in this sequence is associated with thalassemia intermedia. (Pyruvate kinase is a step in glycolysis that makes ATP).3 bPG to 2. which must remove these deformed erythrocytes from the circulation. a greenish pigment that cuases the greenish color to develop in hematomas several days after an injury. and because methemoglobin is unable to carry oxygen. use electrophoresis. including low pH and high 2. anemia (low Hb) or Polycythemia (high Hb) PO2 is always normal. the individual subunits will have a hyperbolic oxygen-dissociation curve. Because thymidine supplementation can moderately increase dTMP levels. Heme oxygenase converts heme to biliverdin. or high sensitivity to chemotherapy. It secretes direct (conjugated) conjugated bilirubin into the biliary system through active transport form an ABC protein known as MRP2 (an organic anion transporter). Prevention of tumor lysis syndrome involves hydration and the use of hypouricemic agents such as allopurinol or rasburicase. CO binds to hemoglobin with much higher affinity than O2. preventing dehydration of erythrocytes and reducing the polymerization of HbS. It binds ferroportin. In the lungs. CO poisoning does not affect the PaO2 and does not precipitate methemoglobiemia. hypocalcemia. Parvovirus is highly tropic for erythroid precursor cells and replicates in the bone marrow. TNFa is shown to induce cachexia. the binding of oxygen to hemoglobin drives the release of H and CO2 from hemoglobin (Haldane effect). a transmembrane ATP-dependent efflux pump protein that has a broad specificity for hydrophobic compounds. Env gene mutations enable espae from host neutralizing antibodies. The conjugated bilirubin is water soluble and will then be excreted in urine. If you block MRP2 you will get an isolated conjugated hyperbilirubinemia. It also reduces oxygen unloading from hemoglobin in the tissues. It is characterized by hyperphosphatemia. It induces paraneoplastic cachexia by suppressing appetite. abnormal mitoses and giant tumor cells. while diminished iron levels and hypoxia decrease hepcidin levels.ferric iron more avidly than to mitochondrial cytochrome enzymes. erythrocyte P antigen and parvovirus B19. You should monitor CBC for 3 months on ticlopidine. [1457] Tumor lysis syndrome can develop during chemotherapy for cancers with rapid cell turnover (poorly differentiated lymphomas and leukemias). CD4 and HIV gp120. causing it to be internalized and degraded. hyperkalemia. The 15. Radiation = double stranded DNA breaks and free oxygen radical damage Anaplastic tumors are composed of pleomorphic cells with large. and hyperuricemia. substantial tumor burden. The calcium-dependent (Gardos) K-channel regulates the transport of K and water throught he red blood cell membrane – when blocked. Type O mothers have antibodies that are predominately IgG and can cross the pplacenta – A and B are IGM Neutropenia with ticlopidine presents with fever and mouth ulcers.17 translocation in AML M3 is the PML/RARalpha retinoic acid fusion gene. hyperchromatic nuclei that grow in a disorganized fashion. high concentrations of CO2 and H facilitate oxygen unloading from hemoglobin (bohr effect). In the peripheral tissues. inhibiting lipoprotein lipase and increase insulin resistance of peripheral tissues. Yeasts and pseudohyphae and a positive germ tube test are diagnostic of candida infection. K and water efflux is reduced. Hepcidin is an acute phase reactant synthesized in the liver hepatocytes. AML M2 is t(8. This decreases absoalteral iron transport in the intestine and also inhibits the release of iron by macrophages. The human multidrug resistance (MDR1) gene codes for P-glycoprotein. Anaplastic tumors may also contain numerous. Preventing intracellular dehydration is a treatment modality for sickle cell anemia using Gardos channel blockers. Liver takes up unconjugated bilirubin through a passive organic anion transporting polypeptide (OATP). This protein can both reduce the . [1386] Dysphagia and spoon nails are specific for iron deficiency anemia. Heparin and drugs that directly inhibit thrombin formation can prolong Thrombin Time (TT). CD21 and EBV gp350.21) M3 – acute promyelocytic leukemia Pol gene mutations are responsible for acquired resistance to HIV reverse transcriptase inhibitors and HIV protease inhibitors. thus preventing oxygen binding to hemoglobin. High iron levels and inflammatory conditions increase the synthesis of hepcidin. which saves these mitochondrial enzymes from cyanides toxic effects. High grade tumors display cellular and ncuelar pleomorphism (variations in shape and size) and a high number of mitoses.influx of drugs into the cytosol and can increase efflux from the cytosol. They peak around 1 week after therapy. the rate of effective erythropoiesis increases immediately and immature erythrocyts are released from the bone marrow into the bloodstream. Benign lymph node enlargement in response to antigenic stimulation is assoacited with a polyclonal proliferation of lymphocytes. Auer rods stain for peroxidase. These 2 tumors can be differenetiated on brain imaging. Individual susceptibility to chemical carcinogens depends on the activity of these CYP enzymes. It is a thymidine analog. once you add B12. CDK 4 Cyclin E. Metalloproteases are zinc containing enzymes. Integrin mediated adhesion of cells to basement membrane and the ECM involves the binding of integrins to fibronectin. Cyclin D. High uptake suggests large numbers of cells in S phase and then high grade and poor prognosis. it doesn’t met. These pro carcinogens are converted into active metabolites by the cytochrome P450 oxidase system. Peau in peau d’orange means pitting. N5-fomryl-tetrahydrogolate = folinic acid. A cerebellar tumor iina child is most likely a pilocytic astrocytoma or a medulloblastoma. Nucleotide uptake is therefore high in the S phase of the cell cycle. and parvo B19 virus. which is genetically determined. Most chemical carcinogens enter the body in an inactive state (pro-carcinogens). Tumor penetration of the wall is the major determinant of prognosis. while medulloblastomas are always solid. In a vit B12 def pt. A monoclonal lymphocytic proliferation is strong evidence of malignancy. Gastric cancer rates drop cimilar to lung cancer rates in women rise. This is seen in SS dz and others. Pure RBC aplasia is a rare form of marrow failure characterized by severe hypoplasia of marrow erythroid elements in the setting of normal granulopoiesis and thrombopoiesis. and collagen. So if you see pitting. thereby preventing the action of chemotherapeutic agents. ARP (attributable risk percent) is ARP = (RR-1)/RR ID: 1284 HER2/neu is a 185 kD transmembrane glycoprotein that has intracellular tyrosine kinase activity aand is a member of the family of epidermal growth factor receptors. We use uptake of bromodeoxyuridine as a measure. The CYPs make the free radicals of carbon tetrachloride. Patients with chronic hemolytic anemia are predisposed to folic acid deficiency and macrocytic changes due to increased erythrocyte turnover. This is true for colon cancer too. lymphocytic leukemias. Pure RBC aplasia is assoacited with thymoma. The laminin in basement membranes may post a physical barrier to the sproudting of new BVs in angiogenesis in neoplastic and granulation tissue induced by VEGF and FGF. Staging/grading by brain tumors is challenging because size doesn’t matter much if its in a bad location. laminin. Overexpression of this protein is associated with increased rates of breast and ovarian cancer. think lymphatic obstruction. leucovorin (can overcome MTX with these) Tumor invasiveness is the biggest prognostic factor in bladder cancer. Pilocytic astrocytomas have both cystic and solid components. This is stage. . CDK 6 Acrolein is the toxic metabolite that causes hemorrhagic cystitis with cyclophosphamide. and grading doesn’t work well. Sickle cell trait RBCs will sickle when SODIUM METABISULFITE is added. and malabsorption syndromes. weakness. and thrombocytopenia. dysphagia. or bacterial overgrowth. Polycythemia vera presentation (ID: 8591): frequent headaches. A pt with signs of renal failure and toe gangrene or livedo reticularis following an invasive vascular procedure likely has atheroembolic renal dz. Pancytopenia in SLE is AI type II HS (ABs against blood cells). Respiratory Umbilical vein ductus venosus IVC . Abnormal bleeding in pts with uremia (kidney failure and on dialysis) is due to a qualitative disorder with normal platelet count. Reticulocytes contain bluish cytoplasm and reticular precipitates of residual rRNA. microangiopathic hemolytic anemia. Blood loss (especially in the GI tract) must be ruled out in a pt with iron-defieincy anemia. PT. Plethora and ruddiness of the face and moderate splenomegaly. TTP occurs in adults with predominant neurologic symptoms. Pt with hypochromic. HUS in children with renal invovelemnt. excessive sweating. T cell ALL is less common (20% of all ALL) and presents as a medistinal mass that can cause respiratory symptoms. Total iron binding capacity (TIBC) reflects increased serum transferrin. Factor VIII is synthesized by the liver and stored in endothelial cells. Pigmented gallstones are a complication of any hemolytic anemia. and PTT. microcytic anemia is most commonly due to iron deficiency. high reticulocyte count Dx of AML requires >20% myeloblasts. Blast cells in the peripheral blood are strongly suggestive of leukemia. Light microscopy shows cholesterol emboli obstructing renal arterioles. To distinguish between aplastic anemia and myeolorpoliferative dz that can cause pancytopenia. bone marrow bx is required. dizziness. ID: 1109 Increased bone marrow erythropoiesis (following iron replacement in an iron deficiency anemia) results in an accelerated release of immature RBCs (reticulocytes) into the blood. G6PD defieicny exacerbation: dark urine.The schilling test helps to differeneitate between dietary deficiency of B12. or SVC syndrome. pernicious anemia. HUS presents in young children as acute renal failure. Low absorption of cobalamin not correctable by intrinsic factor is indicative of a malabsorption syndrome such as ileal dz. reticulate counts. Characteristic laboratory abnormalities include decreased RBC count. pancreatic insufficiency. Steroid use increases RBC production. Only the bleeding time is prolonged. and BUN and Cr. ALL is the most common malignancy in childhood. It is used to treat mild to moderate hemophilia A. High crit and Hb. Sickle trait patients usually have normal peripheral smears and indices. LDH. Desmopressin acetate is a synthetic vasopressin analog that released vW factor and factor VIII from the endothelium. hematocrit and platelet count and increased bleed time. anemia. and MCHC values. including hereditary spherocytosis. The RA makes up the majority of the right border of the heart on PA chest films. INH inhibits mycolic acid synthesis. elastase release from infiltrating neutrophils and macrophages is balanced by the antielastase activity of serum A1AT. Eosinophils release major basic protein. and is in contact with the central tendon of the diaphgram. Kussmaul breathing is in DKA Aspergillus does not invade lung tissue. the intrapleural pressure is -5 cm H20. Mycolic acid is a long branched chain saturated FA used in the mycobacterial cell wall and in the formation of virulence factors. Type IV HS reactions take days to reach their peak activity. The steroncostal (anterior) surface of the heart is formed by the RV. paranasal sinuses. Cheyne stokes respiration describes cyclic breathing in which apnea is followed by gradually increasing tidal volumes and then gradually decreasing tidal volumes untilt he next apneic period. but grows inside the cavity forming a “fungus ball” or aspergilloma. a protent anti-helminthic toxin capable of causing damage to epithelial and endothelial cells. In the respiratory tract. The characteristic pathologic lesion consists of granulomatous ifnlmmation and caseous necrosis. It is commonly seen in advanced heart failure. Medium sized bronchi are responsible for the most airway resistance. Stratified squamous epithelium is found only in the oropharynx. It gets to -7. Elastase is a neutral protease contained in macrophage lysosomes and in the large. and tracheobronchial tree are lined with pseudostratified columnar. upper half of the posterior epiglottis. mucus-secreting epithelium. This condition may be asymptomatic or it may cause hemoptysis. The tissue destruction caused yb MTB infection is the direct result of host immune activation and inflammation through a type IV HS reaction. It is responsible for the acid fast-ness of MTB. it identifies the resting state where the airway pressure equals zero. azurphil granules of neutrophils. terminal bronchioles is the least. the nose. which cause clinical effects within minutes of antigen exposure. Hypoxic vasoconstriction – increase arteriolar resistance increases as the blood oxygen decreases – occurs in the pulmonary circulation so that blood flow is diverted away from underventilated regions of the lung and towards more well-ventilated areas. Lower border of the pleura Right Left *Lower border of lung is 2 Midclavicular line Midaxillary line 7th rib Upper border of 10th rib th 7 rib Lower border of 10th rib spaces above the end of the pleura Paravertebral line 12th rib 12th rib The process of bicarb diffusing out of a RBC and chloride diffusing in to maintain electroneutrality is called chloride shift. It will appear as a radiopaque structure that shifts when the pt changes position. The posterior surface of the ehart is formed mainly by the LA. nasopharynx.Phosphatdiylcholine (Lecithin) and phosphotidylglycerol are major constituents of surfactant. The center of the airway pressure volume curve is the FRC of the lungs. laryngopharynx. The diaphagmantic (inferior) surface is formed by the left and right ventricles. Excess elastase activity in lung acini is thought to be a major factor in the development of centriacinar and panacinar emphysema.5 in inspiration. At the FRC. anterior epiglottis. It is the reason why high RBC chloride content in venous blood. Normally. The apex of the heart lies behind the 5th left intercostal space at the left midclavicular line (LV). The RV forms the anterior wall of the heart and is best seen on lateral CXR. and vocal folds (true cords). The SVC and IVC compose the superior and inferior borders of the cardiac silhouette on the right side. Delayed type hypersensitivity reactions are Th1 lymphocytes that release IFN-g to cause recruitment and stimulation of macrophages. The apex of each lung extends into the neck approximately 3-4 cm above the first rib. . Sphingomyelin stays about constant os the L:S ratio at the end should be 2:1. this is in contrast to the other HS reactions. With excessive Na loss. It is an organism with no peptidoglycan cell wall. pulmonary edema. ZDV) during pregnancy and then IV at brith and then the baby should get it for 6 months post-brith as well. dz that cause high airlow resistance (asthma. confusion. Think legionella of pneumonia. and when the body mounts a response against these antigens. Symptoms frequently include high fever. Sweat is initially isotonic. Mycoplasma lack peptidoglycan cell walls and are resistant thereafore. The ABs cauisn this RBC destruction re referred to as cold agglutinins. The pneumoconiosis are diseases that result from the inhalation of fine dust particles. you know the peptidoglycan cell wall must have been disrupted byt eh ABX so that the osmotic forces destroyed the bacteria. (2116). If the 2 components are summated and the total work is plotted against respiratory frequency. this is 15 breaths per minutes. If a gram + bug treated with an antibiotic is then placed in a hypotonic solution and lyses. Continued proliferation eventually kilsl the macrophage and causes cellular lysis. Eosinophils are recruited and activated yb IL-5 secreted by Th2 helper T cells in asthma. ARDS). Peptidoglycan cell wall protects form osmotic forces. causing bronchiolitis obliterans. meningitidis – it is used in combination therapy for MTB and leprosy. and vancomycin. and diarrhea. so that at the end. necrosis. For pts with stiff lungs (increased elastic resistance). and sputum gram stain shows many neutrophils but few or no organisms. sweat is hypotonic. The most common laboratory abnormality is hyponatremia. allowing MTB to be phagocytozied by and infect additional macrophages. there will be an optimal breathing rate at which the total work of breathing is minimized.Dust particles smaller than 2 microns in size reach the alveoli. leading to lung collapse. fever. carabpenems. They are taken up by macrophages and sitmulate CT growth. Virulence factors expressed by the MTB promote the recruitment of additional native. Characteristic findings on CXR include unilateral pulmonary opacification and deviation of the mediastinum toward the opacified lung. and GI symptoms (maybe confusion and CNS too). and fibrosis of the bronchiolar wall occur. Chronic rejection is a major problem in lung transplant recipients. This occurs 2-4 weeks following initial infection. COPD). The work done against the elastic resistance of the lung is increased when tidal volume is increased. An obstructive lesion in a maintstem bronchus can prevent ventilation of an entire lung. Lymphocytic inflammation. Then CFTR helps reabsorb Cl (and Na follows). pts breathe at a lower rate (slow. Therefore. while the workd one aginst airflow resistance is increased when the breathing frequency is increased. Restrictive lung dz has increased expiratory flow rates due to decreased lung compliance (increased elastic recoil) and increased radial traction exerted on the conducting airways by the fibrotic lung. cephalosporins. IN contrast. For the normal adult. it only has a phospholipid bilayer cell membrane. Mycoplasma infections can be treated with antiribosomal agents like tetracycline and erythromycin. After the immune system is not longer activated (when the bacteria is cleared) the concentration of the antibodies decreases and the anemia resolves spontaneously. to agents that attack the peptidoglycan cell wall such as penicllins. The MTB are phagocytosed by alveolar macrophages (the small ones that make it down there) and the sulfatide virulence factor expressed by MTB allows for intracellular bacterial proliferation. Factulative intracellular gram negative bacilli that can cause a systemic infection. . Ultimately. Rifampin is used as monotherapy prophylaxis for HiB and N. deep rbeaths) in order to mimize the work of breathing. rapid and shallow breaths are facored in diseases that increase elastic resistance (pulmonary fibrosis. CF pts can get hypovolemia and intravascular volume contraction if they sweat too muchc. Eventually antigen carrying macrophages or dendritic cells migrate to the lymph nodes and induce a helper T cell response. HIV+ women should be given zidovudine (AZT. Mycoplasma pneumonia is the causative agent of walking pneumonia and many cases of tracheobronchitis. inactivated macrophages and also undermine the immunologic intracellular signaling between antigen present cells and helper T cells. the work of breathing is minimized when the respiratory rate is high and the tidal volume is low. It shares antigens with human erythrocytes. It affects small airways. there is occlusion fo the bronchiolar lumen. it also lyses red blood cells leading to anemia. cough. Cromolyn and nedocromil are mast cell stbalizing agents. M pneumo also causes SJS and joint poins. Legionella shows neutrophils but no organisms. firm lobe (liver like consistency) o Alveolar exudate contains erythrocytes. In such pts. in turn. It can assist pts with cessation of tobacco use by reducing withdrawal cravings and attenuating the rewarding effects of nicotine. PaO2 below 80 is called hypoxemia. causes cor pulmonale and symptoms of right heart failure (dyspnea on exertion.Dimorphic fungi: sporothrix. HSM). paracoccidio SaO2<92% (PaO2<65) can cause secondary polycythemia. Varenciline is a partial agonist of nicotinic ACh receptors. High A-a gradient will be: V/Q mismatch. Blood PO2 nromally reaches the PAO2 by the time it passes through the first third of the alveolar capillaries due to high rate of O2 diffusion through the respiratory membrane. Lobar pneumonia is in 4 stage: Congestion (day 1) o Red. Then you have to look at the A-a gradient to see the reason. MC benign lung tumor is a hamartoma. Nocardia is also catalase positive. respiration is stimulated by hypoxia (low PaO2) sensed by peripheral chemoreceptors. Pts with COPD usually have a low PO2 (hypoxia) and high PCO2 (hypercapnea). Diffusion barrier (fibrosis). heavy and boggy lobe o Vascular dilatation. Use a spacer and learn to rinse the mouth. alveolar exudate contains neturophils and fibrin Resolution o Enzymatic digestion of the exudate The normal PAO2 is 104. It decreases cerebral vascular resistance leading to increased cerebral perfusion and increase ICP. Incoming systemic venous blood as a PO2 of 40. The azoles (not just ketoconazole) inhibit the CYPs. LE edema. high PaCO2 ceases to sitmulate the respiratory drive. and fibrin Gray hepatization (day 4-6) o Gray brown firm lobe o RBCs disintegrate. This uncommon tumor occurs in nonsmokers and arises form alveolar epithelium. In prolonged hypercapnea. The live virus is prevented from entering cells via receptor mediated endocytosis. these ABs interfere with the bidnign fo the HA to the sialic acid conitaining oligosaccharides of hose cell plasma membrane glycoprotein receptors. An accentuated pulmonary component of the second heart sound suggests an increase in pulmonary artery pressure and PAH. R to L shunt. an essential component of the fungal cell wall. PaCO2 is the major stimulator of respiration in healhy people. Pulmonary alveolar proteinosis present with gradual worsening of dyspnea and productive cough. pCO2 is the most potent cerebral vasodilator. Echinocandins are a newer group of antifungal mediations that inhibit synthesis of the polysaccharide glucan. Rapid increases in the fraction of inspired oxygen may lead to respiratory failure in these pts. Central cehmoreceptors in the medulla are indirectly sensitive to changes in PaCo2 and direcyl sensitive to changes in pH. It is located in the peripheral parts of the lung and is often multifocal. blasto. hwoever. their cerebral circulation is most likely to be increased. coccidio. On . neutrophils. Thus. Even a lsight increase in PaCO2 results in increased pulmonary ventilation. Normal A-a gradient will be: high altitude (low air O2) or hypoventilation. alveolar exudate contains mostly bacteria Red hepatization (day 2-3) o Red. The most common side effect of inhaled glucocorticoids is oropharyngeal candidiasis. histo. On histologic examination there is bilateral patchy pulmonary opacification due to intraalveolar accumulation of amorphous protein and phospholipid material (constituents of surfactant). Post op = PE (not sedative for pain). These receptors are not sensitive to PaO2. Bronchoalviolar carincoma is a subtype of lung adenocarcinoma. Influenza vaccine is thought to prevent serious cases of the flu by increasing the host circulating antibodies against the hemagglutinin of the selected viral strains. Upon subsequent exposure to live virus. pneumo. and a worsened V/Q mismatch. The presence of fluid in the pulmonary interstitium decreases lung compliance. Every time GFR halves. diuretic use. as well as capsular strains other than type B. Nontypable strains of H. S. Now it goes into the metabolic acidosis. (like in CHF leading pulmonary edema). and urinary pH decreases. sinusitis. TNF alpha (and IFNgamma according to FA) mediate systemic inflammatory response and stimulate hepatic secretion of acute-phase proteins (fibrinogen). Tissue damage and resultant abscess formation is primarily caused by lysosomal enzyme release from neutrophils and macrophages. the pulmonary capillary wedge pressure is normal. Tryptase is specific to mast cells and is used as a marker. aureus. the pulmonary capillary wedge pressure is normal. It may be mixed. COPD can cause hypoxia sufficient to stimulate increased EPO production by the cortical cells of the kidney. serum Cr doubles. but can cause otitis media. IL-6. Acid excretion in urine occurs in the form of free hydrogen ions and titratable acids (NH4 or H2PO4). columnar cells that line the alveolar septa without evidence of vascular or stromal invasion. ID: 1620 Cord factor is 2 mycolic acid molecules bound to the disaccharide trehalose. Hypocapnia causes cerebral vasocontrsitction and decreased cerebral blood flow. In noncardiogenic pulmonary edema (ARDS). Salicylates 4-5 hours after ingestion is not acute any longer. so no respiratory alkalosis. They are part of the normal flora of the upper respiratory tract. Concurrent use with NSAIDs and furosemide decrease furosemide diuretic action because it also indeces PGs which helps with blood flow and drug delivery to the kidney. The three cytokines IL1. It is a mycoside. They have a decrease in lung compliance. and synaptophysin. Lung apex = superior sulcus. excretion of free H+ and titratable acids increases. In diabetic ketoacidosis. . Mast cells release histamine and tryptase. Pyraziniamide is not active against extracellular MTB because it needs the acid in the macrophage phagolysosome. flu The green discoloration of pus or sputum noted during bacterial ifnections is associated with the release of MPO from neutrophil azuophilic granules. an increase in the work of breathing. Panic attacks are assoacited with hyperventilation and decreased PCO2. is not conffered by vaccination with the Hib vaccine. Immunity to nontypable strains. During metabolic acidosis. MPO is a heme containing pigmented molecule. and H. influenza that do not form an antiphagocytic capsule. Measuring the urinary chloride concentration and determining the pts volume status helps to identify the cause of metabolic alkalosis. Neuroendocrine cancers are positive for neuroendocrine markers such as neuron specific enolase. It is an exponential looking curve. chromogranin. PaO2 declines to 60. NG suction. there will be high H2PO4 to buffer the acid. Give good hydration with acyclovir to prevent crystalline nephropathy. The pathogens most often responsible for secondary bacterial pneumonia are: S. influenza are strains of H. At high altitude. excretion of bicarb decreases.microscopic examination it is composed of tall. Metabolic alkalosis is most commonly caused yb vomiting. hyperaldosteronism. This is small cell carcinoma and bronchial carcinoid. and bronchitis. In a pt with ARDS. NSAID assoacited chornic renal injury is morphologically characterized by papillary necrosis and chronic interstitial nephritis. The distal tip of the 12th rib can be displaced into the retroperitoneum when fractured. This is goodpasture syndrome. As the blood concentration of PAH increases. When levels exceed the reabsorptive capacity of the tubules. Metbaolic acidosis is normally partially compensated for by a respiratoyr alkalsosis. NSAIDs-assoacited nephropathy is common. Allergic asthma is the most common type (animal dander). Glomerular and vascular abnormalities. These casts impede renal function (obstruct lumens. The increase in urea reabsorption corresponds to a decrease in the frational excretion of urea and a decrease in renal clearance of urea from plasma. Renal vein thrombosis is a complication of nephrotic syndrome and presents with flank pain. The filtration of PAH is not a process that can be saturated. HSP is a leukocytoclastic vasculitis. and at this level. Also increased membrane permeability. especially in patients suffering from chronic pain. compress epithelium). (1979) Vasopressin produces a V2 receptor mediated increase in permability to water and urea at the luminal membrane of the inner medullary collecting duct. and liver transplants. which is useful in the treatment of acute rejection in pts with kidney.The late distal and cortical collecting tubules are the primary sites for regulation of K concentration in the urine. At any given blood concentration. Mediastinal masses cause SVC syndrome. Digoxin is renally excreted and must be reduced dosage in the elderly. IGA mediated HS. This is from nephrotoxicity. These toxicities can result in symptomatic hypocalcemia and hypomagnesemia. principal cells secrete K under conditions of normal or increased K load. lacterating the left kidney. these light chains precipitate with Tamm Horsfall protein and form eosinophilic casts. hematuria. Severe hypokalemia and hypomagnesemia are commonly seen during therapy with amphoterrible B. found in the glomerular BM. heart. Consider MM when an elderly pt present with the following findings: Easy fatigability Constipation (due to hypercalcemia) Bone pain – most commonly in the back and ribs Renal failure Bence jones proteins are filtered by the glomerulus in small amounts and then are reabsorbed in the tubules. and left sided varicoclele. This maximum secretion corresponds with the transport maximum of the secretion enzymes. Decreases GFR and direct toxic effects on the tubular epithelium. the patient has superimposed degree of respiratory acidosis and failure. Minimal change is a selective proteinuria – you just lose albumin and transferrin (the low molecular weight) proteins. 11th and 12th ribs are floating ribs. the secretion of PAH by proximal tubular epithelial cells increases – but only up to a maximum value of 80mg/min. secretion plateaus and any increase in the urine PAH concentration are due to increased filtration. K depletion stimulates alpha interacalated cells to reabsorb extra K. are usually mild or may be seen only in advanced stages. When the steady state PaCO2 persists above the range given by winter’s formula. Anti GBM antibodies react with the alpha3 chain of collagen type IV. 55% of urea is normally absorbed. They also cause atrophy. . Spironolactone reduces mortaility in heart failure pts. Murobonab (OKT3) is an Anti-CD3 anitbody that inhibits T lymphocytes. a constant portion of PAH will be filtered from the glomerular capillaries into BS. Possibly from decreased ventricular remodeling. Secretion of PAH is a carrier enzyme mediated process and therefore is able to be saturated. Foscarnet is an analog of pyrophosphage that can chelate calcium and promote nephrotoxic renal magnesium wasting. if present. Then water. Aflatoxin messes up p53. Crohns gets gallstones because the terminal ileium is affected. ID: 8587 ID: 102 Gastrointestinal The liver has glycerol kinase to make glycerol into DHAP. Black stones from hemolysis are from unconjugated bilirubin increases. or recent repiratory infection. VIP increases intestinal chloride loss in the stool. entomeaba histolytica and giardia is needed. Intestinal carcinoma of the stomach projects into the lumen of the stomach. ID: 1716 The Sabin live attenuated polio virus is good at making IgA in the oral mucosa. Person with history of generalized atherosclerosis and epigastric pain post prandially that does not respond to antacids = chronic mesenteric ischemia. so gastrin is left unchekd. which leads to malabsorption of fat. The unreabsorbed fat then binds calcium in the GI tract. Na. gluconeogenesis. Glutamate then is released at the synapse. C dif diagnosis by detecting toxin genes in stool via PCR. Prolonged PT and albumin level is the worst indicator of liver function. Opioid analgesics can cause sphincter of Odi contraction and spasm leading to biliary colic and RUQ pain. diffuse carcinoma fo the stomach is within the stomach wall. We excrete old ceruloplasmin (alpha 2 microglobulin made form copper) and excess copper in the bile and stool. Low cAMP leads to low CAP-DNA binding. Few shigella. Crohns get oxalate stones because: they can’t reabsorb their bile. Now it isn’t. It lives well in acid. Aspirin can help decrease risk. UC associated CRC is early p53 mutations and late APC mutations. which decreases cAMP. Calcium is normally bound to oxalate. . H pylori leads to ulcers because it reduces the number of antral somatostatin releasing cells. It uses it for triglyceride synthesis. Apoptosis in hepatitis is around councilman bodies. they can’t reabsorb their bile salts. The extendend and duration of colitis is the biggest determinant. PT time will be up. Inhaled anesthetics such as halothane are associated with fulminant hepatitis. and K follow. This accumulation of glutamine in the astrocyte leads to cellular swelling and dysfunction.MCD can be from an atopic problem. immunizations. which upltimately results in low gene expression of the structural genes of the lac operon. H pylori is found in greatest amounts in the prepyloric area of the gastric antrum. Excess is reabsorbed by the astrocyte and converted to glutamine. and oxalate is freely absorbed (it suually is unabsorbale bound to calcium). Glucose decreases adenylate cyclase. AST will be elevated and eosinophilia. Cox-2 increases risk of adenomatous polyp formation int eh colon. glycolysis. Liver is only organ with glycerol kinase. It is post prandial pain out of proportion to exam findings. and the cholesterol precipitates. We don’t have an HCV virus because it the envelope proteins keep mutating. The reabsorbed oxalate leads to stones. Excess ammonia combines with alpha-KG to make glutamate. They are multifocal in nature. If heart sounds are only heard at first during expiration. In order it goes: brain. It is usually undetectable in tissues unless inflammation induces it. In a pt with severe aortic stenosis and subsequent LVH. kidney. The aortic isthmus (conncetion between arch and descending) is the most common cause of traumatic aortic injury. Pulsus peroxus can happen in severe obstructive pulmonary disease such as asthma. Isolated systolic HTN is caused by age-realted decreases in the compliance of the aorta and its proximal major branches. If there is a-fib. QRS is still narrow since ventricular depoarlization proceeds normally. Cardiology/Vessels/Endocrine Daptomycin is a lipopeptide ABX that is used for MRSA. impulses are coming from the AV node. LV filling is dependent significantly on atrial contraction to get the blood into the hypertrophied ventricle. liver. isolated systolic HTN becomes common. mononuclear cell infiltrates. The adaptation to volume overload is eccentric hypertrophy (chamber dilation due to increased end diastolic volume) with predominantly ‘in series’ synthesis of new mycocardial sarcomeres. The major long term hemodynamic compensatory response to the volume overload of AR includes an increase in left ventricular preload (LV EDV) in associated with eccentric LVH. involves ‘in parallel’ dposition of new sarcomeres. The ‘a’ wave on jugular venous tracing is absent in pts with a-fib. . ID: 402 Cholera is very acid labile. Third degree AV block. Numerous alterations in vessel wall structure and function. This can also lead to increased LA pressure leading to acute pulmonary edema. and the LA is no longer contracting properly to fill the LV. CD34 is also an endothelial cell marker as is vW factor. no bx is necessary for dx. ballooning degeneration. A PCWP higher than the LV EDP means that there is something impeding flow (MS) between the LA and LV COX-2 has a MW of 72kD. ID: 1625 Liver can tolerate arterial occlusion better than other organs because it has dual blood supply. and Councilman bodies are seen. then the LV will have reduced preload to the point where systemic hypotension occurs. It is where the left subclavian comes off. and protein synthesis. and any drug that decreases acidity will increase chance of cholera infection (omeprazole). Systolic blood pressure greater than 160 with a diastolic BP below 90 is found in 20% of pts over 80.Appendicitis is caused by an obstruction of the lumen. It causes depolarization of bacterial cellular membrane and inhibition of DNA. have been porposed to explain this stiffening. There is first an intiaiton phase (which transpires within the mitochondria of dead or dying cells) and propagation (which can eventually perforate the cell membrane from within). Beta drenergic agonists control acute asthma exacerrbations by causing bronchial smooth muscle relaxation via increased incracellular cAMP. the response to pressure overload. The HbSAg of hep B must coat the HDAg of hep D before it can infect hepatocytes and multiply. Concentric hypertrophy. spleen. This restricts venous outflow. think about pulsus peridoxus. Dystrophic calcification is a hallmark of preceding cell injury and necrosis (even in heart valves). Mucus then can’t flow out of the appendix and there is a dilation of the appendix. myocardium. including atherosclerotic changes. resulting in hypoxia which causing ischemia and associated bacterial invasion. For HIV. It beats at 45-55 beats per minute. Pressure overload may occur to stenosis or systemic HTN. Pregnant women or on oral contraceptives get cholesterol gallstones because estrogen increases cholesterol secretion and progesterone reduces gallbladder motility. which produces net ventricular wall thciking and a reduction in ventricular chamber size (decreased EDV). Daptomycin is associated with increased CPK (creatinine phosphokinase) and increased risk of myopathy. RNA. After the age of 50. CD31 is PECAM1 which is an endothelial cell marker. In all cases of acute viral hepatitis. Familial hyperchoelsteroemia is HEPATOCYTE underexpression of LDL receptors. A washout (no treatment) period is often added between treatment intervals to limit the confounding effects of prior treatment. In a crossover study. This calcium efflux is necessary for relaxation. The beta subunits contain TK domains. epidermidis. This segmental thrombosing vasculitis often extends into contiguous veins and enrves. TNF alpha is a proinflammatory that induces insulin resistance through the activation of serine kianses. Glucagon does gluconeogenesis in the liver. which can be eliminated by preload reduction and reduced by afterload reduction. Treatment of coagulase-negative staph infection involves initial empric treatment with vancomycin with or without rifampin or gentamicin due to the widespread antibiotic resistance of S. Reactive changes in the pulmonary vasculature (endothelial dysfunction resulting in further vasoconstriction) also contribute to pulmonary HTN. Phosphorylation of threonine residues has similar effects. relieved by leaning forwards. especially in nosocomial infections. It is associated with HS to intradermal injections of tobacco extracts. Nitroglycerine reduces myocardial oxygen consumption. Nitroglycerine causes venous pooling. Downstream signaling is initiated. Phosphorylation of serine residues in the beta subunit of insulin receptors also hinders downstream signaling. which then result in phosphorylation of the IRS-1 serine residues. and is used for treating angina pectoris. and intracellular FFAs are suspected of increasing serine kinase activity as well. Pain of pericarditis is sharp and pleuritic. glucagon has an insignificant effect on skeletal muscle cells and adipocytes. Unlike epinephrine. The resulting chronic venous insufficiency causes stasis dermatitis. The CaATPase pump uses active transport to sequester calcium within the SR and ressstablish the ion gradient. Dilation of the LV in response to increased preload can result in functional MR. resulting in resistance to the normal actions of insulin. gulcocorticoids. The alpha subunits are extracellular and provide the bidning site for snsulin. Romano-ward and Jervell and Lange-Nielsen syndrome are thought to result from mutations in a K channel protein that contributes to the delayed rectifier current (I k) of the cardiac action potential. encasing them in fibrous tissue. started by the autophosphorylation fo the insulin receptor. The sarcolemmal Na/Ca transmembrane protein does not require ATP and accepts 3 extracellular Na ions in exchange for one intracellular Ca ion. which manifests as erythema and scaling with progressive dermal fibrosis and hyperpigmentation. It occurs most commonly in type I DM. Catecholamines.Treatment with statins causes hepatocytes to increase their LDL receptor density as a means of increasing their uptake of circulating LDL Amiodarone does not predispose to Torsades like the other 1As and IIIs. This leads to venous stasis/congestion. Thromboembolism is a very infrequent complication of varicose veins. NE is greater influence on alpha and beta 1. Varicose veins are dilated. Exopthalmous does not improve with beta blocker therapy. leading to reflex tachycardia. Less on beta 2. while venous stasis ulcers are very common and often occur over the medial malleolus. . DKA presents as volume depletion (hypotension and tachycardia) with ketones and glucose in the urine. Beurgers dz is usually seen among heavy cigarette smokers with onset before age 35. subjects are randomly allocated to a sequence of 2 or more treatments given consecutively. A urine osmolality increase above 50% suggests complete central DI. This inhibits IRS-1 tyrosine phosphorylation by insulin. It is exacertbated by swallowing. LV dysfunction can lead to increased pulmonary arterial pressure due to reactive vasoconstriction secondary to pulmonary venous congestion. More than a 10% increase in urine osmolality following administration of vasopressin during a water deprivation test suggests CDI. tortuous veins resulting from impairment of the venous valves and reflux of venous blood. and increased incidence of superficial venous thrombosis. and glucagon can also induce insulin resistance by this same mechanism. edema. Regular insulin is preferred for the acute treatment of DKA. The IR is a tetrameric structure consisting of 2 alpha and 2 beta subunits. Nuclear receptors: thyroid. Prolonged ACTHstimulation casues hyperplasia of the fasciculate and reticularis. predominantly mediated by reactive smooth muscle cells that migrate from the media to the intima. effectively preventing disease. and eyelids and patients can also experience laryngeial edema and difficulty breathing. FAs Treatment of CAH involves low dose exogenous corticosteroids to suppress excessive ACTH secretion and reduce stimulation of the adrenal cortex. Iliohypogastric nerve is derived from T12/L1 and courses in that dermatome to innervate the ksin overlying the iliac crests. Adenosine and dipyridamole are selective vasodilators of coronary vessels that can cause coronary steal. pheynalanine. and as a granular. Finasteride causes a discordant decrease in DHT level.Carotid sinus is acutally part of the internal carotid. retinoids.s. . Reproductive ILioinguinal. Angioedema most commonly involves swelling of the tongue. When the hypercoagulability is the result of the procoagulant effects of circulating products of cancer. The pathogenesis of nonbacterial thrombotic endocarditis (NBTE) often involves a hypercoagulable state. PPAR. methionine. salt and pepper appearance of the calvarium. The pathophysiology of NBTE is similar to that of Trousseau’s syndrome – which may also by induced by disseminated cancers. and genitofemoral blockade would provide complete perineal and genital anesthesia. IGF-1 causes bone growth by stimulating the proliferation of cartilage in bone cells. Combineduse of non dihydropyridine calcium cahnnel blockers and beta blockers can have additive chronotopic effects yielding severe bradycardia and hypotension. isoleucine Subperiosteal thinning is a characteristic feature of hyperparathyroidism. Hydrophobic = valine. this thinning appears as subperiosteal erosions in the medial sides of the second and third phalances of the head. alanine. whereas the glomerulosa is primarily regulated by ATII. the resulting cardiac valve vegetations may also be called amrantic endocarditis. pudendal. resulting in excessive cortisol production (cushing syndrome). GH increases growth through production of IGF-1 from the liver. Immunization with diphtheria toxoid induces production of circulating IgG against the exotoxin B subunit. ACTH is the major trophic hormone of the fasciulata and reticularis. Cortisol has several permissive effects – cortisol increases vascular and bronchial smooth muscle reactivity to catecholamines. Radiologically. High GH levels but low IGF-1 is laron’s dwarfism – a defective GH receptor. lips. SVR decreases during exercise because of massive vasodilation so BP doesn’t increase much. The vascular reaction to endothelial and intimal injury is intimal hyperplasia and fibrosis. Nitrates acut primarily as venodilators causing a decrease in cardiac work by decreasing left ventricular filling volume or preload. Visceral obesity as measured by wasit-to-hop ratio is important determinant of insulin resistance. Cpasaicin reduces pain by decreasing the level of substance P in the PNS. simtulated proteolysis and lipolysis. bleeding. but often heavy. There can be a palpable swelling int eh childs neck which might be the bulging of the SCM contracted. Antimuscarin drugs: atropic. Treatment includes diphtheria antitoxin (passive immunization). Mucor dx needs bx. most commonly an imperforate hymen or a mullerian duct anomly. the ovarian follicle does not degenerate and becomes a CL. which drains lymph from the right upper extremity. Downs has excess skin on the nape of the neck. gonnarhea in a sexually active young adult. passive immunization with antitoxin is the most important and has the greatest effect on prognosis of a pt with cornybacterium diphtheria. Chronically proliferative endometrium becomes disorganized and fragile with unstable venous capillaries. Orbital fractures usually involve the medial or inferor walls because the bone bordering the ethmoid and maxillary sinuses is thin. and active immunization. Cricothyrotomy incision passes through the superficial cervical fascia. TCAs (amitryptaline). They are covered by the external spermatic fascia. Direct hernias is caused by weakness of the transversalis fascia in Hesselbach’s triangle.IN the absence of ovulation. auerus in a non-sexually active child or adult. Maternal insulin resistance results from increased secretion of hPL. placental growth hormone. the right face and neck. and glucocorticoids. They pass lateral to the internal iliac vessels and medial to the gonadal vessels as they enter the true pelvis. IFNgamma is produced mainly by NK and T cells and function to promote Th1 differneitation. or phosphate) to the aminoglycoside and therefore impair antibiotic binding to ribosomal subunits. Chin points away from contracted muscle. progesterone. after which the child prefers to hold the ehad tilted to one side. neuroleptics. It is most commonly the result of malposition of the ehad in utero or birth trauma. H1 antagonists (diphenhydramine). and inhibits gluconeogenesis. The ureters cross over the common/external iliac vessels and under the gonadal vessels (and ovarian vessles in the female). induce MHC class II expression. and the cricothyroid membrane. Human placental lactogen increases insulin resistance. CMV only causes mono in the immunocompetent host. antibiotics. no progesterone is produced and estrogen levels remain persistently high. causing the endometrium to remain in the proliferative phase. Entrococci produce aminoglycose modifying enzymes that transfer different chemical groups (acetyl. Adolescent girls with undiagnosed imperforate hymen commonly present with cyclic abdominal or pelvic pain and physical examination findings suggestive of hematocolpos. As a result. Unbalanced translocations and mosaicism cause downs if it isn’t non-disjunction. pretracheal fascia. resulting in irregiular preiods of stromal breakdown with variable. Right brachiocephalic vein drains the right lymphatic duct. Congenital torticollis is typically noted by 2-4 weeks of age. ID: 1804 Septic arthritis is N. adenyl. It is S. estrogens. Most cases resolve with conservative therapy and stretching exercises. antiparkinsonian drugs. Homologous chromosomes separate in meiosis 1 or a failure of sister chromatids to separate during meiosis II or mitosis (8328). ??? WHAT? ID: 1468 Major adaptive immune mechanisms that prevent reinfection with the influenza virus include antihemagglutinin IgG antibodies in circulation and mucosal anti-hemagglutinin IgA antibodies in the nasopharynx. and the right upper quadrant of the abdomen. the right hemithroax. and activate macrophages. Cardiomyoapthy is the most common cause of death (myocarditis) in diphtheria. . Loss to follow up = selection bias Primary amenorrhea in a pt with fully developed secondary sexual characteristics suggests the presence of an anatomic defect in the gential tract. Of these. and can aid in the dx of prinzmetals. they destroy the parasite via antibody dependent cellular cytotoxicity with enzymes from their cytoplasmic granules. compensatory activation of the RAA pathway and sympathetic nervous system results in increased afterload (from excessive vasoconstriction). Cardiac hibernation. In NDI and CDI the serum Na concentration is >142. Neurophysins are proteins involved in the posttranslational processing of oxytocin and vasopressin. Rheumatic fever and post-strep glomerulonephritis are the late sequelae of strep pyogenes (GAS). It is the sound of blood filling into a partially filled or stiff LV (S4 is also from atrial contraction into a stiff ventricle). and deleterious cardiac remodeling. The hypokalemia may cause muscle weakness. Ergonovine can provoke coronary vasospasm. Urge incontinence is uninhibited bladder contraction by the detrusor. Class ICs antiarrhythmics are potent Na channel blockers that exhibit strong use-dependence by prolonging the QRS duration to a greater extent at higher heart rates. pts with Conns syndrome commonly experience a metabolic alkalsosis. Adrenal crises can be precipitated in these pts under stressful situations (infections. Eosinophils play a role in host defense during parasitic infection. In primary polydipsia it is <137. and they are released into the circulation from axon terminals in the post pit gland. LV heart failure = kurly b lines Early antibiotic tx (penciling) of GAS is important for prevention of acute rheumatic fever. S3 is associated with mitral regurg and CHF – increased filling pressures. Hyperaldosteronism produces renal Na retention and excess K secretion. these drugs suppress reactivation of latent HSV infections. Additionally. If you have RF you need surgery. Hypokalemic alkalosis may promote paresthesias. Another function of eosinophils is regulation of type 1 HS rections. TZDs increase adiponectin levels in type II DM. resulting in hypertension and hypokalemia. surgery) if their glucocorticoid dose is not appropriately increased. excess fluid retention. . or famciclovir. When stimulated by IgE bound to a parasitic cell. hCG can be given in a large dose to simulate the LH surge S3 can be accentuated by having the pt lie in the left lateral decubitis position and fully exhale. Class III antiarrhythmics block the repolarizing K current and demonstrate reverse use-dependence (the slower the heart rate. LVH and prior MI protect against LV rupture (3-7 days out from MI). ACE inhibitors can cause first dose hypotension if the pt is on diuretics before hand.Hypetrophic cardiomyopathy = AD GLUT-3 – placenta IN pts with heart failure. Depression of the entire HPA axis by glucocorticoid therapy is the most common cause of adrenal insufficiency. Post strep glomerulonephritis can follow either a skin infection (impetigo) or an episode of pharyngitis. which are actually normally low in these pts. This condition is treated with vasodilating nitrates and calcium channel blockers. These hormones and their resepective neurophysins are produced within the neuronal cell bodies of the paraventricular and suproptic neucli. Rheumatic fever is associated only with strep throat infection. acyclovir. Ishcemic preconditioning is the development of resistance to infarction by cardiac myocytes preveiously exposed to repetitive non-lethal ischemia. Protease inhibitors cause cushings Recurrences of genital herpes can be reduced through daily treatment with oral valacyclovir. the more the QTc interval is prolonged). In a pt with MR. with contractility gradually returning to normal over the next hours-days. PTU) decrease the formation of thyroid hormones by inhibiting thyroid peroxidase. causing activation of adenylate cyclase and raising intracellular cAMP. It is a paraneoplastic syndrome of hypercoagulability may be seen. One of the most common reasons for elevated AFP in pregnancy screening is underestimation of gestational age. with subsequent conversion to thiocyanate by liver rhodanase. Inactivating mutations of the enzyme result in mild hyperglycemia that can be exacerbated by pregnancy. Pts who overdose on beta blockers should be treated with glucagon. pertechnetate) block iodide absorption by the thyroid gland via competitive inhibition. which increases HR and contractility indepdnent of adrenergic receptors. as the liver is the primary site of lactate clearance. Topical preparations of alpha adrenergic agonists cause vasoconstriction of the nasal mucosa vessels and are used as decongestants. Iodide salts inhibit synthesis as well as release of thyroid hormone. Thionamides (methimazole. Aortic valve infective endocarditis causes aortic regurg. When ischemia lasts less than 30 minuts. Jervell lange neilseon – decreased outward K current during the repolarization phase of the cardiac action potential QT prolongation. Anion inhibitor (perchlorate. Trousseaus syndrome – migratory superficial thrombophlebitis – is an indication of visceral cancer.T3 cannot be conveted to rT3 or to T4. which act upon the thyroid gland to reduce endogenous T4 production (and thus reduce peripheral conversion to rT3). Glomus = thermoregulation Loss of cardiac myocyte contractility occurs within 60 seconds after the onset of total ischemia. resulting in decreased NE synthesis and release from nerve endings. one major disadvantage of its use involves the risk for developing cyanide toxicity. Hepatic hypoperfusion also contributes to the buildup of lactic acid. mentally slow woman of northern European descent who is “lemon colored” (anemic and icteric). only to recur in another site. broad based gait. Superficial venous thrombosis may appear in one site and then resolve. but LV end diastolic volume and ejection fraction are normal. The classic presentation of pernicious anemia is an older. The intensity of the holosystolic murmur does not correlate well with regurgitant volume as larger regurgitant orifices often present with softer murmurs. ID 1973 Isolated diastolic HF: LV end diastolic pressure is increased. However. restoration of blood flow leads to reversible contractile dysfunction (myocardial stunning). which diminishes their effect (tachyphylaxis). Thus. which results in impaired oxidative phosphorylation and the shunting of lactate following glycolysis. Senile calcific aortic valve degeneration becomes clinically apparent in the 7 th decade of life (the guy in the question was 75). Nitroprusside is intiitally metabolized to cyanide. has a smooth shiny tongue (atrophic glossitis). the most reliable auscultatory finding indicating a high regurgitant volume (severe MR) and LV volume overload is a left sided S3 gallop. AS assoacited with congentially bicuspid aortic valves tends to present by the 6 th decade. after 30 minutes of total ischemia. and demonstrats a shuffling. Glucokinase is a glucose sensor within the pancreatic beta cells. Nitroprusside is the agent of choice in treating hypertensive emergency. Na thiosulfate is used to treat cyanide toxicity and works by donating sulfur to liver rhodanase to enhance conversion of cyanide to thiocyanate. Lactic acidosis occurs in pts with septic shock because of tissue hypoxia. . Valvular inflammation and damage and scarring predispose to infective endocarditis. It has a quick onset of action and short duration of action. Exogenous T3 administriation causes decreased TSH levels. Glucagon activates GCPRs on cardiac myocytes. Overuse of these drugs cuases negative feedback. The result is calcium release from intracellular stores and icnresed SA node firing. ischemic injury becomes irreversible. AI dz (polymyositis/dermatomyositis). impaired wound healing. duchennes. Na-channel binding strength is 1C>1A>1B. An ACTH surge with a resultant increase in steroid ‘half-product’ excretion is a normal reaction to metyrapone administration. Ventricular myocyte depolarization is mediated by inward Na movement and can be moedulated by class I antiarrythmics. And because beta blockers stop sympathetic adrenergic impulses). WBC count is necessary in any pt receiving either methimazole or PTU who presents with a fever because they cause agranulocytosis. it can be the first manifestation of hypothyroidism. Dilated cardiomyopathy is dilation of all 4 chambers of the heart. causing muscle weakness. MS is always caused by rheumatic heart disease. and myocardial failure. A systolic pressure gradient between the left ventricle and aorta would not be expected in dilated cardiomyopathy and is more suggestive of LV outflow tract obstruction (AS). acts as a vasodilatory element in the small coronary arterioles. However. 11-deoxycortisol shows up in the urine as 17-hydroxy-corticosteroid. Glucocorticoids are predominantly catabolic. they increase liver protein synthesis. The only way to distinguish between insulinoma and sulfonylurea or meglitidine abuse is by screening the urine or blood for hypoglycemic agents. Nitric oxide is the most important mediator of coronary vascular dilation in large arteries and pre-arteriolar vessels. and class IB drugs have the least. Carveidolol is a particularly good beta blocker at reducing mortality in CHF. Sometimes. SIADH has clinically normal body fluid volume Fenfularmine/phentermine (appetite suppressants) cause pulmonary HTN. the formation of mono and diiodotyrosine. and coupling that forms T3 and T4. because metyrapone blocks the last step of cortisol synthesis. Other common causes of elevated CK include medications (statins). contributes to the development of hyperglycemia. They slow ventricular rate and decrease afterload. S4 – restrictive cardiomyopathy and LVH .SLE can cause acute coronary syndrome at a young age even with angiographically normal coronary arteries. osteoporosis. along with peripheral antagonism of the effects of insulin. Both ventricular hypertrophy and volume overlaod cause release of both ANP and BNP from the ventricular myocytes to facilitate natriuersis. Cyanosis restricted to the lower body in a child is suggestive of patent ductus arteriosus. A-fib occurs due to irregular. a product of ATP metabolism. While some of the atrial impulses are transmitted to the ventricles. Thyroid peroxidase catalyses iodide oxidation. and immunosuppression. most are not due to the AV nodal refractory period. Metyrapone blocks 11-BHydroxylase. specifically enzymes involve din gluconeogenesis and glycogenesis. Coarctation can limit lower extremity exercise tolerance but does not cause cyanosis in children or adults. Hypothryoid is a common cause of an elevated creatine kinase level due to hypothyroid myopathy. This. skin thinning. Propranolol decreases the rate of T4 T3 conversion (which is why we use it along with PTU and prednisone for thyroxicosis. P53 mtuations are common in anaplastic thyroid cancer. ID: 608 Niacin for high TGs after fibrates. systolic dysfunction. Adenosine. For class 1 antiarrhythmics. The QRS complex corresponds to ventricular depolarization and phase 0 on the action potential graph. IC antiarrhythmics demonstrate the most use dependence. chaotic electrical activity within the atria. The increased intracellular solute concentration draws free water into the cell. The defect is in the hypothalamus. Pericardial knock is sounds that occurs earlier in diastole than the S3 heart sound. Niacin can potentiate the effects of some anti-hypertensive medications because of its vasodilatory effects. necrolytic erythema. Pts with adult type coarctation of the aorta commonly die of HTN associated complications. These pts are at increased risk for ruptured intracranial aneurysms because of the increased incidence of congenital berry aneurysms of the circle of willis as well as aortic arch HTN. flushing. Decrease the dose. It is from constrictive pericarditis reducing ventricular compliance via an external force. Damage to the posterior pituitary produces only transient central DI. GLUT transporters are carrier mediated transport. Amenorrhea from anorexia is due to loss of pulsatile secretion of GnRH from the hypothalamus. Effect modification is present when the effect of the main exposure on the outcome is modified by the presence of another variable. and anemia Pericarditis pain radiates to the neck and shoulders and is relieved by sitting up. and oxaloacetate to phosphoenolpyruvate. Glomerulonephritis secondary to circulating immune compelxes can be complicate bacterial endocarditis and result in acute renal insufficiency. . High volume AV shunts can eventually result in high-output cardiac failure. The initital commited step of gluconeogenesis is the conversion of pyruvate to oxaloacetate. with the pt leaning forward at end expiration. Abdominal pain due to acute pancreatitis is the most likely presentation for hyperchylomicronemia. Glucagonoma = DM. Woman who lived in the US her whole life doesn’t have rheumatic fever probably. Loss of consciousness brought about by severe hypoglycemia is typically treated with intramuscular glucagon in the non-medical setting and with IV dextrose in the medical setting. Pretibial myxedema (lower leg skin thickening and induration – it manifests as nonpitting edema that is sometimes scaly in appearance resembling an orange peel) and exopathlamos are SPECIFIC for hyperthyroidism due to Graves. and intracranial hemorrhage. including LV failure. AV shunts increase preload and decrease afterload by routing blood directly from arterial to venous system. The murmur of AR is best heard at the left sternal border. Reduced INTRINSIC ventricular wall compliance is a cause of S3. bypassing the arterioles.Massaging the carotid prolonges the AV node refractory period to help SVT. causing the cellular and mitochondrial swelling that is observed histologically. Adenosine can cause chest burning (bronchospasm). more common in her would be MVP leading to vegitations on the valave. Niacin also increases insulin resistance and oftentimes necessitates an increase in diabetes medications. Ion pump failure due to ATP deficiency during cardiac ischemia causes intracellular accumulation of Na and Ca. Effect modification is not bias. Amyloid specific organ: Cardiac atria: ANP Thyroid gland: calcitonin Pancreatic islets: amylin Cerebrum/cerebral blood vessels: beta amyloid Pituitary gland: prolactin Prednisone is used for Graves opathalmopathy. Permanent central DI usually rsults form dmage to hypothalamic nuclei or the pituitary stalk. not the ovaries or pituitary. ruptured dissecting aortic aneurysm. Can also use adenosine. and high grade block. New onset murmur in a young adult = bacterial endocarditis. FFA and serum TGs are believed to increase insulin resistance in overweight individuals. These lesions are caused by septic microemboli to cutaneous blood vessels. erythematous. The emboli are fragments of infected intracardiac vegetations. . possibly hemorrhagic macules that may appear on the soles of the fett and palms of the hands in a patient with bacterial endocarditis.Janeway lesions are small. PPARgamma is an intracellular nuclear receptor.