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Histology: Phosphorylation of nuclear lamina (by lamin kinase) during mitotic prophase nuclear disassembly into small vesicles.

. The outer nuclear membrane is continuous with the ER. Diplotene stage is the part of prophase in which the chromatids appear to repel one another. Within a Graafian follicle, ovum is surrounded by glycogen rich ZONA PELLUCIDA, which triggers the acrosomal reaction. Around the ZP is the corona radiata; around the CR is a hill of follicular cells around ovum, cumulus oomphorus. Ovary: cuboidal; Fallopian tube: columnar; Uterus: Pst columnar; ECTOcervix: st squamous; ENDOcervix: columnar; Vagina: St squamous non-keratinized Early Follicular: nontortuous glands, no vacuoles; Late follicular: coiled glands, stromal edema. No vacuoles. Early Luteal: tortuous glands and basal vacuoles; Late luteal: apical vacuoles and secretions into gland lumen. Abundant extracellular space indicates PNS, thus Schwann cell. Myelin is made of LCFA metabolism and would be facilitated by peroxisomes. Airway down to RESPIRATORY BRO NCHIOLES is PsCC; down to TERMINAL BRO NCHIOLES has goblet cells CONDUCTING ZONE: NOSE to TERMINAL BRO NCHIOLE; RESPIRATORY ZO NE: Respiratory bronchiole, alveoli Type 1 pneumocytes: Squamous Type 2 pneumocytes: CUBOIDAL w/ round nuclei and washed out foamy cytoplasm. Clara cells: Columnar Mesothelium: Stratified squamous True vocal cords: Stratified squamous Osteoblasts have PTH receptors; OBs arise from mesenchymal stem cells in periosteum. Osteocytes are OBs in matrix; responsible for bone maintenance Osteoclasts resorb bone in Howships lacunae; differentiate by RANKL and M-CSF OCs naturally have tartrate resistant acid phosphatase. Osteocalcin is ALSO a marker for increased bone turnover/growth. Odontoblasts dentin (inner side); Ameloblasts enamel (outer side) BONE: within a single Haversian system, the c entral canal is encircled by multiple concentric lamellae of bony matrix that contains lacunae with osteocytes and extracellular bone fluid Osteocytes communicate via GAP JUNCTIONS Erythrocytes: 90% anaerobic metabolism; 10% HMP shunt. Platelets: of platelet pool is stored in spleen; life span 8-10 days 2+ Dense granules: ADP, Ca , histamine, 5HT, epinephrine -granules: Fibrinogen, fibronectin, Factor V, vWF, PF4, PDGF Basophil: granules contain heparin, histamin e, leuko trienes. Eosinophil ALSO produces histaminases and arylsulfata se; chemotactic by eotaxin. NAACP: Neoplasms, Asthma, Allergy, Collagen vascular disease, Parasites (invasive) Neutrophils: spends 6-10 hours circulation before extravasation; PRIMARY AZUROPHILIC GRANULES (lysosomes): lysozyme (1-4 linkages), myeloperoxidase (responsible for green color of pus/sputum in bacterial infections), lactoferrin, PLA2, acid hydrolases, elastase, defensins. SECONDARY SPECIFIC GRANULES: PLA2, lysozyme, AP, collagenase, lactoferrin, B12 binding proteins. IFN turns macrophage to epith eliod cell (enlarged with pink nuclei) that FUSES to become: 1) Langhans giant cell: peripheral nuclei OR 2) Foreign body giant cell: haphazard nuclei. Dendritic cells are the main inducers of the primary antibody response. Esophagus: St.Sq Intestinal villi/microvilli: Duodenum > jejunum > ileum Jejunum has the largest number of goblet cells in the SI. Only jejunum and proximal ileum have plicae circulares. Paneth granular cells in SI release defensins & lysozyme. Hepatocytes: Apical: faces bile canaliculi; Basolateral: faces sinusoids; ATROPHY: Micro: small, shrunken cells with lipofuscin granules. EM: decreased intracellular components and autophagosomes

Endothelium of CV + lymph vessels: Simple Squamous The DERMIS contains skin appendages (hair follicles, sweat glands) that contain EPITHELIAL STEM CELLS.

Anatomy: DORSUM of HAND sensory innervation: 1) Median nerve gets 2, 3, lateral 4 fingerbed; rd 2) Radial nerve gets thumb and dorsum proximal to 2 and lateral 3 fingerbed; th th rd th th 3) Ulnar nerve gets lateral 4 and 5 fingerbeds and dorsum proximal to lateral 3 , 4 , and 5 fingerbed. st nd MEDIAN NERVE: O AF (brevis); anterior forearms muscles (except FCU), of FDP, and 1 and 2 lumbricals. *Proximal to wrist, median nerve PASSES B/T the TWO HEADS OF THE PRONATOR TERES* RADIAL NERVE: Abductor pollicis longus, extensor pollicis brevis. Lumbricals extend @ IP joints and spread @ MCP. Extensor digitorum helps extend @ IP joints by ASSISTING lumbricals. EDM extends @MP joints (NOT IP joints) Palmaris longus in forearm by MEDIAN NERVE. Making a TIGHT fist requires stabilization by the wrist extensors. Deep laceration of RADIAL side of wrist: Radial A, Median N, Palmaris longus, FCR. Deep laceration of ULNAR side of wrist: Ulnar A, ulnar N, FCU. BRACHIAL PLEXUS: Median nerve from LATERAL & MEDIAL CORDS. Nerve to subclavius & suprascapular nerve from UPPER TRUNK. MC nerve injured with clavicular fractures ULNAR NERVE. Median nerve cutaneous sensation can be BLOCKED @ distal forearm before the carpal tunnel, in a superficial position between the tendons of the Palmaris longus and the FCR. RADIAL N and DEEP BRACHIAL A. go through spiral groove. RADIAL A and MEDIAN N run together. MEDIAN N courses between FDS and FDP muscles before wrist. st Wrist Flexion: C6, C7, C8, T1; Elbow flexion: C6, C7, C8; Deltoid + Sensation: C5, C6; Sensation 1 3 digits: C6, C7, C8 The superficial arch (of ulnar artery) and the deep arch (of radial artery ensure collateral to hand. Colles fracture lunate dislocation into carpal tunnel MEDIAN NERVE lesion. The PHRENIC NERVE lies on the anterior surface of the anterior scalene DEEP to the prevertebral fascia. Postganglionic sympathetic to visceral organs uses catecholamines. Irritation of the phrenic nerve (think mass effect) can cause dyspnea and hiccups. Suboccipital triangle: obliquus capitis superio r, obliquus capitis inferior, rectus capitis posterior major. Supracondylar surface of femur forms the floor of the popliteal fossa (hence popliteal artery) Coarctation: DECREASED BLOOD FLOW THRU DESCENDING AORTA, off of which most intercostals arteries arise. BUT, the st 1 intercostals originate directly off the subclavian artery @ the costocervical trunk. Flow remains anterograde. TRAP: Sternoclavicular joint dislocations can impingeTRACHEA; ****Aorta and SVC are BELOW this level.**** INTERCOSTAL SPACES: Anterio r drainage to internal thoracic (parasternal) nodes; posterio r drainage is to para-aortic nodes. PO2 in the left atrium is LOWER than those in the pulmonary veins because deoxygenated blood from the bronchial arteries (no typo) to the left heart. The bronchial veins return blood to the right heart via the azygous, hemiazygous, or in tercostal v. Intercostal nerves: 12 pairs of thoracic nerves; 11 intercostal pairs; 1 subcostal pair. the VENTRAL PRIMARY RAMI of the THORACIC SPINAL NERVES supply musculature, parietal pleura, and parietal peritoneu m. TRAP: These are found LATERAL to the ANGLE OF THE RIB. Intercostal arteries: 12 posterior/anterior, 11 intercostal pairs, and 1 subcostal pair. ANTERIOR: Pairs 1-6 are from INTERNAL THORACIC ARTERIES; Pairs 7-9 are from MUSCULOPHRENIC ARTERIES *There are no anterio r intercostals arteries in the LAST TWO spaces; branches of posterio r intercostals a rteries supply these. POSTERIOR: Pairs 1-2 are from superior intercostals arteries, a branch of costocervical trunk of subclavian artery. 9 pairs of intercostals and 1 pair of subcostal arteries from the thoracic aorta. INTERCOSTAL VEINS Anterior branches drain to the internal thora cic and musculophrenic veins Posterior branches drains to the azygos.
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**N.A.V. from inferior superior; Going up from the NAVel. CAMPERS FASCIA contains the fat. You get fat while eating smores at camp. **Camper fascia Scarpa fascia external oblique** Great saphenous vein passes ANTERIOR to MEDIAL MALLEOLUS, POSTERIOR TO MEDIAL KNEE, and thru saphenous hiatus to fascia lata (fossa ovalis) to empty into femoral vein. Short saphenous vein drains LATERAL DORSUM OF FOO T and runs on posterior leg; drains into popliteal fossa nodes. Varus for medial; Valgus for lateral. ACL pr events anterior subluxation of knee (hyper extension) Attaches to 1) Anterior intercondylar tibia & 2) Posteromedial side of lateral femoral condyle MCL attaches to medial epicondyle of femur with shaft of tibia; resists valgus and external rotation forces of proximal tibia. LCL attaches to lateral epicondyle of femur with head of fibula; resists varus forces and rotation forces of proximal fibula. PCL attaches to 1) posterior part of intercondylar area of tibia 2) anterolateral surface of medial epicondyle of femur S/S of meniscus injury: 1) pain; 2) knee catches, locks, or fives way when walking; 3) swelling/popping of knee. FEMORAL N (L2-L4) involved in PELVIC FRACTURES. Lesion: weakened hip flexion, loss of extension @ knee, sensory loss @ anterior thigh, medial leg, and foot. MC site of lateral femoral nerve entrapment: inguinal ligament meralgia paresthetica numbness or burning sensation over the lateral part of the thigh when walking or prolonged standing; OBESE PATIENTS. L5-S1 => QUADRICEPS FEMO RIS => LATERAL RO TATION S1-S2 => PIRIFORMIS => LATERAL ROTATION when leg is EXTENDED; ABDUCTION when thigh is FLEXED. OBTURATOR N (L2-L4) injured in ANTERIOR HIP DISLOCATION Lesion: weakened thigh adduction & medial rotation of thigh. SUPERIOR GLUTEAL N can be damaged by POSTERIOR HIP DISLOCATION or POLIO; It travels through greater sciatic fora men ABOV E piriformis & against UPPER BORDER of foramen. INFERIOR GLUTEAL N can be damaged by POSTERIOR HIP DISLOCATION Cant jump, climb stairs, or rise from sitting. It travels through greater sciatic fora men BELOW piriformis & against LOWER BORDER of foramen. PUDENDAL N passes through GSF BELOW piriformis & against LOWER BORDER of foramen and exits LSF to enter perineum. SCIATIC N lesion weak thigh extension, loss of knee flexion, loss of function below knee. Exits GSF BELOW piriformis. Sciatica Compression of lumbar spine affecting sciatic nerve roots (L4-S3 tibial; L4-S2 peroneal) weakened leg extension, loss of knee flexion, loss of function below the knee, pain/sensory loss on posterior thigh, lateral leg, and foot BUTTOCKS: superior medial aspect: superior gluteal nerve (L4-S1); inferior medial aspect: sciatic nerve Superior lateral aspect: SAFE; Inferior lateral aspect: tendinous insertions. PSOAS inserts on lesser trochanter; G.MAX inserts on gluteal tuberosity; G.MED,MIN,PIRIFORMIS inserts on greater trochanter GENITOFEMORAL N & ILIOINGUINAL N (L1-L2) TRAP: Common peroneal injured at fibular head; even though the question only specifies failure of dorsiflexion, do not choose anterior compa rtment of leg, as small pressure (such as wearing a cast) would not damage the nerve there. MC foot fracture from fall from height: calcaneus. Superficial inguinal lymph nodes drain cutaneous lymph from umbilicus to feet, including external genitalia & anus (but excluding the posterior calf, which drains to popliteal lymph nodes) BOUNDED by 1) inguinal ligament, 2) sartorius, and 3) adductor longus muscle, and overlie the femoral NAV. Tumors from penis, vagina, and anal canal drain to MEDIAL SIDE of HORIZON TAL CHAIN of SUPERIFICIAL INGUINAL NODES. Prostate lymph drains to INTERNAL ILIAC NODES (and a minor bit to external iliac + sacral nodes) Superior bladder drains to EXTERNAL ILI AC nodes; inferior bladder drains to INTERNAL ILIAC nodes Ureters pass OVER the external iliac arteries and UNDER the gonadal vessels; As they enter the true pelvis: pass LATERAL to internal iliacs and MEDIAL to gonadal vessels. TESTICULAR TORSION: MEDICAL EMERGENCY + SEVERE PAIN; absen t cremasteric reflex (nega tive Prehns) VARICOCOELE: WORSE w/ EXERCISE; gets LARGER WITH VALSALVA; more common on LEFT b/c of renal vein thrombosis (think anti-coagulation causes) or malignancy; NO ASSOCIATION WITH STARLINGS FORCES. SPERMATOCOEL E: dilated effer ent duct in the epididymis. Sperm flagella derived from CENTRIOLE.

Testicular arteries branch off of aorta; prior to entering spermatic cord, it passes OBLIQUELY + SUPERIORLY to ureter. Ilioinguinal nerve (L1) passes through inguinal ligament on top of spermatic cord. ERECTION: PELVIC NERVE; EMISSION: HYPOGASTRIC NERVE; EJACULATION: PUDENDAL NERVE. PROXIMAL 2/3 of vagina/uterus obturator, external iliac, and hypogastric nodes. Round ligament of uterus carries NOTHING (0 is round): Connects UTERINE FUNDUS to LABIA MAJORA. Trigone is posterior/inferio r bladder floor. Ectopic kidney: tortuosity of ureters pyelonephritis Horseshoe: lower pole fusion, predispose to renal calculi Kidney hypoplasia: Decreased # calyces and lobes. Kidneys @ T12-L3; nephrons 7/8 cortical; 1/8 juxtamedullary LEFT kidney is taken for transplantation because it has a LONGER RENAL VEIN. Cystocoele: prolapsed of bladder into vagina Ureters are RETROPERITONEAL: starts on TOP of PSOAS water under the bridge Crosses the following: 1) ANTERIOR to EXTERNAL ILIAC 2) LATERAL to INTERNAL ILIAC 3) MEDIAL to GONADAL VESSELS FECAL INCONTINENCE: damage to perineal body (bulbospongiosus, external anal sphincter, perineal muscles) URINARY INCONTIN ENCE: damage to levator ani. Nasal mucosa: Sphenopalatine artery, ter minal branch of maxillary artery, branch of external carotid artery. @Exercise: INSPIRATION: External intercostals, Scalene, Sternomastoids. (raise ribs to increase AP diameter) EXPIRATION: Abdomen muscles, internal intercostals. I8 10 eggs At Noon + For lunch I had goose and duck (refers to azygous vein + thoracic duct @ T12) th th th th th th THORACOCEN TESIS: 5 -7 rib MC line; 7 -9 rib Mid Axillary; 9 to 11 rib paravertebral line. LIVER INFARCTS are RARE because it has a dual blood supply (Hepatic artery and portal vein) Notable exception: during liver transplantation, hepatic artery thro mbosis biliary tree infarction severed collaterals. Head of pancreas & duodenum share dual blood supply from gastroduodenal artery; SMA needs to be ligated to reach Portal triad is within the hepatoduodenal ligament; cystic artery is a branch of the R.hepatic artery. Gastric arteries are within the gastrohepatic ligament; ADENOCARCINOMA here will impinge hepatoduodenal ligament. Gastroepiploic arteries are within the gastro colic liga ment (part of gr eater omentum) Short gastric arteries are within the gastrosplenic ligamen t; Splenic artery/vein are found in the splenorenal ligament. Celiac trunk: T12; SMA: L1; Left Renal Artery: L1; Gonadal arteries: L2 ; IMA: L3; Bifurcation: L4. Foregut & Midgut has vagal innervations; hindgut has pelvic innervations. Peritoneal structures: 1) Stomach, 2) Liver, 3) gallbladder, 4) spleen, 5) proximal duodenum, 6) tail of pancreas, 7) jejunum, 8) appendix, 9) transverse colon, 10) sigmoid colon nd rd th Retroperitoneal structures: 1) Duodenum (2 , 3 , 4 parts), 2) Descending colon, 3)Ascending colon, 4) Kidney/ureters, 5) pancreas (except tail), 6) Aorta, 7) IVC, 8) adrenal glands, 9) rectum Gastrohepatic ligament: Part of the lesser omentum that spans between the inferio r surfa ce of liver and the lesser curvatu re of stomatch; this portion of the lesser omentum has NO significant blood vessels and can be incised for surgical access. Greater peritoneal sac is entered through an incision in the anterior abdominal wall and the right side of the lesser peritoneal sac is accessed in order to reach the head of the pancreas. *Insertion of 1) portocaval shunt between the splenic and the left renal veins OR 2) connecting th e portal vein to th e IVC RELIEVES PORTAL HYPERTENSION. Above pectinate line: adenocarcinoma; superior rectal artery; superior rectal vein IMA Below pectinate line: SCC; inferior rectal artery; inferior rectal vein internal pudendal vein internal iliac vein. Femoral sheath ALSO contains the deep inguinal lymph nodes. MEDIAL to femoral hernia is lacunar ligament. Incarcerated hernia strangulation peritoneal effusion with increased NH3 (bacterial) WITHOUT increased Cr. Indirect inguinal hernia is WORSENED by lifting, chronic cough, and constipation.

Protrudes if pressure is applied to superficial inguinal ring and coughing (effort) No protrusion if pressure is applied to d eep inguinal ring and coughing (effort) Word game: INDIRECT is due to a weakened transversalis fascia. Direct inguinal hernia protrudes with effortand retracts with rest. Protrudes if pressure is applied to d eep inguinal ring and coughing (effort) No protrusion is pressure is applied to superificial inguinal ring and coughing (effort) Ileocecal valves are normally CLOSED; distension of ileum relaxes sphincter///// distension of colon nervous reflex to constrict sphincter. SPLEEN: T cells found in PALS and RED PULP; B c ells found in FOLLICLES and WHITE PULP Pulmonary artery is RALS (Right Anterior; Left Superior) to the bronchus. Bronchopulmonary segment: 2 arteries at center; veins + lymphatics at border. Trachea has 23 generations of bronchi: BRONCHI > 2 mm (first 10 generations) provide greatest summated frictional resistance to airflow. Gen 2-5 have HIGHER RESISTANCE than all of upper airway AIRWAY < 2 mm have low resistance because of increased total CSA. SVC syndrome affects BOTH sides of the body; brachiocephalic trunk obstruction affects right side only. Maxillary sinus drains into middle meatus via hiatus semilunaris PAIRED umbilical arteries arise from INTERNAL ILIAC ARTERIES. SMA leaves aorta at L1; the angle between SMA and aorta is normally 45 degrees; if this angle diminishes, the transverse po rtion of th e duodenum can be entrapped bowel obstruction. PCL attaches to the anterior lateral surface of the medial epicondyle of the femur Buccinator functions to hold food against the teeth while it is chewed. Paralysis food/saliva between teeth/cheek VENTRICLES: Telencephalon: Lateral ventricles; Diencephalon: Third Ventricle; Midbrain: Cerebral Aqueduct; Metecephalon/Myelencephalon: Fourth ventricle; CEREBELLUM Neocerebellum/cereb rocerebellum: Lateral; fine movements of hands/face; dysdiadochokinesis Paleocerebellu m/spinocerebellum: Anterior vermis; trunk balance, vocal con trol, saccades; scanning speech & abnormalities of aforementioned; MOST DAMAGED BY ALCOHOL Archicerebellum/vestibulocerebellu m: flocculonodular lobe; connected to vestibular nu clei; responsible for eye movements. Problems of pursuit & nystagmus CEREBRUM: Parasagittal region and falx cerebri are located SUPERIORLY between the two hemispheres. Artery of Adamkiewicz supplies ventral spinal cord from T8 to L4. Superior cerebellar artery aneurysm CN III palsy Vertebral arteries are first branches of subclavian arteries. Internal carotid artery ACA + MCA MCA is not part of the Circle, so its ligation will lead to greatest ischemia of its coverage area. LESIONS OF CIRCL E OF WILLIS: (Selected) ASA (medial medullary syndrome): IPSILATERAL CN XII & CONTRALATERAL CST + DC. PICA (lateral medullary syndrome):IPSILATERAL VPM, Horners, ataxia, dysphagia, ; CONTRALATERAL spinothalamic. AICA (lateral inferior pontine syndrome: IPSILATERAL CN VII, CNVIII, VPM, ataxia (MCP, ICP). Medial pontine syndrome: Contralateral spastic hemiparesis + loss of vibration and position sense; ipsilateral CN VI palsy Medial midbrain syndrome: (W eber syndrome): Contralateral spastic hemiparesis of UL & lower face; ipsilateral CN III palsy. AComm: MCC site of aneurysm; visual field defects PComm: Aneurysm; CN III palsy Lateral striate (of MCA): infarct of posterior limb of internal capsule PURE MO TOR hemiparesis. WORD GAME: Locked in Syndrome is ultimately due to a problem @ the PONS. Pterion: where frontal, parietal, temporal, and sphenoid bones meet.

Epidural hematoma: CANNOT cross suture; CROSS falx, tentorium Fell down, loses consciousness for 15 minutes, gets up and calls a friend for help. LUCID INTERVAL Subdural hematoma: CROSS suture; CANNO T cross falx, tentorium; gyri preserved since pressure is distributed equally. SAH: Berry aneurysm s are centered near base of the brain; AVM involve the cerebral hemispheres. Intermediate horn sympathetic in thoracic horn ONLY Spinothalamic tract: MEDIAL: Cervical; LATERAL: Sacral Lateral CST: MEDIAL: Arms; LATERAL: Legs Legs are Lateral Clasp knife spasticity: initial jerking resistance to passive extension followed by sudden release of resistance. Due to lesions @ CST, medulla, pons, midbrain, in ternal capsule, p recentral gyrus. DC: decussates @ caudal medulla Spinothalamic: decussates @ anterior white comissure CST: decussates @ cervicomedullary junction (pyramids) WORD GAME: Some still call this caudal medulla. Internal capsule: Anterior limb: Frontopontine fibers; Genu: CTB fibers; Posterior limb: CST fibers Caudate nucleus: C-shaped structure that comprises part of wall of the LATERAL VENTRICLE. Hippocampus: adjacent to the inferior (temporal) horn of the LATERAL VENTRICLE. Hypothalamus: abuts the third ventricle. Pons: forms part of floor of fourth ventricle. SPINDLE MUSCLE CON TROL Parallel to extrafusal fibers: MUSCLE STRETCH INTRAFUSAL STRETCH (detected by spindle afferents) (+) Ia afferent dorsal horn (+)MN reflex extrafusal contraction Perpendicular to intrafusal fibers: GOLGI (+)Ib afferent (-)MN (Loss of this pathway hyperreflexia) Gamma loop from CNS (+) MN INTRAFUSAL CONTRACT INCREASE SENSITIVITY OF REFLEX ARC CN VII: LMN lesion affects whole face and is IPSILATERAL. UMN lesion affects CONTRALATERAL lower face; upper face is bilateral UMN. TRAP: Stapedius muscle PARALYSIS increased sound sensitivity (hyperacuisis) CN IX innervates stylopharyngeus (elevates pharynx, larynx) Distal to above *Glossopharyngeal nerve lies in the tonsillar fossa.* CN X involves taste from epiglottic region. Gag reflex differential: 1) CN IX and X loss uvula deviates AWAY + no gag when IPSILATERAL side touched 2) CN IX loss no gag when IPSILATERAL SIDE touched 3) CN X loss uvula deviates AWAY + touching either side causes a gag. Pyriform cortex contains the PRIMARY OLFACTORY CORTEX Insula contains the PRIMARY GUSTATORY CORTEX Dorsal motor nucleus: Sends PARASYMPATHETIC FIBERS to heart, lungs, and upper GI. CN III palsy: down and out; CN IV palsy: down and in. CNV3 : Aurico temporal nerve- Anterior of external ear canal. Grea ter auricular nerve- Lower part of auricle Lesser o ccipital nerve- Upper part of auricle CN X: Auricular b ranch : Posterior of external ear canal. (Note VAGUS nerve FAINTING) CN IX: Inner tympanic membrane As pituitary adenoma expands LATERALLY, CN VI (ABDUCENS) is affected first. LESIONS CN XII: tongue deviates TOWARD lesion (lick your wounds); Ex. Paralysis of RIGHT tongue deviates to RIGHT. decussates before medulla and synapse on CONTRALATERAL HYPOGLOSSAL NUCLEUS CN V: jaw deviates TOWARD lesion; bilateral cortical input to lateral pterygoid CN X: uvula AWAY from lesion CN XI: (SCM) weakness turning head AWAY from lesion; (trapezius) ipsilateral shoulder droop Bells Palsy is a complication in Herpes Zoster, Sarcoidosis, Tumors, Diabetes. Tensor tympani (CNV3)- draws tympanic membrane MEDIALLY to dampen sounds

INNER EAR within TEMPORAL BONE Bony labyrinth (perilymph): cochlea, vestibule, and semicircular canals Membranous labyrinth (endolymph): cochlear duct, utricle/saccule, and semicircular canals *LINEAR ACCELERATION: Utricle (horizontal) & saccule (vertical) the maculae within have otoliths ENDO LYMPH made by STRIA VASCULARIS; r esorbed by endolympathic sac. Hair cells sit on phalangeal cells, which in turn rest on the basilar membrane. Corneal endothelial cells pump out ions from the corneal stroma during aging, corneal swells becomes cloudy Optic cup (neuroectoderm) gives rise to ciliary body, iris, retina. RETINAL ARTERY OCCLUSION acute, painless loss of vision; pale retina plus cherry red macula (supplied by choroid artery) VISION + OUTER ROD SEGMENT: light on rhodopsin Gt cGMP PDE CLOSE cGMP mediated Na channels (at rest -30mv) HYPERPO LARIZIATION Because membrane is partially depolarized in dark, glutamate is continuously release, which inhibit the optic nerve bipolar cells, with which the rod cells synapse. THUS: HYPERPOLARIZATION eliminates this inhibition to allow signal to be sent to the brain. PUPILLARY CON TROL Constriction- Circular muscle/Pupillary sphincter (Parasympathetic); CN III via ciliary ganglion (via M3) Dilation Pupillary Dilator muscle/ raDial muscle; T1 preganglionic sympathetic superior cervical ganglion postganglionic sympathetic long ciliary nerve (via 1) Anti-muscarinics lead to PARALYSIS OF ACCOMODATION only w ay to get CYCLOPLEGI A. ACCOMODATION is ciliary muscle contraction relaxation of lens (fatter, shorter, more convex) Marcus Gunn pupil: afferent papillary defect (optic nerve damage or detached retina) A.Comm defect bitemporal hemianopsia Internal carotid defect binasal hemianopsia MCA defect quadrantic (use your mnemonic to figure out upper or lower) TRAP: They may not mention central clearing, thus technically PCA lesions homonymous hemianopsia. HERN IATIONS 1) CINGULATE (SUBFALCIN E) can compress ACA 2) Downward transtentorial Coma and death if brain stem is compressed. 3) Uncal CN III palsy, PCA compressed, contralateral crus cerebi compr essed (ipsilateral paresis), Duret hemorrhages (paramedian artery rupture) 4) Cerebellar tonsillar Cardiopulmonary arrest CT BRAIN LESIONS 1) RING ENHANCING metastasis (more common), abscess*, toxoplasmosis, AIDS lymphoma 2) UNIFORMLY ENHANCING Lymphoma, meningioma, metastasis 3) HETEROGENO US ENHANCING GBM 4) NONENHANCING PML *Cer ebellar ABSCESS is specific to OTITIS MEDIA.

BS: INCIDENCE is the CONSTANT in the equation P = I*D 100% sensitivity NPV is 100% (no FN s); PPV is variable because results will be a TP or a FP. 100% specificity PPV is 100% (no FPs); NPV is variable be cause results will be a TN or a FN. INCREASIN G upper limit of normal for TEST REFERENCE RANGE (0-4 ng/ml to 0-10 ng/ml) Increases SPECIFICITY and PPV (abnormal test results are likely to be TP > FP) Decreases SENSITIVITY and NPV (nor mal test results are likely to be FN > TN) DECREASING upper limit of normal for a TEST REFERENCE RANGE (lowering fasting glucose from >140 to >126) Increases SENSITIVTY and NPV (negative test results are more likely to be TN > FN) Decreases SPECIFICITY and PPV (fewer people have the disease, so a lower result is more likely FP > TP)

Sensitivity = 1 False Negative Rate Specificity = 1 False Positive Rate Case-Control: Compares group of people WITH DISEASE and WITHOUT DISEASE. (regardless of exposure) Cohort: Compares group of people RISK FACTOR and NO RISK FACTOR. Nominal data is categorical (N for Name); Ordinal data has a hierarchy (O for Order) If SIMILAR RISK RATIO, but DIFFERENT p values in 2 studies => DIFFERENCE IN SAMPLE SIZE This CANNOT be design flaws because the RR is similar. If RR and p values VARY GREATLY for two experiments that vary in time, consider LATENT PERIOD of chronic diseases. ATTRIBUTE RISK = (RR-1) / RR RELATIVE RISK REDUCTION = [ (Riskcontrol)-(Risktreatment)] / (Riskcontrol) Pooled t-test: assumes variances of the two groups are the same Matched pairs t-test: 2 groups, linked data pairs, before and after Repeated measures ANOVA: More than 2 groups, linked data; multiple measurements over time One-Way ANO VA: Compares means of many groups of a single nominal variable using an interval variable. Significant pvalues means at least two of the groups are different. Two-Way ANOVA: compares means of many groups of two nominal variables using an interval variable. Can test effects of several variables at the same time. Narcolepsy involves orexin neurotransmitter & HLA DR2 As prevalence INCREASES: PPV INCREASES; NPV DECREASES WORD GAME: For child abuse, 1a) TAKE CHILD INTO CUSTODY 1b) TREAT CHILD 2) CALL CHILD SERVICES T-test for SAMPLE variance; Z-test for POPULATION variance. Paired-t test compares data that are related somehow; independent-t test compares unrelated data. To calculate odds ratio without the table: OR = [p/(1-p)] / [q/(1-q)] WORD GAME: Tarasoff: 1) WARN TARGET; then 2) W ARN POLICE As PREVALENCE declines, NPV decreases and PPV increases; no change in sensitivity or specificity Be very aware if they are asking for a 95% confidence interval or if asking what # of people fall within the top 95%? Be very aware of calculating RELATIVE RISK (division) vs ATTRIBUTABLE RISK (subtraction). WORD GAME: For RR or OR, exposed group can also refer to exposure to medication. When a baby can sit unsupported and crawl (7-9 months), the baby can also roll onto his back. PRETEST PROBABIL ITY refers to PREVALENCE. With difficult news to give: 1) Immediately inform patient of the news, 2) give them a moment to think, 3) explain what it means and give options 4) answer questions. TRAP: Effect modification occurs when the effect of a main exposure on an outcome is modified by another variable. *NO T A BIAS* Its just the nature of the experiment set up. Ex. Testing the effec t of a new estrogen agonist on the incidence of DVT is modified by smoking status in control vs experimental. Yes, he really hurt you. A lot of abused children have the same reactions. Is an example of SUPPORT Facilitation is merely saying Go on or What else do you have to add? If a question asks for the most appropriate next step in screening without any other qualifiers, choose the cheapest and easiest screening. (ex. VDRL) Case fatality rate is the fatality rate amongst those WITH THE DISEASE. Flooding or implosion are extreme forms of exposure. Projection Paranoia. Undoing: Acting out the r everse of unacceptable behavior. Repairs or fixes the impulse. Ex. Man who is sexually aroused by woman he meets immediately leaves and buys his wife flowers Knock on wood. Obsessive Compulsive behavior is undoing. The Rorschach test is a projective test. Halsted-Reitan Battery: tests for presence and localization of brain dysfunction; 5 basic tests: 1) category test,2) tactual performance test, 3) rhythm test,4) speech sounds perception test, and 5) finger oscillation test. Luria Nebraska Battery: tests level of impairment and functioning; subscales: motor, rhythm, tactile, visual-spatial, receptive speech, expressive speech, writing, reading, arithmetic, amnestic, intellectual, right and left hemisphere function.

Sleep deprivation facts: 1) Cerebral cortex shows the greatest effects of sleep deprivation but CAN COPE 2) Physical restitution of the rest of the body comes from rest (a byproduct of sleep), NO T sleep itself. 3) 80% of Stage 4 sleep is recovered; about one half of the missing REM is recovered. 4) Getting <5 hours of sleep or less per night person functions as someone who is legally drunk. 5) The longer the period of wakefulness, the mor e Stage 4 sleep increases during first part night & the mor e REM declines. 6) Short sleepers lose the latter part of REM 7) Lymphocytes decline, cortisol rises, BP rises, glucose tolerance reduced, greater amygdala activation, lower prefrontal cortical activity, increased negative mood. 8) REM increases after learning in the previous waking period. 9) REM deprivation: does NOT impede SIMPLE tasks; DOES impede complex tasks; IMPEDES LEARNING complex tasks; DECREASES ATTENTION, but NOT capacity to deal with crisis 10) DELTA SLEEP increases after exercise and seems to be the result of raised cerebral temperature. NIGHT TERRORS: Stage 4/Delta sleep; EXTREME physiologic arousal; NO RECO LLECTION; anxiety @ awakening; familial, more in boys, can be a precu rso r to tempo ral lobe epilepsy. NIGHTMARES: REM; ELEVATED physiologic arousal; RECOLLECTION; anxiety @ awakening *Getting 30 minutes more sleep each night reduces the incidence of BOTH. Somnambulism: (Sleep walking); first 1/3 of night, stage 4 sleep; if awakened confused and disoriented Enuresis: Stage 3 and 4; often history with same sex parent Bruxism: Stage 2 sleep; SAND: 5HT: initiates sleep; ACh: erections in men; NE: lower @ REM; begins in pons regulates REM sleep; DA: arousal/wakefulness SCN controls ACTH, PRL, melatonin, nocturnal NE release. SCN NE pineal melatonin. Extraocular movements during sleep due to PPRF activity. BZs SHORTEN Stage 4 sleep (useful for night terror/sleepwalking) TYPES OF HMOs: 1) Staff model: salary; owned by HMO; 2) Group model: fixed capitation/p rofit sha ring; owned by HMO; 3) Network model: negotia ted capitation; owned by practice; 4) Individual Practice Association: Many contracts, n egotiated fee schedules; owned by practice MEDICARE: Part A pays for hospital care; Part B pays for physician services. NOT COVERED by Medicare: Routine physicals, eye/ear p rescription exam, immunizations, routine foot ca re, ho me nursing, most self-adminstered drugs. COVERED by Medicare: Hospital stays, lab workups, non-self administered drugs, surgery, rehabilitation, dialysis, ambulance, diabetes equipment, pneumococcal and HBV vaccine, and (physical, speech, & occupational) therapy. WORD GAME: If both present, MEDICARE IS USED FIRST, then Medicaid. CHIP (Childrens Health Insurance Program): Matching state and federal government funding for child health care. REPORTABLE in ALL STATES: HAV, HBV, Salmonella, Shigella, Syphillis, MMR, AIDS, TB, gonorrhea. REPORTABLE (not all States): HCV, HIV, VZV Minor emancipation: Married, self supporting, children, military. Impaired automobile drivers ALSO fall under exceptions to confidentiality. TRAP: If a competent patient made NO indication of whom to share info do NOT give info to anyone but the health care team. EXCLUDE FAMILY until patient wants to tell them.

BC: -

DEVELOPMEN T (selected) 0-3months: ROOTING ; orients to voice 3 months: Holds head up social smile 7-9 months: Sits alone, crawls; 15 months: Walks 12-24 months: Climbs stairs 24-36 months: Gender; parallel play 3 years: LINE 4 years: STICK FIGURE Coop play, groom, clean ELDERLY CHANGE ALSO DECREASED psychiatric disorders. STRESS ALSO affects water absorption, muscular tonicity, gastrocolic reflex, and mucosal circulation.

Glycine, aspartate, glutamine are required for PURINE synthesis. Guanine has a KETONE; Thymine has a METHYL Most DNA is in B form right handed; ~10bp per complete turn of helix. Z Rare Z for m left handed; GC rich sequences involved in GENE REGULATION Regulatory proteins bind at the GROOVES Euchrom atin ENDS after 30 nm scaffold. During mitosis, DNA is compacted into HETEROCHROMATIN. Orotic aciduria: defects in OROTIC ACID PHOSPHORIBOSYLTRA NSFERASE OR OROTIDINE 5PHOSPHATE DECARBOXYLASE PRPP synthetase: Adds PPi (via ATP) to Ribose 5 phosphate. Allopurinol can DECREASE purine SYNTHESIS by inhibiting PRPP amidotransferase if HGPRT is still active. hnRNA processing: N UCLEUS: 5Gcap polyA tail splicing CYTOPLASM: methylation of 5cap INITIATION : aminoacyl-tRNA first binds GTP & EF-1 => When tRNA binds A site, GTP -> GDP => the EF-1-GDP complex binds EF-1, allowing GDP release. If EF-1 has greater affinity for GDP, then translation is DIMISHED. INCREASE EF-1 affinity will INCREASE translation. tRNA: 5: terminal guanine => D arm => anticodon => TC arm => -OH bind amino acid 3 Xeroderma pigmentosum ALSO has excessive freckling & corneal ulcerations. AT CHEMICAL EQUILIBRIUM, G would be 0. If it is not 0, then follow the direction (IGNORE concentrations) TRANSCRIPTION -factor helps PROKE RNA polymerase bind to PROMOTER GENERAL TFs: basal level transcription SP-1 is a TF with a zinc finger motif @ GC rich; housekeeping allows transcription genes to work NF-1 binds CAAT @ -75 TFIID binds w/ TBP to TATA before RNA pol II can bind. TISSUE SPECIFIC TFs: bends DNA to bring itself closer to the promoter. Ex. Steroid hormone receptor, CREB, homeodomain. TERMINATION: 1) -independent: new RNA folds on itself to GC rich hairpin loop followed by 6-8Us dissociate from DNA. 2) -dependent: binds and moves to RNA pol displaces RNA pol from 3 of mRNA. RNA processing: NUCL EUS 1) G-cap, 2) polyA, 3) splicing CYTOPLASM: methylation of Gcap. LAC OPERON: 1) Lactose + NO glucose basal cAMP + allolactose on REPRESSOR increased transcription 2) with GLUCOSE decreased cAMP decreased transcription. tRNA: 50S: 5S, 23S; 30S: 16S; 60S: 5S, 5.8S, 28S; 40S: 18S Shiga toxin: inactivates 28S by RNA glycoslyases that remove a single A from 28S. TRANSLATION PROKE: 16S binds to Shine Dalgarno; EUKE: 18S binds 5cap and slides over to AUG. 1) tRNA aminoacylation: ATP AMP; 2) loading tRNA: GTP GDP; 3) Translocation: GTP GDP Prenylation is a post translational modification (addition of farensyl or geranyl lipid groups to membrane)

WORD GAME: Microsatellite instability is characteristic of individuals with loss of function mutations in mismatch repair genes. Areas of DNA with dinucleotide repeats (example of microsatellite). Nucleotide excision repair: G1 Base excision repair: G1; Glycosylase (recognize + remove damag ed base) AP endonuclease @5end lyase cleaves sugar @3 end filled & resealed. Mismatch repair: G2 N-glycosylation starts in ER, ends in Golgi; O-glycosylation starts in Golgi. Peroxisomes 1) ox of LCFA + VLCFAs to make H2O2, 2) ox of branched chain FAs, 3) -ox of ordinary FAs. Zellwegger syndrome: defect of peroxisome FA efflux; accumulation of unusual FAs; enlarged liver, increased blood Fe, Cu, vision problems, failure to thrive, abnormal muscle tone, MR COP1: Golgi ER; COP2: ER cis-Golgi; Clathrin: trans Golgi lysosomes, plasma membrane Word game: CENTROSOME has no role in spindle apparatus. MEMBRANE: High cholesterol or saturated fats increased melting temp and decreases fluidity. WRINKLES are due to DECREASED SYNTHESIS and NET LOSS of DERMAL collagen & elastin. Mineral oil intake Fat Soluble Vitamin Deficiencies. Vitamin A is needed to create orderly epithelium; also essential for differentia tion to specialized tissu e (pancreatic cells, mucus-secreting cells) *C-11 double bond must be made cis for use in vision* IN a deficiency state, squamous epitheliu m undergoes a metaplasia to a keratinized epith elium. Vitamin D and K are not in breast milk Must give 1,25 Vit D for 1) ESRD, 2) Fanconi syndrome, 3) Genetic deficiency of 1-hydroxylase Vitamin E: Protects erythrocytes and membranes from ROS. Deficiency hemolytic anemia, muscle weakness, neurodysfunction, ataxia, retinitis pigmentosa, acanthoysis *High levels of Vit E decreases synthesis of vitamin K clotting factors hemorrhage in patients on WARFARIN Anticonvulsants during pregnancy DECREASED VITAMIN K. Vit B2 in milk, eggs, meats, fruits; deficiency cheilosis, corneal vascularization, and MAGENTA tongue Vit B3 in yolk, liver, poultry. **B3 in corn must be TREATED** Note: the dementia can simply be depression. Vit B5 deficiency dermatitis, enteritis, alopecia, adrenal insufficiency Vit B6 in vegetables, cereals, fruit Zinc deficiency Delayed healing, hypogonadism, decreased ADULT hair, dysgeusia, anosmia, scaling on extremities Child with milk allergies develops macrocytic anemia. taking goats milk, which is deficient in folic acid. During ethanol metabolism: Recycling NAD+ ALSO Oxaloacetate to malate CF infertility is due to absence or obstruction of vas deferens. MARFAN: Chr 15 Collagen formation ONCE AND FOR ALL: 1) Self-assembly of -chain fibrils CYTOPLASM 2) N-terminal has targeting sequence to RER 3) N-terminal hydrophobic signal peptides are cleaved to yield pro-alpha chains RER 4) Proline and lysine are hydroxylated by prolyl hydroxylase RER 5) Glycosylation of hydroxylysine residues can occur RER 6) Disulfide bond formation in C-terminal propeptide RER 7) Triple helix formation RER 8) Secretion into Golgi then out of cell 9) Cleaved @ N- and C- termini by N- and C- procollagen peptidase Extracellular Now known as collagen, its solubility has decreased by 1000 fold. 10) Collagen monomers crosslink to form staggered fibers via lysyl oxidase Extracellular Type 1 collagen: ALSO in dentin and fascia Type 3 collagen: ALSO in uterus, fetal tissue; *during wound healing, Type 3 1 w/ Zn as a cofactor Type 4 collagen: ALSO in lens Type 10 collagen: Epiphyse al plates

EHLER DANLOS SYNDROME: Type 1 : DIAPHRAGMATIC HERNIA Type 3 : AD; MCC Type 4 : AD; type 3 collagen; ARTERIAL OR COLO NIC RUPTURE Type 6 : AD; lysyl hydroxylase; RETINAL DETACHMENT + KYPHOSCO LIOSIS Type 9 : XR; copper metabolism, DECREASED LYSYL OXIDASE activity. Menke disease: XR: deficient cross linking due to functional copper deficiency; depigmen ted hair, arterial to rtuosity/rup ture, cerebral deg enera tion, osteoporosis, anemia Osteogenesis imperfecta can have a DECREASE IN HYDROXYLATION EFFICIENCY. Cystinosis: mutation in lysosomal membrane transporter cystine accumulation in lysosomes w/ crystals in lens of eye + renal PCT short stature, photophoba, progressive renal disease. Allele specific oligonucleotide requires a known DNA seqence; *it can detec t the # of copies of an allele* Types of DNA polymorphism s: RFLP: Pr esence/absence of restriction site *Best way to detec t relationship of a new bacteria* VNTR: differences in # of tandem r epeats b/t 2 restriction sites. STRP: differenc es in # of microsatellite repeats b/t 2 PCR primer sites. SNP: single nucleotide difference G1P to free glucose ratio: HIGH means FEW BRANCHES (thus fewer -1 ,6 linkages) I cell disease: defect in N-acetylglucosamine-1-phosphotransferase @ cis Golgi PRESENTS WITH: Clouded corneas, kyphoscoliosis, claw hand defo rmity, restrict joints, fa cial deformities. Glutathione ALSO brings certain amino acids into cells; requires GGT. Deficiency of GGT produces MR, seizures, and increased plasma/urine levels of glutathione. Other AAs do not increase because there are other transport methods. GLUT 1: RBCs, brain; may be part of BBB to limit glucose transport. GLUT 2: Liver, pancreatic -cells, and basolateral SI; high capacity, low affinity. BIDIRECTIONAL GLUT 3: Neurons, placenta, and testes. Very low Km. GLUT 5: Small intestine, testes, and sperm; FRUCTOSE TRANSPORTER. SLGT 1: Enterocytes AND neurons. NOTES: GLUT 4 also increased by exercise via 5AMP activated kinase; @normal [glucose], GLUT1 and GLUT3 at Vmax. For GLUT2, when [glucose] < Km, much glucose leaves liver for peripheral circulation. Because GLUT 2 and glucokinase have high Km, glucose is transported and phosphorylated via FIRST ORDER KINETICS. DOLICHOL is a very long phosphate lipid that serves as the substrate for forming the branched carbohydrate trees that are transferred to proteins. PROCESS DO NE IN RER. HEPATOMEGALY + HYPO GLYCEMIC SEIZURES => GLYCOGEN STORAGE DISEASE. Diffusion through membrane: CO2 > O2 CYSTIC FIBROSIS: Channel is gated by ATP hydrolysis. Be aware: 9 +2 axoneme is in CILIA; propulsion of sperm is by FLAGELLA. (Dynein + kinesin) VILLI: are associated with microfilaments (actin + myosin) B12 catalyzes methymalonyl CoA to succinyl CoA => Methylmalonyl CoA ISOMERASE/MUTASE Lack of Signal Recognition Particle (SRP) will prevent a protein from ENTERING the RER in the first place. Misfolded proteins are prevented from LEAVING the RER by chaperone proteins such as calreticulin. RATE LIMITIN G ENZYMES (selected) TCA cycle: Isocitrate dehydrogenase De novo pyrimidine: CPS II De novo purine: Glutamine- PRPP amidotransferase Urea cycle: CPS I GLUCOkinase is a GLUTTON so HIGH VMax. *Link VMax and Km together * NADH in glycolysis is made during G3P 1,3BPG. **NOTE: any glycolytic enzyme deficiency can cause HEMOLYTIC ANEMIA**

Arsenate inhibits G3P to 1,3BPG by mimicking phosphate the product is water labile, enabling glycolysis but no ATP. Fructose 1-P is converted to glyceraldehydes via aldolase B. It enters the glycolytic pathway AFTER the rate limiting PFK-1. Therefore, has a faster rate of metabolism than the other monosaccharides. FRUCTOSE-2,6-bisphosphate INDUCES PFK-1 and INHIBITS fructose 1,6 bisphosphotase. (PFK-1 and PFK-2 work together) 2+ PDH is activated by INCREASING Ca ALSO. TCA cycle makes 3NADH, 1FADH2 , 2CO2, 1 GTP 12ATP per acetyl-CoA. ETC: Complex 3: Cyt b/c 1 (Fe/heme); Complex 4: Cyt a/a 3 (Cu/heme) Rotenone, barbituates block COMPLEX 1; Rotenone & doxorubicin block CoQ. Antimycin A blocks Cyt b/c1 Oligomycin blocks Fo CN & CO block Complex 4 conversion of O2 H2O. Pentachlorophenol (used to treat wood to prevent insect invasion) is ALSO an uncoupler. Gluconeogenesis: MITOCHONDRIA: Pyruvate carboxylase: requires BIOTIN, ATP O AA leaves in malate-aspartate shuttle. CYTOSO L: PEP carboxykinase: requires GTP AND Fructose 1,6bisphosphatase ER: Glucose-6-phosphatase HMP shunt found in lactating mammary glands, liver, adrenal cortex, RBCs. Aldose reductase & so rbitol dehyd rogenase UTILIZE NADPH. Acetyl CoA-carboxylase is the RLS of fatty acid synthesis and is ACTIVATED BY INSULIN KWASHIOKOR: Low animal protein => DEFICIENT in LYSINE and TRYPTOPHAN. HISTIDINE is essential only during times of increased anabolic states; but USUALLY NONESSENTI AL because human body can synthesize it. GLUTAMINE is the *MOST ABUNDANT AA*; it is the major carrier of ammonia; amino group carrier from SkM to other tissues in fasting state; fuel for kidney, gut, and cells in immune system in FASTING state. ARGININE is essential for children because it STIMULATES GH & insulin. HISTIDINE: effective physiologic buffer; essential for child growth; *zero charge at pH7.4* ATTENUATION is a process of gene regulation that interrupts transcription after it has started. Tends to occur in operons that produced amino acids; only prokaryotes where transcription/translation occur at once. USUALLY FORMS HAIRPIN LOOP (mRNA secondary structure) Glycogenolysis can provide energy for up to a day (24 hours) during fasting. N-acetylglutamate synthetase is a cofactor for carbamoyl phosphate synthetase I Benzoate or phenylbutyrate both bind amino acid and lead to excretion given to decrease ammonia levels. Most tissues have glutamine synthetase, which captures nitrogen by IRREVERSIBLY animating Glu to Gln. + Glutaminase in KIDNEY will IRREVERSIBLY dea minate Gln and excrete the amino group as NH4 . + In INTESTINE sends NH4 to liver for urea cycle. Glutamate dehydrogenase: in many tissues: catalyzes REVERSIBLE oxidative deamination of Glu to KG SAM does methyl transfer; THF does methylene, methenyl, formyl transfer. AMINO ACID DERIVATIV ES Tryptophan + BH4 Serotonin Melatonin Glutamate + B6 GABA Arginine Creatine ++ Phe + BH4 Tyr + BH4 DOPA + B6 Dopamine + Vit C* + Cu NE + SAM ** Epinephrine *Thus, pheochromocytoma can cause Vit C deficiency; **Note, PNMT requires cortisol

Glycogen Storage Diseases (selected) Von Gierkes ALSO leads to HYPERURICEMI A (increased AMP uric acid), HYPERLIPIDEMIA due to increased VLDL Coris disease (Type 3); defect in DEBRANCHING ENZYME similar to Type 1 but NORMAL LACTATE. Andersens disease (Type 4): defect in BRANCHING ENZYME infantile hypotonia, cirrhosis, death by 2 years. Hers disease (Type 6): defect in HEPATIC GLYCOGEN PHOSPHORYLASE mild fasting hypoglycemia, hepatomegaly, cirrhosis, hyperlipidemia. Lysosome Storage Diseases (selected) MISSING; BUILDUP Fabrys: -glucosidase A Ceramide trihexoside; Peripheral neuropathy, ocular, angiokeratomas, CV/renal Kidney Bx: va cuolated visceral epith elial cells which co rrespond with la mella r bodies on EM. Gauchers: -glucocerebrosidase Glucocerebroside; HSmegaly, AVN, bone crises, crumpled tissue macrophages. Adult type massive HSmegaly & increase in serum total acid phosphatase fro m ma crophages. NiemannPick: Progressive neurodegeneration, HSmegaly, FOAM CELLS; EM: Zebra bodies in inclusions. TaySachs (4 BP insertion): Progressive neurodegeneration, developmental delay, onion skin lysosomes, NO HSmegaly. Krabbes: Galactocerebrosidase Galactocerebroside; P. neuropathy, development delay, optic atrophy, globoid cells Metachromatic Leukodystrophy: Arylsulfatase A Cer ebroside sulfate; P + C Demyelination w/ ataxia, dementia. Hurlers: -L-iduronidase Hunters: Iduronate sulfatase Apolipoproteins (once and for all) ApoA-1: LCAT activation ApoB48: Chylomicron assembly and secretion by the intestine. ApoB100: LDL particle uptake by extrahepatic cell ApoCII: LPL a ctiva tion ApoE3&E4: VLDL and chylomicron remnant uptake by liver cells. WORD GAME: LPL is on the luminal surface of VASCULAR ENDO THELIUM of adipose, SkM,myocytes, and lactating breast WORD GAME: HSL is located within the adipocytes. *Fasting affects chylomicron and LDL; does NOT affect HDL or total cholesterol. TGs increase turbidity falsely LOW enzyme and sodium measurements. Chylomicrons form a SUPRANATE (very little protein, less dense than VLDL) VLDL forms an INFRANATE HYPERL IPIDEMIAS: Type 1 : LPL deficiency OR altered C-II increased CHYLO MICRONS & TGs pancreatitis, HSmegaly, eruptive xanthomas; standing chylomicron test: supranate but no infranate Type 2 : (AD) defect of LDLr transport from ER (70% LDL cleared by liver) 2a) increased LDL & cholesterol; normal TG; 2b) increased LDL, cholesterol, and TG Type 3 : (Dysbetalipoproteinemia) DEFECT in ApoE3,E4 ; INCREASED VLDL remnant & CHYLOMICRON remnant; BETA MIGRATING VLDL on electrophoresis; EII/EII genotype is nearly pathognomonic. XANTHOMAS, PREMATURE CVD & PVD, hyperuricemia, obesity, diabetes. Type 4 : (AD) Defect in ability to internalize bound LDL increased VLDL + TGs; standing chylomicron test: turbid infranate can lead to pancreatitis; can be ACQUIRED from alcoholism, diu retics, -blockers, renal failure. Type 5 : (1 + 4) Defec t in recycling of LDLr increased CHYLOMICRONS w/ NORMAL LDL; standing chylomicron: supranate and infranate; common in alcoholics and DKA; hyperchylomicronnemia syndrome: abdominal pain, pancreatitis, dyspnea, HSmegaly, papules on skin. Mutation in LDLr causes LOSS of FEEDBACK INHIBITION of HMG-CoA reductase. Abetalipoproteinemia: AR; mutation in MICROSOMAL TG TRANSFER PROTEIN (MTP) which is essential for packaging of hepatic TGs with other components of VLDL. Also deficiencies in apoB100 and B48. Failure to thrive, steatorrhea, acanthocytosis, ataxia, night blindness (secondary Vit A deficiency), hemolytic anemia (VitE) Clear, foamy enterocytes due to accumulation of lipid in enterocytes and inability to export as chylomicrons. Tangier disease: Lack of cholesterol transporter ABCA1 cannot load cholesterol to HDL foam cells form Orange yellow tonsils, lo w serum cholesterol, senso ry neuropathy, muscle wasting of hands

Linoleic acid: C18:26 arachidonic acid; NOT cardioprotective; corn/safflower oil. Linolenic acid: C18:33 CARDIOPROTECTIVE (lower TGs, inhibit platelet aggregation, anti-inflammatory PGs, less damage to tissue in infarction; fish, canola oils. *Only muscle can metabolize branched chain fa tty acid s* Morquios syndrome: short stature, joint laxity, MSK abnormalities, HSmegaly, mild corneal clouding, valvular heart disease. Sanfillippos syndrome: Many enzyme deficiencies cause this mucopolysaccharidosis; also present are: developmen tal delays, behavioral problems (aggressive tend encies & hypera ctivity), sleep diso rders. Sly syndrome: defec t in -glucoronidase; AR; presents similarly to Hurlers syndrome, but no MR. Tay-Sachs: Frameshift mutation @ Chr 15 WORD GAME: In CF, reduced ductal epithelial chloride secretion & increased sodium and net water reabsorption, results in dehydrated mucus and a widened transepithelial potential different. (This is true only of exocrine glands, NOT sweat) In patients with essential fructosuria, fructose fructose 6 phosphate (via hexokinase) is the primary method of metabolism. NOTE, this pathway is NOT SIGNIFICANT in normal individuals. Boy with vision problems, MR, stroke, MCA thrombosis, and old renal infarcts homocystinuria RECALL you can give B6, which is a cofactor for cystathionine synthase. Branched chain -ketoacid dehyd rogenase: converts LEUCINE Ac etyl CoA; ISOLEUCINE & VALINE Propionyl-CoA Hereditary tyrosinosis: deficiency of fumarylacetoacetate hydrolase (maleylacetoacetate to fumarylacetoacetate) increased serum tyrosine; cabbage like odor, cirrhosis & HCC, aminoaciduria, death in first year of life.

Genetics: Loss of heterozygosity refers to the two hit hypothesis. In VAST MAJORITY of Downs, nondisjunction @ ANAPHASE 1 **increased inhibin A is also a marker for Downs** LOW YIELD DOWN symptoms: hypotonia, hyperflexible joints, anomalous auricles, p elvic dysplasia, low nasal bridge, micropenis, iris sp eckling. Turners syndrome: ALSO has bicuspid aortic valve and hypothyroid; MOST are mosaics (thus MITOTIC nondisjunction) TRUE hermaphrodite: 46XX or 47 XXY Androgen insensitivity syndrome: XR; Xq11-12; DEVELOPS testes in the labia minora (remove to prevent cancer) Recurrent miscarriages in FIRST trimester: signify MEIOSIS 1 nondisjunction; of these, Robertsonian is MC. Note: an autosomal monosomy is incompatible with life (will not even make it to first trimester) WORD GAME: Fragile X syndrome: Increased CGG repeats hypermethylation in FMR1 gene symptoms Fragile X: ALSO poor eye contact, perseveration, and impulsivity (echoalia) Dominant negative means abnormal gene product interferes with the normal gene product (two alleles) Ex. Osteog enesis imperfecta: abnormal collagen subunits assemble with no rmal ones d estruction of the entire macromolecule. Ex. Mutation of TF in allosteric site still binds DNA prevents wild type TF from binding. Haploinsufficiency: mutant product is nonfunctional. Trisomy 8 CAN lead to live offspring (tend to be mosaics) Trisomy 16 will NOT lead to live offspring. WILLIAMS SYNDROME: Congenital microdeletion of 7q (includes ELASTIN gene) elfin facies, MR, hypercalcemia (sensitivity to Vit D), CV problems (supravalvular aortic stenosis) WORD GAME: Marfans syndrome has HIGH PENETRANCE (so you are free to choose new mutation) TRAP: Marfans ALSO has double jointed and hyperflexible joints. **Look for the clue on body habitus** Confined placental mosaicism is the consequence of a genetic aberration in the trophoblast or inner cell m ass. The trisomy leads to an abnormal placental development and intrauterine growth retardation. Trisomy is ONLY in the placenta. For a multifactorial trait, if DZ < 1/2MZ cannot be simple AD; if DZ < 1/4MZ cannot be simple AR; Either way, the true risk will be LARGER than that for the general population, but LESS than predicted by genetics. CAG repeats in 5 coding region; CGG repeats in 5UTR; CTG in 3 UTR. Myotonic dystrophy: muscle loss, arrhythmia, testicular atrophy, frontal baldness, cataracts

Prader Willi: DELETION of NORMAL (non-imprinted) Paternal allele AngelMann: DELETION of NORMAL (non-imprinted) Maternal allele RECURRENCE RISK FOR MULTIFACTO RIAL DISEASES 1) Increased as # of affected relatives increases (reflects more info, NO T true risk) 2) Increased as SEVERITY of disease increases (reflects greater liability) 3) Increased if proband is of LESS COMMO N SEX. 4) DECREASES rapidly for more remote relatives 5) Increased as PREVALENCE increases. Myoclonic epilepsy with ragged red fibers: muscle spasms, myopathy, ataxia, generalized seizures, intellectual deteriorations, hearing loss. LOD score: >3 linkage; <2 no linkage; the value of at the highest LOD score is the most likely estimate of recombination frequency. AD enzyme disorders: 1) uroporphyrinogen syn thase 2) C1 esterase inhibito r. HLA haplotypes for transplant : Siblings are best choice chance of sibling with 0, 1, 2 haplotypes (25%, 50%, 25%); Parents automatically have 1 haplotype.

MB: GRAM STAIN Step 1) Crystal violet (small dye molecule) & Grams Iodine (large dye complex) purple/blue for GP and GN Step 2) Acetone/Alcohol GP: purple/blue; GN: colorless Step 3) Safranin (pale dye): GP: purple/blue; GN: red/pink ZIEHL NEELSEN (or Kinyoun) Step 1) Carbol Fuchsin with heat (needed to get dye into mycobacterial cell): AF& non-AF RED (Hot Pink) Step 2) Acid alcohol: AF RED ; non-AF colorless Step 3) Methylene Blue: AF RED; non-AF BLUE GIEMSA STAIN (an aniline dye) Borrelia, Plasmodiu m, trypanosomes, Chlamydia. VDRL FALSE POSITIVE: Viruses (mono, hepatitis), Drugs, Rheumatic FEVER, Lupus/Leprosy CAMP test: GBS is -hemolytic but makes an additional polypeptide that complements the sphingomyelinase of S.au reus to produce an additional zone of -hemolysis that appears as an ARROWHEAD. ELEK test is the immunodiffusion test to ID toxin producing strains of C.diptheriae. Obligate aerobes: Nocardia, Pseudomonas, MTb, Bacillus Nagging Pests Must Breathe. Obligate anaerobes: Clostridium, Bacteroides, Actinomyces Cant Breathe Air. Facultative intracellular: Salmonella, Neisseria, Brucella, Mycobacteria, Listeria, Francisella, Legionella Some Nasty Bugs May Live FacultativeLy Mycoplasma is EXTRAc ellular; do not get confused. Exotoxin: destroyed rapidly at 60C (except staphylococcal enterotoxin) Endotoxin: Stable at 100C for 1 hour; poorly antigenic. Lysogeny: ShigA, Botulinum, Cholera, Diptheriae, Erythrogenic toxin (Scarlet) Specialized transduction MOST LIKELY transfers the genes CLOSEST to the INSERTION SITE; ther efore, literally look at the distance on the genome. IgA protease ALLOWS o ropharynx colonization. COLON FLORA: Bacteroides >> E.Coli. GN bacilli do NOT allow penicillin G and vancomycin through the OM. L.monocytogenes is -hemolytic; ALSO amnionitis, septicemia, spontaneous abortion, granuloma tosis infantiseptica. Cardiolipin (diphosphatidyl glycerol) in INNER MITOCHO NDRIAL MEMBRANE & BACTERIAL MEMBRANES CATALASE POSITIVE: S.aur eus, Nocardia , Aspergillus, P.cepacia, Serratia(SNAPS) UREASE POSITIVE: Proteus, Ur eaplasma, Nocardia, Cryptococcus, Helicobacter (PUNCH) OXIDASE POSITIV E: Campylobact er, Neisseria, Helicobact er, Vibrio

Heterophile Neg Mono-like with unprotected sex: think acute HIV infe ction (high viral load, check RNA) H.influenzae: NONTYPEABLE: OM, sinusitis, conjunctivitis; Type B: meningitis, pneumonia, sepsis, epitglottitis + Note, -hemolysis of agar by S.aureus releases NAD for Ha emophilus. H.ducreyi: Pleomorphic gram negative rods in short parallel chains (school of fish); Also satellites around S.aureus Botulinum SPORES cause floppy baby syndrome. But PREFORMED TOXIN causes botulism in adults. C.perfringens in REHEATED MEAT DISHES TRAP: There is no antibody or toxin assay for tetanus; must rely on a good physical/history. Intravascular devices account for increased incidence of nosocomial bacteremia/sepsis. POSITIV E VDRL + CSF pleocytosis => N EUROSYPHILLIS; thus any lesion on genitals is a GUMMA. DEMENTIA is a part of neurosyphillis. *Tabes dorsalis may not be present yet.* TRAP: Dont fall for the chancre. Tertiary syphilis ALSO has stroke without hyper tension. Warthin-Finkeldy giant cell is pathognomonic for measles OR post-vaccine lymphadenopathy. Paraco rtical expansion & sca ttered multinu cleated giant cells w/ eosinophilic cytoplasmic and nuclear inclusion bodies (fusion of lymphocytes) R.ricketssiae infects endothelial cells intracellularly. R.prowa zekii: EPIDEMIC TYPHUS (lice); R.typhi: ENDEMIC TYPHUS (rodents => flea); R.tsu tsugamushi: SCRUB TYPHUS (mite) Erlichia: morulae in granulocytes; no rash, leucopenia, thrombocytopenia, increased transaminases. *Ixodes or A mblyoma ticks* Shigella has to INVADE the intestinal mucosa (M cells) first in order to cause disease; thus, toxin is NOT the most important pathogenic factor. *Mini-epidemics have o ccu rred in the dayca re setting* no flagella, but CAN propel within a cell by ACTIN POLYMERIZATION. Salmonella: Initial defense is due to ALT COMPLEMENT activated by endotoxins; MONOCYTIC response; antibiotics make worse; Ab to O, Vi, H antigens by WIDAL TEST; invades ileocecal. S.typhi: Highly motile with Vi capsule, sensitive to acid; REMAINS IN GALLBLADDER CHRO NICALLY. S.paratyphi: MCC of osteomytelitis in patients with SCD. C.jejuni: from animals to humans directly. LOW INFECTIVE DOSE *SELECTIVE GROW TH @ 42C; NO NALKALINE GROW TH Vibrio : ALKALINE GROWTH V.parahaemolyticus: SELF LIMIT in SEAFOOD V.vulnificus: Brackish water; diarrhea OR cellulitis Pseudomonas can cause nosocomial UTIs; in a CF patient, the most important pathogenic factor is the CAPSULE, because it overburdens the already overworked neutrophils. TRANSMITTED VIA W ATER (ventilator pneumonia) ALSO causes DIABETIC OSTEOMYELITIS; Ecthyma gangrenosu m is due to elastases. **Resistant to mediations because mutation of porin protein prevents flow of antibiotics into cell. B.recu rren tis is transmitted by the human louse, Pediculus humanus. Pertussis toxin causes lymphocytosis by altering function of chemokine receptors, blocks immune effector cells, and INCREASES HISTAMINE SENSITIVITY. M.pneumoniae can also cause serous otitis media and bullous myringitis in 20% of patients. U.urealyticum: fried egg colony on Eatons media; urethritis, prostatis, renal calculi. L.monocytogenes has a VERY NARROW ZO NE OF -hemolysis V.cholerae leads to an ISOTON IC DIARRHEA. C.diptheria e stains metachromatic (blue and red) with aniline dyes (methylene blue) (May be referred to as polar granules) Enterobacteria ceae: O antigen polysaccharide of endotoxin; K antigen virulence of bug E.Coli ALSO causes pneumonia. E.coli O157:H7 does NOT ferment lactose or produce glucoronidase (unlike other E.coli) EHEC does not ferment sorbitiol (select for it on MacConkeys agar with sorbitol) EIEC (only one to INVADE mucosa) ALSO has shiga like toxin. EPEC (no toxin) binds to the M cells, flattens villi, and PREVENTS ABSORPTION. The K-1 capsular Ag of E.Coli is MOST IMPORTANT for neonatal meningitis. (INHIBITS COMPLEMENT, PHAGOCYTOSIS) S.epidermidis is NOT found in the oral cavity (other bugs can affect artificial valves)

Brucella is partially acid fast. N.gonorrhoae is fastidious and will ONLY GROW on chocolate agar with CO2; ALSO causes neonatal conjunctivitis. L.monocytogenes: granulomatosis infantseptica (fatal); amnionitis & abortion in pregnant women; *SEL ECTIVE @ 42C* G.vaginalis causes a thin, gray discharge. NO T AN STD; (FLO URISH @ HIGH pH) Mobiluncus, an anaerobe, is ALSO involved. Chlamydia: Discharge shows sloughed epithelial cells with scant neutrophils. Inclusions stain with iodine or Giemsa. WORD GAME: Failure to treat urethritis with 3G + AZ (such as using only one) is called inappropriate antibiotic therapy. Chlamydia Neonatal pneumonia has EOSINOPHILIA Lymphogranuloma venereum: initial papule painFUL inguinal nodes that rupture and ulcera te; ALSO rectal strictures. Donovanosis papule ulcerates exophytic, soft, painLESS mass with indurated borders. OR painful, serpingous raised sores & Bx reveals macrophages with intracellular organisms. In vitro: antibody to a capsule will cause swelling: quelling rea ction. Klebsiella granuloma tis can cause granuloma inguinale : painLESS genital ulcers that ooze blood and pus. T.pertenue causes keloids & severe limb deformities. VDRL positive. B.anthra cis on microscopy forms serpentine, medusa head chains. B.cereu s: Emetic toxin (1-6 hours): RICE PREFORMED. Diarrhea toxin (18 hours): Heat labile; in vivo. WORD GAME: Viridans strep can make dextrans from sucrose dextrans can bind to fibrin HENCE when there is valvular damage, platelets/fibrin form on the valves dextrans bind to fibrin on the valve and SBE occurs. DONT FORGET, THEY ALSO CAUSE DENTAL CARIES WORD GAME: Colonization of hospital water system L.pneumophilia Failed sterilization of mechanical ventilators E.Coli, K.pneu moniae, Acinetobacter, and Pseudomonas. M.tuberculosis: Niacin +, heat sensitive catalase, sulfatides inhibit phagolysosome; cord factor causes serpentine growth (inhibits leukocyte migration; disrupts mitochondria/oxphos.) *M.Tb ALSO taken by up Peyers patches intestinal Tb TERMINAL ILEUM. M.lep rae in ARMADILLOS. M.scrofulaceum: scotochromogen associated w/ painless cervical adenopathy in children. M.ma rinum: swimming pool granuloma. M. kansasii: photochromogen that produces pulmonary Tb. M. fortuitu m: rapidly growing TB associated w/ infection in IC hosts and in prosthetic devices ShYPS: Nonmotile, nonH2S Shigella, Yersinia; Motile, H2S Proteus, SalMonella Yersinia enterocolitica: DAYCARE; can GROW AT 4C; ORAL TRANSMISSION via milk/pork; at times blood transfusion; Pseudoappendicitis: appendix NORMAL, mesenteric lymph nodes enlarged with focal areas of MICROABSCESSES; Also mimics Crohns disease. **MC organism contaminating blood transfusions & MAY trigger ankylosing spondylitis** E.co rroden s: bleach odor. CELLULITIS C.canimo rsus: c ellulitis, splenectomy, sepsis L.pneumophila : detected clinically by presence of antigen in urine. LEGIONNAIRES severe pneu monia, fever, hyponatremia, hypophosphotemia, in creased BUN & Cr, thro mbocytopenia ; PONTIAC mild flulike L.interrogans: Leptospirosis: flulike, fever, headache, abdominal pain, jaundice, photophobia w/ conjunctivitis Weils disease: severe for m w/ jaundice, azotemia (liver and kidney dysfunction), fever, hemorrhage, anemia. Bacteroides: weakened LPS, capsule, septicemia, peritonitis, abdominal abscess SYSTEMIC MYCOSES mimics TB (granuloma formation) Conidia are ASEXUAL FUNGAL SPORES blastoconidia = buds; arthroconidia = spores on joints. Sporotrichosis can ALSO be obtained from a lobster spine prick (one that has been packed in sphagnum moss) Coccidioidomycosis and Histoplasmosis are INHALED by ASEXUAL SPORES. Histoplasmosis: ACUTE PNEUMONIA calcification relapse with T cell immunosuppression. *In starlings* Blastomycosis: Inflammatory lung disease disseminate to SKIN and BONE GRANULOMATO US NODULES

Coccidiodomycosis: PNEUMO NIA & MENINGITIS Aspergillus: Air-crescent sign: cresecentic radiopaque masses representing air between infarcted/normal tissue. Allergic bronchopulmonary aspergillosis is a hypersensitivity reaction in patients with long standing atopic asthma. Very high seru m IgE levels, eosinophilia, and IgE + Ig G serum antibodies to Aspergillus UNTREATED LEADS TO proximal bronchiectasis & recurrent transient pulmonary infiltrations. WORD GAME: Aspergillus fungus ball in a TB cavity & ABPA colonizing aspergillosis. Invasive aspergillosis refers to development of necrotizing pneumonia and granulomas in immunocompromised; cellulitis in burn patients also falls under invasive. M.furfu r can lead to FUNGEMIA in premature infants on IV lipids. Candida: Vulvovaginitis with high vaginal pH, diabetes, use of antibiotics; MPO deficiency => Increased Candida infections TREAT oral with clotrimazole troches or fluconazole tablets T-cells prevent SUPERIFICAL candidiasis; Neutrophils pr event hematogenous dissemination. Candida is normal flora in the GI tra ct (in cluding mouth); Candida found in mouth befor e entering sputum Systemic pathogen that is oftend associated w/ presence of indwelling venous/arterial catheters and IC patients pneumonia with diffuse nodular infiltrates and evidence of vessel infiltration C.albicans Fungal meningoencephalides: Aspergillus + Muco r tropism for blood vessels (vasculitis, hemorrhage) (Mucor: nonseptate hyphae with right angle br anching.) Rhinocerebral, frontal lobe abcess. TRAP: Mu cor/Rhizopus ALSO in leukemic patients. Cryptoco ccus (ur ease positive) diffuse; invades brain through Virchow-Robin space (continuation of subarachnoid around BV entering the neuropil); *SOAP BUBBLE LESIONS* P.jiroveci is an extracellular, atypical fungus kills Type I pneumocytes excess replication of Type 2 pneumocytes damage to alveolar epithelium HONEYCOMB (on silver stain, the holes show cysts/trophozoites) Neonatal PCP increased Type 2 pneumocytes increased surfactant ASPHYXIATION C.neoformans is a round/oval NARROW BASED BUDDING yeast. MOLD FORMS: S.schenckii: Branching hyphae. C.immitis: Boxcar hyphae-like with endospores (arthroconidia) H.capsulatum: Hyphae with microconidia & tuberculate macroconidia. B.der matitidis: Hyphae with nondescript conidia. YEAST FORMS: B.der matitidis: 5 to 15 m H.capsulatum: 3 to 5 m with thin wall, no capsule. C.neofor mans: 4 to 10 m with BRO AD SLIMY CAPSULE Paracoccidiodes: 10-60 m with multiple budding verrucoid lesion on skin S.schenckii: Round or cigar-shaped budding yeasts UNEQUAL BUDDING PROTOZOA Toxoplasma gondii is INTRACELLULAR. Thus, CMI controls it. : chorioretinitis, hydrocephalus, intracranial calcifications. TRAP: Most people have latent toxoplasma that is reactivated during immunosuppresion. Babesia is intraerythrocytic, thus no MHC I; NK cells destroy it. E.histolytica has anchovy paste liver abscess (increased AP); causes hepatic abscess through oral route; invades submucosa diarrhea; The cyst form is spherical, 10-20m in diameter, and have granular cytoplasm containing up to four nuclei Dientamo eba fragilis is an intestinal ameba that may also produce infectious diarrhea; NO CYST FORM. C.parvus: minute intracellular spheres (2-5m) OR arc shaped merozoites; cysts are 4-5m Mechanism of diarrhea is through direct lysis of cells of the brush border as the intracellular parasites multiply there. Acid fast CYSTS that do NOT fluoresce UV Isospora belli: Acid fast cysts are asymmetrical, almond-shaped, about 30m MIMICS giardiasis; transient diarrhea in AIDS; 2 sporocysts each with 4 sporozoites; Cyclospora cayen tanensis: Diarrhea in IC; spherical, partial acid fast, FLUORESCE BLUE under UV. Microsporidia: diarrhea in AIDS; acid fast spores in stool.

Naegleria: severe prefrontal headache, nausea, high fever, ALTERED SMELL Amoeba form outside, but WITHIN HUMAN BODY: flagellated trophozoite. Acanthamoeba: KERATITIS, GRANULO MATOUS AMEBIC ENCEPHALITIS; multifocal hemorrhagic necrotizing meningoencephalitis; Star shaped cysts on biopsy (NOT in CSF) Affects immunocompromised Giardia does NO T INVADE intestinal mucosa; it will just DECREASE SURFACE AREA for absorption. WORD GAME: In biopsy, Giardia is captured at an angle and will appear as crescent shaped protozoa next to brush border. Visceral leishmaniasis: spiking fevers, HSmegaly, pancytopenia. T.vaginalis has a yellow, frothy discharge; also causes cervical erythema. STD Schuffner dots are multiple brick-red dots on RBCs under stain; indicates P.vivax (Western) or P.ovale (Africa). Vivax: ameboid trophozoites Ovale: oval, jagged RBCs. Malariae: bar/band rosette schizonts. Balantidium coli: large cysts; colonic ulcers w/ bloody diarrhea. HEMOFLAGELLATES Leishmanial form = within macrophages; trypanosomes are extracellular and circulate within blood Leish maniasis only leishmanial form are in humans sandly (Phlebotomus) 1) visceral (Leishmania donovani complex): massive HSmegaly and anemia 2) cutaneous (Leishmani tropica complex): ulcers African trypanosomiasis only trypanosomal forms are in humans tsetse fly encephalitis, increased IgM America trypanosomiasis leishmanial (tissue destruction) and trypanosomal forms are in humans. NEMATODE/ROUNDWORM O. volvulus: DIMINISHED VISUAL ACUITY, GENERALIZED ITCHING during shower, HYPOPIGMENTATION of SHINS, NODULES ON ILIAC BONES, KNEES, ELBOWS; SCLEROSING KERATITIS and CHORIORETINAL LESIONS on EYE EXAM Microfilaria do not enter blood, no periodicity; skin Bx: unsheathed microfilaria that do not have nuclei extending into tail. Eosinophilia; diethylcarba mazine produ ces severe pru ritis, rash, fever, and conjunctivitis. **Allergic reaction to microfilaria: LEOPARD RASH Loa loa (another EYE wo rm): transmitted by deer fly, horse fly, and mango fly; can see worm crawling in conjunctiva . Brugia malayi also causes lympathic filariasis. (Brugia and Wucheria transmitted by FEMALE MOSQUITO; both have microfila ria in the blood @ night: sheathed and lack nu clei in tail.) Ascaris lu mbricoides (giant roundworm): LARVAL FORM: cough, pneumonitis, eosinophilia. ADULT FORM: eggs visible in feces, intestinal INFECTION, bile stained eggs, NO EOSINOPHILS. T.spiralis: periorbital edema, fever, myalgia, splinter hemorrhage, eosinophilia. muscle cysts tend to calcify. Strongyloides sterco ralis: larvae from soil; vomiting, diarrh ea, and anemia. In AIDS common cause of autoinfection and superinfection. Trichuris trichuria: diarrhea, rectal prolapsed, eosinophilia. Dracunculus medin ensis: from drinking water w/ copepods; skin infla mma tion and ulcera tion. Guinea worm, fiery serpent Toxocara canis/catis: from egg contamined food; GRANULO MAS (if retinal blindness) and visceral larva migrans. Ancyclosoma spp. (cutaneous larva migrans or creeping euprtion) children playing on sandy beaches or playgrouds were dogs and cats urinating. Anisakis simplex: eating raw fish & pickled herring larvae penetrate GI mucosa and produce cramping abdominal pain, epigastric distress, vomiting and diarrhea. Dirofilaria mimitis (hea rt worm): dog heart wor m that is normally in dogs RV mosquito transmits microfilaria larva enters right heart and embolize to lung small pulmonary infarct presenting as a coin lesion. No effec tive Rx TREMATODE/FLUKES (Leaf shaped; most hermaphrodite) S.mansoni: onset of egg laying (sharp lateral spine) is the TRIGGER for disease; granulomas form around lodged eggs. sharp inflammatory response concentric fibrosis (pipe stem cirrhosis) Liver flukes: Clonorchis sinensis (bilirubinate stones) ; Fasciola hepatica (sheep) found in watercress; FEVER, NIGHTSW EAT, MALAISE Intestinal fluke: Fasciolopsis buski in aquatic vegetation(abdominal pain, diarrhea, intestinal mucosal abscesses) Lung fluke: Pa ragonimus westermani (cough, bronchiectasis, and hemotypsis) Mimics Tb Blood fluke: Schistosoma haematobium infects pelvic veins.

CESTODE/ TAPEWORM (Hermaphroditic; Head/scolex; neck/proglottids) E.granulosis: Hydatid cysts (ENCAPSULATED, CALCIFIED CYST; EGGSHELL) that contains fluid and budding cells. DH in Sheep; IH in humans. Spilling contents into peritoneum => ANAPHYLAXIS; **Ethanol to NEUTRALIZE antigens. E.multiloca ris: IH in rodents; DH in dogs/cats; Alveolar hydatid cyst disease SURGERY D.latum: Larvae of RAW freshwater fish; DH B12 anemia; IH larva encyst in intestinal wall. T.solium: IH cystercercosis*; DH same as saginatum * multiple punctuate calcifica tions and two cystic lesions with surrounding edema. Hymenolepis nana & diminutus: MC tapewor m in US. Destroy NAKED viruses: Chlorination, bleach, formaline, UV, boiling to 85C. Release of NAKED viruses lyse host cells NO PERSISTENT INFECTIONS Release of ENVELOPED viruses budding senescence of cell Papiloma- & Polyoma- viruses are CIRCULAR. RNA viruses replicate in cytoplasm (except influenza and retrovirus) NAKED: Hepe,PCR and PAPP DNA ENVELOPE: Herpes-, hepadna, variola DNA NUCLEOCAPSID: Adeno-, papilloma-, parvoRNA ENVELOPE: Influeza, parainflueznza, RSV, MMR, rabies, HTLV, HIV RNA NUCLEOCAPSID: picorna-, reoWORD GAME: Viruses can undergo recombination to generate new cytopathic effects. Choose if viruses are non-cytopathic. WORD GAME: Phenotypic mixing refers to two viruses that create a progeny with a capsid from one virus and genomic material from another. This REQUIRES at least 1 cytopathic virus in the co-infection. For HSV, treat with DAILY NRTI. During LATENCY, only dsDNA and latency mRNAs are DETECTABLE. HSV: glassy, intranuclear eosinophilic inclusions. HSV1 temporal lobe encephalitis LARGE # RBCs in CSF EBV: symptoms COINCIDE with EARLY ANTIGEN. CMV: purple intranuclear inclusions combined with granular cytoplasmic inclusions, and markedly enlarged cell size. HHV6 can cause FEBRILE SEIZURES before rash. WORD GAME: virus-encoded polypeptide with protease activity essential for generating functional viral proteins from a large precursor polypeptide refers to polycistronic mRNA found in +ssRNA, nonsegmented viruses. Adenovirus has WATERY diarrhea; ALSO has hemorrhagic cystitis in boys 5-15; ALSO keratoconjunctivitis in SHIPYARD. HPV: SERO TYPE: 1: plantar, 2,4: palmar Variola has guaneri bodies. Rotavirus is WATERY diarrhea, but ALSO can lead to transient lactose intolerance due to flattening of brush border. Remember this is the MCC of diarrhea DO NOT FORGET THIS. CFTV (West and NE United States): *Virus infects eryth roid precurso rs* flu like illness, biphasic fever, conjunctivitis, rash Coxsackie A => Herpangina => HIGH FEVER, SORE THRO AT, GRAY-WHITE VESICULAR LESIONS over SOFT PALATE/TONSILS Picornaviridae has polycistronic mRNA that requires PROTEASE cleavage. Ebola + Ma rburg (filovirus) => Primary infection site in macrophages (immunosuppression) => Dissemination via lymphatic and vascular systems (endothelial cells are targets for replication) => LUNGS, SPLEEN, LIVER, ENDO THELIAL CELLS Dengue breakbone fever: rash, muscle, and joint pain reinfection can result in hemorrhagic shock. Yellow fever: liver, kidney, heart, and GI (black vomit) damage. ALSO has Cowdry type A bodies (intranuclear eosinophilic droplet like bodies) Unlike other viral hepatitis, YELLOW FEVER flavivirus has AST > ALT, r eflecting damage to myocytes. Togaviridae ALSO has Western & Eastern & Venezuelan Equine Encephalitis. Only Influenza A can do antigenic SHIFT. (Bring your A game) Coronavirus is **HELICAL & +ssRNA** SARS atypical pneumonia from BIRDS & CIVET CATS; Paramyxoviridae ALSO has Human Metapneumovirus (colds and pneumonia in KIDS) Morbilivirus can lead to giant cell pneumonia (rarely; in IC) Lassa fever encephalitis & LCMV spread by MICE

Bunyavirus ALSO has California encephalitis, Sandfly-Rift valley fevers, Crimean Congo hemorrhagic fever. MCC of diarrhea in AIDS and MCC of biliary tract disease and pancreatitis in AIDS CMV MCC of gastroenteritis in ADULTS Norwalk agent COMMON COLD Rhinovirus (15%-40%):Binds ICAM-1; acid labile (thus no gastroenteritis) EARLY AUTUMN & EARLY SPRING RSV (25%): LATE AUTUMN SPRING Coronavirus (10%-20%): LATE AUTUMN EARLY SPRING Parainfluenza (5%): SPRING inspiratory stridor; lateral XR shows steeple sign. Adenovirus (>2%): AUTUMN SPRING Coxsackie (9%): SUMMER & EARLY FALL HTLV-1 does cause adult T-lymphocyte leukemia, but it also causes HTLV-1 associated myelopathy (tropical spastic paraparesis): myelin destruction within the spinal cord and white matter, as well as periventricular regions of the brain => Gradual unremitting course with LOWER EXTREMITY W EAKNESS, BACK PAIN, URINARY INCO NTINENCE, SPASTIC PARAPLEGIA. CN and cognitive function intact. HTLV-2 causes HAIRY CELL LEUKEMIA Cirrhosis* (and its stigmata) PRECEDES HCV-mediated HCC; HBV caused HCC does not have cirrhosis. *nodules are regenerative nodules of hepatocytes with no cord-sinusoid-cord pattern. HAV is MOST LIKELY anicteric; however, it can be icteric; ALSO, HAV is NOT affected by alcohol. *Also, HAV is most common type of hepatitis in homosexuals through anal intercourse. HBV can be transmitted nosocomially by RENAL DIALYSIS UNIT. Parvovirus B19 infection in pregnant women can cause non-immune hydrops. HBsAg is part of ENVELOPE, is a noninfective glycoprotein that forms spheres and tubules 22nm in diameter and poorly correlates with viral replication. NUCLEOCAPSID contains HBeAg and HBcAg. The MCC of HBV infection is *subclinical disease followed by complete recovery. Chronic active hepatitis is defined as chronic infla mma tion with continuing necrosis of h epatocytes su rrounding the po rtal tract (limiting plate) AND extending into th e lobule with individual hepatocyte destru ction (piecemeal necrosis) Trap: 1) IV drug abuser in prison HBV; 2) county jail w/ outbreak HAV Respiratory secretion with multinucleated giant cells w/ inclusion bodies in nuclei + cytoplasm WARTHIN-FELDINKSY VIRAL ENCEPHALITIDES: perivascular cuffs, microglial nodules, neuron loss, neuronophagia. Due to arbovirus, HSV-1, Rabies (Negri bodies found in hippocampal & Purkinje neurons), HIV (dementia; microglial nodules, *multinucleated giant cells*, and sub acute combined degeneration; NOTE, brain is damage due to inflammation, not the virus itself) JC virus (bizarre shaped astrocytes; oligodendrocytes have viral INTRANUCLEAR inclusions) Rhabdoviridae: binds AChR; Progression: fever, malaise agitation, photophobia, hydrophobia paralysis,coma death HIV Gene products Gag: p24 capsid protein (surrounds genomic RNA); p7p9 co re nucleocapsid; p17 matrix protein. Pol: RT, Integrase, Protease Env: gp120 binds CD4 and CCR5/CXCR4; gp40 is involved in FUSION. LTR (U3, U5): In teg ration and viral gene expression. Tat: (a transactivator) Upregulates transcription Rev: (a regulatory protein) Upregulates transport of unspliced and spliced transcripts to the cytoplasm. Nef: (a regulatory protein) Decreases CD4 and MHC I expression; manipulates T cell activation; REQUIRED FOR AIDS Postherpetic neuralgia is a stabbing persistent pain over a localized area following a zoster eruption. RSV, MMR, herp esvirida e all make *multinucleated giant cells* (syncytia) AIDS Dise ases (selected) CMV retinitis: Loss of central vision w/floaters cotton wool spots necrotizing retinitis retinal detachment (last) HIV encephalitis: LATE; enters CNS via infected ma crophages. Microglial nodules with multinucleated giant cells. NHL (large cell type): by EBV in oropharynx on Waldeyers ring.

CD4 counts: <400: Oral thrush, tinea pedis, reactivationaal VZV & Tb <200: Reactivational HSV, cryptosporidiosis, Isospora, coccidioidomycosis, PCP. <100: Candidal esophagitis, toxoplasmosis, histoplasmosis <50: CMV, MAC, cryptococcal meningitis Creutzfeld-Jakob: ACQUIRED; GERSTMANN-STRAUSSLER-SCHEINKER: INHERITED; KURU: ACQUIRED. PNEUMONIA <4 weeks: GBS, E.coli (K1 capsule prevents phagocytosis) 4 wk 18yr: RSV, Mycoplasma, C.pneumoniae, 18-40yr: Mycoplasma, C.pneumoniae, S.pneumoniae 40-65yr: S.pneumoniae, H.influenzae, Anaerobes, Viruses, Mycoplasma Elderly: S.pneumoniae, H.influenzae, Anaerobes, Viruses, GN rods TRAP: They are going to hide S.aureus/H.influenzae bronchopneumonia post-influenza/post-rubella very cleverly. Look for young and old person with an illness that involves no exudates followed by a second illness WITH exudates. MEN INGITIS ( * indicates MCC) 0-6 months: GBS*, E.coli (K1 capsule), Listeria 6mo- 6yr: S*HiN, Enteroviruses (PECH of PERCH) 6-60yrs: S.pneumoniae*, N.meningitidis, Enteroviruses 60+: S.pneumoniae*, GN rods, Listeria OTHER VIRA L: HIV, WNV, VZV, CMV (AIDS) ToRCHeS (Toxoplasmosis, Rubella, CMV, HIV, HSV, Syphillis) Nonspecific signs: HSmegaly, jaundice, thrombocytopenia CMV: blueberry rash (purple splotch), microcephaly, periventricular calcifications, deafness, seizures Toxoplasmosis: FIRST trimester: CNS disease (e.g. necrotizing encephalitis); SECOND/THIRD trimesters: chorioretinitis (yellow white lesions), hydrocephalus, intracranial calcifica tions(BG). Syphillis: <2 years: hepatomegaly, osteochondritis, mucocutaneous lesions, lobar pneumonia, persistent rhinitis >2 years: Saber shins, saddle nose, CN VIII, Hutchinson teeth, notched incisors, mulberry molars, deafness Rubella: (Arthritis in mom); PDA/PA stenosis, cataracts, deafness, blueberry rash. VZV: chorioretinitis, limb hypoplasia, cortical atrophy in the brain, vesicular skin lesions. TREATMEN T P.aeruginosa (otitis externa): topical polymyxin B + neomycin + hydrocortisone S.epidermidis: few strains are susceptible to penicillin GO STRAIGHT TO VANCOMYCIN +/- rifampin or gentamicin. S.sanguis: Pen G + AG S.pyogenes: -lactam or macrolide Enterco cci: ampicillin (though all strains have resistances) C.diptheria e: 1) Antitoxin (affects prognosis), 2) Penicillin/erythromycin, 3) DPT vaccine Tetanus: hyperimmune human globulin, metronidazole, penicillin, diazepam, debride & delay closure Botulism: If in wound, amoxicillin & respiratory support C.perfringens: Debride, clindaymycin, penicillin, hyperbaric O2 Anthrax: FQ or Doxy Listeria : Gentamicin for IC patients. Treat ETEC with empiric fluoroquinolone. M.lep rae: Dapsone; alternate: rifampin + clofazimine + dapsone (for lepromatous). H.influenzae: Ceftriaxone for MENINGITIS; Rifampin for close contact prophylaxis L.pneumophila : Erythromycin, FQ V.cholerae: Fluid replacement; Doxy or FQ V.vulnificus: 3G or Tetra for CELLULITIS EPEC: FQ K.pneumoniae: 3 G + AG S.typhi: FQ or 3G H.ducreyi: AZ, 3G, FQ

Imm: -

L.interrogans: Pen G or Doxy C.jejuni: Fluid/electrolyte; Erythromycin, FQ P.mirabilis: FQ, 3G, TMPSMX E.co rroden s: FQ, 3G C.canimo rsus: FQ, 3G B.hensalae: AZ, DOXY Brucella: Rifampin, DOXY Fransicella: Streptomycin Yersinia pestis: AG P.multo cida:Amoxicillin/clavulanate Bacteroides: Metro, clinda, cefoxitin; DRAIN ABSCESS Ureaplasma: Erythro or Tetra C.neoformans: AMB + 5FC until afebrile and culture negative fluconazole. Mucor: Debride necrotic and AMB. Isospora: TMPSMX or pyrimethadine/sulfadizine. Cyclospora: TMPSMX Microsporidia: NO TREATMENT Cryptosporidiu m: TRY nitrazoxamide, puromycin, AZ; Goljan says paromomycin Naegleria: AmpB may work. Acanthamoeba: Keratitis: miconazloe, propramidine; GAE: ketaconazole, sulfamethazine T.cruzi: Nifurmitox/ benzimidazole Plasmodium: If falciparum RESISTS use quinine sulfate & pyrimethamine sulfadexine Babesia: Quinine, clindamycin Enterobius,Asca ris, An clyostoma , Neca tor : -bendazole or pyrantel pa moate Strongyloides: -bendazole or IVERMECTIN T.spiralis: -bendazole; STEROIDS for SEVERE D.medin ensis: metronidazole or niridazole Loa loa: diethylcarbamazine + surgery Wucheria, Brugia: diethylcarbamazine + ivermectin + surgery Toxocara: diethylcarbamazine + mebendazole Ancyclosto ma spp: ethyl chloride spray & ivermectin. Balantidium coli: Tetracycline T.solium/saginatum/D.latu m: Praziquantel (-bendazole for neurocysticercosis) E.granulosus: -bendazoles + surgery All trematodes: Praziquantel HPV CIN: Cryotherapy, electrocautery, imiquimod (increased inflammatory cytokines), INF-, cidofovir. M.contagiosu m: For IC, ritonavir, cidofovir. SARS: supportive; TRY ribavirin/INF Rhabdoviridae: hRIG, 5 doses of killed vaccine.

Testing the complement system: 1) Classical pathway low C4 or C2, if activated 2) Alternative pathway low Factor B, if activated 3) Either pathway low C3, if activated CD2 is LFA-2 on T c ells, thymocytes, and NK cells. CD10 is CALLA CD16 is the Fc receptor CD21 is the receptor for C3d; also forms coreceptor with CD19 for B-cell activation CD32 on macrophages that get stimulated by GM-CSF

CD25 (anti-CCP related) on B, TH, Tr eg cells that bind IL-2 CD34 are all hematopoietic precursor cells, endothelial cells in HEV; binds L-selectin. CD45 is common to all leukocytes. IL-1 ALSO *activates* B cells. IL-7 on targets lymphoid stem cells differentiation into proB and proT cells. IL-12 activates CD8, NK, LAK, Th1 cells IL-17 increases inflammation, attracts PMNs, induces acute phase cytokines, TGF, IL-8; involved in autoimmune & allergy IFN enhances macrophages, increases MHC I and II, promotes class switch to IgG2a, blocks IL-4 class switch to IgE and IgG1, inhibits Th2, mediates Type 4 HS. TGF can induce class switch to IgA TNF- has cytotoxic effects like & enhances phagocytic activity. (Note cachexia for ONLY) Use IL-2 (aldesleukin) to increase lymphocytes and NK cells for RCC and METASTATIC MELANOMA. NK cells AMPLIFIED by IL-12, IFN-, and IFN-. NK cells important in EARLY RESPONSE to viruses. CD56 is UNIQUE marker of NK cells; CD16 is not specific. CD4 T cells attack protozoans. **HLA-D code for Class II antigens** CVID: 1) Recurrent bacterial infections SECONDARY to DECREASED Ab (plasma cell), ~10-30 years; B cell #s NORMAL. 2) Some have intact CMI; 3) Other autoimmune may be present; 4) may have bronchiectasis, ca rcino ma, lymphoma. Brutons agammaglobulinemia has LACK OF B CELLS. Tr eat with IVIG. Wiskott-Aldrich due to mutations on WASP on Xp. Platelets missing CD43; splenectomy corrects thrombocytopenia; DECREASED IgM; TREAT with bone marrow transplant Ataxia-telangie ctasia on CHR 11; ALSO has IgA deficiency ( respiratory infections) IL-12 receptor deficiency: Decreased TH1 response; decreased IFN- disseminated mycobacterial infections. SCID is ALSO caused by failure to synthesize MHC II antigens. Recurrent staphylococci and streptococci Chiediak Higashi. HIV: ELISA: W estern blot to p24, gp120, gp41 (need 2 out of 3); if only 1 is present, redo in 6 months OR do PCR for CONFIRMATION Type 4 HS: Macrophages are the most common cells present at the site of skin lesion. Type 4 HS with CD8 T cells: virus, immune reaction to tumor, contact der matitis, graft rejection. Cardiac allograft vasculopathy ~5 years postop shows thickened intimal layer of modified smooth muscle cells w/ lymphocytes + histiocytes; stenosis of lumen; CANNOT BE PREVENTED BY IMMUNOTHERAPY. The organisms that are not destroyed in CGD will lead to autoimmunity Without B7-CD28 costimulation, CD4 Th2 cell will undergo ANERGY Hereditary angioedema: Decreased C4 (BEST SCREENING); decreased C1 inhibitor (CONFIRMATORY) and C2; normal C3, normal IgE; Death may result from laryngeal edema. During toxic shock: IL1, IL6, TNF from MACROPHAGES; IL2, IFN from TH1 lymphocytes A neonates immune system is still not mature; therefor e, neonatal hepatitis will only have mild liver damage. CVID: B cell maturation defect & HYPOgammaglobulinemia. CHEDIAK-HIGASHI: Large lysosomal vesicles in phagocytes TRYPTASE is specific to mast cells. SABIN vaccine is ORAL; when a live-attenuated is given to a mucosal surface, there is more MUCOSAL IgA production WORD GAME: Inactivated vaccine refers to a killed vaccine. DTP vaccine is CONTRAINDICATED in seizure disorder. CSF are glycoproteins (transmembrane receptor). G-CSF made by FIBROBLASTS; GM-CSF made by m acrophages & T cells. WORD GAME: Elimination of Mycoplasma and the cold agglutinins can be referred to as Faded Immune Response Donor kidney renal a/v anastomosed with recipients external iliac a/v; donor proximal 1/3 ureter by renal artery Increased ESR is due to high levels of circulating fibrinogen fibrogen is an acute phase protein. WORD GAME: Toxoid is a modified toxin that still maintains some antigenic similarity (cross reactivity) MMR is the only live vaccine given to an AIDS patient because natural measles is WORSE than attenuated virus.

Vaccines contraindicated in those with egg allergies: MMR, VZV Killed vaccines CANNO T generate mucosal IgA. Adjuvants: stimulate TLRs. 1) Prolong antigen persistence (aluminum potassium sulfate) 2) Enhancing costimulatory signals (muramyl dipeptide) 3) Inducing granuloma formation 4) Inducing nonspecific lymphocyte proliferation (LPS and synthetic polyribonucleotides) Serum sickness: Type 3 HS characterized by deposition of circulating, complement fixing immune complex es vasculitis, fever, urtica ria, arthralgias, glo merulonephritis, lymphadenopathy, low seru m C3. REMEMBER, DRUGS CAUSE IT. *Takes at least 5 days to occur because time is needed for antibody formation* TREATMENT: Oral prednisone and diphenhydramine. Arthus reaction: A local sub acute Type 3 HS. Intradermal injection of Ag induces Abs immune complexes in skin edema, n ecrosis, and co mplement a ctiva tion. Type 4 HS: GBS, GVHD, Celia c disease. Hyperacute rejection: vascular fibrinoid necrosis, neutrophils infiltration, and infarction of graft. Acute c ellular rejection: interstitial mononuclear infiltrate Acute humoral rejection: graft vasculitis Chronic rejection: humoral; obliterative intimal smooth muscle hypertrophy & fibrosis of cortical arteries. *A syngeneic graft also requires immunosupression (cyclosporine) because of differences in MHC sites from crossover of chromosomes during meiosis. Influenza: Antibodies to hemagglutinin protect vs. INFECTION T cell response to neuraminidase protect vs viral shedding. HLA-B27: ALSO Psoriasis and IBS B8: Graves DR2: MS, Hay fever, SLE, Goodpastures DR7: Steroid responsive nephrotic syndrome Lipopolysaccharide is a thymus-independent antigen (like polysaccharide capsule). Antigenic variation ALSO found in Salmonella (2 flagellar variants) and HCV. Anti-smooth muscle Abs- Autoimmune hepatitis. To Identify MHC I or II antigen: use MICROTOXICITY TEST: Add different antisera & impermeable dye to donor or recipient lymphocytes If Ag-Ab binds, then dye will give color. To Identify MCH II antigen: use MIXED LYMPHOCYTE REACTION: Lymphocytes are irradiated so they CANNOT proliferate, but will act as stimulators for presentation of MHC Ag. The other persons cells are added to culture and uptake of 3H-thymidine is followed If MHC II are DIFFERENT, proliferation will occur (increased uptake)

Embryo: SHH: produced @ BASE of limbs in zone of polarizing activity. Involved in patterning along the ANTERIOR-POSTERIOR axis. Wnt-7: produced @ apical ectodermal ridge (thickened ectoder m @ distal end of each developing limb); necessary for DORSAL-VEN TRAL axis FGF: produced @ apical ectodermal ridge. STIMULATES mitosis of underlying mesoderm lengthening of limbs Homeobox: codes for DNA TRANSCRIPTION FACTORS. Segmental organization. Week 4 : Part of ectoderm THICKENS o tic pla code, which INVAGIATES o tic vesicle 1) saccular portion: cochlea, sa ccule, spiral ganglion 2) utricular portion: endolympathic duct/sac, utricle, semicircular duct, vestibula r ganglion. Umbilical arteries and veins DERIVED from ALLANTOIS. Selected heart: Bulbis cordis smooth outflow tract + RV; Prim itive Ventricle LV Left Sinus Venosus Coronary sinus; Right Sinus Venosus Smooth RA. nd Endocardial fibroelastosis: endocardium thickens 2 to a marked INCREASE in fibrous and elastic tissue, which may extend into ventricle.

Branchial ar ch 1 ALSO has Mylohyoid, anterior belly of digastrics, anterior 2/3 of tongue. Treacher Collins syndrome: mandibular hypoplasia, zygomatic hypoplasia, down-slanted palpebral fissures, colobomas, and malformed ears. Branchial ar ch 2 ALSO has posterior belly of digastrics. Branchial ar ch 3: ALSO greater horn of hyoid; Congenital pharyngocutaneous fistula: persistence of cleft and pouch fistula b/t tonsillar area & cleft in lateral ne ck. Branchial ar ch 4: Cricothyroid; Branchial ar ch 6: larynx muscles Branchial POUCH 2: Epithelial lining of PALATINE TONSIL Branchial POUCH 3/4: DORSAL WINGS Parathyroids Diaphragm: Septum transversum; Pleuroperitoneal folds; Body wall; Dorsal mesentery of esophagus (crura) Some Parts Build Diaphragm. Defects of ANTERIOR ABDOMINAL WALL: ROSTRAL FOLD CLOSURE: STERNAL DEFECTS; LATERAL FOLD CLOSURE: OMPHALOCOELE, GASTROSCHISIS CAUDAL FOLD CLOSURE: BLADDER EXSTROPHY Omphalocoele is herniation into UMBILICAL CORD. Alphabetical: Accessory pancreatic duct Dorsal bud; Main duct Ventral bud Cake kidney r efers to complete fusion. In MALES, the paramesonephric ducts DEGENERATE to appendix testes (hydatid of Morgagni) Spina bifida aperta is COMPLETE FAILURE of fusion of neural plate malformation of vertebral arches underdeveloped neural plate is covered ONLY with skin; MANY MAJOR NEUROLOGIC DEFICITS. Increased AChE indicates NTD; closure of neuropore = fusion of neuropore. CAUDAL REGRESSION SYNDROME: born with agenesis of sacrum/lu mbar spine; flaccid paralysis legs; dorsiflexed contracture of feet; urinary incontinence; MATERNAL DIABETES ASSOCIATION NEURAL CREST CELLS migrate caudally; thus the RECTUM is ALWAYS affected in Hirschsprungs. TRAP: In Hirschsprungs, BOTH the Auerbach and Meissners plexi are affected. Duodenal atresia and annular pancreas BOTH HAVE the *double bubble sign* TRAP: Annular pancreas post-na tal bilous vomiting Pyloric stenosis & TE fistula post-na tal non-bilous vomiting CHARGE syndrome: Colobama of iris, choiroid, and/or microphthalmia; Heart defect (ASD); Atr esia of choanae; Retarded growth; Genitourinary abnormalities; Ear defects. Fetal Alcohol Syndrome is a neural crest migration error. Buzzwords: Mother with ascites/varices; baby with microcephaly, holoprosencephaly, limb dislocations, fistulas in heart/lungs. Hyperphenyalanemia is a tetratogen at any time during pregnancy. (Maternal PKU) BE AWARE: MIF is from Sertoli cells; XY missing Sertoli cells ONLY => Male and female internal genitalia; external male. Arnold Chiari 1: Tonsils & medulla into foramen magnum; may cause hydrocephalus. th Arnold Chiari 2: Midbrain, ver mis, 4 ventricle herniated obstructive hydrocephalus; ALSO sm all posterior fossa Type 2 Associated with lumbar meningomyelocoeles. th Dandy Walker malformation: Noncommunication hydrocephalus without dilation of 4 ventricle & hypoplasia of vermis. Lissencephaly: agyria; absence of normal cerebral convolutions and a poorly defined Sylvian fissure. Porencephaly: Cavities or cysts within the brain that represent abnormalities of cell migration: MR, optic atrophy, seizu res. Schizencephaly: Presence of clefts within cerebral hemispheres due to abnormalities in morphogenesis. MR & seizures Holoprosencephaly: Hemispheres fail to separate; due to haploinsufficiency of SHH. With imperforate anus, there is association with genitourinary tract malfo rmations (renal agenesis, hypospadias, epispadias, and bladder extrophy) TRAP: VACTERL is far less common. Bilous vomiting AFTER 24 hours of life jejuna, ileal, colonic atresia. Small intestinal and colonic atresias are due to vascular a ccid ents in u tero . If SMA was obstructed apple peel atresias: the mesentery is absent and the bowel segment spirals around the artery. SIDS: leading cause of death between 1 month to 1 year. Delayed development of arousal and cardiorespiratory control. Histo: ASTROGLIOSIS; hypertrophy of astro cytes; in creased GFAP staining

Path: -

Klein Waardenburg Syndrome: all affect tissues derived from embryonic tissue in which PAX-3 is expressed: 1) Dystopia canthoru m (lateral displacement of inner corner of eye) 2) Pigmentary abnormalities (frontal white blaze of hair, hypopigmentation of skin, heterochromia irides) 3) Congenital deafness 4) Limb abnormalities Robin sequence presents with : poor mandibular growth, cleft palate, posteriorly placed tongue. Ebsteins phenomenon Tricuspid regurgitation TRAP: Embryonal rhabdomyosarcoma: MCC site is HEAD/NECK ; Sarcoma botyroides is not as common (GU tract) Teratogens (sele cted): Ribavirin, Griseofulvin, Metronidazole ACEi renal damage; Alkylating agents absence of digits; Cocaine: addiction, placental rupture, MICROCEPHALY, infarction (CNS, bowel, missing digits) Heroin: irritability/hyperactivity, high pitched cry, salivation, sweating, tremors, seizures, temperature instability Isotretinoin: 3Cs: Craniofacial (small ear, micrognathia, cleft palate), Cardiac, CNS (hydrocephalus, microcephaly) Phenytoin: Nail hypoplasia, CNS abnormalities, cleft lip/palate, congenital heart disease. Diabetes open NTDs, cleft lip/palate, RDS (hyperglycemia inhibits surfactant) Smoking vasoconstrictive effects pla cental ischemia preter m labor, placental problems, IUGR, ADHD SLE If anti-SS-A IgG is present complete heart block Warfarin CNS defec ts, nasal hypoplasia, bone deformities, fetal hemorrhage, and abortion. DES interfer es with Mullerian structures;

Caspases digest nuclear & cytoskeletal proteins AND activate endonucleases. Pyknosis: nuclear shrinkage and basophilia. Karyorrhexis: pyknotic nuclear fragmentation. Karyolysis: nuclear fading. REVERSIBLE CELL INJURY: cell swelling, chromatin clumping, decreased ATP, decreased glycog en, myofib ril relaxation, fatty change (TG droplet accumula tion), ribosomal detachment, disaggr egation of granular/fibrillar elements of nucleus. 2+ IRREVERSIBLE CELL INJURY: pyknosis/ka ryolysis/ka rryohexis; Ca influx caspase ; plasma membrane damage, lysosomal rupture, mitochondrial permeability/vacuolization. + 2+ Cell swelling caused by increased intracellular Na and Ca . Russell bodies are intracytoplasmic accumulation of Ig in plasma cells @ cell injury. During inflammation, there is BLOOD STASIS, due to increased viscosity, that allows neutrophils to marginate. Abscess is fibrosis surrounding pus. Kallikrein is involved in neutrophilic chemotaxis 5HT by platelets increased vascular permeability & vasodilation. PGE2 pain & open PDA; PGD2, E2, F2: Vasodilation Leukocyte adhesion defects ALSO found in DM, co rticosteroids, acute alcohol. Leukocyte extravasation: (V asculature/Stroma; Leukocyte) 1) ROLLING: E-selectin, P selectin Sialyl Lewis & PSGL-1 Selectins bind weakly and initiate rolling. P-selectin are in Weibel Palade bodies and go to cell surface w/ exposure to histamine or thrombin Neutrophils are stimulated by chemokines to expr ess their integrins. 2) TIGHT BINDIN G: ICAM-1 LFA-1 (integrin) Integrins allow for stable binding and adhesion. Chemotactic agents convert LFA-1 to HIGH AFFINITY STATE. *IL-1 and TNF induce E-selectin, ICAM-1, and VCAM-1 3) DIAPEDESIS: PECAM-1 PECAM-1 Superoxide Dismutase: O2 * H2 O 2 Glutathione peroxidase: OH* or H2 O 2 H2 O

Dialysis associated amyloid: A2 M: 2-microglobulin derived from MHC class 1 Pituitary amyloid: derived from prolactin Cardiac atria amyloid: ATTR (a primary); not to be confused with senile cardiac amyloid. Angiogenesis is driven by VEGF (vascular endothelial growth factor) and FGF (fibroblast growth factor) TRAP: Do not fall for EGF (epidermal growth factor) Angiostasis is driven by Endostatin and Angiostatin. ACTIVE HYPOphosphorylated Rb PREVENTS G1 to S. INACTIVE HYPERphosphorylated Rb ALLOWS mitosis. SUDAN RED stains for fat globules with vessels. Pro-carcinogens are converted to active metabolites by P450 monooxygenase; overactivity => cancer RADIATION induces DNA damage through dsDNA br eaks and ROS. EXCESS MMP myofibroblast (actin-containing fibroblasts) accumulation in wound margins => CONTRACTURE => DEFORMITIES of wound and surrounding tissue. nd Active hyper emia: 2 to vasodilation (inflammation, exercise, blushing) nd Passive hyperemia: 2 to decreased venous outflow (CHF, DVT, Budd-Chiari) Temperature over 40C is hyperpyrexia and can cause brain damage. CRITICAL to COO L PATIENT FIRST; then use antipyretics second because they take time to work. ISCHEMIA: without ATP, membrane Na/K and SR Ca++ ATPases do not work. Thus INCREASED IC Na+ and Ca++, both of which contribute to cell swelling. Bax, bad, bcl-Xs, and bid PROMOTE APOPTOSIS; p53 STIMULATES bax. CarboxyHb @ 60%+ => DEATH Smoking => EARLY MENOPAUSE and INCREASED POSTMENOPAUSAL OSTEOPOROSIS AP: Bone vs Liver can be differentiated by electrophoresis, antibodies, and heat denaturation (Bone is easier to Boil) ALSO , get a GT level, because that is not found in bone, so elevated AP and GT biliary problem. High nucleotide uptake large number of tumor cells in S phase HIGH GRADE. AV shunts high output failure increased preload TRAP: there is no increased contractility. Thrombus: Intravascular; platelets +fib rin + RBCs, + WBCs; LINES OF ZAHN; has shape Blood Clot: Extravascular orHntravascular; fibrin + RBCs + WBCs; no lines; no shape. Hypoxic Cell injury: 1) Decreased Na/K Cell swelling, ER swelling, loss of microvilli, membrane blebs 2) Increased glycolysis decreased glycogen, in creased la ctic acid 3) Ribosomal detach men t decreased protein synthesis. 2+ 4) Severe membrane damage Influx Ca ; en zyme leakage. TOXICOLOGY: Arsenic: Chronically: Neurotoxic > GI toxic; burning sensation in glove/stocking distribution; severe bilateral arm weakness, arsenic melanosis: gray skin with dark macules; raindrop depigmentation; Aldrich Mees lines over nails Rice water stool like cholera. MC COD: convulsions/coma Can cause skin/lung SCC & liver angiosarcom a Iron: cell death due to peroxidation of membrane lipids; ACUTE: gastric bleed; CHRONIC: M.Ac scarring GI obstruction Copper poisoning: can ALSO use tiren tine and zinc. Formaldehyde: denatures protein/nucleic acids & alkylates amino acids and SH groups. Phenols: damage membrane and denature proteins. Chlorine, iodine, H2O2: oxidizing agent inactivating SH groups. Ag/Hg: bind and inactivate SH on enzymes Gold fatal dermatitis/stomatitis, myelosuppression, flushing, hypotension, tachycardia, renal disease. Ethylene oxide: alkylating agent. MERCURY *VISIBLE ON X-RAYS* Acut e- ATN(PCT) + co rrosive gastroenteritis Chronic- Proteinuria, so matitis, CNS signs (insomnia, irritability, ataxia, nystagmus, convulsions), constrictive visual fields; In fish, dental amalgams, and fungicides. Methylene chloride: converted to CO; solvents, lead, petroleum H2S gas: sulfhemoglobinemia (Green/blue pigment that CANNOT be reversed); sewer worker Amanita: abdominal pain, bloody diarrhea, jaundice, extensive fatty change.

Petroleum: drunk; toxic doses Convulsions, tinnitus, noncardiogenic pulmonary edema Strychnine: identical to tetanus. MC Pit vipers: rattlesnake , water moccasins, copper heads swelling/necrosis, DIC, antivenin serum sickness True cobras: coral snake (botulinum like toxin) red and yellow kill a fellow. (harmless) scarlet king snake red and black friend of jack. Fire ant bites: sharp, painful bite Type 1 HS ensues vesiculation/skin necrosis WOUNDS: Gunshot : EXIT wounds are larger & more irregular than ENTRANCE wounds; 1) Contact: soot & gunpowder in wound (fouling) 2) Intermediate: powder tattooing (stippling of skin around entrance) 3) Distant: No powder tattooing. Drowning: 1) Near drowning: Survival following asphyxia secondary to submersion; 2) Wet drowning: 90%; initial laryngospasm on contact with water relaxation/aspiration of water surfactant is destroyed atelectasis with intrapulmonary shunting diffuse alveolar damage and intiates spasm in bronchioles IMMEDIATE COD is CARDIAC ARRHYTHMIA. rd Burns: 3 degree extensive scarring complicated by keloid formation. propensity for SCC. To PREVENT keloids intralesional injection of corticosteroids. Heat: Hyperthermia: >37.2C; Heat cramps: afebrile, common in volume depleted workers/athletes, lose excess amounts of salt/water Heat exhaustion: <39C; common in athletes in hot/humid; severe volume depletion. Exertional heat stroke: >41C; working/running on hot day; skin HOT/DRY; LACTIC ACIDOS IS; rhabdomyolysis Nonex ertional heat stroke: elderly/chronically ill; skin HOT/DRY W/O sweating; Malignant hyperthermia: AD Walking briskly on a HOT day: vasodilation of skin Marathon on a HOT day: vasodilation of skin & increased rectal temperature Cold: Frostbite: loca injury secondary to DIRECT (ice crystallization)&INDIRECT (vasodilation/thrombosis) damage. PAINLESS Hypothermia: <35C; uncoupling of ox-phos; venous pooling circulatory failure/death Electrical: *Current * is the most important factor in electrocution AC > DC; Dry skin has HIGHEST tissue resistance to DC; wet skin lowers resistance to current voltage is constantRAISES current. Current from LEFT ARM to RIGHT LEG V-Fib. Ionizing: Shorter wavelength greater penetration ( > /); Indirect injury: produces hydroxyl free radicals from hydrolysis of water in the tissue (DNA most susceptible) *Peak sensitivity @ G2 and M; Lymphocytes most affected; Brain MOST RESISTANT. MCC UV: A-Woods lamp; B- Sunburn, corneal burn from skiing BCC , SCC, melanoma; C- ger micidal rd Laser like 3 degree burn Microwave skin burn, adversely affects pacemarkers; *cataracts, cancer, sterility* Infrared burns, cataracts Ethanol: Absorption: 75% SI; 25% stomach. CNS effects in descending order: Cerebral cortex limbic system cerebellum lower brain stem; *Potentiates INHIBITOR NTs like GABA. Hemosid erosis: Alcohol INCREASES the reabsorption of iron Type 4 hyperlipidemia: Alcohol INCREASES synthesis of VLDL. Isopropyl alcohol: end product ACETONE NO M.Ac increases osmolal gap (>10) deep coma with hyporeflexia. Smoking: ALSO affects GI system delays rate of ulcer healing & increases risk of oral, upper and lower GI cancer. ALSO leads to CONVERSION of estrone to inactive metabolite increase risk of OSTEOPOROSIS and MENOPAUSE Smokeless tobacco verrucous squamous cancer. nd 2 hand on child: ALSO increases risk of otitis media & recurrent URI and LRI. Miscellaneous: increa ses risk of PROTEINURIA in DM, Vitamin C deficien cy, 25% house fires.

Pharm: 5HT1a-h: CNS (inhibitory) + smooth muscle (excitatory o r inhibitory) Ex. Busipirone (1a), Sumatriptan (1b, 1d) 5HT2a-c: CNS (excitatory) + periphery (vasodilation, GI contraction, bronchial, uterus, platelet aggregation) Ex. Atypical antip sychotic & cyproheptadine a re antagonists @ 2a AUTONOMICS 1: ALSO increases glycogenolysis, decreases renin, increases intestinal and bladder sphincter contraction (retention). 2: ALSO platelet aggregation 2: ALSO increases heart rate, contractility (no typo), lipolysis. M1: In CNS, enteric nervous system, GI glands M2: Decre ases HR and contractility in ATRIA (no effect on Purkinje/ventricle) M3: Increases exocrine secretions, gut peristalsis (GI sphincters all relax, except LES), bladder contraction; + D1: Relaxes renal, mesenteric, & corona ry vascular smooth muscle (increase RBF, GFR, Na secretion) V1: Increases VASCULAR smooth muscle contraction. CHOLINOMIMETICS Bethanecol: post-op & neurogenic ileus and urinary reten tion Carbachol: Glaucoma, papillary contraction, and release of IOP Pilocarpine: resistance to AChE; potent stimulator of sweat, tears, saliva; for open angle glaucoma and xerostomia. Physostigmine ENTERS CNS (all others do not); for glaucoma and atropine OD. -stigmine AChEi *carbamylate* Echothiophate: For glaucoma AChEi dose is too high: CHO LINERGIC CRISIS muscle overfires/weakness NEOSTIGMINE NO EFFECT lower dose AChEi dose is too low: MYASTHENIC CRISIS NEOSTIGMINE EFFECT raise the dose. Muscarinic agonists: can bind receptors on ENDOTHELIAL c ells release NO (aka. EDRF) MUSCARINIC AN TAGON ISTS Atropine, homatropine, tropicamide (topical)- For eye Benztropine, tryhexylphenidyl- CNS (Parkinsons) Oxybutynin, glycopyrrolate, tolterodine- Genitourinar y Methscopolamine- GI Pirenzepine & propanthelin (belladonna alkaloids) that block M1 receptors on ECL cells and M3 on parietal cells. Hexamethonium: Nicotinic antagonist; ganglionic blocker prevent vagal reflex responses to changes in BP. Sever e orthostatic hypotension, blurred vision, constipation, sexual dysfunction. Methoxamine: 1 antagonist: used for paroxysmal atrial tachycardia thru vagal reflex. Metaproterenol: 2 agonist (for acute asthma like albuterol) Clonidine, methyldopa: no reduction in RBF. Mirtazapine: sedation, increased serum cholesterol, increased appetite. Yohimbe: for postural hypotension and impotence. Pindolol, acebutolol: Partial -agonists less bradycardia, slight vaso & bronchodilation, minimal lipid change. Botulinum interacts with *synaptobrevin* to prevent ACh release. Vesamicol inhibits ChAT Metyrosine inhibits tyrosine hydroxylase. MAO A is found in the prejunctional nerve terminal; COMT in the synapse. Phase 1 metabolism (redox, hydrolsys) yields slightly polar, water soluble active metabolites Phase 2 metabolism (acetylation, glucurondiation, sulfation) yields very polar, inactive metabolites (renal excretion) Phenobarbital and MTX are weak acids. ss *If MEC = C , then LD = 2MD; otherwise, use the equations.* Ketotifen is an ophthalmic anti-histamine that is a non-competitive H1 antagonist & mast cell stabilizer. Shown to DECREASED chemotaxis and eosinophil activation. Epinastine is an ophthalmic anti histamine that is reversible, competitive H1 blocker & does NOT stabilize mast cells WORD GAME: Permissive refers to a hormone (without a desired effect) augmenting another hormones desired effect. Additive/synergistic refers to two hormones (both with desired effect) leading to summation/far increased effects.

A deflection of the membrane potential toward ZERO would increase the permeability of ions with opposite and nearly + + equilibrium, such as Na (+60mV) and K (-80mV) + + Resting membrane potential (-70mV) is created by HIGH K conductance and some Na conductance. IGNORE THE O THER IONS IN THE QUESTION STEM. Resting membrane potential of -70mV means that the charge within the cell is negative with respect to the EC space. + + However, K r esting potential is -80mV, so opening the ion channels will have K flow OUT OF THE CELL until it reached a resting membrane potential of -80mV. + + Conversely, opening the ion channels would lead to flow INTO THE CELL of Na and Ca because their membrane potentials are higher than -70mV. ANABO LIC STEROIDS are associated with ERYTHROCYTOSIS; *intense exercise is NOT* Atovaquone is an ETC inhibitor is used for PCP prophylaxis for sulfa allergy. Ammonium chloride can ACIDIFY blood; Sodium lactate ALKALINIZES blood. Milrinone is a inotropic agent that also causes VASODILATION IN THE ARTERIES. Niacin can potentiate anti-hypertensives thru vasodilation (thus decrease anti-hypertensives) AND can lead to insulin resistance (thus increased insulin drugs) Nitroprusside is a veno + vaso-dilator. ANP r esponds to increased volume and ATRIAL PRESSURE. CONSTRICTS EFFERENT; DILATES AFFERENT Neseritide is a recombinant BNP used for ACUTELY DECOMPENSATED CHF. Dobutamine ALSO causes increased conduction velocity, which is undesirable because of arrhythmias. Fenoldopam is D1 selective vasodilation of most arterial beds (including renal, mesenteric, and coronary) It is the ONLY AGENT THAT improves renal perfusion while it lowers blood pressure. Hydralazine is given with -blocker to prevent reflex tachycardia. -1 blockers have GOOD LIPID PROFILE. CCB: Toxicity ALSO: peripheral edema, flushing, dizziness, and constipation. ALL nitrates are associated with HEADACHE and FACIAL FLUSHING, esp. @ high doses when arterial vasodilation occurs. TRAP: For essential HTN only: use thiazides; for essential HTN with CHF or previous MI: use ACEi. Statins have decreased TGs (because of decreased VLDL); hepato toxic Niacin inhibits HSL, reduces hepatic VLDL secretion into circulation to decreased delivery of TGs. Causes insulin resistance and hyperu ricemia. Bile acid resins ALSO cause gallstones. Ezetimibe MAY increase LFTs. Fibrates upregulate LPL (increased TG clearance via peroxisomes); hepatotoxic and gallstones (via reduced 7hydroxylase reduced conversion of cholesterol to bile, thus excess cholesterol in bile) Statin + Fibrate ALSO polyuric acute renal failure. Statin + Nicotinic acid + Fibrate drug induced hepatitis Probucol is an antioxidant that is used to treat recurrent xanthelasmas; lowers HDL ; may cause torsades de pointes Digoxin can force signal through Kent bundle in WPW => Vtach/Vfib -blockers (especially carvedilol) will slow progression and reduce mortality of CHF. Atropine has NO EFFECT on MAP. Digoxin toxicity: ECG increased PR, decreased QT, scooping, T inversion, arrhythmia, hyperkalemia + 2+ Treatment: 1) Nor malize K , 2) lidocaine, 3) cardiac pacer, 4) anti-dig Fab fragments, 5) Mg + 2+ Adenosine activates K channels to prolong APD; also inhibits L-type Ca channels, prolonging the time to thr eshold. DOC for abolishing SVT; flushing, hypotension, chest pain; Blocked by theophylline. Can cause coronary steal dilation of coronary vessels in MI blood flow diverted WORSENS ISCHEMIA. ANTIARRHYTHMICS Class 1: LOCAL ANESTHETICS; 1A: For reentrant and ectopic SVT and VT ; Quinidine: also has thro mbocytopenia ; 1B: Post MI arrhythmias & digitalis induced arrhythmias. CNS stimulation/depression, CV depression. 1C: Useful in VT, VF & intractable SVT. LAST RESORT DRUG; proarrhythmic, CI in post MI. Significantly prolongs refractory period in AV node.

Class 2: For VT, SVT, AFib, Aflutter; metoprolol dyslipidemia Class 3: Used when other antiarrhythmics fail. Class 4: Constipation, flushing, edema, CHF*, AV block, sinus node depression, gingival hyperplasia. *potent negative inotropic effect CV drugs Prolonged QRS quinidine, amiodarone Prolonged QT sotalol, amiodarone Prolonged PR digitalis, -blockers, CCB Giant U wave quinidine ST depr ession digitalis (hockey stick configuration) & quinidine Short QT interval digitalis Flat T wave quinidine Bradycardia quinidine Serotonin syndrome has NEUROMUSCULAR EXCITATION (hyperreflexia, myoclonus, rigidity), autonomic stimulation (hyperthermia, tachycardia, diaphoresis, and tremor), and altered mental status (agitation/confusion) Be aware that corticosteroids can block PLA2 & COX2; it also has MAXIMAL bone loss by increased OCs and decreased OBs. Alprostadil is a PGE1 analog for ED Misoprostol is a PGE1 analog Dinoprostone is a PGE2 analog induce labor Epoprostenol is a PGI2 analog for Pulm HTN. Carboprost is a PGF2 analog abortifacent. Low dose aspirin hyperuricemia High dose aspirin uricosuria Other NSAIDs: keto rolac, sulindac, diclofenac Ketorolac and indomethacin can cause aplastic anemia. COX2 inhibits have an increased risk of thrombosis. 2+ Bisphosphonates inhibit OCs & redu ce fo rma tion/resorption of hydroxyapatite;ALSO for malignancy associated hyperCa Probenecid inhibits reabsorption of uric acid in PCT. Promethazine: is a first generation anti-H with some -block and anesthetic action. Mupirocin is an anti-infective for topical impetigo. Other DMARDS: Hydroxychloroquine: stabilizes lysosomes and decreases chemotaxis; retinal degeneration, dermatitis, myelosuppresion. Sulfasalazine (mesalamine): decreases B cell activity Gold salts: decrease lysosomal and macrophage activity Penicillamine: suppresses T cells and circulating Rh factor. Aplastic anemia, membranous glomerulonephritis Leflunomide: Inhibits dihydro-orotic acid dehydrogenase decrease ribonucleotides arrests lymphocytes in G1. Anakinra: IL-1 receptor antagonist Teriparitide: PTH analog pulsatile stimulates OBs continuous stimulates OCs. CHRONIC amphetamine effects: anorexia, pulmonary edema, stroke, eroded teeth, cellulitis, psychotic reactions. Fenfluramine & phenter mine (dieting drugs) can cause PRIMARY PULMONARY HTN. Cladribine is a purine analog that is resistant to degradation by ADA. DOC for HAIRY CELL LEUKEMIA Chlorambucil is a nitrogen mustard that is used primarily to treat CLL and ovarian ca rcinoma. When used for CLL, chlorambucil is often combined with prednisone. Streptokinase & anistreplase (APSAC) causes plasminogen plasmin; cleaves the arginine-valine bond of plasminogen. Enoxaparin has more activity on Xa, better F, and longer half life. Urokinase operates the same as tPA. tPA affects fibrin and fibrinogen levels, thus PT and PTT are affected. Warfarin gamma carboxylates the gluta matic acid residues on its clotting factors. Tranexamic acid is like aminocaproic acid. Cilostazol inhibits platelet aggregation AND vasodilates.

Cliostazol & dipyramidole: PDEi. Eptifibatide & tirofiban are like abciximab. st Log Kill Hypothesis: Cancer drugs operate under 1 order kinetics hence use combinations Tumors with higher growth fraction are more susceptible G0- Aklylating agents, antibiotics, nitrosureas, cisplatin ANTIMETABOL ITES MTX: does not cross BBB; inhibits DHF reductase (DHF to THF); use for leukemia, lymphoma, chorioca rcino ma, sa rcoma , abortion, ectopic p reg, RA, psoriasis; Macrovesicular fatty change in livier; mucositis (ex. Diarrhea), teratogenic 5FU: 5F-dUMP which covalently binds folic acid to inhibit thymidylate synthase (dUMP to dTMP); use for colon can cer, solid tumors, BCC; SYNERGY with MTX; photosensitivity 6MP: activated by HGPRTase; use for leukemia, lymphomas (not CLL or Hodgkins); toxicity increased by allopurinol (because 6MP is deactivated by xanthine oxidase) 6TG: same as 6MP; used for ALL. CAN BE GIVEN WITH ALLOPURINOL Cytarabine: (ara-C); pyrimidine antagonist inhibition of DNA pol; used for AML, A LL, high g rade NHL; Leukopenia, thrombocytopenia, megaloblastic anemia. ANTITUMOR ANTIBIOTICS Dactinomycin: Intercalates; used for Wilms, Ewings, rhabdomyosacroma (child hood tumors); Doxorubicin, daunorubicin: Free radicals + intercala te; used in ABVD, also for lymphomas, myelomas, sa rco mas, and solid tumors; marked alopecia; toxic to tissues with extravasation. Bleomycin: Free radicals; used for testicular cancer, ABVD; hyperpig menta tion, MINIMAL MYELOSUPPRESSION. Etoposide, tenoposide: (vs topoisomerase II) used for Small cell,p rostate/testicular carcinoma ; GI irritation, alopecia ALKYLATING AGEN TS Cyclophosphamide, ifosfamide: cross link DNA @ guanine N-7; requires bioactivation in liver (forms acrolein); used for NHL, neuroblasto ma, ovarian carcinomas. IMMUNOSUPPRESANT; N-acetylcysteine can also be used vs acrolein. Nitrosureas (carmustine, lomustine, semustine, streptozocin): require bioactivation, crosses CNS; dizziness,ataxia. Busulfan: used for CML & ablating bone marrow stem cell transplants. Hyperpigmentation, 100% myelosuppression REGIMENS: ABVD: Adriamycin, Bleomycin, VinBlastine, Dacarbazine MOPP: Mechlorethamine, VinCristine, Prednisone, Procarbazine Hodgkins, Wilims, cho rioca rcinoma Cisplatin, carboplatin: cross link DNA, r elease ROS; used for testicular, bladder, ovary, and lung carcinomas; cisplatin is ina ctivated with high chloride concentra tion. Amifostine is a thiol based free radical scavenger that decrease s nephrotoxicity in platinum agents (cisplatin, carboplatin) Hydroxyurea for melanoma, CML Trastuzumab binds to EGFR2; cardiotoxic Imatinib is ALSO used for GI stromal tumors; fluid retention Sorafenib is a blocks RTK and downstream Ser/Th r kinase for RCC and HCC. (anti-VEGF effect too) Megestrol increases appetite for those on antineoplastic therapy. Bevacizumab, ranibizumab, pegaptanib, sorafenib, and sunitinib are ANTI-VEGF agents. Bevacizumab is used to treat solid tumors (COLON, BREAST, and non-small-cell LUNG cancers) MAIN ADVERSE EFFECTS include HTN and elevated risk of bleeding. Ranibizumab: anti VEGF; for wet macular degeneration Pegaptanib: pegylated anti VEGF aptamer ; for wet macular degeneration Do NOT use chloroquine in those with PSORASIS. ALTERNATIVE TREATMENT for malaria in this case: Atovaquone/proguanil. Perchlorate & pertechnate prevent iodide uptake into the thyroid by COMPETITIVE CO MPETITION. LONG ACTING benzodiazepines cause more daytime drowsiness SHORT ACTING benzodiazepines cause more addiction. BZs decrease REM sleep & retrograde amnesia. BZ1 receptor mediates sedation; BZ2 receptor mediates anti-anxiety and cognitive functions. + GABAA = Cl ; GABAB = K Z-hyponotics: short acting BZ1 agonists; REVERSIBLE by flumazenil; lower risk of tolerance/dependence than BZs.

ANESTHETICS For inhaled anesthetics: HIGH AV concentration gradient => High solubility (tissue) => SLOW O NSET of action. LOW AV concentration gradient => Low solubility => FAST ONSET of action Inhaled anesthetics: increase cerebral blood flow UNDESIRABLE be cause of increased ICP. Other toxicities: myocardial depression, hypotension, respiratory depression, and decreased renal function. TOXICITIES: Halothane (hepatotoxic), methyoxyfluran e (nephrotoxic); enflurane (p roconvulsant); NO (expansion of trapped gases) MAC is lower in elderly & those on opiates or hypnotics. LOWER BLOOD SOLUBILITY Rapid induction and recovery times (redistribute to fat/muscle) HIGH FAT SOLUBILITY More potent Anesthetic tension in blood rises higher/faster if anesthetic is insoluble. IV anesthetics: Thiopental (barb)high potency, high lipid solubility, rapidly CNS entry used for INDUCTION & short procedures. Decreases blood flow. Propofol potentiates GABAA ; used for rapid anesthesia induction and short procedures. LESS POSTOP NAUSEA (antiemetic) has CNS and cardiac depression. Midazolam for endoscopy; anterograde amnesia. PCP reacts with opiod like sigma receptors and subtypes of glutamate receptors Ketamine is a PCP analog dissociative anesthetic (patient is awake and has good muscle tone) Block NMDA receptors; CV stimulants; cause disorientation, vivid hallucination, bad dreams, delirium, increased ICP + Local anesthetics: Preferentially bind to activated Na channels, so most effective in rapidly firing neurons. SLOWS RECOVERY & PREVENTS PROPAGATION of APs IMPORTANT POINTS: 1) In infected (acidic) tissue, alkaline an esthetics cha rged and cannot penetrate as well. NEED MORE 2) Order of nerve blockade: SIZE PREDOMINATES OVER MYELINATION 3) Order of loss: PTTP in alphabetical order Pain, Temperature, Touch, Pressu re 4) Except fo r co caine, give with vasoconstrictors (epinephrine) DECREASED BLEEDING + increased anesthesia locally. Bupivacaine: severe CV toxicity; allergies to the esters are because of PABA. NM blocking drugs: Selective for nicotinic receptors; used for muscle paralysis in surgery or mechanical ventilation. DEPOLARIZING (noncompetitive NM agonist): 1) Succinylcholine (hypercalcemia & hyperkalemia) leads to initial fasciculations; rapidly hydrolyzed by pseudocholinesterase; Reversal of blockade: PHASE I (prolonged depol) NO ANTIDOTE: block is made WORSE by cholinesterase inhibitors. PHASE II (repolarizing but blocked) ANTIDOTE: use cholinesterase inhibitors. NONDEPOLARIZING (competitive NM antagonist): 1) Tubocurarine & -riums block is reversible with cholinesterase inhibitors. Cyclobenzaprine is a central acting SkM relaxant that is related to TCAs structurally. (Also has Anti-M effects) Methocarbamol produces muscle relaxation by general CNS depression; no direct action on contractile mechanism. Bromocriptine can ALSO be used for NMS & malignant hyperthermia. Along with cabergoline, can ALSO be used to shrink prolactinomas. Carbidopa CANNOT reduc e the central effects of levodopa (anxiety, agitation, and behavioral) Peripheral conversion to dopamine ARRHYTHMIAS Vitamin B6 will REDUCE the c entral F of dopamine by INCREASED PERIPHERAL METABO LISM of levodopa. increased motion restriction despite compliance on carbidopa/levodopa Bromocriptine & pergolide are ERGOT ALKALOIDS Pramipexole & ropinirole are NON-ERGO T ALKALOIDS; *PREFERRED Tolcapone is HEPATOTOXIC TRAP: En tacapone inhibits PERIPHERAL methylation of levodopa INCREASES CENTRAL dopamine availability. Tolcapone inhibits CENTRAL methylation of levodopa. Benztropine, trihexylphenidyl and other anti-muscarinics are used for ANTIPSYCHO TIC INDUCED PARKINSONISM (remember anti-M have little effect on b radykinesia) 2+ Memantine is a NMDA antagonist used in Alzheimers; helps prevent excitotoxicity (mediated by Ca )

Donepezil, galantamine, rivastigmine are AChE inhibitors for Alzheimers. Reserpine & tetrabenazine can deplete amines; used in Huntingtons. Haloperidol is also used in Huntingtons to block dopamine. Sumatriptan is a 5HT1B/1D agonist causes vasoconstriction to prevent trigeminal activation; used for acute migraines or cluster headaches. TOXICITY: coronary vasospasm MALIGNANT HYPERTENSION Migraine prophylaxis: propanolol, verapamil, amitryptiline, valproic acid. Methysergide for cluster: blocks 5HT; TOX: retroperitoneal & pleuropulmonary fibrosis, fibrotic thickening of cardiac valves. Ergotamine is a partial and 5HT2 agonist vasoconstrictive action decreases pulsation in cerebral vessels. TOXICITY: GI distress, ischemia/gangrene, abortion. WORD GAME: Corticosteroid implies mineralo- and gluco- activity; PREDNISONE is a corticosteroid. Prednisone: TOXICITY: ALSO hypocalcemia & fluid RETENTION GLUCOCORTICOIDS will lead to demargination of neutrophils from vessel walls (thus increasing serum neutrophils). This can lead to fevers, chills, fatigue. NOTE O THER GRANULOCYTES / LYMPHOCYTES ARE DECREASED IN # BOSENTAN: antagonizes endothelin-1 (to treat pulmonary HTN) PGI2 (eprop rosterol) & sild enafil can ALSO used for pulmonary HTN GUAIFENESIN: removes excess sputum; does not suppress cough reflex. SALMETEROL: can cause TREMOR and ARRHYTHMIA (working with Salmoneus makes you shake and skip a beat) THEOPHYLLINE: can cause CARDIOTOXICITY, NEUROTOXICTY, SEIZURES, ABDOMINAL PAIN, VOMITING, DIARRHEA. ZILEUTON: can elevate LFTs. Synthetic progestins (medroxyprogesterone, norethidrone, desogestrel) have increased oral F and increased feedback Danazol: androgen to treat endometriosis (via feedback inhibition); menstrual, thrombotic, hepatic adenoma, pseudomotor cerebri, weight gain, acne. Sildenafil, vardenfail: TOX: headache, flushing, dyspepsia, impaired blue-green vision. Tamsulosin: Selective 1A,D antagonist for BPH (vs 1B for vascular) Dinoprostone: PGE2 analog to induce labor. @high doses, estrogen decreases antithrombin III & increases II, VII, IX, X; progestins increase TGs. Mifepristone: competitive inhibitor of progestins & glucocorticoid inhibitors. Progestins: reduce growth & increase vascularization of endometrium; FOR ENDOMETRIAL CANCER + abnormal bleeding Anastrozole/exemestane: Aromatase inhibitors for postmenopausal women with breast cancer. Estrogens (ethinyl estradiol, DES, mestranol) can be used in men with androgen-dependent prostate cancer. Spironolactone acts as flutamide does; ketaconazole inhibits desmolase. BOTH used for PCOS to pr event hirsutism. Testosterone: also promotes recovery after injury; also for ER-positive breast cancer. TOX: Increases LDL, decreases HDL Menotropin (human menopausal goandotrophin) acts like FSH Formation of a dominant follicle hCG simulates the LH surge ovulation A drug that binds less avidly will take less time to dissociate from the target (and be MORE selective for rapidly depolarizing targets); examples include the 1B antiarrhythmics. IMMUNE AGENTS (MC side effe ct infection & SCC of skin) Cyclosporine: Tox: viral infections, lymphoma, nephrotoxicity (preventable with mannitol) Tacrolimus: Tox: nephrotoxicity, peripheral neuropathy, HTN, pleural effusion, hyperglycemia. Both decrease IL-2, IL-3, IFN; Cyclosporin e is DOC for transplant; Tacrolimus is ALT for renal/liver Muromonab-CD3 (OKT3): binds epsilon chain of CD3 to prevent signal transduction. Used for RENAL TRANSPLANT. TOX: Cytokine release syndrome (cytokines are released from T cell before shut down) Sirolimus (rapamycin): Binds to mTOR: inhibits T cell proliferation in response to IL-2; Used after KIDNEY with cyclosporine and corticosteroids.TOX: hyperlipidemia, thrombocytopenia, leucopenia. *No nephrotoxicity* Mycophenolate mofetil: inhibits de novo guanine synthesis to block lymphocyte production ADJUNCT to cyclosporine Daclizumab: monoclonal Ab with high affinity for IL2r on ACTIVATED T cells. Used for KIDNEY Aldesleukin (IL-2) is used for RCC and metatstatic melanoma. Filgrastim (G-CSF); Sargramostim (GM-CSF): are GLYCOPROTEINS that bind a transmembrane receptor.

ANTIMICROBIALS Bacitracin blocks peptidoglycan synthesis (like vancomycin) Polymyxin are CATIONIC, BASIC proteins that act like detergents. Bacteriostatic: Erythromycin, Clindaymycin, SMX, TMP, Tetracycline, Chloramphenicol (ECSTaTiC) Bactericidal: Vancomycin, FQ, Penicillin, AG, Cephalo, Metronidazole (Very Finely Proficient At Cell Murder) *Lincom ycin (like clindamycin) is STATIC; Linezolid is VARIABLE. Naficillins BILE EXCRETION AmOxicillin > Ampicillin in terms of Oral F Spectrum: penicillin + H.influ, Ecoli, Listeria, Proteus, Salmonella, enterococci HELPS kill Enterococci. Pen + AG Synergistic; Pen + Tetra Antagonistic. Cephalosporins 1G: Cephalexin, Cefadroxil, Cephradine, Cephalothin, Cephapirin, Cefazolin. Spectrum: GP cocci + Proteus + E.coli + K.pneu moniae (PEcK) DS DS 2G: Cefaclor, Cefamandole , Cefoxitin, Cefuroxime, Cefonicid, Cefmetazole, Cefotetan , Cefprozil, Cefpodoxime, Loracarbef Spectrum: GP Co cci + H.influ + Enterobacter + N eisseria + Proteus + E.Coli + K.pneumoniae, Serra tia (HEN PEcKS) DS 3G: Cefixime, Ceftibuten, Cefdinir, Cefoperazone , Cefotaxmine, Ceftriaxone, Ceftazidime, Cefepime, Moxalactam Spectrum: for serious GN infections resistant to o thers; Crosses BBB. 4G: Cefepime; Spectrum: Increased activity vs. Pseudomonas and GP organisms. Imipenem/cilastatin TOXICITY: GI distress, skin rash , CNS toxicity (seizu res); Meropenem has less chance of seizures. Vancomycins Red Man Syndrome ALSO has thrombophlebitis. Linezolid: 50S inhibits initiation complex by preventing N-formyl-Met tRNA forming a complex with the ribosome. Spectrum: VRSA, VRE, resistance S.pneu moniae, en teroco cci.TOX: thrombocytopenia Quinupristin-Dalfopristin: 50S; 1) prevent interaction of aminoacyl tRNA w/ acceptor site, 2) stimulate its dissociation from ternary complex, 3) decrease release of completed polypeptide. Spectrum: VRSA, VRE, E.facium, (NOT faecalis) AG: ultimately causes misreading of mRNA. TOX (select): Nephrotoxic (esp. with CEPHALOSPORIN) ; cura re (anti-N) effects can worsen MG; Resistance by plasmid mediated acetylation, adenylation, phosphorylation. AG + Amp for EMPIRIC UTI. Strep tomycin is DOC for bubonic plague and tularemia. Tetra: ultimately prevents attachment of aminoacyl-tRNA. **Divalent cations PREVENT its absorption** Doxy via biliary. Resistance by 1) increased efflux, 2) ribosome binding site change; Spectrum: ALSO for Vibrio; Tigecycline used in complication skin, soft tissue, intestinal infections due to MRSA, VREF, GN, anaerobes. Macrolides: @23S; TOX: prolonged QT, GI discomfo rt, ACUTE CHO LESTATIC HEPATITIS, eosinophilia, rash, increased [theophylline & oral anticoagulants]. Clindamycin: blocks peptide bond formation. Concentrates in bone; has value for osteomyelitis. Silver sulfadiazine (destruction of bacterial/fungal cell walls) or mafenide are topical antimicrobials used for BURNS. **For more severe full thickness burns or for sulfa allergy use cefadroxil. Sulfasalazine is the prodrug 1) 5-ASA for UC; 2) sulfapyridine for RA FQ: *CANNOT be taken with antacids or divalent cations* Amphotericin B => Renal dysfunction => hypokalemia and hypomagnesemia => arrhythmias. ALSO: fever/chills, hypotension, anemia, IV phlebitis *Hyd ration reduc es nephrotoxicity; liposomal reduces toxicity Ketoconazole inhibits ACTH effects because it inhibits P450 activity of cholesterol testosterone/cortisol. Fluconazole crosses BBB; Clotrimazole & miconazole for topical fungal infections; Flucytosine + AMP-B SYNERGISTIC vs SYSTEMIC FUN GAL INFECTIONS. Caspofungin for *invasive* aspergillo sis; TOX: GI upset, flushing. Terbinafine used for DERMATOPHYTOSES; TOX: GI, rash, headache, increased LFTs. Acyclovir is a GUANOSINE analog; TOX: crystalline nephropathy (keep hydrated) Ganciclovir: TOX: leucopenia, neutropenia, thrombocytopenia, renal toxicity. Cidofovir is already monophosphorylated and does NOT require VIRAL KINASES. Foscarnet causes *hypocalcemia and hypomagnesemia* via nephrotoxicity.

Ribavirin competitively inhibits IMP dehydrogenase inhibit synthesis of GUANINE. ALSO use for Lassa fever, hantavirus. TOX: Hemolytic anemia (due to decreased ATP) Amantadine @ M2 protein; Rimantidine does not cross BBB. HIV protease inhibitors ALSO cause lipodystrophy (like the kind caused by steroids), hyperglycemia , and inhibition of P450. Thrombocytopenia & renal stones (indinavir) NRTIs: General TOXICITY: BM suppression, peripheral neu ropathy, la ctic acidosis; *(ZDV) Megaloblastic anemia; (didanosine) increased LFTs, pancreatitis & hyperuricemia; NNRTIs: General TOX: rash Fusion inhibitors may cause INCREASED RISK OF BACTERIAL PNEUMONIA; Maraviro c is a CCR5 antagonist. INTERFERONS: Induce production of ribonuclease inhibits viral protein synthesis by DEGRADING viral mRNA & : inhibits viral protein synthesis; : increases MHC I and II expression in ALL CELLS; Tox: fever, chills, myalgias, DEPRESSION, fatigue, pancytopenia, neurotoxic, autoimmune effects (thyroiditis, AIHA) 2b: HBV, HCV, HDV; 2b,n3: HPV; 2a,2b: CML, Hairy cell, Kaposi, 2b: melanoma 2b: CGD Anti TB: Ethambutol: inhibits CW synthesis by blocking arabinosyl transferase (which polymerizes arabinose to arabinan to arabinogalactan) Dont forget this has RED-GREEN color vision problems Pyrazinamide: works in lysosomes (low pH environment; best for intracellular Tb); inhibits synth esis of mycolic acid. MAC prophylaxis: azithromycin; Treatment: clarithromycin, ethambutol, rifabutin. Chloroquine: blocks DNA + RNA synthesis; TOX: headache, defects in lens accommodation, diarrhea, itching, gray hair For chloroquine RESISTANT: Prophylaxis: mefloquine; Rx: quinine + doxy, clinda, or pyrimethamine. Mebendazole: DECREASES glucose uptake & degrades MT structure; USED for MOST intestinal nematodes Pyrantel pamoate: NM agonist spastic paralysis 2+ Praziquantel: INCREASED Ca influx, INCREASED vacuolization; USED for most cestodes and trematodes. Opioids bind opioid receptors which activate a GPCR. One pathway OPENS potassium efflux, another pathway CLOSES 2+ Ca channels to HYPERPO LARIZE a cell. Butorphanol is a partial agonist at -receptors & -receptors. Use for PAIN; less respiratory depression. Naltrexone can be used for alcoholism to decrease craving. Pentazocine & nalbuphine are -agonists (spinal analgesia, dysphoria) & -antagonists: precipitate withdraw al Methylnaltrexone is used to treat opioid induced constipation (does not cross BBB) Meperidine: Full -agonist metabolized to normeperidine (SSRI) serontonin syndrome + seizures. Tramadol: very weak agonist; also inhibits 5HT and NE reuptake; use for CHRONIC PAIN; LOWERS seizure th reshold. ANG II: GFR decreases, RPF decreases MORE; thus FF increases. Recall ANG II has effects on afferent + efferent arterioles. Cimetidine has weak anti-androgenic effect: gyneco mastia , galacto rrh ea, hyperp rolactinemia , sexual dysfunction. ALSO , crosses BBB (confusion, dizziness, headaches) and placenta; Cimetidine & ranitidine DECREASE renal excretion of creatinine. DIGOXIN: Renally cleared. MCC of death in TCA overdose is refractory hypotension and cardiac arrhythmia (quinidine like effect: QRS & QT prolongation and cardiac dysrhythmias). INHIBITION OF FAST SODIUM CHANNELS in cardiac myocytes and His-Purkinje system causes it. GIVE HYPERTON IC SODIUM BICARBONATE. WORD GAME: To pr event serotonin syndrome, must wait 2 weeks for MAOi discontinuation before SSRI to allow for MAO regeneration (enzyme r esynthesis) ASPIRIN MIXED DISORDER: 1) Respiratory alkalosis first then 2) SUPERIMPOSED (over all acidic pH) metabolic acidosis later. Positive ferric chloride test means INCREASED PHENOLS suggests salicyla tes TRAP: Tinnitus is the EARLIEST side effect at LOW DOSES; Hyperven tilation only occurs at VERY HIGH DOSES. For lipophillic anesthetics, after it enters CNS, it quickly redistributes to adipose AND SkM. CCB: blocks SA to AV conduction; occurs @ diastole (before ventricular contraction): blocks DIASTOLIC DEPOLARIZATION Levodopa/carbidopa on-off effects are NOT TEMPORARY and will NOT SPONTANEOUSLY RESO LVE. UNPREDICTABLE

Phenytoin: (Also a 1B) blockage of INACTIVE Na+ channels; increase refractory period; inhibition of glutamate release. Can cause generalized lymphadenopathy without a serum sickness like syndrome. (Pseudolymphoma) *By revving up P450 Vitamin D deficiency Primidone is metabolized to Phenobarbital and phenylethylmalonamide (thus increased blood levels of the latter two) Barbituates will precipitate a porphyria attack; also inhibit Complex I of ETC; SAFE in PREGNANCY + Lamotrigine & felbamate block voltage gated Na channels & blocks glutamate channels. PARTIAL + TO NIC- CLONIC Felbamate may cause aplastic anemia. + Topiramate blocks Na channels, INCREASES GABA action, and blocks AMPA rec eptors. PARTIAL + TONIC-CLO NIC; ALSO used for alcohol abstinence: GABA blocks glutamate slows release of DA on NAC pathway. Tiagabine inhibits GABA r euptake. ONLY FOR PARTIAL SEIZURE Vigabatrin irreversibly inhibits GABA transaminase; induces psychosis. O NLY PARTIAL SEIZURE Levetiracetam: unknown; may modulate GABA and glutamate release. Acamprosate: helps prevent relapse; lowers the activity of receptors for glutamate (chronic alcohol abuse increases these receptors); effects persist after treatment ended. Ergonovine constricts vascular smooth muscle by STIMULATING 1 and 5-HT; WORSENS PRINZMETAL ANGINA Cinacalcet suppresses the secretion of PTH by increasing sensitivity of calcium receptors. PABA esters in sunscreen block UVB (290-320nm); no effect on UVA. Avobenzone absorbs both UVAI and UVAII Zinc oxide sunscreens protect against UVAI, UVAII, and UVB 2+ Foscarnet is a pyrophosphate analog that can chelate Ca and promote nephrotoxic renal magnesium wasting. WORD GAME: Penicillins are analogs of D-Ala-D-Ala that inhibit transpeptidase. COX-2 inhibitors do not affect platelets. MAOi are useful atypical depression (mood reactivity, limb fatigue, rejection sensitivity, increased sleep/appetite) & treatment r esistant depression. Thiazides cause LITHIUM TOXICITY most lithium is reabsorbed in PCT lithium also follows sodium, so using thiazides will increase PCT reabsorption. NSAIDs cause LITHIUM TOXICITY renal ischemia R-A-A fires to retain sodium (hence lithium) Rifampin can ALSO cause drug induced interstitial nephritis Mannitol works mainly on LOH Furosemide also causes gout and hypomagnesemia. Thiazides: indapamide, metolazone, chlorthiadone use thiazides for nephrolithasis + Amiloride for Li induced nephrogenic DI. ACEi are the best initial treatment of HTN in CHF. AVOID ACEi with bilateral renal artery stenosis. Atomoxetine is a non-stimulant SNRI for ADHD. Clomipramine (TCA) can ALSO be used for OCD. Mirtazapine: (2 antagonist + 5HT2 & 5HT3 antagonist) use for depression with insomnia. Typical HIGH potency antipsychotics (haloperidol, fluphenazine, pimozide, trifluoperazine) cause more extrapyramidal symptoms (WORD GAME: skeletal muscle tone) Typical LOW potency antipsychotics (chlorpromazine*, thioridazine**) cause more anticholingeric/anti-H effects. *also an anti-emetic; Corneal deposits ; **quinidine like; ReTinal deposits Antipsychotics: HIGHLY LIPID SOLUBLE; anti-M, anti-, anti-H. Torticollis (dystonia): painful muscle spasm due to unopposed cholinergic activity. Atypical antipsychotics: block 5HT2 , M, , and H. Ziprasadone long QT syndrome; apripazole is a 5HT2 partial agonist Olazapine is ALSO used for OCD, anxiety disorder, depression, mania, and Tourettes. **Use anticholinergics for (antipsychotic) drug induced Parkinsonism; using levodopa will PRECIPITATE psychosis Lithium prevents recycling of inositol (decreased PIP2 , decreased cAMP); it is an ADH antagonist; can cause heart block, tremor, and hypothyroidism with goiter. Buspirone is a 5HT1A agonist. It may take several weeks for it to take effec t. TCAs: ALSO used for fibromyalgia; TOX: convulsions, coma, cardiotoxic (QRS+ QT prolongation). CV toxicity is due to + inhibition of fast Na channels.

Desipramine is the least sedating and has lower seizure threshold. Others include doxepin and amoxapine. SNRI: Venlafaxine is ALSO used in GAD; Duloxetine is also used for DIABETIC PERIPHERAL NEUROPATHY Buproprion is a NE and DA reuptake inhibitor. Maprotiline blocks NE reuptake Trazadone primary inhibits serontonin reuptake. Use for INSOMNIA, as high doses are needed for antidepressant effect. Sertonin syndrome: hyperpyrexia, hyperreflexia, myoclonus, CV collapse, mental status changes, sympathetic stimulation. NMDA rec eptors are UNIQUE in that they require both 1) agonist & 2) neuronal depolarization to be activated. 2+ + Permeable to Ca and Na . Morphine tolerance is modulated by glutamate (phosphorylating opioid receptors + increasing NO levels) Thus ketamine, PCP, or dextromethorphan can antagonize glutamate and PREVENT MORPHINE TO LERANCE. GLAUCOMA -agonists: 1) Epinephrine decreased humor synthesis via vasoconstriction DO NOT USE IN CLOSED ANGLE 2) Brimonidine decreased humor synthesis (no pupil or vision changes) -blockers: Timolol, betaxolol, carteolol decrease humor secretion Diuretics: Acetazolamide decreased humor secretion due to decreased bicarbonate Cholinomimetics: Pilocarpine, carbachol, physostigmine, echothiophate increase outflow of aqueous humor; contract ciliary muscle and OPEN trabecular meshwork; SIDE: cyclospasm Latanoprost (PGF2): increased humor outflow (darkens color of iris) Open/wide angle glaucoma: Painless; USE dorzolamide, epinephrine, lat anoprost, timolol Closed angle glaucoma: very painful; do NOT use epinephrine, anticholinergics; USE osmotic diuretic or acetazolamide. DHEA: used in AIDS (increases CD4 in females), Alzheimer disease and aging, diabetes, hypercholesterolemia, and SLE (decrease symptoms and flare ups in females) Melatonin: Serotonin derivative for jetlag and sleep disorders; CONTRAINDICATED IN PREGNANCY; decreases LH and PRL. 3The ANTACIDS can all cause HYPOKALEMIA; Calcium Carbonate can DECREASE PO4 . Sulfasalazine is combination of sulfapyridine (antibacterial) and 5-ASA (mesalamine); activated by colonic bacteria; Can cause reversible oligospermia. Metoclopramide is a D2 antagonist: {INCREASES resting tone, contractility, LES tone, motility}; USED FOR diabetic and post surgical gastroparesis. INTERACTS WITH: digoxin and diabetic agents; CONTRAINDICATED in small bowel obstru ction (tinkling sounds) Meperidine is the narcotic of choice for acute cholecystitis as it is least likely to spasm the Sphincter of Oddi (Anti-M) Ursodiol is a primary bile acid that lowers cholesterol secretion into bile acid and is effective in dissolving cholesterol stones. Loperamide: antidiarrheal; CONTRAINDICATED in child due to risk of toxic megacolon. Diphenoxylate: usually given with atropine because of its anti-M effec ts @ high doses. Megestrol: a progesterone derivative with appetite stimulating and antineoplastic properties. ALSO USED TO TREAT ADVANCED BREAST CARCINOMA Dronabinol is a cannabinoid used for appetite stimulation in chemo/HIV regiments. Sibutramine is primary a MAOi (also blocks NE, 5HT reuptake) used for appetite suppression. Hyoscyamine is an anti-M that may alleviate the postprandial abdominal pain of a patient with IRRITABLE bowel syndrome when given 30 to 60 minutes before a meal. ANTIEMETICS 5HT3 antagonist on CTZ (ondansetron, g ranisetron) DA2 antagonist on CTZ (prochlo rperazine, metoclop ramide) H1 antagonist M antagonist (on vomiting center): scopolamine CB1 on CTZ: dronabinol NK1 antagonist on spinal cord: aprepitant NOTE: opioids decrease emesis by decreased Substance P on NK1, but INCREASE emesis by activating CTZ. Metformin only leads to lactic acidosis in those with impared renal functions; so check Cr beforehand. Glitazones lead to edema, hepatotoxicity, CV toxicity; NO HYPO GLYCEMIA; DECREASED TGs, CRP, glucose; INCREASED HDL.

CV: -

Pramlintide is a synthetic amylin that slows the rate at which food is absorbed from intestines decreases glucose production (decreases glucagon) & decreases appetite. Exenatide: Incretin analog; PANCREATITIS Sitagliptin: inhibits DPP-4 (breakdown of GLP-1) Diazoxide opens ATP K+ channels INHIBITS insulin secretion; maintains euglycemia in patients with an insulinoma; NOTE, this is ALSO used to relax vascular smooth muscle (for hypertensive emergency) Use INSULIN for gesta tional diabetes; do not use the oral agents because of fetal hyperinsulinemia/hypoglycemia. Orlistat INHIBITS PANCREATIC LIPASES. Sibutramine: Sympathomimetic SNRI (some DA as well); DECREASED APPETITE. Levothyroxine and triodothyronine OSTEOPOROSIS in POSTMENOPAUSAL WOMEN Perchlorate/thiocyanate are ionic channel inhibitors that block iodide entrance into thyroid HERBALS: Echinacea: decreases cold symptoms via INCREASED ILs and TNF. Garlic: Inhibits HMG-CoA reduc tase & ACE; CAUTION WITH ANTICOAGULANTS, hypotension, antiplatelet action Gingko: for claudication & Alzheimer via ROS scavenging & increased NO. CAUTION WITH ANTICOAGULANTS Ginseng: Possible increase in mental and physical performance. Saw Palmetto: Symptomatic treatment of BPH via 5-reductase inhibitor & androgen receptor antagonist St. Johns wort: For depressive disorder; may enhance brain 5HT functions; Kava: sedative Jojoba: Cosmetic, hair growth Soy: phytoestrogen Valerian: sleep OTHER EXAMPLES OF DRUG REACTIONS Torsades: Cisapride (5HT4 agonist & indirect parasympathomimetic that increases upper GI motility and increases LES tone) Agranulocytosis: Colchicine, dapsone Aplastic anemia: benzene, NSAIDs Hypothyroidism: Lithiu m Hyperuricemia: Furosemide Osteoporosis: Heparin Photosensitivity: Sulfonamides, a miodarone SJS: Phenobarbital, penicillin, allopurinol Parkinsonism: reserpine Disulfiram like: Procarbazine. Neuro/nephro: Polymixin Nephro/Oto: Vancomycin Yellow skin: (Not jaundice) quinacrine Blue-gray skin: chlorp romazin e & arsenic

Circulation: Liver has LARGEST SHARE OF CARDIAC OUTPUT; Kidney has HIGHEST BLOOD FLOW PER GRAM. Chemoreceptors: TPR goes in the same direction as PCO2. Ex. Increased PCO2 systemic vasoconstriction by sympathetic outflow increased TPR Baroreceptors can be BLOCKED @ the ganglionic synapse with NN antagonists. + Autoregulation: Hea rt (O2, adenosine, NO), Kidneys (myogenic & tubuloglomerular feedback), SkM (lactate, adenosine, K ), Skin (sympathetic stimulation most important) Platelets are involved in PLAQUE for mation because of initial platelet adhesion, SMC migration, and PDGF and TGF-B. SBP mainly determined by STROKE VOLUME (direct) & ARTERIAL COMPLIANCE (inverse) DBP mainly determined by TPR Arteriole dilation (decreases); constriction (increases) Decreased HR or SV will DECREASE DBP. Widened PP increased SV or decreased vessel compliance

During hemorrhage, sympath etic signal venules & veins to CONSTRICT in order to tighten circulation. SPHEROCYTOSIS increases viscosity When heart stops, blood flows from high pressure arterial system to venous system until pressure is equalized @ MSFP. WIDE SPLITTING: delayed RV emptying (pulmonic stenosis, RBBB); Split S1 can be heard in RBBB PARADOXICAL SPLITTING: delayed LV emptying (AS, LBBB) ASD ALSO has a systolic ejection murmur in the PULMONIC AREA. MVP: Standing/Valsalva makes it SOONER; Squatting/Handgrip makes it LATER. Palpitations particularly when anxious. HIGHEST SaO2 in TETRALOGY OF FALLOT: PVs, LA LOWEST SaO2 in PDA: RA, RV Tranposition of Great Vessels: RVH; enlarged heart; diabetic mother; dome shaped, fried egg yolk on side; pulmonary vascular markings are increased. DEPOL: Endocardium to Epicardium; REPO L: Epicardium to endocardium. + RESPONSIVENESS refers to the capacity of the cell to depolarize (associated with # of Na channels in ready state) The more negative the resting potential, the FASTER the response. CONDUCTANCE (velocity) is greater with a more negative resting potential. + ISCHEMIA: Increased K in interstitium Less negative resting membrane slower conduction = easier to block. Funny Current: an inward depolarizing current that OPENS during repolarization & CLOSES during depolarization. Purpose of this is to reverse the membrane potential at the end of the phase 3 Ik current. INCREASED by 1 (increased cAMP) 1)increased upstroke velocity by increased I Ca, 2) shortened AP Duration by increased I k, 3) increased HR by increased If, which reduces phase 4 slope DECREASED by M2 (decreased cAMP) OPPOSITE OF ABOVE ++ Dromotropy: AV node conduction velocity; related to phase 0 depolarization (Ca current) + Chronotropy: SA node firing rate (Na current) ++ Inotropy: (Ca current) Left axis deviation (-90 to -30 degrees) : LVH or dilation; LV conduction defect, RIGHT acute MI Right axis deviation (+110 to -90 degrees): RVH or dilation; RV conduction defect; LEFT acute MI. U wave is caused by hypokalemia and bradycardia. Prolonged QT can ALSO be caused by thioridazine and TCAs. Torsades treatment: 1) Correct hypokalemia, 2) correct hypomagnesemia, 3) discontinue prolong QT drugs, 4) shorten APD with drugs or electrical pacing. A-Fib: can be precipitated by binge alcohol consumption (holiday heart syndrome), sympathetic tone, and pericarditis. Treat with -blockers or CCB. A-flutter: back to back atrial depolarization waves. Use IA, IC, III, or esmolol rd Stage 2 Lyme disease leads to a 3 degree heart block (treat with pacemaker) V-fib: If defibrillation fails, give epinephrine, amiodarone (first lin e), or lido caine. Myocardium uses ox (60%, largest O2 requirement), glucose oxidation (30%), glycolysis (5%); hence diverting energy production away from ox will relieve angina. TRAP: During ischemia, loss of cardiac contractile function occurs within 60 seconds; 30 minutes is the point of irreversible cell death. Subendocardial infarcts: due to mural thrombosis, AS, global hypoperfusion. RCA occlusion affects SA and AV nodes susceptible to AV block & arrhythmias. 2+ CONTRACTION BANDS are due to hypercontraction of sarcomeres due to massive Ca influx. Post-MI 10-14 days (2 weeks) is granulation tissue. 2 months is DENSE collagen scar. Repetitive ischemia or persistence hypoperfusion of cardiac myocytes => CHRO NIC but REVERSIBLE loss of contractile function: HIBERNATION . REVERSED by CABG or angioplasty STUNNING is a less severe form of hibernation. Brief ischemic episodes (<30 minutes) followed by reperfusion can cause this. 2+ Dephoshorylated phospholamban BINDS SERCA ATPase => Ca influx back to SR. 1 signaling phosphorylates phospholamban. 1 mediated VENOconstriction is what leads to INCREASED VR => INCREASED PRELOAD => INCREASED ARTERIAL PRESSURE.

With toxic levels of hydralazine, the body may compensate with SEVERE TACHYCARDIA => ANGINA Electrical alternans due to tamponade and blood attenuating the electrical signal. WORD GAME: Slow growth rate of an atherosclerotic plaque will allow collateral formation to slow progression of CVD. PDA: ALSO presents with differential cyanosis, which is cyanosis of the lower extremities but not upper body. Coarctation of aorta leads to INCREASED UPPER LIMB HTN => HCM & ascending aortic dissection. Only ADULT coarctation has rib notching; consequences: BACTERI AL ENDOCARDITIS and CEREBRAL HEMORRHAGE. Infantile typ e- only weak LL pulses; RVH; associated with PDA Both: AR, bicuspid aortic valve, HTN cardio myopathy, ascending aortic dissection, endocarditis, cereb ral hemo rrhage FULLY COMPENSATED/UNCO MPENSATED coarctation still has brisk upper pulses but weak lower. BUT BLOOD FLOW IS NORMAL. Thus it is clear that decreased pulse is due to decreased resistance. GREATEST DROP in blood pressure occurs in ARTERIOLES because they contribute the most to RESISTANCE. *LEFT HEART sounds increase in EXPIRATION; RIGHT HEART sounds increase in IN SPIRATION* S3 can be accentuated on expir ation by decreasing the volume in the lungs / heart is closer to the stethoscope. AR leads to increased LVEDV (thus PRELO AD); ALSO causes increased contractile force, thus eventually increased LV afterload => increased RV afterload. Increases in intensity by 1 grade after a pause. AS has DECREASED PP because of diminished blood flow through valve. The pressure backup can cause a cystic medial necrosis in the LV and cause a dissecting aneurysm. Age related stiffening of aortic valve leads to ISOLATED SYSTOLIC HYPERTENSION (normal DBP): Treat with thiazides or DHP CCBs TRAP: DURING acute rheumatic fever, if a patient dies (rare), it is due to MYOCARDITIS cardiac dilation functional MR heart failure. Chronic AS reduced LVEDV reduced CO systemic hypotension Acute AFib can also increase steady state pulmonary venous pressure to cause acute pulmonary edema. JERVELL LANGE-NIELSEN SYNDRO ME: AR; congenital long QT syndrome + congenital neurosensory deafness. ROMANO WARD SYNDRO ME: AD; congenital long QT & NO deafness; + BOTH are thought to r esult from mutations in a K channel protein that contributes to the delayed rectifier current (I K) Increased AST with normal ALT and GGT indicates MI; confirm with other markers. Fragile X syndrome: Aortic root dilatation & MVP MVP involves myxomatous degeneration of the zona fibrosa of the valve. In utero MUMPS causes ENDOCARDIAL FIBROELASTOSIS => RCM; Other finding: mural thrombi, flattened trabeculae, stenosed valves. HYPERTENSION : increased wall/lumen ratio; decreased numerical density as arterioles are LOST; decreased cross sectional area. OVERPERFUSION CAUSES A WASHOUT OF VASODILATORY METABO LITES => LO NG TERM VASOCO NSTRICTION With hemorrhage and hypotension, the venous system rec eive sympathetic input to constrict, thus enabling easier blood flow to INCREASED VENO US RETURN (also increased MSFP) Monckeberg arteriosclerosis: DYSTROPHIC calcification in MEDIA of arteries (radial, ulnar, femoral, tibial) Increased RAP => Increased venous pressure, PVC does not allow P wave, so EDV is REDUCED. Sepsis leads to INCREASED PERMEABILITY which causes ARDS. Increased MSFP can be due to sympathetic nerve reflexes initiated by the decreased in BP (renal retention of salt and water) Varicose veins aggravated by INCREASED VENOUS PRESSURE (prevents pumping of blood back to heart) Third degree heart block: HR is decreased (dictated by ventricles) with the same CO; thus SV is INCREASED. PROLONGATION of QRS usually due to BBB secondary to CAD. Arteriosclerosis: calcification of arteries => DECREASED DISTENSIBILITY => SBP INCREASED dispropo rtionately because vessels cannot dilate sufficiently in response to increased blood flow. Atherosclerosis: taregets areas of high turbulence, such as where arteries branch. Abdominal aorta > Coronary Artery > Popliteal Artery > Carotid Artery. CAN cause AAA TRAP: the initial step in AAA formation (secondary to atherosclerosis) is intimal streak. VELOCITY OF BLOOD FLOW is inversely proportional to CSA; Aorta/large vessels > VC > large veins > small arteries > arterioles > small veins > venules > capillaries

Removal of CNX will lead to INCREASED HR and MAP; will STILL allow carotid message (CN IX) Carotid massage will PROLONG THE AV NODE REFRACTORY PERIOD At high altitudes, carotid bodies undergo HYPERPLASIA Carotid body tumor (paraganglioma) secretes catecholamines. If venous pressure is increased, then (MAP-RAP) = CO *TPR Removing 1 kidney: DECREASED CO , INCREASED TPR, DECREASED Q (MAP stays same) BUERGERS DISEASE: (HLA A9, B5) On biopsy: Thrombus, inflammation, and microabscesses. MEDUM VESSELS. Churg Strauss (pANCA): ALSO has peripheral neu ropathy. Osler Weber Rendu: AD; recurren t epistaxis, skin discoloration, mucosal telangiectasia , and GI bleeds. SMALL VESSEL Sturge Weber: SMALL VESSEL; port wine stain on face, ipsilateral leptomeningeal angiomatosis (intracerebral AVM), seizures, early onset glaucoma; *XR: Skull shows tram-track calcifications. CHF: With decreased CO, the R-A-A activates and INCREASES ARTERIOLAR RESISTANCE. However, this will lead to a vicious feedback cycle to worsen the CHF. To compensate for a decreased CO heart operates @ a higher EDV and ESV. BNP is sensitive for CHF; S3 is specific for CHF. TRAP: Only chronic CHF has hemosiderin laden macrophages. For post MI orthopnea and dyspnea acute pulmonary edema transudate accumulating in the alveolar lumen. When CVP increases (as in RHF), the interstitial fluid pressure rises and increases lymphatic drainage => no edema. But with significantly higher CVP increases, lymphatic drainage cannot keep up and edema develops. Hemosiderin laden macrophages: alveolar cells containing golden cytoplasmic granules that stain with Prussian blue. An INCREASED pulse pressure should make you think DIASTOLIC HEART FAILURE right away: Normal heart cavity, normal EF, increased LVEDP. CN IX syncope can occur through excessive carotid sinus stimulation. Henoch Schonlein purpura: Rash, abdominal pain, polyarthritis. The hand grip INCREASES AFTERLOAD. The SHORTER the S2 to OS gap, the mor e SEVERE mitral stenosis is. Acute AV fistula: decreases TPR increased CO and VR (no shift of VR curve yet) Chronic: SANS and kidneys compensate by INCREASING TPR, contractility, and circulating blood volume. These changes further increase cardiac function curve and RAP, causing rightward shift of VR. Pathologic ventricular hypertrophy ALSO ALTERS transcription such that ventricles can produce natriuretic peptide. Unstable/crescendo angina: thrombosis but NO necrosis. Nitroglycerin has NO EFFECT. Repeated STABLE angina gradual loss of myocytes patches of fibrosis & vacuolization of damaged myocytes, typically in subendocardial locations (poorly perfused) DILATED CARDIOMYOPATHY: ALSO Chronic alcohol, Coxsackie B, chronic cocaine, peripartum cardiomyopathy. With VOLUME OVERLOAD: Laplace law states greater TENSION is needed to maintain the same PRESSURE. Chronically, to normalize wall tension, the ventricle develops ECCENTRIC HYPERTROPHY systolic failure. S3 present; balloon appearance on Xray; dilated heart on ultrasound. DECREASED EF, PP, and INCREASED JVP. HYPERTROPHIC CARDIOMYOPATHY : S4, systolic murmur (mitral outflow blocked) made worse by decreased VR. Treat with -blocker or CCB; Restrictive/Obliterative: thickened, inelastic ventricular walls; formation of granulation tissue in pericardium that interferes with filling of ventricles. Reduc ed biventricular EDV + increased DBP implies pericardium is restricting compliance of the ventricular walls. ALSO caused by sarcoidosis, amyloidosis, postradiation fibrosis, endocardial fibroelastosis, Loefflers syndrome (endomyocardial fib rosis with a pro minent eosinophilic infiltrate), hemochromatosis Remember for DIASTOLIC FAILURES, EF is normal; moreover, with decreased LV compliance, there should be an INCREASED LVEDP to maintain the same SV. Palpitations + chest pain + MR in health adult acute viral myocarditis (Coxsackie B, Lassavirus, HIV) Genitourinary manipulation Enterococcal endocarditis. Tricuspid valve endocarditis with IV drugs ALSO associated with Candida and Pseudomonas. Pulsus paradoxus is ALSO in croup.

Endo: -

Pericarditis: SEROUS SLE, rheumatoid arthritis, Coxsackie B, uremia FIBRINOUS Dresslers syndrome, post MI, rheumatic fever, uremia. HEMORRHAGIC Tuberculosis, malignancy (melanoma) Pyogenic granuloma: Polypoid capillary hemangioma that can ulcerate and bleed. Associated with trauma and pregnancy. TRAP: Trauma of PANCREAS r etroperitoneal hematoma Trauma of abdominal aorta hemorrhagic shock. Culture negative endocarditis: by Bartonella, Coxiella, Mycoplasma, Histoplasma, Chla mydia, HAECK .

TRH ALSO stimulates PRL release. Somatostatin ALSO blocks TSH release. Cortisol ALSO upregulates 1 receptors on arterioles, decreases bone formation, and is an anti-inflammatory. It ALSO specifically DECREASES glycogenolysis in muscle/adipose; but INCREASES glycogenolysis in LIVER (increase enzyme synthesis in liver) It ALSO induces NE epinephrine in medulla. Weightlessness, ethyl alcohol, cortisol, thyroid hormone SUPPRESS ADH. Calcitonin is from parafollicular cells (C cells) of THYROID. cAMP: FLAT/G CCHAMP: FSH, LH, ACTH, TSH, Glucagon, CRH, Calcitonin, hCG, ADH (V2), MSH, PTH cGMP: ANP (receptor has intrinsic GC), NO (aka EDRF; diffuses thru membrane) IP3: GGOAT: GnRH, GHRH, Oxytocin, ADH (V1), TRH, ANGII ALDOSTERONE is a STEROID TK: 1) monomeric p21ras: insulin, IGF-1, FGF, PDGF 2) JAK-STAT: PRL, GH, CSF, EPO, somatotropin, IFNs. Recall, ras is a G protein. Insulin, glucagon, catecholamines are WATER SOLUBLE. TK: (insulin example): Autophosphorylation IRS-1 binds intracellular receptor IRS-1 phosphorylated on tyrosines allows proteins with SH2 domains to bind phosphotyrosines on IRS-1 CASCADE 1) PI-3 kinase increase GLUT4; 2)Activate protein phosphatase (paradoxically); 3) Stimulate p21ras to alter transcription Neuroblastoma does NOT have episodic hypertension. The supraoptical/hypophyseal tract is the conduit through which ADH & oxytocin are delivered to posterior pituitary for storage (no vasculature involved) Purpose of the hypophyseal portal system is to deliver hormones in HIGH CONCENTRATION. CSFs, PRL, GH, and cytokines utilize JAK-STAT MAGNESIUM EFFECT ON PTH: 1) Acute decrease INCREASE PTH; 2) CHRON IC decrease DECREASE PTH Common causes of hypomagnesemia: diarrhea, AGs, diu retics, and alcohol abuse. Loss of consciousness by hypoglycemia: Non-medical setting: IM glucagon; Medical setting: IV dextrose Microalbuminuria is the PREFERRED method of diagnosing INCIPIENT DIABETIC NEPHROPATHY If diet/exercise fails to improve GESTATIONAL DIABETES, start insulin. Cushings leads to hyperPLASIA of the zona fasciulata. Treat Graves opthalmopathy by glucocorticoids => Proptosis is caused by retroorbital fibroblasts producing excessive GAGs due to inlfiltration of lymphocytes and macrophages. ANTITHYROID AGENTS DO NOT AFFECT PROPOTOSIS. Excess iodine can lead to clinical hypothyroidism (shut down of thyroid to prevent thyrotoxicosis) Thyroid hormone ALSO increases glucose absorption. TRAP: T4 rT3 ; **T3 does NOT become rT3.** Non-toxic multinodular goiter: F>M; euthyroid; Hypothyroidism: ALSO has 1)facial/periorbital myxedema; 2) late amenorrhea; 3) reversible psychosis, dementia in old; 4) deep voice, 5) macroglossia, 6) myopathic process of Type II fibers Hashimotos: *tender*; has increased risk for 1) thyroid lymphoma, 2) IDDM, 3) celiac sprue, 4) NHL B cell type Cretinism ALSO has 1) hypotonia, 2) prolonged jaundice, 3) hoarse cry; born w/ puffy face, sluggist and diminished DTRs. De Quervains: elevated ESR, jaw pain, *very tender*, GRANULO MAS;

Reidels: fibrous replacement, *painless* goiter; anti-thyroid peroxidase; extends to adjacent neck muscles mimics malignancy by hoarseness. Hyperthyoidism: ALSO has 1) ammenorhea 2) stress induced catecholamin e surge death by arrhyth mia (Type II antiarrythmics are DOC); Graves: hyperplastic follicles with scalloped colloid; Plummer: focal patches of hyperfunctioning follicular cells working independently of TSH due to mutation in TSH receptor Jod-Basedow phenomenon- thyrotoxicosis in a patient with iodine deficiency goiter that is made iodine replete. Iodine Scan: Diffuse Goiter + High radionuclide uptake GRAVES DISEASE Diffuse Goiter + Low radionuclide uptake TSH tumor Nodular goiter + High Uptake Toxic multinodular goiter (Plummer syndrome): no ophthalmic involvement. Nodular goiter + Low uptake Primary hyperthyroidism Low T3 syndrome (euthyroid sick syndrome) occurs with systemic illnesses, post-surgery, and with malnutrition or starvation. The decrease is T3 is thought to be a protect adaptation to decrease catabolic processes. Thyroid storm: precipitated by trauma, infection, radio-iodine treatment, and childbirth. CHF, pulmonary edema, death Be aware that there are other forms of thyroxine (T5, T6 , T7) Pretibial myxedema skin filtration of the lower legs and proptosis are SPECIFIC to Graves disease. Papillary thyroid carcinoma is preceded by prior history of radiation to head/neck; PLUS: solid balls of neoplastic follicula r cells with microscopic blood vessels and stro ma in the cen ter refers to broken off papillary clusters. TRAP: Enlarged thyroid gland, heat intolerance, and palpaitations are NORMAL in pregnancy. Afib, tr emor, increased AP, heat intolerance can be found in any hyperthyroid state. PITUITARY APOPLEXY : acute bleeding into pituitary adenoma => Symptoms of preexisting adenoma + meningeal irritation (mimics a SAH). BITEMPORAL HEMIANOPSIA is the key difference. Patients DIE of CV collapse because of adrenocortical insufficiency (lack of ACTH) Primary adrenal insufficiency ALSO has hypochloremia and metabolic acidosis. One can DIE from Waterhouse-Friedrichsen Partial glucocorticoid resistance (@receptor): INCREASE ACTH + cortisol production (normal cortisol effect); but also increase mineralocorticoid production + increased adrenal production. Nelson syndrome is hyperpigmentation via ACTH secondary to adrenal removal. + Insulin ALSO increases Na retention (kidneys) Oral glucose tolerance test: 1) NORMAL: fasting <110; 2hours <140; 2) Impaired fasting glycemia fasting 110-126; 2 hours < 140 3) Impaired glucose tolerance fasting <126; 2 hours >140 4) Diabetes fasting > 126; 2 hours >200 DKA: there is overall potassium depletion (with hyperkalemia) as sustained M.Ac increases potassium excretion. (Thus negative potassium balance) Treatment with insulin ALSO decreases osmolality & increases bicarbonate and sodium. Macrosomia: Gestational diabetes in mother leads to high glucose environment for fetus fetal islet cell hyperplasia once born, the lower glucose environment with high insulin hypoglycemia in fetus. TRAP: There is no transfer of maternal insulin to fetus. With diabetes, removal of anterior pituitary (loss of ACTH/cortisol & GH) will increase insulin sensitivity and reduce blood glucose level with the insulin that remains. Maternal transfer of T4 to neonates lasts 2 weeks. Be aware, that in the liver, glucocorticoids PROMOTE glycogenesis. Glucagon works ONLY on liver; epinephrine works on liver and muscle. WORD GAME: The zona glomerulosa is able to synthesize aldosterone because of a LACK OF 17-OHase, so none of the mineralocorticoid precursors are shunted toward androgen production (unlike the cortisol precursors) Drug induced SIADH: cyclophosphamide, carbamazepine, cisplatin, vincas, amitryptiline, amiodarone, MAOi. In pancreatic -cell, the first glycolytic enzyme is glucokinase. NF Type 1 & VHL can ALSO cause PHEOCHROMOCYTOMA

Conn Syndrome: hypernatremia is rare because of aldosterone escape, referring to hypervolemia and ANP secretion. 18-hydroxylase (aka Aldosterone synthase) is stimulated by ANGII. Normally, fetuses lack 3-hydroxysteroid dehydrogenase in order to build up DHEA. TRAP: Transien t neurogenic DI is due to a problem in the posterior hypophysis; ch ronic neu rogenic DI (say 2 months) is due to a problem in the hypothalamic nuclei. Decreased ALBUMIN hypocalcemia *NO TETANY* because ionized levels are normal PTH levels NORMAL. Hypercalcemia is ALSO caused by hyperthyroidism, Addisons disease, RCC (via PTHrP), Zollinger-Ellison, ex cess Vitamin A. Pagets disease is normocalcemic but if immobilized, can become hypercalcemic. Hyperparathyroidism: PRIMARY: usually an adenoma; *INCREASED cAMP in urine* 2+ SECONDARY: hyp erplasia ; due to decrea sed Ca absorption and increased phosphorous TRAP: Renal failure SECONDARY HYPERPTH increased phosphorous + increased PTH. Acromegaly: failure to suppress serum GH following oral glucose tolerance test. Sheehans syndrome: Enlargement of anterior pituitary (increased lactotrophs) during pregnancy WITHOUT corresponding increased blood supply ALSO can cause loss of pubic and axillary hair. Central DI can ALSO be caused by histiocytosis X. Nephrogenic DI can ALSO be TREATED with indomethacin and amiloride. SIADH: TBW is constant over time as salt is wasted. (isovolumic) DIABETES MELLITUS: Unopposed secretion of GH and epinephrine (exacerbating hyperglycemia) ORDER OF APPEARANCE: Retinopathy Neph ropathy Moto r Claudica tion NEG: Small vessel dise ase 1) Retinopathy (hemorrhage, exudates, microaneurysms, vessel proliferation); 2) glaucoma, 3) nephropathy (nodular sclerosis, progressive proteinuria), 4) chronic renal failure, 5) arteriosclerosis leading to HTN, 7) K-W nodules NEG: Large vessel atherosclerosis, CAD, peripheral vascular occlusive disease, gangrene, CVD Osmotic damage: 1) Neuropathy (via nerve ischemia due to microangiopathy); 2) cataracts (sorbitol accumulation, 3) neovascularization retinal detachment DM causes a Type IV hyperlipidemia (increased VLDL) Normally: ACETOACETATE = 3-HYDROXYBUTYRATE; In DKA, ACETOACETATE << 3-HYDROXYBUTYRATE + DKA: Overall glucose uptake is INCREASED in LIVER due to glucokinase; total body K is DECREASED due to diuresis; relative hyponatremia (water followed glucose) DKA complications ALSO include: cerebral edema, cardiac arrhythmias, and heart failure. Note, MEN2A also has PARATHRYOID TUMO RS. *Dont mix this up* Insulinoma: greater fraction of proinsulin. APS1 (AIRE gene): autoimmune hypoparathyroidism, hypogonadism, pernicious anemia, adrenal insufficiency APS2: Addision, Hashimoto, IDDM. Metabolic syndrome: 1) decreased HDL, 2) increased TGs, 3) increased glucose, 4) HTN, 5) central obesity, 6) prothrombic, 7) proinflammatory. These clusters of risks m ay le ad to CVA and N IDDM

GI: PORTAL VEIN: UNCONJUGATED bilirubin > Conjugated Bilirubin Hemolysis from spleen deposits UNCONJUGATED into splenic vein portal vein; A smaller amount of CONJUGATED bilirubin is from reflux from h epatocytes. Frequency of basal electric rhythm (slow w aves: depols + repols of muscularis propria that determine frequency of contractions) Stomach 3 per minute; Duodenum 12 per minute; Ileum 8-9 per minute G cells are found in the antrum, duodenal/jejunal mu cosa; acts on CCK-B receptors. Gastrin ALSO increases gastric mo tility and gro wth of gastric mucosa (streng thens gastric barrier) and trophic effect on parietal cells (hyperplasia); PHE & TRP are POTENT STIMULATORS NOTE: Gastrin increases acid secretion primarily through ECL cells (Histamine release) rather than direct effect on parietal. Also: Gastrin will lead to increased density of parietal cells in the body of the stomach.

The acid secretagogues are SYNERGISTIC (you know what losing one means) *This is DESPITE the fact that atropine will NOT block vagal GRP stimulation of G cells.* Bile salts WEAKEN the gastric mucosal barrier. NOTE: Enteric nervous system stimulates ECL cell via M1, but stimulates parietal cell by M3. WORD GAME: Physiologically, gastric emptying is ONLY affected by CCK (NO NE of the other gastric enzymes) I cells (duodenum/jejenum) stimulate CCK, which ALSO decreases gastric emp tying (the ONLY GI hormone to do so) and decreases gastric acid secretion; ALSO increases blood flow to intestines; trophic effect on exocrine pancreas; FAs and AAs STIMULATE, carbs do not stimulate. D cells produce somatostatin K cells(duodenum/jejunum); produce Glucose-dependen t insulinotropic peptid e (GIP) aka. Gastric inhibitory pep tide. PROTEIN/FAT/CARBS stimulate its secretion. This accounts for greater insulin release ORAL > IV. PS ganglia in sphincters, GB and SI make VIP; STIMULATED by vagus n and distension; INHIBITED by adrenergic. Increases intestinal water/electrolyte secretion AND increases relaxation of intestinal smooth muscle and sphincters. P/D1 cells (stomach) or -cells (pancreas): Gh relin : INCREASES GH, ACTH, cortisol, and PRL secretion. HUNGER Salivation: Sympathetic (T1-T3 superior cervical ganglion) & parasympathetic (CN VII, CN IX) Salivary amylase hydrolyzes 1,4 linkages to yield disaccha rides Pancreatic amylase hydrolyzes starch to disaccharides and oligosaccha rides. SALIVARY GLAND TUMORS Pleomoprhic adenoma BENIGN: painless, movable, high recurrence. Warthins tumor:BENIGN: heterotopic salivary gland tissue trapped in a lymph node Mucoepidermoid carcinoma: INTRA-ORAL CARCINOMA: MC sites LATERAL EDGE TONGUE > Floor of mouth. WORD GAME: 5% of leukoplakias become malignant, BUT it hs as HIGH PROBABILITY of progressing to oral cancer. Squamous papilloma in mouth is from HPV 6,11 and has a TINY chance of becoming cancer. Abdominal pain/discomfort + distension + fever + diarrhea + shock in INFLAMMATORY BOWEL DISEASE => TOXIC MEGACOLON. XR: Colonic dilatation (SUFFICIENT FOR Dx); Do not give barium or do colonoscopy. Hepatic angiosarcoma has CD31 (PECAM1) Diffuse esophageal spasm is uncoordinated contractions of esophagus which are inefficient in propelling food into stomach and can cause DYSPHAGIA & CHEST PAIN MIMICS ANGINA PECTORIS. Periodic, non-peristaltic contractions of a large amplitude and long duration. Esophagitis: HSV: small vesicles (punched out ulcers); CMV: linear ulceration. Esophageal strictures: associated with lye ingestion and acid reflux. Varices are PAINLESS Mallory Weiss is PAINFUL. BOORHAEVE = All layers torn; vomiting, lower thoracic pain, subcutaneous emphysema; *Will see a pleural effusion on XR MALLORY-WEISS = only superficial esophageal layer torn. Note: M-W tears are caused by increased intra-abdominal pressures secondary to vomiting/retching/coughing. IT has NOTHING to do with acid. *Nothing on XR DUMPING SYNDROME: A complication of duodenal surgery (ex. Gastric bypass): RAPID, UNIMPEDED PASSAGE OF HIGHOSMOLARITY FOOD TO THE JEJUNUM, with onset half an hour after meals. INCREASED tonicity in SI causes an osmotic fluid shift from ECF to lumen in gut increasing distension of SI increasing motility; Symptoms associated with HYPOGLYCEMIA. Eat a low carbohydrate, high protein/fat, small meals; use octreotide for strong gastric inhibitor effect. RICHTER HERNIA: only ONE WALL of the intestine (usually the antimesenteric border) is trapped by the constriction ring of the hernia. Presents as a very tense and tender mass that is NOT REDUCIBLE and causes INTENSE PAIN. TOXIC MEGACOLON results from complete shutdown of colonic NT function due to inflammation of the MYENTERIC NEURAL PLEXUS. Seen in CD, ischemic colitis, PMC, UC. Zenker diverticulum: Cricopharyngeal muscle dysfunction (diminished relaxation during swallowing) leads to increased pressure necessary to move the food bolus downward. More intense contractions of the pharyngeal muscles increase oropharyngeal intraluminal pressure. With time, the pharyngeal mucosa will herniate through the muscle fibers in the zone of weakness. FALSE DIVERTICULUM ESOPHAGEAL SCC: In US is caused by cigarette smoking and alcohol; in Asia, by betel nuts and nitrosamines. Tylosis and lye can cause SCC;

African America: SCC more; Caucasian : Adenocarcinoma mo re. Worldwide: SCC more; U.S.: Adeno = SCC Menetriers disease: increased gastric cancer risk; mucous cell hyperplasia; PRO TEIN LOSING ENTEROPATHY. Celiac sprue affects *PROXIMAL SMALL BOW EL*; p rima rily affects jejunum; IMPAIRED VITAMIN D absorption; moderately increased risk of T cell lymphoma. Tropical sprue affects ENTIRE SMALL BOWEL; treat with antibiotics, B12, folate. Whipples Disease ALSO presents with arthralgias, cardiac/neurologic symptoms. nd Congenital pyloric stenosis: associated with EDW ARDS and TURNERS. Onset of regurgitation/vomiting in 2 week of life Congenital diaphragmatic hernia is due to intestinal malrotation. GASTRITIS: Acute (erosive; hemorrhagic): can ALSO be caused by uremia (r enal failure/dialysis patient) nausea, epigastric pain, burning sensation, vomiting nonbloody, nonbilous food material. Chronic (nonerosive): Type A (fundus/body): ADCC to parietal cells; CHRONIC gastric car cinom a. Type B (antrum): H.pylori. GASTRIC ULCERS increase the risk of gastric carcinoma. Gastric STRESS ulcers caused by INCREASED PEPSIN PRODUCTION at times of stress. DUODENAL ULCERS found in the proximal area; distal duodeunal ulcers (or another atypical location) suggest ZES. EARLY: decreased somatostatin; LATE: increased somatostatin. Note, although duodenal ulcers have acid hypersecretion, fasting serum gastrin levels are NORMAL. ANTERIOR duodenal ulcers can cause PERFORATION; POSTERIOR duodenal ulcers are associated with hemorrhage secondary to ulcer erosion into gastroduodenal artery. PROXIMAL LESSER CURVATURE: L.gastric artery DISTAL LESSER CURVATURE: R.gastric artery PROXIMAL GREATER CURVATURE: L.gastroduodenal artery DISTAL GREATER CURVATURE: R.gastroduodenal artery PROXIMAL GREATER CURVATURE ABO VE SPLENIC ARTERY: short gastric arteries The main site of ABSORPTION of dietary lipids is the JEJENUM. Blood type A is associated with gastric cancer; acanthosis nigricans may be pr esent. WORD GAME: Risk of gastric cancer: H.pylori > Tobacco > Pernicious anemia > Ethanol > Nitrate The two most common causes of acute hemorrhagic pancreatitis are ALCOHO L & GALLSTONES PBC and GVHD have similar histology: 1) Granulomatous bile duct destruction 2) heavy lymphocyte portal tract infiltrate Irritable bowel syndrome: abdominal pain & altered bowel habits in the absence of demonstrable organic pathology. Alternating diarrhea/constipation, chronic abdominal pain; NO FEVER, BLEEDING, LEUKOCYTOSIS, W EIGHT LOSS. Dysentery: abdominal cramps, tenesmus, pus, blood in stool; INVASIVE BACTERIA in COLON Diarrhea: profuse watery diarrhea, NO INFLAMMATORY CELLS Pseudomembranous colitis has a SECONDARY accumulation of necrotic debris; but PRIMARY APOPTOSIS; Toxin A Neutrophil chemoattractant, diarrhea, mucosal death; Toxin B actin depolymerization, loss of cytoskeleton integrity, cell death, and mucosal necrosis. New research says COX-2 is involved in recurrent adenomatous polyps. Duodenal ulcers are NOT associated with increased cancer risk. (BENIGN) WORD GAME: Right sided colon can cer presents with iron deficiency anemia (think pallor/fatigue), malaise, weight loss; Recurrent, grossly bloody stools is in UC, but NOT in R.sided colon cancer. *Key phrase is recurrent, grossly bloody* **Lower fiber is positively correlated with increased incidence of COLO N cancer.** Ulcerative colitis can lead to COLON CANCER; TRAP: Diverticulosis/diverticulitis do NOT lead to colon cancer. Note: Diverticulitis can also go to the right side too (not just left side), hence mimic appendicitis. PBC: GRANULOMAS; middle aged female with long history of pruritis and fatigue who develops pale stool/xanthelasma and *hyperlipidemia* PSC: in UC patients; segmental inflammation and fibrosing destruction; pANCA; hyper IgM. WORD GAME: Mucosal EROSION is defined as NOT PENETRATING the muscularis p ropria.

In a non-drinker and a non- fat, female, fertile, forty patient, consider hypertriglyceridemia (>1000mg/dL; FFAs are directly toxic) as a cause of acute pancreatitis. nd Brown (or dark) pigment stones typically arise 2 to biliary tract infection release of -glucoronidase by injured hepatocytes and bacteria hydrolysis of bilirubin glucuronides increases unconjugated bilirubin in bile stones. Suppression of cholesterol 7-hydroxylase activity (fibrates) reduces conversion of cholesterol to bile acids, resulting in excess cholesterol secretion in bile cholesterol gallstones. S.aureus causes hepatic abscess through hematogenous seeding of the liver Hemochromatosis (Chr 6p) is affected iron absorption from the GI tract. + Lactase deficiency will lower stool pH because the H produced by gut flora metabolism of lactose will acidify the stool. Crohns disease: HLA DR1 + DQw5 ; Ulcerative colitis: HLA-DR2 Both involve a gene NOD2 (nucleotide binding oligomerization domain); expressed in both epithelial cells and leukocytes. The NOD2 protein appears to act as an intracellular microbial receptor that triggers the NF-kB pathway. TRAP: In Crohns disease: Transmural inflammation chronic inflammation leads to edema and fibrosis strictures Transmur al inflammation inflammation/necrosis leads to ulcer formation penetrate wall fistula TRAP: recurrent diarrhea and abdominal pain + GN flora in urine and WBCs Crohns with fistula into bladder. DOC for Crohn flare ups are steroids. Elevated AP can indicate liver metastases. WORD GAME: Biliary sludge results from gallbladder hypomotility and results from bile precipitation; it is composed of cholesterol monohydrate crystals, calcium bilirubinate, and mu cus precursor to stone formation. Crohns has migratory polyarth ritis, eryth ema nodosum, ankylosing spondylitis, uveitis, immunologic diso rders 2+ NOTE: Impaired bile reabsorption Ca is bound to bile oxalate is not bound and freed to be absorbed. UC: has pyoderma gangrenousum (give steroids), PSC. **Colon adenocarcinoma with UC arises from areas of dysplasia in macroscopically normal mucosa, are more aggressive, and occur at multiple sites simultaneously. Appendicitis can ALSO be initiated by lumen obstruction by LYMPHOID HYPERPLASIA. WORD GAME: Pulsion diverticulum is the same thing as a colonic diverticulum. Intussusception: adenovirus hyperplasia of Peyer patches that serve as a nidus. Volvulus can occur at cecum and sigmoid colon (more common), where there is redundant mesentery (poor structural support). Corkscrew sign on barium. Ischemic colitis: Pain after eating. Deletion of APC is PANCOLONIC + ALSO duodenal carcinoma & papilla of Vater adenocarcinoma, & thyroid & CNS tumors. Gardner syndrome ALSO has retinal hyperplasia. HNPCC is AD mutation in mismatch repair gene; PROXIMAL CO LON ALW AYS; also endometrial + ova rian carcinoma . COX-2 is increased in CRC. 5 nucleotidase is ALSO a marker of biliary tract damage. Amylase ALSO is a marker for MUMPS. 1-AT is on Chr 14. CODOMINANT. Type 2 Criggler Najjar responds to Phenobarbital, which increases liver enzyme synthesis. ++ Wilsons Disease is on Chr 13; ALSO has HCC, hemolytic anemia, cardiomyopathy, decreased biliary Cu excretion, and ++ increased urinary Cu excretion. *Rhodamine-positive cytoplasmic granules* indicate copper build up. Hemochromatosis: leads to CHF and HCC; her editary form is on Chr 6p (encodes molecule that affects iron absorption from GI tract leading to increased absorption); Total body iron regulated by intestinal epithelial cell absorption of dietary iron 2+ 3+ NOTE: Gut iron DMT-1 enters enterocytes as Fe ferroportin enters blood as Fe on transferrin. Cholecystitis (Gall Bladder inflammation) RARELY associated with ischemia or CMV; **STONE IN THE CYSTIC DUCT** ACUTE: perforation peritonitis; fistula; gallstone ileus; CHRONIC: Rokitansky-Aschoff sinus Charcot triad (fever, jaundice, RUQ pain) is a sign for **cholangitis** (think common bile duct) ZES causes diarrhea because 1) excess gastric secretions to intestines, 2) maldigestion because low pH in duodenal lumen creates poor environment for pancreatic enzymes.

HEENT: -

Acute pancreatitis: GET SMASHED: Gallstones, Ethanol, Trauma, Steroids, Mumps, Autoimmune, Scorpion, Hyperlipidemia/Hypercalcemia, ERCP, Drugs (sulfa). ALSO lack of lipase leads to decreased fat soluble vitamins (hence increased PT and PTT) Gallbladder hydrops/mucocoele: chronic obstruction of cystic duct leads to resorption of normal GB contents and enlargement of GB by production of large amounts of clear fluid or mucous. Infant with septic shock (*hypother mia is also a sign*) secondary necrotizing enterocolitis presents with: Formula fed (lack of maternal antibodies) neonate with a distended abdomen, mild GI illness OR life th reatening gangrene of the terminal ileum and ascending colon. TRAP: A vague stem on clinical severe Reyes syndrome: Vesicular rash 5 days later pernicious vomiting, lethargy progressing to coma, and hepatomegaly. Hepatic encephalopathy: increase in aromatic AAS (Phe, Tyr, Typ) increased false NTs (GABA, octopamine); Branched chain amino acids inhibit synthesis of false NTs. Carcinoid tumor: *LOCATION and SIZE* are the most important indicators of metastatic potential: Appendix and cecum: metastasize to liver ONLY. Stomach, ileum, and colonhigher metastatic potential, especially when larger than 2cm in diameter. An intestinal air fluid level is found in MECONIUM ILEUS and GALLSTONE ILEUS. Polycythemia vera (not ectopic EPO) Budd Chiari abdominal pain, severe ascites and tender hepatomegaly DEFECATION REFLEX: Rectum is distended Internal anal sphincter RELAXES External anal sphincter CONTRACTS conscious urge to defecate is perceived. This neural reflex involves the PELVIC NERVE, which provides parasympathetic pregangionic sensory afferents to internal anal sphincter and carries information to the spinal cord. The PUDENDAL NERVE carries somatic efferents to the ex ternal anal sphincter. PELVIC NERVE lesion ALSO has no urge to defecate. High pitched tinkly sounds heard over abdomen = small intestine obstruction. Causes: hernia, adhesion, SI tu mor, Meckels, Crohn, Ascaris, midgut volvulus, intussussception, meto clopra mide. Dubin Johnson: The black liver is caused by a dense pigment composed of epinephrine metabolites within lysosomes. Postprandial pain, no response to antacids, hyperlipidmeia, HTN mesenteric ischemia secondary to atherosclerosis. MCC of ascites associated with nephrotic syndrome in child S.pneumoniae.

Labyrinthitis may result from acute OM, operations on staples, or fracture lines; in CHRONIC OM, cholesteatoma may cause erosion of semicircular canals, exposing labyrinth to infections => MENINGITIS is CONSEQUENCE Pseudomotor cereb ri is benign intracranial hypertension of OBESE FEMALES (mainly). Associated with OCs, steroids, nalidixic acid, tetracycline, pregnancy, excessive vitamin A. Complications include OPTIC NEUROPATHY. Retinitis pigmentosa is a slow degenerative disease of the retina that is ALWAYS BILATERAL. It primary affects the rods and cones. Symptoms: Vision as if through a narrow tube, night blindness (loss of rods), bone spicule pigmentation in midperiphery of fundus, waxy appearance of optic disk. Retinoblasto ma: HEREDITARY FORM: BILATERAL; non-her editary: SINGLE tumor. A PNET tumor. Peripheral vertigo: positional testing DELAYED horizontal nystagmus Central vertigo: positional testing IMMEDIATE nystamus in ANY DIRECTION; may change directions. ++ Menieres disease: XR: mutation in Cu efflux protein; episodes of vertigo with associated fluctuation and progressive nd LOWER FREQUENCY sensorineural hearing loss w/ tinnitus. Due to INCREASE in volume of endolymph 2 to malfunction of endolymphatic sac. TREATMENT: Diuretics and low salt diet. Strabismus is misalignment of eyes Amblyopia is reduction of vision due to disuse. Amaurosis fugax is a painless, transien t, monocular vision loss caused by a small embolus to the ophthalmic artery. It does not last more than a few seconds. Old woman with eye pain and dilated vessels on sclera that DO NOT BLANCH with vasoconstricting drugs glaucom a. Crateriform lesion on inner side of eye BCCderives from basal cell layer.

Hem: Regarding folate deficiency: RBC folate is more sensitive than serum folate. RES system: Heme biliverdin via heme oxygenase. *Heme is made in the CYTOPLASM & MITOCHO NDRIA* Reticulocytes are remnant RIBOSOMES due to Pb breakdown of ribonuclease. BC 5HT promotes platelet aggregation as ADP and TXA2 do. (Nonmegaloblastic) Macrocytosis can be due to alcohols direct toxic effect on bone marrow, INDEPENDENT of folate & B12. ALSO , liver disease, orotic aciduria, 5FU, AZT, hydroxyurea. Acquired MetHb by OXIDIZING DRUGS (dapsone, benzocaine , lidocaine, nitrates, nitrites), DYES (anilines), and ENZYME DEFICIENCIES (cytb5 oxidase, G6PD) Abnormal bleeding in UREMIA due to qualitative platelet disorder (thus only increased bleeding time) HAIRY CELL LEUKEMIA is characterized by ATYPICAL MYCOBACTERIAL INFECTIONS; also leads to pancytopenia. FIRST LINE TREATMENT is 2-chlorodeoxyadenosine (2-CdA; CLADRIBINE); also use penostatin, INF-, and splenectomy HISTIOCYTOSIS X: Diagnosed by localized destructive lesion arising form inside the marrow cavity (SKULL, MANDIBLE, SPINE are common); S-100+, CD1a +; HAND-SCHULLER-CHRISTIAN subtype: has DI and exophthalmos (due to orbital infiltration by histiocytes) LETTER-SIWE subtype: Children under 3 years; fever then diffuse maculopapular eczematous purpuric skin rash. Solitary mastocytoma: infants; localized mast cell hyperplasia with release of mediators. Urticaria pigmentosa: increased dermal mast cells multiple oval, red brown macules that heal with hyperpigmentation; dermatographism; sever e pruritis. Systemic mastocytosis: mast cell infiltration in multiple organs, splenomegaly, decreased marrow, histamine release with food; increased risk of MPS, leukemia, or lymphoma. Kernicterus will have its most TOXIC DAMAGE on the developing CNS (basal ganglia, thalamus, cerebellu m, cerebral g ray matter, and spinal cord) DOWNEY CELLS are CD8 T cell in origin. WORD GAME: If the question is vague and merely asks which is this cell most likely to be in mononucleosis, go with the CD8 Downey cell. t(8:21) is AML:M2 (some Auer rods) Patients with sickle cell disease or other hemolytic anemias are predisposed to develop folic acid deficiency because of increased erythrocyte turnover. Petechiae and ecchymoses are products of PLATELET PROBLEMS. With an anemia, RBC turnover is low, resulting in LONGER LIVED red cells. This can distort measurements such as A1c. Pure RBC aplasia with parvovirus infection or THYMOMA AIHA: use DIRECT COOMBS to look for donor RBCs ALREADY coated with AutoAb. TRAP: a question can omit the M-spike; moreover, multiple myeloma may affect other bones aside from the spine. Multiple myeloma: recurring bacterial infections, especially pneumococcal pneumonia, because the overall production of normal immunoglobulins is DECREASED. 55% IgG; 20% IgA TRAP: Plasmacytoma has an IgG spike and has a SOLITARY MYELOMA involving soft tissue (lungs, nasopharynx, nasal sinus) **Do NOT choose MGUS unless th ere are literally NO SIGNS.** The Bence Jones protein will be monoclonal of the same type the M-spike indicates. MOST OF THE TIME KAPPA. CML presents with markedly increased Neutrophils & metamyelocytes (decrease LAP) and DECREASED other myeloid cells, with a small number of blasts. Decreased ESR: cells are not sticking together and thus settling out slowly: polycythemia , cancer, CHF. WORD GAME: All the myeloproliferative disorders are most closely related. Reed Sternberg cells are B lymphocytes with evidence of somatic hypermutation. TRAP: Only a minority of RS cells (5%, mainly lymphocyte predominant HD) still display CD20. SLE is a major cause of thrombocytopenia. PARANEOPLASTIC EPO : HCC, RCC, hemangioblastoma, pheo chromo cyto ma, and uterine fib roids + Renal Transplant Crew cut skull is in sickle cell an emia and thalassemia. C1 esterase inhibitor deficiency hereditary angioedema (increased bradykinin) AVOID ACEi. Plasmin is an enzyme.

Acanthocytes are found in abetalipoproteinemia (defect in lipid or protein composition of RBC membrane) Basophillic stippling: Baste the TAIL (Thalassemia, AOCD, Iron deficiency, Lead poisoning) Spherocyte ALSO in AIHA Echinocyte: have mor e regular spikes than acanthocytes; seen in uremia or as an artifact. Heinz bodies are ALSO found in -thalassemia. Pappenheimer bodies are made of iron and found post-splenectomy. -thalassemia (Chr 16): 4 deletions: HbBarts (4 ) hydrops fetalis (CHF, anasasrca, HSmegaly) 3 deletions: HbH (4 ) Heinz body ; Hereditary sideroblastic anemia: X-linked defect in -ALA synthase gene treat with B6 AIHA: Cold IgM intravascular hemolysis ||| warm IgG extravascular hemolysis. WARM: SLE, CLL, -methyldopa, penicillin COLD: M.pneumoniae (vs I Ag), EBV (vs i" Ag) Post-hemorrhage decreased Hct is due to hemodilution of water shifting from interstitium to ECF. AOCD: Inflammation increased hepcidin decreased release of iron from macrophages ALSO increased IL-2 increased lactoferrin sequestering of iron. TREAT UNDERLYING or give EPO to help. Aplastic anemia: can ALSO be caused by EBV, HIV, Fanconis anemia, and may follow a cute h epatitis. Fanconis anemia: inherited defec t in DNA r epair pancytopenia and BM failure; need BM transplant; presents with: abnormal radii/thumbs, kidney malformation, hypogonadism, microcephaly, increased HbF; SENSITIVE TO CHEMO/RADIO Diamond Blackfan: congenital pure RBC aplasia due to primary failure in BM. Hereditary elliptocystosis is caused by a defect in spectrin. PNH: Su crose lysis test: sucrose in vitro||Ha m test: acidosis in vitro ANEMIA causes a systolic ejection murmur at aortic region. TRAP: In a vague question regarding low Hb (and no other hints): RECALL iron is given orally, B12 parentally. Ferritin is an acute phase reactant hat may be elevated artificially in inflammatory states. Barbituates worsen AIP because increased P450 will decrease heme and increase the defective pathway; Belly full of scars. TREAT AIP with: glucose and heme. TREAT PCT with -carotene (decrease ROS) Porphobilinogen deaminase is ALSO CALLED HMB synthase and u roporphyrinogen I syn theta se. Abnormal bleeding in patients with uremia (dialysis for ESRD) have a qualitative platelet disorder with increased BT only. Antiphospholipid syndrome: hypercoaguable IN VIVO; but increased PTT in vitro that is NOT CORRECTED by FFP. Consider OCs in women with von Willebrands disease. Prothrombin gene mutation: mutation in 3 UTR venous clots. Protein C and S inactivate Factors V and VIII. Factor XII deficiency: THROMBOSIS; shows: Dohle bodies (RER aggregates), toxic g ranulations, and cytoplasmic vacuoles. Chronic Myeloproliferative Disorders: JAK2 involved in hematopoietic growth factor signaling. Polycythemia rubra vera : increased LAP; hyperuricemia (due to increased RBC turnover); also an increase in WBCs and platelets (not as great as RBC increase) Thrombo cytosis: TREAT w/ hydroxyurea; may progress to myelofibrosis Myelofibrosis: Fibrotic obliteration due to PDGF; dacrocytes CML: bcr-abl leads to increased cell division and inhibition of apotosis; Blast crisis2/3 myeloid; 1/3 lymphoid NOTE: Secondary polcythemia is due to renal cortical cells sensing hypoxia and releasing EPO. TRAP: SLE leads to anemia, thrombocytopenia, and leukopenia **NOT from aplastic anemia.** Rather: War m AIHA, ITP, and anti-body mediat ed destruction of WBCs. Rationale for giving warfarin and heparin Factor VII and Protein C have shortest half lives.

MSK: Contraction velocity is related to ATPase activity of muscle; Recruiting additional motor units = increased muscle mass increase the maximum load lifted. STRETCHING a muscle (severed ends of the tendon are overlapped) INCREASES PT, DECREASES AT. PASSIV E TENSION curves upward like the letter U; ACTIVE TENSION curves downward like the letter A Abnor mal passive abduction of knee torn MCL. Joint laxity under valgus stress torn MCL Positive McMurray test 1) click on internal rotation of knees lateral meniscus tear 2) click on external rotation of knees medial meniscus tear. Baker (popliteal) cysts are ENLARGED SEMIMEMBRANOSUS BURSA. Beware of COMMON PERON EAL N during removal Traumatic knee dislocations are associated with INTIMAL TEARS of the popliteal artery. CAPUT SUCCEDANEUM r efers to a benign edema of the soft tissues of the head during delivery; it characteristically CROSSES THE MIDLINE AND CRANIAL SUTURES and is NOT associated with an underlying fracture. With Klumpke palsy, concomitant damage to the sympathetic fibers of T1 may produce HORNER SYNDROME. Clavicle fr acture leads to MEDIAL SEGMENT DISPLACING UPW ARD by SCM, wher eas the DISTAL END is depressed by the weight of the shoulder. Monteggia Fracture is a fracture of the upper third of the ulna with dislocation of the radial head caused by a fall on an outstretched hand, with the for earm forced into excessive pronation. RADIAL NERVE INJURY may be associated Legg-Calve-Perthes dise ase is a type of avascular necrosis in the femoral heads of children between 3-10 years, affecting males more. Osgood-Schlatter Disease: With repeated trauma/infllammation, the tibial tubercle is avulsed and cut off from the blood supply, causing avascular necrosis. SWELLING AND PAIN below the knee at the tibial tuberosity. PAIN when leg is EXTENDED AGAINST RESISTANCE. SELF LIMITING. Compartment syndrome: Anterior compartment of leg has rigid boundaries (tibia, fibula, crural fascia, anterior intermuscular septum) that can trap blood, contribute to increased pressure, and lead to an ischemic process. ACUTE can be caused by a crush injury of fracture to the involved extremity or in CHRONIC VIGOROUS EXERCISE. Forearm compartment syndrome can lead to VOLKMANN ISCHEMIC CONTRACTURE, which results in a stiff, nonfunctioning claw hand from muscle necrosis and resulting fibrosis. Lateral epicondylitis is made worse by *resisted wrist extension* & *passive wrist flexion* ALSO caused by hammer or screwdriver. Klumpke palsy & thoracic outlet syndrome: disappearance of radial pulse upon moving the head toward the opposite side. ANTERIOR TALOFIBULAR LIGAMENT most likely damaged on inversion of ankle. Slipped Capital Femoral Epiphysis: is a Salter Type 1 epiphyseal injury that involves fat boys. The ACROMIOCLAVICULAR LIGAMENT pr events anterior-posterior displacement of clavicle. The CORACOCLAVICULAR LIGAMENT prevents vertical displacement of clavicle. McCune Albright syndrome: (Mosaic G-protein signaling mutation): polyostotic fibrous dysplasia*, precocious puberty, unilateral caf au lait (Coast of Maine), short stature in girl. * bone is replaced by fibroblasts, collagen, and irregular bony trabeculae* WORD GAME: Osteogenesis imperfecta type 1 is impaired bone matrix formation. Sickle cell disease leads to avascular necrosis due to thro mbotic occlusion of arteries; Embolic occlusion (fat, air) can also cause AVN Lumbar disc degeneration lumbar spinal stenosis neurogenic claudication TRAP: Most patients with chronic joint pain take NSAIDs can lead to interstitial nephritis. Patient with joint pain and renal insufficiency. The latter resolves once surgery corrects joint pain. Osteopetrosis: deficiency of carbonic anhydrase II. TREATMENT: Bone marrow transplant. Rickets: Craniotabes & frontal bossing, Rachitic rosary (chest wall deformity due to cartilage overgrowth), Pectus carinatum, & Lumbar lordosis Osteitis fibrosa cystica: Brown tumors are cystic spaces lined by osteoclasts, stroma, and blood. Primary hyper PTH and increased ALP. Pagets disease: increased ALP; paramyxovirus may cause it; long bone chalk-stick fracture; can osteogenic sarcoma.

BONE TUMORS Osteoma :New pieces of bone grows on another piece, often in skull Benign vs Malignant DIAPHYSIS: Osteoid osteoma: interlacing trabecular of woven bone surrounded by OBs. PAINFUL; <2cm and found in proximal tibia and femur; most common in men <25; XR: radiolucency surrounded by sclerotic rim <2cm. NSAID HELPS Osteoblastoma: larger & in vertebral column. Ewings Sarcom a: @ long bones, p elvis, scapula, and ribs; Homer Wright pseudorosettes. METAPHYSIS: Osteochondroma: (exostosis) MC benign; mature bone with ca rtilaginous cap . Men < 25 Osteosarcom a: @distal femur, p roximal tibia, knee; anaplastic cells producing osteoid & bone. NOT r elieved by NSAID EPIPHYSIS: Giant cell tumor (osteoclastoma): 20-40 years; @distal femur, proximal tibia, knee; XR: double bubble or soap bubble.; spindle shaped cells with multinucleated giant cells INTERMEDULLARY: Enchondroma: @distal extremities Chondrosarcoma: age 30-60; @pelvis, spine, scapula, humerus, tibia, o r femur. Expansile glistening mass. TRAP: Osteochondroma can become chondrosarcoma. Osteoarthritis: Morning stiffness may occur, so rely on other signs. Bouchard (PIP) & Heberden (DIP): Alphabetical ord er means from p roximal to distal Cartilage loss on media knee bowlegged RA: Rheumatoid nodules (fibrinoid necrosis surrounded by palisading histiocytes); also presence of Bakers cysts. NO NODULES on DIP; HLA DR-1 & DR-4; Boutonniere: Flexion PIP; extension DIP; Swan-neck: Extension PIP, flexion DIP Felty syndrome: RA + splenomegaly +netruopenia Gout: can be caused by Von Gierkes disease. NEGATIVE BIREFRINGENCE: Yellow parallel; blue perpendicular. Gout is more popular: all the Ls POSITIVE BIREFRINGENCE: Yellow perpendicular; blue parallel. Ankylosing spondylitis: also causes Aortic Regurg. Reiters syndrome synovial aspirate MOST RESEMBLES rheu matoid arthritis. (neutrophils) Trap: do NOT choose Gram Negative aspirate unless gonorrhea is suspected. Dupuytren Contracture (inability to extend fingers) is associated with alcoholism, manual labor, diabetes, anticonvulsants **Caused by myofibroblast interaction with collagen fibrils of fascia contracture of palmar fascia. Drug induced SLE: hydralazine, procainamide, INH, pheytoin. IM DAMN SHARP Immunoglobulins (2), Malar rash (3), Discoid rash (3), ANA (2), Mucositis (oral ulcers; 3), Neurologic disorders (3); Serositis (pleuritis, pericarditis; 3), Hematologic (pancytopenia; 2), Arthritis (3), Renal (3), Photosensitive (3) In ankylosing spondylitis, there may be involvement of the costovertebral and costosternal junctions may limit chest movements resulting in hypoventilation. Monitor the chest expansion. Polymyositis: Autoantigens presented on MHC1 of muscle cells; increased CD8 infiltration; NO SKIN INVOLVEMENT Dermatomyositis: perimysial & vascular lymphocytic infiltration. INCREASED RISK MALIGNANCY Increased CK, aldolase; positive ANA, anti-Jo-1 Fibromyalgia: widespread MSK pain in association w/ stiffness, paresthesias, poor sleep, emotional disturbances. WORSE IN MORNING, and WORSE BY EXERCISE; multiply symmetrical distribution. Sarcoidosis: Bells palsy + uveoparotitis. WORD GAME: Partial lack of T-tubules in SkM will lead to UNCOODRINATED CONTRACTION OF MYOFIBRILS One Small & Slow Red Ox Calcium released from SR ALSO binds to glycogen phosphorylase to degrade glycogen. MYOEPITHELI AL associated with gland contracture. MYOFIBROBLAST associated with collagen binding and contracture. 2+ 2+ + 2+ Muscle relaxation: Ca ATPase pump sequesters Ca into SR & sarcolemmal 3Na /1Ca exchanger MG: is also associated with thymic hyperplasia (thymoma is actually not the MCC) Young person with SWOLLEN & PAINFUL upper arm after falling during spo rts over weeks the a rea becomes mo re CIRCUMSCRIBED and FIRM evolves to a PAINLESS, HARD, WELL DEMARCATED MASS. This is MYOSITIS OSSIFICANS: Following muscle trauma, area of damage heals with a fibroblastic proliferation that ossifies, even though ther e is no connection to bone. XR: flocculent radiodensities surrounding a radiolucent center Duchennes Dilated CM.

Skin: -

DeQuervains disease chronic stenosing tenosynovitis of the first dorsal compartment of wrist (AbPL & EPB); *overuse*; *excessive friction causes thickening of the tendon sheath and stenosis of the osseofibrous tunnel. * Pain occurs on the radial aspect of wrist and is aggravated by moving the thumbpain in radial styloid process. Ganglion cyst bulge on wrist dorsum (during flexion); ganglion is filled with mucinous material. Shin splints repetitive loading of anterior compartment muscles of tibia inflammation @ musculotendinous insertions stress fractures. MCC of lower back pain spasm of paraspinal muscles. Herniation of L3-L4 disc: 1) medial leg to malleolus sensory; 2) knee jerk ; 3) quadriceps, 4) loss of dorsiflexion Herniation of L4-L5 disc: 1) dorsum of foot; 2) webbed space between great toe, 3) EHL Hernation of L5-S1 disc: 1) lateral and posterior calf; 2) plantar foot; 3) Achilles reflex, 4) loss of plantarflexion/eversion

ZONA OCCLUDENS: claudins + occludins 2+ ZONA ADHERENS: Cadherins (Ca dependent ADhesion molecules) connect to ACTIN. MACULA ADHERENS: Cadherins connect to INTERMEDIATE FILAMENTS; anchored by DESMOPLAKIN HEMIDESMOSOME: Integrins bind to laminin in BM. Melanosomes found in STRATUM BASALIS Psoriasis : hyperparakeratosis, acanthosis, rete ridge elongation, mitosis above S.basale, reduced/absent S. granulosum Neutrophils form spongiotic clusters in dermis and parakeratotic S.corneum (Munro microabscess) Treatment: TOPICAL STEROIDS +UV; severe: MTX Scleroderma: fibroblasts stimulated by IL-1 and PDGF CREST syndrome: Also has fingertip ulcerations; ALSO leads to Right CHF due to P.HTN secondary to intimal thickening. Esophageal dysmotility is due to ATROPHY and FIBROUS REPLACEMENT of esophageal muscles severe acid reflux WORD GAME: Sclerodactyly is ALSO referred to as atrophic skin changes. PURPURAE: 5 mm to 1cm; PETECHIAE < 5mm; ECCHYMOSES: >1cm; can arise without trauma. CREST syndrome tends NOT to have tightening of skin. SHAGREEN PATCH of tuberous sclerosis is a ROUGH, RAISED LESION that has the consistency of ORANGE PEEL in the lumbrosacral region. Sjogrens: increased risk of B-cell lymphoma. Seborrheic dermatitis: papulosquamous skin rash involving areas rich in sebaceous glands. Abnormal immune response to Pityro sporum ovale. Seborrheic keratosis: flat, greasy, pigmented squamous epithelial proliferation with keratin-filled cysts (horn cysts) that look pasted on. Sign of Leser Trelat present. Epidermal inclusion cyst: benign cyst lined with St.Sq, filled with keratin pearls. Acanthosis refers to HYPERPLASIA of stratum SPINOSUM WORD GAME: microscopic blisters dermatitis herpetiformis; der mal edema + dilated superficial lymphatic channels urticaria Bullous pemphigoid: eosinophils within blisters. Erythema multiforme (on a spectrum with SJS): associated with M.pneumoniae, HSV, Chla mydia, histoplasmosis, enteroviruses, sulfa d rugs, penicillins, phenytoin , sarcoidosis, leukemia, lymphoma , MM, internal malignancy,autoimmune diseases, o r FOODS (emulsifiers like ma rgarine). Presents with multiple types of lesions and target lesions. Or patches have pale, vesicular, or eroded centers with surrounding erythematous rings. NO MUCOSA INVOLVEMENT; due to immune complex deposition in the DERMAL BLOOD VESSELS Steven Johnson: MUCOSA INVO LVEMENT. Lichen planus: sawtooth infiltrate of lymphocytes @ dermal-epidermal junction; Associated with HCV. Erythema nodosum: inflammatory lesions of subcutaneous fat; associated with coccidioidomycosis, histoplasmosis, TB, leprosy, strepto coccal infections, sa rcoidosis. Granuloma annulare: Chronic inflammatory condition in DM erythematous papule/plaques on back of hand/foot Keratoacanthoma is a well differentiated SCC variant that regresses quickly. Dome nodule with central keratin crater WORD GAME: IMMUNOSUPRESSION is a risk factor for SCC.

BCC subtypes Lentigo maligna: face & neck of elder; best prognosis Superficial spreading: MCC; horizontal growth Acral lentiginous: MC in blacks; palms, soles, subungual Nodular: WORST PROGNOSIS A blue neoplasm underneath a nail bed is either 1) Glomus tumor (AV anastomosis involved in thermoregulation) or 2) subungual melanoma WORD GAME: Actinic chelitis = actinic keratosis of the lip Local cutaneous adverse effects of chronic topical steroids atrophy/thinning of dermis, loss of d ermal collagen, drying, cra cking, tightening of skin, telangiectasias, and ecchymoses. Mycosis fungoides: malignant CD4 cells; generalized pru ritic erythematous rash, NO hypercalcemia. Sequenc e: inflammatory eczematous plaque tumor nodule stage Micro: atypical PAS+ lymphocytes in epidermis aggregates to Pautrier microabscess. Xanthoma are tumor-like DERMAL collections of foamy histiocytes containing cholesterol/lipids; may contain MULTINUCLEATED GIANT CELLS (Touton giant cells) w/ clustered nuclei and foamy cytoplasm ALSO r elated to leukemia/lymphoma. Stasis dermatitis is a complication of chronic lower leg edema ankle edema and erythema and brown discoloration of the skin near both ankles. 1cm diameter shallow ulcerated area is seen within the erythematous area.

Neuro: Transcutaneous electrical nerve stimulation can LESSEN severe, chronic pain by OVER STIMULATING the involved neurons in order to ACTIVATE the INHIBITORY INTERNEURO NS in lamina 2 of the spinal cord. Gate-keeper theory of pain. Jamais vu is when one fails to recognize familiar events that have been encountered before. Following transaction of nerve with close contact, the nerve can REGROW @ 1mm/day, optimally. TRAP: Brocas aphasia will often become frustrated at their inability to speak. Wernickes aphasia will speak garbled word salad WITHOUT any distress. Moreover, W ernickes aphasia may also have a superior quadrantanopsia because of the nearby lingual loop. Global aphasia: wide lesions in Presylvian speech area. Damage to Broca & Wernicke. Labored telegraphic speech with poor comprehension & trouble repeating statements Transcortical aphasia: lesion in prefrontal cortex; capacity to repeat statements is unimpaired; cannot speak spontaneously. Meningitis: Pr essure increases (purulent > Granulomatous > viral); Viral leptomeningeal inflammation (leptomeninges + superficial cortex) Mycobacterial basal surface of brain **Fungal/TB have INCREASED LYMPHOCYTES. + Astrocytes ALSO involved in K metabolism and removal of excess NT. Stain GFAP+ Sensory corpuscles C- slow, unmyelinated A fast, myelinated Meissners large, myelinated; in glabrous (hairless) skin under dermal papillae; encapsulated; position sense, dynamic fine touch (manipulation), adapt quickly; detect shape/texture during active touch. Pacinianlarge, myelinated; deep skin, ligaments, joints; vibration (pac man vibrates), pressure; onion Merkelslarge, myelinated; hair follicles, dermal papillae; position sense, static touch (shapes, edges, textures), adapt slowly (Urkel was a slow learner at sensing Lauras feelings) Ruffinideep dermis; intensity, senses skin stretch; Rough around the edges (intense) Perineurium surrounds a fascicle of nerve fibers; must be rejoined for limb reattachement. Anxiety: decrease GABA, 5HT; increase NE GABA is made in the nucleus accumbens. Nucleus accumbens and septal nucleus are involved in reward center. The septal is also for sexual urges INFARCTION destroys endothelial cell tight junctions (of BBB) vasogenic edema.

Oxytocin is stored in herring bodies (specialized nerve endings) Ventral anterior/ Ventral lateral nuclei of thamalus MOTOR Thalamic blood supply: P.Comm, PCA, and ICA (anterior choroidal arteries) Cerebellum: TRAP: Ataxia + NORMAL heel to shin, rapidly alternating movements, finger to nose can STILL BE cer ebellar lesion. CORTICAL INPUT (climbing + mossy fibers): contralateral via MCP; ipsilateral via ICP OUTPUT: Purkinje fibers to deep nuclei SCP contralateral cortex; NO TE, net ipsilateral body. Dont Eat Gr easy Foods or else itll end up in your stomach (Food ends up in the middle fastigial nucleus is medial) Basal Ganglia (Striatum Caudate [Cognitive] & Putamen [motor]) Direct: (+)D1 on striatum & (+) ACh (-) GPi/SNr (via GABA, SP) (-) Thalamus (+) Cortex DIRect : D1, GPi, SNr Indirect: (-) D2 on striatum & (+)ACh (-) GPe (via GABA, enkephalin) (-) STN (+) GPi (-) Thalamus (+)cortex Around the world in alphabetical order: E to I (GPe sTn GPi) MPTP is oxidized to MPP+, which selectively destroys DA neurons in SNg. (Illicit production of meperidine) Essential/postural tremor is an action tremor (worsens when holding posture); AD Frontal Eye Fields lay anterior to the premotor area. Heschls gyrus (primary auditory cortex) is on superior temporal lobe (anterior to Wernickes area) WORDS Prosopagnosia: inability to recognize faces; BILATERAL LESION OF VISUAL ASSOCIATION CORTEX Agnosia: Normal perception, but devoid of meaning. Anosognosia: deficit in cognition about ones illnesses; LARGE LESIONS OF NON-DO MINANT PARIETAL LOBE Asomatognosia: lack of knowledge about ones own body can lead to neglect. LESIONS OF: Non-dominant parietal lobe: Spatial neglect syndrome (agnosia of contralateral side of the world) Reticular activating system (midbrain): reduced levels of arousal/wakefulness Frontal eye fields: ipsilateral gaze deviation. Eyes front, look towards me Central Pontine Myelinolysis: ALSO has acute paralysis, dysarthria, dysphagia, diplopia. Superior laryngeal nerve injury: External branch: Loss of cricothyroid. Internal branch: (supplied by superior thyroid artery)Loss of sensation to the laryngeal mucosa above the vocal folds Huntingtons: Neuronal death via NMDA-R binding and glutamate toxicity; CAG= Caudate loses ACh and GABA Brain Injury: Concussion: mild traumatic brain injury w/ transient loss of brain function: (loss of consciousness/reflexes, temporary respiratory arrest, amnesia of the event) Contusion: bruise @ crests of orbital gyri in frontal & temporal poles; coup and contrecoup occur if head was moving. Diffuse axonal injury: Damage to axons @ Nodes of Ranvier w/ impairment of axoplasmic flow. Although diffuse, has predilection for corpus callosum, periventricular white matter, hippocampus, cerebral & cerebellar peduncles. DELTA WAVES on ECG indicate lesion Axonal reaction refers to the changes in the body of the neuron after the axon is severed; cell body swollen, nucleus to periphery, Nissl substance dispersed. Cerebral amyloid angiopathy is the MC presentation of RECURRENT LOBAR HEMORRHAGE due to -amyloid depositing in cerebral and leptomeningeal arterial walls. Space const ant is a measure of how far along an axon an electrical impulse will travel. Directly proportional to degree of myelination. Lacunar infarcts (<15mm diameter) usually involve BASAL GANGLIA, PO NS, INTERNAL CAPSULE, DEEP WHITE MATTER: Due to **hyper tensive arteriolosclerosis of small arterioles.** Charcot Bouchard microaneurysms would show hemorrhagic stroke on CT. Lesions: Posterio r limb of IC: HEMIPARESIS Base of pons: Ataxia/hemiplegia Genu of the IC: Dysa rth ria-clu msy hand syndrome

LOW dose aspirin (MAINLY COX-1 block) is used to PREVENT primary and secondary coronary artery events and ischemic strokes. WERNICKE (Confusion, ataxia, ocular issues, drowsiness) is REVERSIBLE with B1 KORSAKOFF (damage to MEDIAL DORSAL nucleus: memory loss, learning impairment) PERMANENT Schwannomas: ANTO NI A: palisading spindle cells with WHIRLING appea rance; ANTONI B: Loosely arranged tissue after degeneration. BRANCHES TO FACIAL NERVE : To Zanzibar By Muscle Car (Temporal, Zygomatic, Buccal, Mandibular, Cervical) CAUDA EQUINA SYN DROME: Any mechanism (osteoarthritis, disk prolapsed, surgery, spondylolisthesis, Paget disease) that superimpose on a congenitally narrow spinal canal => NARROWING OF CORD DURING EXTENSION, which tends to COMPROMISE blood supply of cord, resulting in symptoms: PAIN IN CALVES AFTER EXERCISE, RELIEVED BY REST; LOSS OF LUMBAR LORDOSIS; LOW ER LIMB REFLEXES DIMISHED. Saddle anesthesia + bowel/bladder dysfunction Stooping forward relieves symptoms. Conus Medullaris Syndrome: Pain @ night and rest; relatively rapid, bilateral onset of moderate back pain w/ a minimal radicular component & preserved ankle reflexes. TEND TO HAVE perianal weakness & urinary retention with ATONIC rectal sphincter. EMPIRIC STEROIDS + MRI MYOTO NIC DYSTROPHY: AD; CTG; Chr 19; distal muscle weakness in all extremities, gradual dimunition of vision, fron tal balding, facial wasting, myotonia, a trophic testicles; DECREASED PLASMA Ig G. Biopsy: Nu clei in center of fib er rather than periphery. PSEUDOBULBAR PALSY results from an UMN lesion to the corticobulbar fibers. Common causes include bilateral CVA involving the INTERNAL CAPSULE, motor n euron disease, and MS. Sympto ms include dysphagia, spastic weakness of lower limbs, Donald Duck dysa rthria (high pitched, slu rred speech) SUPRANUCLEAR PALSY: widespread neuronal loss, gliosis in subcortical sites, with SPARING of CEREBRUM & CEREBELLUM. Opthamoplegia, pseudobulbar palsy, axial dystonia, bradykinesia. Primary CNS lymphoma (ex. EBV) is primarily B cell in origin. Craniopharyngioma: stratified squamous epithelium; calcified cysts with a yellowbrown-viscous fluid containing cholesterol. Alzheimers disease: Decreased ChAT in nucleus basalis; DIFFUSE ATROPHY (esp .FRONTAL LOBES & HIPPOCAMPUS) WORD GAME: flame shaped intracytoplasmic inclusions in neurons of neocortex and hippocampus; EM shows the inclusions consist of paired helical filaments. Neurofibrillar y Tangles. Huntingtons disease: Increased AChE in caudate nucleus; Neuronal death via NMDA-R binding and glutamate toxicity; CAG= Caudate loses ACh and GABA Normal pressure hydrocephalus is wet because of traction on cortical efferent and afferent fibers (corona radiate). This disrupts periventricular pathways that transmit impulses from the cortex to the sacral micturition center. Any hydrocephalus will stretch the periventricular pyramidal tracts, causing hypertonicity and hyperreflexia ISCHEMIC BRAIN DISEASE: irreversible after 5 minutes; MOST VULNERABLE: hippocampus (hit first), neo cortex, cerebellu m, watershed WORD GAME: Water shed infarcts appear as wedge shaped areas of necrosis over the cerebral convexity, lateral to the interhemispheric fissure. Aka hypoxic encephalopathy. **Internal capsule stroke = Contralateral ARM & LEG hemiplegia of same intensity Red neurons show up @12-48 hours Imaging: bright on diffusion weighted MRI in 3-30 minutes for 10 days; dark on CT ~24hours Werdnig-Hoffman (Type 1 Spinal Muscular Atrophy): AR; floppy baby; degeneration of anterior horns; LMN. Death @ 7 Type 2 SMA: proximal muscle weakness before 18 months; ability to sit, but not walk unaided; survival beyond age 4 Type 3 SMA: proximal muscle weakness after 2 years; ability to walk; survival to adult + ALS: defec t in SOD1 (Chr 21) or betel nut ingestion; give Riluzole (glutamate blocker; Na channel blocker) to prolong time to tracheotomy; give baclofen (GABAB agonist) for symptomatic relief. Syringomyelia: Ependymal lined, CSF filled channel parallel to and connected with the c entral canal of spinal cord Friedreichs: Chr 9; GAA causes decreased translation; impaired mitochondrial function; pes cavus (high plantar arch); hammer toes; childhood scoliosis SPINAL CORD ATROPHY Brown-Sequard above T1 = Horners in addition. Subacute combined degeneration (B12, E, Friedreich): DC, spinocerebellar, CST Sc Kuru plaques: are amyloid sheets of PrP

Alzheimers: granulovacuolar degeneration & Hirano bodies Lewy Body dementia: Parkinsonism with dementia & hallucinations. MS: Type 4 HS vs self myelin Ag; DR2 on Chr 6; SIN = Scanning speech, Intention tremor, Incontinence, IOM, Nystagmus Affec ts FARTHER FROM EQUATOR more; MO VING after age 15 maintains original risk. TRAP: IFN mediates the demyelination; Oligoclonal IgG bands in CSF are just markers, NOT INVOLVED IN PATHOGENESIS. WORD GAME: Lymphocytic infiltrate and myelin breakdow n products in ACUTE MS; Gliosis in CHRO NIC MS. Metachromatic leukodystrophy: Buildup of sulfatides impairs myelin production. Charcot Marie Tooth disease: progressive hereditary nerve disorders related to the defective production of proteins involved in the structure and function of peripheral nerves or myelin sheath. MOTOR + SENSORY Leigh disease: (sub acute necrotizing encephalomeylopathy) mtDNA defect at cytochrome oxidase seizures, weakness, ataxic death within years. Migraines due to irritation of CN V and release of Substance P, CGRP, vasoactive peptides. Sturge W eber disease ALSO has ipsilateral leptomeningeal angiomas & pheochromocytomas; CAN ALSO CAUSE glaucoma, seizures, hemiparesis, MR Patient deterioration AFTER trauma. Herniation. BRAIN TUMORS: GFAP stains for gliomas; Synaptophysin stains for neuron-origin. GBM: cross corpus callosum; GFAP+; spreads thru CSF TRAP: Adults cerebral cortex; Child Brain stem. Meningioma: arises from arachnoid cells external to brain Schwannoma: Antoni A: spindle, palisading whirled appearance; hypercellular Antoni B- loosely arranged; hypocellular Oligodendroglioma: Accompanied by seizures Pilocytic astrocytoma: eosinophilic, corkscrew fibers (Rosenthal fibers; cystic lesion with mural nodule) GFAP+ Well differentiated comprised of spindle cells that have hair-like glial processes and microcysts. Medulloblastoma: HIGHLY MALIGNANT; PNET; arises from vermis; rosettes or perivascular pseudorosette pattern of cells; solid; small blue cells; RADIOSENSITIVE Ependymoma: Papillary architecture. Characteristic perivascular pseudorosettes. & Rod-shaped blepharoblasts (basal ciliary bodies) near nucleus Hemangioblastoma: mostly cerebellar; associated with VHL when retinal angiomas also present; produce EPO. Foamy cells and high vascularity Craniopharyngioma: (ameloblastoma) MCC childhood supratentorial tumor; resembles adamantinoma (Tooth enamel) rd Tumor in 3 ventricle colloid cyst or choroid plexus papilloma. NEUROTOXINS + + Tetrodotoxin (puffer fish) & Saxitoxin (red tide): Blocks activated Na channels; decreases Na influx. + Ciguatoxin (exotic fish) & Batrachotoxin (frogs): Bind to activated Na channel to inactivate; prolongs Na+ influx. SEIZURES Tonic clonic: Loss of consciousness Myoclonic: No loss of consciousness. Atonic: Sudden loss of postural muscle tone (possible brief loss of consciousness; no postictal confusion) Suddenly fell to the ground. + EEG: abnormal spiking pattern

Onc: Asparagine is insufficiently synthesized by neoplastic cells thus, asparaginase is used for treatment of leukemia. TUMOR MARKERS Prostatic acid phosphatase is a marker for prostate carcinoma CEA in colorectal, pancreatic, gastric, and breast. CA 15-3 is a marker of BREAST cancer. Bombesin is a marker of NEUROBLASTOMA, LUNG and GASTRIC cancers. CA-125 is ALSO used for malignant epithelial tumors. S-100 is ALSO use for astrocytomas.

Ki-67 is a nuclear factor whose expression correlates with neoplastic replicative activity; CORRELATES with neoplasms rate of growth Lipoma has adipocytes with a single large cytoplasmic droplet that displaces nucleus to periphery. Liposarcoma has cytoplasm filled with lipid filled vacuoles that indent the nucleus. Up to 45% of patients with DERMATOMYOSITIS have L UNG MALIGNANCY. Oncogenes: (myc & jun are TFs; ras is a GPCR) hst-1 & int-2: makes FGF; overexpression cancer of stomach, breast, bladder, and melanoma sis: makes PDGF; overexpression astrocytoma erb-B1: makes EGFr; overexpression Lung SCC erb-B2: makes EGFr; am plification cancer of breast, ovary, lung erb-B3: makes EGFr; overexpression breast ret: makes glial neurotrophic fa cto r receptor; POINT MUTATION abl: is ALSO expressed in ALL via translocation. K-ras: makes GTP binding protein; POINT MUTATION lungs, pancreas, colon L-myc: makes nuclear regulato ry protein; amplification Small cell carcinoma N-myc: makes nuclear regulato ry pro tein ; amplification Bcl-1 : makes a cyclin D protein; t(11:14) Mantle cell lymphoma. CDK4: makes a cyclin dependen t kinase; amplification melanoma, GBM Tumor supressor s: involved in DNA repair and cell cycle regulation. p53, p16, VHL, and WT1 are on the p arm. (P and Pee on the P arm) VHL: normal gene product is to ubiquitinate products. Ataxia-telangiectasia has a mutation at 11q22-23 and codes for a (TUMOR SUPPRESSOR) DNA dependent protein kinase localized in the nucleus. HIGH INCIDENCE OF MALIGNANCY, especially lymphoreticular (Hodgkin and non-Hodgkins leukemia/lymphoma). *This ATM tumor suppressor is also found in Bloom Syndrome and Fanconis syndrome. TUMOR SUPPRESSORS NF1 : neurofibromin => INHIBITS p21ras oncoprotein => INCREASED risk of meningioma + pheochromocytoma NF2: merlin => a critical regulator of contact dependent inhibition of proliferation => INCREASD risk of meningioma + ependymoma. WORD GAME: N-myc has two markers: 1) Chr 1p deletion, 2) N-myc (Chr 2p) amplification; Amplification of this gene POORER PROGNOSIS TRAP: Peutz Jegher has melanin pigmentation ALSO on the buccal mucosa, palms, soles, and skin NOT exposed to sun ALSO leads to carcinoma of pancreas, stomach, SI, breast, ovary, uterus, cervix, and lung. Choristoma (heterotopic rest) normal tissue in a place that it is not normally present; ex. Meckels. Polycyclic aromatic hydrocarbons (soot): Scrotal cancer Benzene: leukemia Aromatic amines: HCC Alkylating agents: leukemia/lymphoma Ionizing radiation affects cells in G2 and M phases => causes crosslinking and chain breaking in nucleic acids. E-cadherin mutations can disrupt cell junctions and also cause gastric adenocarcinoma and breast carcinoma. p53 => transcription factor BRCA1 + 2 => DNA r epair products APC => membrane cell adhesion products 1) Loss of APC decreased intercellular adhesion and increased proliferation POLYPS 2) Loss of DNA methylation EARLY ADENOMA 3) K-ras mutation unregulated intracellular signal transduction INTERMEDIATE ADENO MA 4) Loss of DCC LATE ADENOMA 5) Loss of p53 increased tumorigenesis ADENOCARCINOMA Lynch syndrome vs Li Fraumeni: Only Lynch has colon involvement. Be aware that TUMORs are NOT LIKELY to be bilateral; think hyperplasia for bilateral.

Paraneoplastic syndromes also have an AUTOIMMUNE MECHANISM: antibodies vs tumor cells cross react with organs. Paraneoplastic cerebellar degen era tion occurs with cancer of ovary, uterus, breast, and small cell carcinoma. Trisomy 21 ALSO associated with AML. Tuberous sclerosis: Subependymal giant cell astrocytoma (walls of the lateral ventricle) is PATHOGNOMON IC. nd Pagets disease of bone: associated with 2 OSTEOSARCOMA & FIBROSARCOMA. Radiation exposure: ALSO leads to SARCOMA Dukes St aging: A- mucosa & submucosa B1- Into muscularis propria B2- Thru muscularis propria C1- Positive lymph nodes + B1 C2- Positive lymph nodes + B2 D- Distant metastasis. Ann Arbor Staging: I: Single node/extralymph organ II: >2 sites on same side of diaphragm III: >2 sites on both sides of diaphragm IV: Disseminated disease A: w/o constitutional symptoms B: w/ constitutional symptoms ANAPLASIA- undifferentiated tumors: 1) Loss of cell polarity/normal tissue architecture with cells coalescing into disorganized, infiltrative sheets/islands. 2) Cellular pleomorphism 3) Hyperchromatism and nuclear pleomorphism 4) High N to C ratio 5) Numerous, abnormal mitoses 6) *Giant, multinucleated tumor cells* Desmoplasia fibrous tissue formation in response to neoplasm DESMOID TUMORS are a type of fibromatosis in the anterior abdominal wall in women that is associated with previous trauma and multiple pregnancies. ILL DEFINED, PAINLESS, NON MOVABLE MASS. It occurs more in GARDNERS SYNDROME. FREQUENTLY RECURS AFTER EXCISION. Axillary node dissection is a risk factor for chronic lymphedema of ipsilateral arm => PREDISPOSES to ANGIOSARCOMA. N-acetylcysteine can be used in lieu of MESNA for hemorrhagic cystitis. Follicular lymphoma: INDOLENT; marked by remissions and recurrences. Presents as lymphadenopathy or abdominal mass. Germinomas of pineal gland Precocious puberty by -hCG, obstructive hydrocephalus, Parinaud syndrome. OCs, multiparity, breastfeeding DECREASE risk of OVARIAN cancer; OCs also decrease risk ENDOMETRIAL cancer. BRCA1 and HNPCC are risk factors for ovarian non-germ cell tumors. HER2/neu oncogene codes for 185kD RTK => increases cell proliferation (Non-rhythmic conjugate eye movements) Opsoclonus-myoclonus is a paraneoplastic syndrome of neuroblastoma HIV positive: reactivation of latent EBV infections with INCREASED INCIDENCE of EBV-induced lymphoproliferative disorders (ex. diffuse B cell lymphoma) HODGKINS LYMPHOMA Nodular sclerosing: (No EBV); RS cells are called LACUNAR CELLS because they rest in a lake. Mixed cellularity (Most; 70% EBV); Most RS cells Lymphocyte predominant (No EBV); RS cells are popcorn cells; <35 male; CD15- CD30-; B cell markers present. Lymphocyte depleted: Lots of RS cells; older males with disseminated disease Lymphocyte rich (40% EBV); few RS cells. Nodular lymphoma with predominately small lymphocytes with scanty cytoplasm and irregular, twisted, and indented nuclei small cle aved cell follicular lymphom a MCC non Hodgkins; indolent; *remissions/recurrences* 28 year old woman with anterior mediastinal mass and non-tender RIGHT supraclavicular node NODULAR SCLEROSING

Burkitts lymphoma: Other translocations: 1) t(2,8)(p12,q24) kappa light chain & c-myc 2) t(8:22)(q24;q11) c-myc & lambda light chain High Ki67 in Burkitts indicates HIGH PROLIFERATION. Diffuse large B cell lymphoma: Most common adult NHL; 20% T origin; enlarged spleen with large cells that resemble lymphocytes; subtypes involve EBV & HHV8; immunosuppression has a role. Mantle cell lymphoma: CD5 +, CD19+, CD20+, CD23-; bcl-1 (cyclin D) on Chr 11; Lymphoblastic leukemia: young male with mediastinal mass; leukemic phase similar to T-ALL; CD1+, CD2+, CD5+, CD7+ MALToma began as a polyclonal reaction. AML: Auer rods are abnormal lysosomes stain with MPO or Sudan Black; tissue form= granulocytic sarcoma (chloroma) M0: undifferentiated M1: myeloblastic leukemia w/o maturation M2: M1 w/ maturation M3: promyelocytic M4: myelomonocytic M5: monocytic (may have gingival infiltrates) M6: binucleate + megaloblastic change M7: associated with acute myelofibrosis due to PDGF. Richter transformation: SLL/CLL prolymphocytic leukemia OR large cell lymphoma CLL: CD19+, CD20+, CD5++, CD23++, CD22+ weak. B cell neoplasms have increased risk of infection because NO ANTIBODY IS MADE Adult T cell lymphoma/leukemia: malignant CD4 cells due to HTLV-1; skins lesions, hypercalcemia, enlarged lymph nodes, liver, spleen ; MICRO: 4 leaf clover lymphocytes in peripheral blood. Aniline dyes ALSO predispose to Renal Pelvis TCC. Analgesic abuse (chronic pain or headaches) leads to TCC. Metastasis to brain: Lung, Br east, Skin (melanoma), Kidney (RCC), GI Lots of Bad Stuff Kill Glia WORD GAME: spherical mass of the lateral aspect of the cer ebral hemisphere at the junction of white/gray matter. Metastasis to liver: Colon > Stomach > Pancreas > Breast > Lung Cancer Sometimes Penetrates Benign Liver Metastasis to bone : Prostate
Blastic

, Thyroid

Lytic

, Testes, Br east

Both

, Lung

Lytic

, Kidney

Lytic

P.T.T. Barnum Loves Kids

Pulm: Terminal bronchioles: Turbulent Laminar because of parallel branching of the airways. *Site of Asthma, CF, CB* Aspiration while lying on RIGHT SIDE Right Middle Lobe, Right Upper Posterior nd Cavitary lesions in UPPER LOBE: 2 TB, histoplasmosis, K.pneumoniae, SCC Klebsiella infection LIQUEFACTIVE necrosis. PAO2 = 150 (PACO2 / R); @sea level; R = exchange ratio. Pulmonary embolism V/Q mismatch hypoxemia hyperventilation (R.Alk) Peripheral chemoreceptors stimulate breathing in response to O2 levels < 60mmHg Lung HAMARTOMAS have hyaline cartilage, fat, smooth muscle, clefts with respiratory epithelium. The MCC of hypersensitivity pneumonitis is FARMERS LUNG, which is caused by inhalation of a thermophillic Actinomyces organism present in moldy hay and grain. (Hence, serum antibodies) Diffuse, nodular interstitial infiltrates; buzzword: organic dust HS pneumonitis in 1) textile workers byssinosis; 2) farmers with fermenting corn NO2; CHRONIC REJECTION of lungs => BRO NCHIOLITIS OBLITERANS (an obstructive lung disease) Small airways => Lymphocytic infiltration, necrosis, fibrosis of bronchiolar wall => OCCLUSION OF LUMEN LUNG ABSCESSES are due to suppurative collections in lung parenchyma => necrosis of lung tissue due to LYSOSO MAL ENZYME release from neutrophils/macrophages. If it communicates with air, the exudate will partially drain (AIR FLUID LEVEL) ELASTINs plasticity and ability to recoil is attributable to a UNIQUE FORM of desmosine crosslinking 4 Lys on 4 elastin chains via extracellular lysyl hydroxylase. In positive pressure ventilation, ALVEOLAR PRESSURE INCREASES, which also INCREASES V/Q and compresses capillaries, limiting blood flow. APEX OF LUN G like this. Acute asthma can be caused by: ASPIRIN, TARTRAZINE, -BLOCKERS, SULFATING AGENTS. Smoking leads to bronchial metaplasia (PsCC to StSq) due to a GENETIC MUTATION, not protection. MESOTHELIOMA on EM has LONG, THIN MICROVILLI TB, bronchiectasis, CF are ALSO associated with clubbing.

ASPIRATION of fresh OR salt water damages Type 2 pneumocytes => diffuse alveolar damage. Asbestosis: Serpentine: curved, flexible fibers (CHRYSOTILE); Amphibole: straight, brittle fibers (crocidolite, tremolite, amostite) MORE PATHOGENIC Berylliosis: Type 4 HS with granuloma; AEROSPACE + NUCLEAR REACTORS Acute: pneumonitis; Chronic: granuloma dissemination. Aspirin induced asthma is due to DECREASED PG/LT ratio. With a PARALYZED DIAPHRAGM: on inspiration: intercostals contract and causes pressure in pleural space to become mor e negative => DIAPHRAGM MOVED UP; ABDOMINAL VISCERA MOVED UP; ABDOMINAL WALL INW ARD Schumann body of sarcoidosis is merely DYSTROPHIC calcification Cheyne-Stokes breathing: oscillating slow/fast breathing (central apnea in CHF; or INCREASED ICP) NRDS: Use of supplemental O2 => temporary hyperoxia in retina => increased VEGF upon return to room air => retinal neovascularization => retinal detachment. NOT due to lack of Type 2 pneumocytes; PERSISTENTLY LOW O2 => PDA & intraventricular brain hemorrhage. RISK: maternal diabetes (elevated insulin) and C-section (decreased glucocorticoids) TREAT: maternal steroids before birth; thyroxine + surfactant for baby METHACHOLINE TEST: assesses bronchial hyperreactivity (BHR) A decrease in FEV1 by mor e than 20% asthma PLEURAL EFFUSION: Transudate: CHF, nephrotic syndrome, or hepatic cirrhosis; Exudate: malignancy, pneumonia, collagen vascular disease, trauma; DRAIN EXUDATE B/C INFECTION RISK. METASTASIS TO LUNG: DYSPNEA + multifocal; PRIMARY IN L UNG: COUGH Bronchopneumonia: (S.aureus, H.flu, Klebsiella, S.pyogenes) Acute inflammatory infiltrates from bronchioles into adjacent alveoli: patchy distribution involving more than 1 lobe No increased fremitus. Lung car cinoid tumor is a polyploidy intrabronchial mass. Large cell carcinoma: highly anaplastic; peripheral; surgery; pleomorphic giant cells with leukocyte fragments in cytoplasm Small cell car cinom a: L-myc; stain for enolase, chromogranin, synaptophysin ADENOCARCINOMA k-ras; Bronchial: mu cin glands; develops in site of p rior infla mma tion/injury. Bronchioalveolar: columnar tumor cells along walls of alveloli; presents like pneu monia; CAN CAUSE hypertrophic osteoa rthropathy: periosteal new bone formation, clubbing, arthritis. SCC: StSq epithelium SVC syndrome chances of occurrence: Small cell > epidermoid > adeno > large cell BRONCHIAL OBSTRUCTION has ipsilateral tracheal deviation. Ex. Smoker with decreased lung sounds, opacification of right lung on X-ray, and ipsilateral deviation => TUMOR in the R. mainstem bronchus is causing obstruction. SPONTANEOUS PNEUMO THORAX has ipsilateral tracheal deviation. Eosinophilic granuloma and atelectasis are RESTRICTIVE LUNG DISEASES. High expiratory flow rates despite low lung volume => INCREASED recoil + radial traction on conducting airway by fibrosis If lung volume DECREASES, radial traction DECREASES, causing airway diameter to DECREASE. Centriacinar- worse at APEX; Panacinar- worse at BASE. Chronic bronchitis: CD8 lymphocytic, monocytic; Reid index >50%; early hypoxemia (shunting) & late dyspnea. @Exercise: No change in PaO2 or PaCO2, but INCREASED venous CO2 content & V/Q ratio becomes more uniform HALDANE EFFECT: in lungs, oxygenation of Hb promotes dissociation of H+ from Hb. This favors CO2 release from RBCs. BOHR EFFECT: in periphery, increased H+ from tissue metabolism shifts curve to right. Giving 100% O2 will INCREASE: PAO2, PaO2, A-a. HYPOXEMIA: Normal A-a: high altitude, hypoventilation; Increased A-a: V/Q mismatch, diffusion impairment, R-L shunt 1g Hb can bind 1.34mL O2 |||||||| blood O2 binding capacity = 20.1mL O2 / dL PaO2 DECREASES with chronic lung disease because physiologic shunt decreases O2 extraction ratio. Pulmonary HTN => atherosclerosis, medial hypertrophy, and intimal fibrosis. Cheyne Stokes: cyclical changes in T.V.; Apneustic: I > E; head trauma; Biots: Nor mal interrupted by periods of apnea PVR is LOWEST at FRC; Forced exhalation INCREASES PVR b/c of collapsing positive pressure on lung. Lungs ALSO produce: prostaglandins, kallikrein.

Psych: -

The Heerfordt-Waldenstrom syndrome of acute sarcoidosis includes FEVER, PARTOID ENLARGEMENT, A NTERIOR UVEITIS, FACIAL NERVE PALSY. With CHRONIC LUNG DISEASE (ex. COPD), hypercapnia no longer stimulates central chemoreceptors. The only remaining stimulation of breathing will be LOW O2 detected by the peripheral chemoreceptors. THUS, giving high dose oxygen may depr ess the respiratory center. Central chemoreceptor responsible for: Cushing re action increased ICP constricts arterioles cerebral ischemia HTN (sympathetic) reflex bradycardia Cushing triad: HTN, bradycardia, respiratory depression. Pulmonary HTN in a CHF patient (but a non smoker) is due to reactive changes in the pulmonary vasculature (endothelial dysfunction r esulting in vasoconstriction) may contribute. *Smoking leads to absolute neutrophilic leukocytosis by DECREASING LEUKOCYTE ADHESION TO ENDOTHELIUM. Pulmonary pathogens that have tropism for vessels infarctions: C.albicans, P.aeruginosa, A.fumigatis, Mu cor spp.

Stanford-Binet: IQ = (mental age / chronological age) x 100 WAIS III- 7 verbal, 7 performance tests; can quantify intellectual decline WISC- 6 to 16 years IQ: <70: MR; <40 severe MR; <20 profound MR Superego is moral (Superman is moral) Shaping is rewarding closer and closer approximations. Erikson + Freud 0-18 months: Trust/Mistrust; ORAL 18mo 3 yrs: Autonomy/Shame; ANAL 3 yr 6 yrs: Initiative/Guilt PHALLIC 6yr 12 yr: Industry/Inferiority LATENT Teenage to Adult: Identity/Role Confusion GENITAL Late adulthood: Ego integrity/despair EGO DEFENSES Fixation: Partially remaining at more childish level Identification: is modeling behavior after anyone else (another example could be wearing someones clothing) Altruism: Guilty feelings alleviated by unsolicited generosity toward others. Retts disorder: X-linked in girls (males die): Normal to age 4 loss of development, MR, loss of verbal skills, ataxia, *stereotyped hand wringing* Childhood disintegrative disorder: more in boys; significant regression after 2 years of normal development. ANXIETY: increased NE; decreased GABA, 5-HT Normal: Oriented to person, place, and time. Order of loss (reversed): Time, place, person AIDS dementia: slowed cognition, depressed mood, ataxia, seizures, incontinence. Delusional disorder: >1 month Shared psychotic disorder: development of delusions in a person with a close relationship with someone with delusional disorder; resolves on separation. Dissociative Identity Disorder: associated with history of sexual abuse. Sleep patterns of depression: repeated night time awakening, *early morning awakening* DECREASED: slow wave sleep, REM latency INCREASED: REM early in sleep cycle, total REM ECT side effects can be minimized when performed unilaterally. Panic disorder has INCREASED ADRENERGIC STIMLUATION PANIC ATTACKs are most associated with HTN and PEPTIC ULCERS. OCD is associated with Tic disorders.

GAD: >6 months with at least 3 of fatigability, irritability, inability to concentrate, insomnia, muscle tension, restlessness. Adjustment: >3 months after stressor; once stressor is TERMINATED, symptoms (anxiety/depression) do NOT last more than 6 months NARCISSTIC involves the highly arrogant individual who demands the best and reacts to criticism with rage. MDMA: adrenergic stimulation, rhabdomyolysis, bruxism, DIC, depletes 5HT, stimulate 5HT release, prevent r euptake of 5 HT, DA, epi. LO NG TERM DESTRUCTION OF 5HT impulsiveness; DESTRUCTION OF MEMORY GAPS Barbituate WITHDRAWAL: anxiety, seizures, delirium, CV collapse death. Cocaine WITHDRAW AL: depression, suicidal thoughts, hypersomnolence, fatigue, craving. PCP blocks glutamate receptors. Mescaline and peyote contain LSD Marijuana has injected conjunctiva; chronic use leads to schizophrenia. Alcohol WITHDRAWAL: FIRST presents with tremulousness. nd IV heroin: foreign body granulomas in lung; pulmonary abscess; pulmonary edema; FSGS, 2 amyloidosis. Blue discoloration on undersurface of ring finger.

Renal: *Do not forget: Filtered load = GFR * Po TRAP: Autoregulation aims to *maintain FF constant amidst an INCREASING MAP.* Normally, increased MAP would increase GFR and decrease RPF (increase FF); THUS, autoregulation aims to*CONSTRICT AFFERENT & DILATE EFFERENT* *The ONLY substance that is freely filtered/secreted in the PCT is creatinine.* (about 10-15% secretion) + + PCT: ANGII stimulates Na /H antiporter here to per mit contraction alkalosis; + PTH works here to inhibit Na /phosphate cotransport + Ammonium (from glutamine) is made here to buffer secreted H . + + DCT: PTH works here to INCREASE Ca2 /Na exchange + ALDOSTERONE leads to insertion of Na channel on LUMINAL SIDE of the p rincipal cells. s s - + + TF/P: >1: PAH , creatinine , inulin, urea, Cl , K , Na ; <1: Pi , HCO3 , AAs, glucose Autor egulation maintains a constant FF by afferen t constriction and efferen t dilation Macula densa uses the same NKCC triple transporter as TAL; thus furosemide blocking it will allow a decrease in renin, despite INCREASED tubular NaCl. **Acetozolamide is thus the only diuretic upstream of the MD that can increase sodium delivery to the MD. POTASSIUM SHIFT OUT OF CELL: -blocker (Na/K), acidosis & severe ex ercise (K/H), hyperosmolarity, digitalis (Na/K). SHIFT INTO CELL: insulin (Na/K), epinephrine, -agonist (Na/K), alkalosis (K/H), hypoosmolarity WINTERS FORMULA: PCO2 = 1.5(HCO 3 ) + 8 +/- 2 TRAP: You actually have to use this formula: Ex. In DKA, given the [HCO3], calculate the expected PCO2. If the actual PCO2 is higher than what is calculated, then this person has M.Ac with a superimposed R.Ac secondary to respiratory failu re. Normal gap M.Ac: glue sniffing, hyperchloremia + During M.Ac: Urine pH is decreased, acid excretion in the form of NH4 and H2 PO 4 , and decreased HCO 3 excretion. For M.Alk: measuring the urinary chloride concentration and deter mining the patients volume status can ID the cause. Type 1 RTA: SEVERE hypokalemia, renal calculi, Sjogrens; urine pH > 6.0 Type 2 : mild hypokalemia, hypophosphatemic rickets^; *Fanconi syndrome can cause a Type 2 RTA* Type 3 : inability to produce NH3 due to low GFR; nor mokalemic; Type 4 : hypoalderonsteronism OR lack of response; hyperkalemia inhibition of ammonia excretion in PCT; low urine pH ^ Hypophosphatemic rickets (XD) increased phosphate wasting @ PCT & no 1-hydroxylase rickets presentation. *Legionella interstitial nephritis with type IV RTA destruction of JGA w/ hyporeninemia and hypoaldosteronism. Bartters syndrome: defect in ion channels of thick LoH; *elevated renin elevated ANGII endocytosis of ANG II receptors decreases ANGII sensitivity in vascular smooth muscle. Lo w to normal BP, sho rt statu re, hypokalemia, M.Alk, hyperaldosteronism (tolerance by decreased ANGII), hypercalciuria Hyperglycemia will overload the TAL and disrupt the countercurrent exchange, r endering ADH u seless.

Effective RPF (using PAH) underestimates true RPF by ~10% because PAH is actively secreted. Think of SECONDARY HYPER-PTH in CHRONIC renal failure. LONG TERM SIADH equilibrates to NORMAL total body volume BECAUSE of SAL T WASTIN G via suppressed R-A-A Nephrotic syndrome leads to hypercoagulability due to loss of ANTITHRO MBIN III. Even in a HYPERKALEMIC state, reabsorption of potassium follows the same pattern in the PCT and LoH; however, at the CD, there will be more potassium loss. **WORD GAME: The MAIN form in which acid is secreted by kidneys is via AMMONIUM For RENAL COMPENSATION, choose AMMON IUM SECRETION over MAINTAIN BICARBONATE Berger disease presents with gross hematuria. CHRONIC ESRD: Waxy casts with very low urine flow. Shwartzman reaction (Following second exposure to endotoxin): Vasculitis from exposure to endotoxin causing glomerular thrombosis + CF: LOSS high Cl , low HCO3 sweat => CONTRACTION ALKALOSIS (R-A-A conserves volume but H is secreted in the process) Loop diuretic: Also loss of low HCO3 sweat => CO NTRACTION ALKALOSIS. Renal angiomyolipomas are associated with TUBEROUS SCLEROSIS. 2+ Familial hypocalciuric hypercalcemia is due to defective Ca sensing receptors on parathyroid cells. Thus, PTH is not 2+ suppressed by an increase in serum calcium levels. (Urinary Ca excretion is what differentiates this from hyperparathyroidism) TRAP: Another cause of ADH insensitivity is Diabetes Mellitus; extra glucose distal to the PCT destroys the countercurrent exchange mechanism, thus rendering ADH useless for reabsorption of water. WORD GAME: ADH regulates sodium concentration; ANP has no regulatory role of sodium. Cyanotic toe discoloration and renal failure post- invasive vascular procedure atheroembolic disease of renal arteries. Cholesterol containing debris is lodged into smaller vessels, causing ischemia. Extra renal embolization livedo reticula ris, cholesterol emboli on retinal exam, and skin infarcts. MM: Benc e Jones proteins precipitate into Tamm Horsfall protein large, glassy, eosinophilic casts atrophic tubular epithelium, obstruct lumens, impede renal function. RBC casts ALSO in ischemia , malignant HTN WBC casts ALSO in tubulointerstitial inflammation, transplant rejection GRANULAR casts in ATN WAXY casts in renal failure SAA can cause NODULAR GLO MERULOSCLEROSIS Hydrocarbon solvents increase risk of GOODPASTURES PSGN: IgG, IgM, C3; granular IF Diffuse proliferative: subendothelial; wire looping of capillaries; RX: Cyclophosphamide, motefil mycophenolate, steroids Bergers disease flares with URI or gastroenteritis Alports syndrome: CO L4A5 ; Boy with bilateral sen sorineu ral hearing loss, ocular abnormalities, and glomeruloneph ritis. IF and EM are NEGATIV E; foam c ells are noted in visceral epithelial cells. Diabetes ALSO can be diffuse membranous glomerulopathy Membranous: proteinuria is DUE TO DEFECT IN PORE SLITS; subepithelial d eposits. Minimal change: caused by abnormal lymphokine secretion reduce the production of anions in the GBM. FSGS: Segment sclerosis and hyalinosis; high recurrence in transplants. Membranoproliferative: -itic/-otic; progresses slowly to CRF. Type 1: tram track by mesangial ingrowth; association with HBV > HCV Type 2: dense deposits = granular IgG/C3 in BM association with C3Nef. Tuberculosis can cause NODULAR amyloid deposits in the glomerulus (SAA amyloid) EM: fusion of the podocytes and increased collagen deposition in the mesangium and BM. Kimmelstein-Wilson Small stones obstruct ureter COLIC; Large stones are SILENT microhematuria & recurrent acute pyelonephritis Oxalate stones can result from ethylene glycol or vitamin C abuse. Uric acid stones CAN BE SEEN on noncontrast CT. ALSO, uric acid will precipitate at low urine pH (DCT and CDs); Treat by alkalinizing the urine.

Cystine stones: POSITIVE NITROPRUSSIDE/CN test (r ed/purple); treat with alkalinzation of urine. RENAL CELL CARCINOMA: originates in PCT; ectopic EPO, ACTH, PTHrP, and PRL. TRANSITIONAL CELL CARCINOMA: also caused by PHENACETIN and CYCLOPHOSPHAMIDE DIFFUSE CORTICAL NECROSIS: due to vasopasm + DIC; associated with obstetric catastrophes and septic shock. ANURIA. ATN affects PCT & aLOH; DEATH most often occurs during initial oliguric phase. Oliguria after IV pyelogram nephrotoxic ATN dangerous to give IVP in MM and DM. PAPILLARY NECROSIS: associated with Diabetes Mellitus, acute pyelonephritis, chronic phenacetin use, sickle cell anemia *Affects the vasa recta* AKI: PRERENAL: [Na]urine < 10, FENa <1%; RENAL: [Na]urine >20, FENa >2%; POSTRENAL: [Na]urine >40, FENa >4% ****Creatinine levels are near normal for PRERENAL; but FAR INCREASED for POSTRENAL. **** Note for all AKI OLIGURIA; **Increased BUN with normal creatinine but NORMAL urine output increased urea synthesis** + + + TRAP: Renal shutdown edema, M.Ac, increased Na , K , H , increased non protein nitrogens. + + TRAP: GFR decreases in renal failure; if Na and K intake remains unchanged, the FE of both has to INCREASE to maintain a + + constant excretion rate plasma Na and K levels must DECREASE or stay CONSTANT. TRAP: Bila teral RAS initial decrease GFR decreased NaCl at MD increases renin GFR normalizes. TRAP: Decreased GFR plasm a creatinine INCREASES until rate of filtration = rate of production continued excretion. Creatinine CLEARANCE: 1) Increased pregnancy, early diabetic nephropathy; 2) Decreased renal failure, increasing age FeNa+ = [ (UNa+ x PCr) / (PNa+ x UCr) ] x 100 FANCONIS SYNDROME: decreased PCT transport; 1) DECREASED PHOSPHATE REABSORPTION rickets 2) Type 2 RTA + + 3) DECREASED PCT Na reabsorption increased DCT Na reabsorption hypokalemia ARPKD: multiple small cysts in the CDs of the co rtex & medulla; may also have hepatic cysts + hepatic fibrosis; LOW EPO Death due to HTN (increased renin) ADPKD: large bulging cysts w/ fluid (10% of nephrons); functioning nephrons between the cysts; also hepatic cysts, MVP, colonic diverticula; failure in utero could lead to Potters sequence. pain and abdominal discomfort (dilation of cysts and stretching of renal capsule), hematuria , proteinuria, polyu ria, HTN Be aware: ADPKD ALSO leads to DECREASED EPO (anemia), HTN (increased renin) Renal dysplasia: MC cyst in child; enlarged renal mass with cartilage and immature CDs. Medullary sponge: multiple cysts of CDs with Swiss cheese appearance recurrent UTI, hematuria, renal stones. Acquired polycystic: in dialysis patients; cortical & medullary; small risk of RCC. TRAP: With renal failure, should eat a low protein, high carbohydrate, high fat, LOW WATER (<3-4L) diet. Hypokalemic periodic paralysis: AD; sporadic episodes of severe muscle weakness that occur after severe exercise, meals rich in carbohydrates, tension, anxiety, and high salt diet; also night time a tta cks leading to paralysis. Muscle biopsy shows vacuolation or damage to myofibrils. **Primary defect is in calcium channels; the main serum finding is decreased potassium (but hard to prove since values are normal in between attacks.TREATMENT: potassium during attacks; prophylactic acetazolamide or potassium saving direutic. A person develops CHF and decreased GFR; renal tubule shows hydropic change damage to Na-K pump. ELECTROLYTE DISTURBANCES: Hyponatremia: disorientation, stupor, coma; Hypernatremia: irritability, delirium, coma nd nd Hypochloremia: 2 to M.Alk, hypokalemia, hypovolemia, hyperaldosteronism; Hyperchloremia: 2 to non gap M.Ac. Hypercalcemia: delirium, renal stones, abdominal pain Hypomagnesemia: NM irritability, arrhythmias; Hypermagnesemia: Delirium, decreased DTR, cardiopulmonary arrest Hypophosphatemia: low ion product bone loss, osteomalacia; Hyperphosphatemia: high ion product renal stones, metastatic calcifications.

Repro: Androgen insensitivity: The hypothalamic and pituitary androgen receptors are also defective, thus there is loss of negative feedback on the gonadotropins thus estrogens are also increased thru peripheral aromatization.

TRAP: AIS has no female or male internal genitalia; 5-reductase deficiency has male internal genitalia. Epididymitis: Young have more sex ; older cant pee (<35 : N.gonorrhae + C.trachomatis; >35: E.coli + Pseudomonas) (Scrotum is red, hot, swollen with a white penile discharge) SEMEN prevents capacitance until sperm reaches ZP; SEMINAL VESICLE (60%): fructose, Vit.C, PGs, phosphorycholine, flavins, and coagulation proteins. PROSTATE (20%): ALKALINE: zinc, citric acid, phospholipids, acid phosphatase, fibrinolysin, and spermine. SPERMATO GENESIS takes 2 months for FULL development. BPH: age r elated INCREASE in estradiol that sensitizes prostate to DHT. Prostate carcinoma: PAP & PSA; INCREASED total PSA, but decreased FREE PSA; spreads to obturator + pelvic nodes. MC site of undescended testes is inguinal canal. ONE presentation of syphilis in enlarged testicles is obliterative endarteritis with perivascular cuffing of lymphocytes and plasma cells; a diffuse interstitial inflammation with edema and prominent plasma cell infiltration is also present Klinefelter: testicular biopsy shows sparse, completely hyalinized seminiferous tubules. TESTICULAR GERM CELL TUMORS: 95% of testicular tumors Seminoma: INCREASED PLAP; MALIGNANT; painless, large, gray-tan bulky mass; homogenous testicular enlargement. 15-35; Large cells in lobules with watery cytoplasm; granulomas; GOOD PROGNOSIS. RADIOSENSITIVE + CHEMOSENSITIVE Embryonal carcinoma: INCREASED AFP, hCG; MALIGNANT; painful; glandular/papillary; 20-40; hemorrhage/necrosis; CHEMOSENSITIVE ONLY Yolk sac (endodermal sinus) tumor: INCREASED AFP; Yellow, mucinous; Schiller-Duval (like glomeruli); peak @ 0-3 eosinophilic cytoplasm globules w/ AFP & 1-AT; CHEMOSENSITIVE ONLY Choriocarcinoma: INCREASED HCG; MALIGNANT; disordered syncytiotrophoblast/trophoblast; HEMATO GENOUS to liver/lungs; extensive necrosis + hemorrhage; CHEMOSENSITIVE ONLY MIXED TUMORS can also have elements of all of the above; note, a teratoma is a kind of mixed tumor. Teratoma: Unlike in female, mature teratoma is malignant. TESTICULAR NON-GERM CELL TUMORS: 5% of testicular tumors Leydig cell: androgen producing; gynecomastia in men; precocious pubety in boys; GOLDEN YELLOW ; REINKE CRYSTALS: Rectangular, crystal like inclusions Sertoli cell: Androblastoma from sex cord stroma Testicular lymphoma: MCC testicular cancer in older men; non-Hodgkins: diffuse large cell type MCC OTHER LESIONS: Bowens disease: gray, solitary, crusty plaque; SHAFT + SCRO TUM; 10% to SCC Erythroplasia of Queyrat: Red, velvety plaques; GLANS Bowenoid papulosis: multiple reddish-brown papular lesions; affects younger; does not invade. Normal changes in pregnancy: gr eater increase in plasma volume than RBC mass ALSO increases GFR and CCr. increased PLACENTAL AP; estrogen/progesterone R.Alk; ESTRO GEN: ALSO increases ciliation & height of oviductal lining cells; INCREASES myometrial excitability; stimulates and blocks prolactin. Low estrogen negatively regulates FSH/LH; but high estrogen eliminates the feedback (allows surge) PROGESTERO NE: ALSO decrease myometrial excitability; produces thick cervical mucus to block sperm; INCREASE TEMP; uterine smooth muscle RELAX; DECREASE estrogen receptor expressivity. Other effects: estrogen upregulates HMG-CoA r eductase activity bile is supersaturated with cholesterol. progesterone reduces bile acid secretion and slows GB emptying. *Causes gallstones during pregnancy* Human placental lactogen (hPL) increases linearly throughout pregnancy, correlated to fetal mass. Around Week 28 of gestation, CRH rises sharply, in anticipation of labor. Recurrent menses after positive pregnancy test hCG is not able to maintain corpus luteum LOW PROGESTERONE Kallm an syndrome: mutation in KAL-1 or FGFr1. PRESENCE of basophilic cells in Pap Smear indicate estrogen + progesterone (maintenance of corpus luteum) PREGNANT

ANO VULATORY CYCLE is the MCC of variable menstrual cycles. Refers to unopposed estrogen in prolifera tive phase leading to endometrial hyperplasia. Progestin challenge: administration +withdrawal of progesterone will lead to menstrual bleeding and CONFIRM anovulation. Metorrhagia: fr equent but irregular menstruation; Menometrorrhagia: heavy menstruation. Initial estrogen rise is due to FSH/LH; @days 10-14, estrogen rise is due to granulose cell follicles aromatase. Mittelschmerz: blood from ruptured follicle causes peritoneal irritation that can mimic appendicitis. Decidua (endometrial lining during pregnancy) is RICH WITH TISSUE FACTOR can trigger DIC. VAGINAL NORMAL FLORA: Prepubertal/postmenopausal: S.epidermidis; Adult: La ctobacillus, Candida, Strep. Following fertilization, Ca2+ influx causes HARDENING OF VITELLINE LAYER. The zona pellucida must degenerate for implantation to occur. The blastocyst usually implants in the posterior wall of the uterus; The embryonic pole implants first Human placental lactogen rises in concentration throughout pregnancy and is PROPORTIONAL to fetal mass. CRH sharply increases around WEEK 28 (role in initiating labor) SMOKING decreases vascularity of placenta => lower birth weight. After labor, the DECREASE in maternal steroids induces lactation. Ectopic pregnancy => can also affect uterus => endometrial biopsy shows decidual (gestational) changes in the endometrium BUT NO CHORION IC VILLI. AMPULLA > ISTHMUS > FIMBRIAE > INTERSTITIUM (An Incredibly Fucked INTERchange) WORD GAME: Ectopic pregnancy is due to delayed blastocyst transport due to pathology. For suspected preeclampsia, do a urine dipstick to measure proteinuria over 24 hours. Preeclampsia due to PLACENTAL ISCHEMIA due to impaired vasodilation of spiral arteries; HELLP syndrome due to DIC-mediated ischemia. WORD GAME: in a question that asks for INITIAL EVENT, go with PLACENTAL ISCHEMIA OTHER causes of anovulation: Ashermans syndrome, thyroid disorders, Cushings syndrome, adrenal insufficiency. Hydaditiform mole: Snowstorm = lucent and echogenic areas. TRIAD: hyperemesis, vaginal bleeding, hyperthyroidism COMPLETE: 90% 46XX; 10% XY; 15-20% trophoblastic disease; 2% choriocarcinoma PARTIAL: 69XXY; TREATMEN T for both: dilatation and curettage and MTX; RISK OF UTERINE RUPTURE nd Bicornuate uterus causes miscarriage in 2 trimester. Preeclampsia is induced by placental ischemia due to impaired vasodilation of spiral a rteries. MORTALITY due to cer ebral hemorrhage and ARDS. Abruptio placentae associated with SMOKING, HTN, COCAINE USE Placenta accreta defective decidual layer allows attachment to myometrium. No separation after birth PRIOR C-section, inflammation, and placenta previa predispose. HYSTERECTOMY REQUIRED. Placenta previa: attachment of placenta to lower uterine segment. Multiparity and prior C-section predispose. *RETAINED PLACENTAL TISSUE POSTPARTUM HEMORRHAGE TRAP: the above are all LATE PREGNANCY manifestations; WORD GAME: EARLY pr egnancy severe bleeding is spontaneous abortion; MCC are chromosomal abnormalities (meiosis1) CERV ICAL LESIONS: SCC: HPV 16, 18, 31, 33; RISKS: multiple sex, SMOKING, EARLY first sex, HIV Lateral invasion of SCC can block ureters RENAL FAILURE; Spr ead to Obturator nodes. Cervical polyps: non-neoplastic polyps that can be covered with columnar or StSq epithelium. VAGINA LESIONS: Bartholin gland cyst: 3-5cm diameter w/ transitional epithelium or metaplastic squamous. PAIN in LABIA MAJORA. Flocculent swelling below the skin of th e posterolateral labia majo ra Gartner-Duct Cyst are larger than 2 cm, which are of mesonephric origin; anterolateral SCC: Primary: HPV; Secondary: extension from cervical cancer. Rokitansky-Kuster-Hauser: Congenital absence of upper vagina and uterus. VULVAR LESIONS: Papillary hidradenoma: benign tumor of modified apocrine glands in labia majora. *similar to intraductal papilloma breast* Pagets: Labia majora; erythematous, crusted rash; MICRO: intraepidermal malignant cells w/ Pagetoid spread. Melanoma: Similar to Paget but do NOT stain with PAS; will stain for melanin.

SCC: HPV16, smoking, & immunodeficiencies Lichen sclerosis: epidermal thinning & dermal changes in postmenopausal => risk of SCC. Lichen simplex chronicus: squamous hyperplasia and dermal seaming due to chronic itch; white plaque ENDOMETRIAL WORD GAME: La te menopause (>53 years) Carcinoma (adeno is MC); OBESITY(#1); diabetes, HTN, nulliparity, LATE menopause, PCOS, Lyn ch syndrome. OVARIAN: Follicular cyst: MCC of ovarian enlargement; distention of UNRUPTURED GRAAFIAN FOLLICLE hyperestrinism & endometrial hyperplasia. Corpus luteum cyst: Hemorrhage into persistent corpus luteum Theca lutein cyst: Bilateral/multiple: due to gonadotropin stimulation choriocarcinoma and moles. OVARIAN GERM CELL TUMORS: MC in adolescents; Dysgerminoma: (hCG, LDH) risk in XO & pseudohermaphrodites; MALIGNANT; sheets of uniform cells; = male seminoma Choriocarcinoma: (hCG) MALIGNANT; develop in mother or fetus; large, hyperchromatic synctiotrophoblastic cells. Hematogenous spread to lungs, brain liver; RX: MTX or Actinomycin D. Yolk sac/endodermal sinus tumor: MALIGNANT; ALSO in sacrococcygeal area; yellow masses; Schiller-Duval bodies (glomeruli like) Mature teratoma: (dermoid cyst in ovary) MC BENIGN; Immature teratoma: MALIGNANT; ALL terato mas are 90% of ovarian germ cell turmors. WORD GAME: Struva ovarii can be referred as monodermal teratoma OVARIAN NON-GERM CELL TUMOR: spread by SEEDING. Serous cystadenoma: (20%); columnar epithelium; Serous cystadenocarcinoma: (50%) Psammoma bodies; bilateral; walls of epithelial cells form papillary fronds Mucinous cystadenoma: Multilocular cyst; intestine like tissue. Mucinous cystadenocarcinoma: can cause pseudomyxoma peritonei (ovary or appendix) TRAP: Borderline mucinous tumor refers to cell atypia, epithelial stratification, high mitoses, but NO INVASION. Brenner : Benign; like Bladder (transitional epithelium) Fibroma: Meigs syndrome fibroma, ascites, and hydrothorax; pulling sensation in groin Granulosa cell tumor: yellow white mass; CARL EXNER BODIES are disarrayed granulosa cells in eosinophilic fluid; CAN CAUSE abnormal uterine bleeding RISK FACTOR FOR ENDO METRIAL CARCINOMA OCs decrease the risk of endometrial & ova rian cancers because fewer ovulations fewer repairs less chance for cancer. Breast feeding & multiparity also decrease the risk of ovarian cancer. Breast pathology locations: Nipple: Pagets, abscess; Lactiferous sinus: Intraductal papilloma, abscess, mastitis; Major duct: fibrocystic change, intraductal papilloma, ectasia; Terminal duct: Tubular carcinoma, cystic Lobules: lobular carcinoma, sclerosing adenosis; Lobular stroma: fibroadenoma, phyllodes Interlobular stroma: fat necrosis, lipoma, fibrous tumor, fibromatosis, sarcoma BENIGN BREAST TUMORS: Fibroadenoma: <25; estrogen r esponsive; myxoid stroma encircling epithelium lined glandular & cystic spaces; popcorn calcifications; well circumscribed tan, rubbery mass with small cleft like spaces Intraductal papilloma: serous/bloody discharge; small risk of carcinoma (2x) if multiple; grows in lacteriferous duct; fibrovascular core with both epithelial and myoepithelial cells in papillary fronds Phyllodes tumor: >50; large bulky mass of connective tissue and cyst; leaf like; stromal increased cellularity, stromal overgrowth, irregular margins

MALIGNAN T BREAST TUMORS: arise fro m ma mma ry duct epith elium or lobular glands. Risks: OBESITY, older first birth, nulliparity, increased estrogen exposure, increased total # of menstrual cycles. Invasion of Coopers ligament by invasive breast cancer causes retraction of the overlying skin. Ductal carcinoma in situ: Arises from ductal hyperplasia; fills ductal lumen; may contain mucin filed cells. Comedocarcinoma: Ductal; Solid sheets of pleomorphic, high grade cells with caseous necrosis SUBTYPE OF DCIS Inflammatory: Der mal lymphatic invasion/obstruction (not hyperplasia); Peau de orange; firm mass under area of erythema Invasive ductal: Firm, fibrous, rock-hard mass with sharp margins & small, glandular, duct-like cells. WORST, MOST INVASIVE, MCC; tu mor cells form ducts within a desmoplastic stro ma small glandular structures lined by dysplastic cells Invasive lobular: Orderly row of cells; expansion of lobules by monotous proliferation of small cells. BILATERAL/MULTIPLE Medullary: syncytial; fleshy, cellular, lymphatic infiltration; GOOD PROGNOSIS Pagets: eczematous patches on nipple; infiltration of nipple by large cells with clear cytoplasm (Pagets cells); ALSO suggests underlying ductal carcinoma. Stains PAS+, diastase Mammary duct ectasia: simulate cancer; disorder of premenopausal women that manifest with 1) retraction 2) inversion, 3) nipple discharge 4) Marked dilation (ectasia) of large ducts with fibrosis + chronic inflammation. COMMON BREAST CONDITIONS: Fibrocystic change: estrogen-dependent; premenstrual b reast pain + multiple lesions; usually does not increase cancer risk (unless multiple or complex); SUBTYPES: 1) Fibrosis- hyperplasia of STROMA 2) Cystic- fluid filled, BLUE dome; DUCTAL dilation 3) Sclerosing adenosis- INCREASED acini and INTRALOBULAR fibrosis; calcifications. INCREASED CARCINOMA if atypical 4) Epithelial hyperplasia INCREASED # of epithelial cell layers in terminal duct lobule. INCREASE CARCINOMA RISK. Some Drugs Cause Awesome Knockers (Spironolactone, Digitalis, Cimetidine, Alcohol, Ketoconazole)

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