Cardiovascular o Stroke Ischemic Stroke Management o Maintain sufficient cerebral perfusion Permissive Hypertension – perfusion of penumbra depends on the mean arterial pressure. Treat severe hypertension if BP >220/120 mmHg o CHF Vasodilators Hydralazine and Isosorbide Dinitrate added if ineffective with diuretics, beta blockers, and ACE inhibitor (or ARB) Treathypertension with ACE Inhibitors and Beta Blockers Treatment Digoxin o Sinus Bradycardia Treatment = Atropine o Diastolic Dysfunction Due to LVH as a response to chronic systolic hypertension. Ventricle becomes stiff and unable to relax or fill adequately, thus limiting its forward output o SVT Treatment: Radiofrequency ablation o Hypertension ACE + Arb will lead to higher creatinine levels causing an increased likelihood that dialysis will become necessary o Aortic Stenosis Hemolytic Anemia + Schistocytes Low haptoglobin and elevated bilirubin o Kawasaki Disease o Acyantonic Congenital Heart Defects o Heart Sounds Mitral Valve Prolase o Cyanotic Congenital Heart Defects HEENT o Chronic Otitis Media ** Chronic Suppurative Otitis Media Otitis Media with Effusion (Glue ear) o Inflammation of the Eyelids Hordeolum (Stye) Definition: common acute inflammation of the TEAR GLAND or EYELASH FOLLICE Blepharitis
Definition: Chronic and/or recurrent scally inflammation of the eyelid margins Chalazion Definition: Focal granulomatous swelling of the SEBACEOUS GLANDS Diagnostics: everting the eyelid may allow for better visualization of the lesion Biopsy: for persistent or recurrent chalazion Treatment: o Conservative: wait and watch; warm compresses o Persistent chalazia: Incision and curettage Persisnte or recurrent chalazion may be a sign of sebaceous carcinoma (of Meibomian gland!) o Traumatic Eye Injuries Closed Globe Contusion (Bruising) Open Globe Injuries Ortbial Floor Fracture Ocular Chemical Burns o Keratitis Inflammation of the cornea, a clear and transparent covering over the iris and pupil Bacterial Keratitis Mainly: Staph, Strep, Pseudomonas Syphilis; Klebsiella Risk Factors: Contact Len Use Clinical Features: o Progressive Pain o Foreign Body Sensation o Purulent Discharge o Photophobia o Excessive Tearing o Conjunctival Injection Diagnostics o Slit Lamp: Hypopyon (collection of leukocytes at the bottom of the anterior chamber); Fluorscein staining: round corneal infiltrate Treatment o Topical broad spectrum antibiotics Cefazolin Oflaxacin Ciprofloxacin Complications o Irreversible vision loss
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o Corneal destruction Viral Keratitis Herpes Simplex Keratitis o Infection due to HSV Type 1 from trigeminal ganglion o Clinical Unilateral Eye Redness +/- Eye Pain Foreign Body Sensation Photophobia Blurry Vision o Diagnostics Fluorescein staining: superficial corneal ulcers (dendritic ulcers) that resemble the branches of a tree o Treatment Topical trifluridine or ganciclovir Oral antiviral Herpes Zoster Keratitis o Reactive herpes zoster virus (ophthalmic nerve) o Clinical Features: Prodrome of headache fever Impaired vision, eye irritation; photophobia; eye pain o Diagnosis: Slit Lamp 1-2 punctate lesions 4-6 days: dendritic lesions on the corneal surface Treatment Oral Acyclovir, Valacyclovir Acanthamoeba keratitis Acanthamoeba infection Inflammation of the Eyelids Blepharitis Treatment: Warm compresses Otosclerosis Idiopathic Intracranial Hypertension Etiology – Vitamin A analogs, tetracyclines Treatment Adopt a low sodium weight loss diet Begin acetazolamide (believed to reduce the rate of CSf production, thereby decreasing intracranial hypertension) Laryngitis
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Viral infection causing inflammation of the vocal cords lasting less than 3 weeks Symptoms – loss/muffling of the voice Treatment – Reassurance Do not treat children under the age of 2 years of age with OTC cough and cold medications Central Retinal Vein Occlusion (CRVO) Diagnostics Fundoscopic Exam - Tortuous an dilated retinal veins Esotropia Light Reflex over the lateral portion of the iris Exotropia Light reflex over the medial iris Hypertropia Light reflex over the inferior iris Involvement of the superior oblique muscle innervated by CN IV Hypotropia Light reflex over the superior iris Conjunctivitis Viral Etiology o Adenovirus o Herpes Simplex o Varicella Zoster Virus Bacterial Herpangina Caused by the Coxsackie A Virus Multiple 1-mm vesicles on the posterior oropharynx and tonsils Meniere’s Disease Multiple episodes of vertigo lasting for 20-120 minutes accompanied by a fluctuating hearing loss, tinnitus, and a sense of aural fullness; Treatment Lifestyle: Avoid caffeine, alcohol, stress; Low sodium diet Bed Rest Medical Therapy o Vestibular Suppressants (Dimenhydrinate); Antiemetics o Prophylaxis: Histamine Analog (Betahistine) Glaucoma Acute or chronic destruction of the optic nerve with or without concomitant increased intraocular pressure Open Angle Glaucoma Slowly progressive and asymptomatic but leads to bilateral peripheral vision loss
Treatment = Non-selective beta blockers (can cause bradarrhythmias by blocking B1 and orthostatic hypotension by blocking B2) Etiology o Increased IOP; Age >40 Pathophysiology o Secondary clogging of the trabecular meshwork or reduced drainage gradual increase in IOP vascular compression Ischemia to the optic nerve Clogging Due to inflammatory cells (uveitis); red blood cells (hemorrhage); retinal detachment Reduced drainage due to: increased episcleral venous pressure; damaged trabecular meshwork after a chemical injury Diagnostics o Tonometry: Measures IOP o Gonioscopy: Eye examination that allows direct visualization of the anterior chamber and the chamber angle o Fundoscopy: Cupping and pallor of optic disc Therapy o Conservative: Topical prostaglandins o Improve drainage: Topical prostaglandins (latanoprost) o Reduce aqueous humor production: topical beta blockers (timolol) alpha 2 agonists (apraclonidine) o Avoid epinephrine in angle closure glaucoma Acute Angle Closure Glaucoma Sudden and sharp increase in intraocular pressure caused by an obstruction of aqueous outflow (most commonly occlusion of the chamber angle) Unilateral red, hard, and severely painful eye Steamy cornea and blurred vision Etiology: Advanced age; Female gender; Inuit and Asian ethnicity; Rubeosis iridis; Mydriasis (blocked by the iris) due to drugs (anticholinergics e.g. atropine; sympathomimetics; decongestants; darkness stress/fear response Pathophysiology Flow of aqueous humor against resistance generates an average intraocular pressure between 10-21 mmHg Blocked trabecular meshwork decreased drainage of aqueous humor from the eye sudden IOP Primary: chamber angle narrowed due to the peripheral iris obstructing the trabecular meshwork
Secondary: scarring, lens luxation, or rubeosis iridis Clinical Features Unilaterally inflamed, reddened, severely painful eye (hard on palpation) Diagnostics: Rock hard globe on palpation Gonioscopy (gold standard) Tonometry: increased IOP Treatment First Line: o Eye drops: Beta blockers (timolol); Alpha 2 agonist o Systemic: Carbonic anhydrase inhibitor oral or IV (acetazolamide) Topical Cholinergics (pilocarpine) added once IOP is <40 mmHg Analgesics and antiemetics Definitive surgical treatment o Once acute attack controlled o Shunt from posterior to anterior chamber through the peripheral iris Neodymium YAG laser iridotomy o Otitis Malignant Externa Commonly caused by an infection with pseudomonas aeruginosa; Connection between diabetes and MOE may be related to increased pH in diabetic cerumen Diagnostic: Blood Cultures Treatment: High Dose IV Ciprofloxacin Pharmacology o Renin-Angiotensin-Aldosterone System Inhibitors
Drops in blood pressure reduce renal perfusion. If the pressure in the renal artery falls by more than 10–15 mm Hg → proteolytic renin is released from the juxtaglomerular apparatus → renin converts angiotensinogen to angiotensin I → ACE cleaves Cterminal peptides on angiotensin I, converting it to angiotensin II → increases the blood pressure in two ways: (1) vasoconstriction and (2) stimulation of the release of aldosterone, which increases the retention of water and sodium
Types of RAAS Inhibitors ACE Inhibitors = Enalapril, Lisinopril, Ramipril, Captopril, Benazepril ARBs = Valsartan, Candesartan, Losartan, Irbesartan Indications: o Arterial Hypertension o Diabetes Mellitus Nephroprotective Arterial Hypertension Microalbuminuria (>300 mg/g)
Coronary Heart Disease Heart Failure with reduced EF History of Myocardial Infarction Nondiabetic Associated CKD with Proteinuria Scleroderma associated hypertensive crisis
o o o o Effects Side Effects o ACE Inhibitors = Dry cough due to increase in bradykinin concentration; angioedema; hyperkalemia; pemphigus vulgaris Contraindications o Absolute Hypersensitivity C1 esterase inhibitor deficiency Pregnancy Breastfeeding o Relative Aortic Stenosis Renal Dysfunction Bilateral Renal Artery Stenosis (reduced GFR too low) o Chemotherapeutic Agents Overview - Indications Alkylating Agents o Oxazaphosphorines o Nitrogen Mustards o Hydrazine o Plantinum Based Agents Topoisomerase Inhibitors o Topoisomerase I Inhibitor o Topoisomerase II Inhibitor Mitotic Inhibitors o Vinca Alkaloids o Taxanes Antimetabolies o Antifolates o Pyrimidine Antagonists o Purine Analogs o Purine Antagonists o Ribonucleotide Reductase Inhibitors Other o Antibiotics o Enzymes
o Proteasome Inhibitors o Tyrosine Kinase Inhibitors Mode of Action Side Effects Alkylating Agents o Oxazaphosphorines Hemorrhagic Cystitis Mesna (neutralizes acrolein, a metabolite product) o Nitrogen Mustards o Hydrazine o Platinum Based Agents Nephrotoxic (prevent with amifostine, free radical scavenger) Topoisomerase Inhibitors o Anthracyclines = Dilated Cardiomyopathy o Topoisomerase I Inhiitors o Topoisomerase II Inhibitors Mitotic Inhibitors o Vinca Alkaloids Neurotoxic (Vincristine) o Taxanes = Pulmonary Fibrosis Antimetabolies o Antifolates Folinic acid (Leucovorin) Resuce o Pyrimidine antagonists = Leucovorin increases effect o Purine analogs Toxicity increases with allopurinol and febuxostat (metabolized by xanthine oxidase) o Purine Antagonist o Ribonucleotide Reductase Inhibitor Antibiotics o Bleomycin = Pulmonary Fibrosis o Malignant Hyperthermia o Diuretics Thiazide Diuretics 1st line drug for black patients with isolated systolic hypertension Inhibition of Na/Cl cotransport in the DCT o Increased reabsorption of calcium o Increased excretion of sodium, chloride, and potassium Side Effects o Hypokalemia and Metabolic Alkalosis o Hypercalcemia – beneficial in osteoporosis o Hyperglycemia – Avoid in diabetics
o Hyperlipidemia – Avoid in metabolic syndrome/hypercholesterolemia o Hyperuricemia Potassium Sparing Diuretics Indications o Hypertension o Ascites/Edema due to CHF o Hyperaldosteronism o Chloroquine and Hydroxychloroquine Effects Anti-malarial: the drugs stabilize the lysosomes of the schizonts and reach a high concentration in the vacuoles → their alkaline nature raises the internal pH → bind to heme to form the hemechloroquine complex, which is highly toxic to the schizont → the parasite perishes Anti-Rheumatoid: these drugs interfere with "antigen processing" in macrophages and other antigen-presenting cells → decrease the formation of peptide-MHC protein complexes → downregulate the immune response against autoantigenic peptides Side Effects Visual Disturbances o Irreversible retinopathy “Bull’s Eye Maculopathy” o Blurred Vision Indicatios P. malaria, P. ovale, P. falciparum (NOT P VIVAX) o Pain Management Types of Pain Referred Pain Phantom Limb Pain Evaluation of Pain Treatment of Pain Additional Methods of Pain Management o Antibiotics Beta Lactam Antibiotics Penicillins Carbapenems Monobactams Cephalosporins o Cefazolin = Recommended prophylactic antibiotic for most patients undergoing orthopedic procedures o Third Generation – Ceftriaxone Glycopeptides (Vancomycin) Epoxides (Fosfomycin)
Lipopeptides (Daptomycin) Sulfonamides and Trimethoprim (Cotrimoxazole (TMP/SMX) = (Trimethoprim + Sulamethoxazole) Fluoroquinolones Nitroimidazoles (Metronidazole) Aminoglycosides (Gentamicin, Amikacin, Tobramycin, Streptomycin, Neomycin) Tetracycline Glycylcyclines (Tigecycline) Lincosamides (Clindamycin) Amphenicols (Chloramphenicol) Oxazolidinones (Linezolid) Macrolides (Erythromycin, Azithromycin, Clarithromycin) Adverse Effects o Increased intestinal motility GI Discomfort o QT Interval Prolongation Torsades de Pointe Contraindications o Pregnancy Nitrofurans (Nitrofurantoin) Polymyxins Antimycobacterial Drugs Rifamycins Isoniazid Pyrazinamide Ethambutol Dapsone Contraindications Infants = Chloramphenicol < 8 years = Tetracyclines < 18 years = Fluoroquinolones Pregnant Women o All Trimesters Tetracyclines Fluoroquinolones Erythromycin Clarithromycin Streptomcyin Breastfeeding Women o Sulfonamides o Tetracyclines o Metronidazole o Fluoroquinolones o Nitrofurantoin
Renal Failure o Absolutely Contraindicated: Tetracyclines o Relatively Contraindicated: Aminoglycosides, Cephalosporins, Fluoroquinolones
o Opioids Tramadol Lowers seizure threshold Complications Long term = Hypogonadism Causes constriction of the sphincter of Oddi Prevention of constipation: Polyethylene glycol (MiraLax) o Non-Opioid Analgesics NSAIDs Side Effects o Increased risk of heart attack and stroke WITH THE EXCEPTION OF ASPIRIN AND NAPROXEN o Beta Antagonists Contraindications Absolute Contraindications o Symptomatic Bradycardia o Sick Sinus Syndrome o Cardiogenic Shock/Hypotension o Decompensated Heart Failure o Asthma o Combination with Calcium Channel Blockers Relative Contraindications o Psoriasis o Raynaud’s Phenomenon o Pregnancy (Atenolol is ABSOLUTELY CONTRAINDICATED) o Pharmacokinetics 3A4 Inhibitor Clarithromycin is a strong 3A4 inhibitor Other Inhibitors: Antifungals (azoles), Macrolides (Erythromycin, Clarithromycin), anti-HIV medications, Grapefruit Juice, Cimetidine Inducers: Carbamazepine, Rifampicin, St. John’s Wort, Barbiturates, Several, anti-HIV medications, Griseofulvin Substrates o Amlodipine is metabolized by 3A4 o Others: Statins (Except pravastatin), Steroid hormones (estrogen, glucocorticoids, testosterone), Immunosuppressives, Macrolides, Carbamazepine,
Haloperidol, Benzodiazepine, Oral Anticoagulants, Calcium Channel Blockers (Amlodipine) o Glucocorticoids Inhibit apoptosis in neutrophils; Promote apoptosis in monocytes, lymphocytes, and eosinophils o Statins Names Atorvastatin Simvastatin Pravastsatin Lovastatin Fluvastatin Pitavastatin Rosuvastatin Effects Competitive inhibition of HMG-CoA Reductase Reduced intrahepatic cholesterol biosynthesis upregulation of expression of LDL receptor gene via sterol regulatory element binding protein (SREBP) o Decreases LDL; Increased HDL; Decreased Triglycerides Side Effects Hepatic: Increased LFTs (CYP3A4 & CYP2C9) Muscular: Decrease the synthesis of coenzyme Q10 and impair energy production within muscle which can result in myalgia, muscle weakness, and increased serum creatine kinase concentrations due to myositis and/or rhabdomyolysis o Myalgia – continue as long as CK remains normal o Statin associated myopathy Muscle pain and weakness Increased CK Progress to rhabdomyolysis: may lead to myoglobinuria AKI (Increased BUN & Creatinine) Indications LDL > 190 mg/dL Atherosclerotic CVD, stroke, PAD 40-75 with diabetes and LDL levels of 70-18 mg/dL 40-75 with an estimated 10 year ASCVD risk >7.5% and LDL levels 70-189 mg/dL Contraindications Hypersensitivity Active Liver Disease Muscle Disorder Pregnancy, Breastfeeding
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Interactions Lipid Lowering Agents o Fibrates o Nicotinic Acid o Both together may cause myopathy CYP3A4 Inhibitors o HIV/HCV protease inhibitors o Macrolides (especially erythromycin and clarithromycin) o Azole antifungals o Cyclosporine Warfarin
Digoxin Cardiac Glycoside Poisoning o Etiology Digoxin overdose Hypokalemia (potassium depleting diuretics) Renal Failure Treatment with verapamil, diltiazem, amiodarone, and/or quinidine (can cause overdose) Volume depletion o Clinical Features Nausea/Vomiting; Diarrhea; Gastrointestinal Pain; and Anorexia Blurry vision with a yellow tint and halos; disorientation; weakness o Diagnostics: ECG; PVCs, T wave inversion/flattening; Decreased QT interval; Increased PR interval o Laboratory Studies: Serum digoxin concentration; Hyperkalemia; Creatinine and BUN o Treatment: Digoxin specific antibody fragments Atropine for symptomatic bradycardia; Slowly normalize serum K+; Magnesium; Class IB antiarrhythmics; o Digoxin contraindicated in ventricular fibrillation; must use coaution in pregnant women o Oral Anticoagulants Direct inhibition of thrombin (dabigatran) Warfarin = reduced activation of the vitamin K dependent clotting factors 2, 7, 9 and 10 Direct Inhibition of Factor Xa (Apixaban and rivaroxaban) GPIIb/IIIa complex inhibition (Abciximab, Epitifibatide, tirofiban)
Thrombocyte Phosphodiesterase III Inhibitor (Cilostazol and dipyridamole) Recombinant tissue plasminogen activator (alteplase, reteplase, tenecteplase) and streptokinase – increase conversion of plasminogen to plasmin Heparin = Induction of conformational change in antithrombin III o Signal Transduction Receptors Intracellular Receptors Cell Surface Receptors G Protein Coupled Receptors o Receptor Type & Connected G proteins Alpha 1 = Gq; alpha 2 = Gi Beta1, 2, 3 = Gs M1, M3 = Gq; M2 = Gi Histamine H1 = Gq; Gs = H2 Dopamine D1 = Gs; D2 = Gi Vasopressin V1 = Gq; V2 = Gs o Gs = Adenylyl Cyclase; Gi = Inhibit adenylyl cyclase; Gq = phospholipase C Receptor Tyrosine Kinase Non-Receptor Tyrosine Kinases o Nitrates Agents Nitroglycerin Isosorbide Dinitrate Isosorbide Mononitrate Sodium Nitroprusside Effects Exogenous supply of nitric oxide through nitrate activation of guanylyl cyclase increased cyclic guanosine monophosphate (cGMP) Activation of Protein Kinase G o Peripheral Vasodilation o Coronary Dilation Anginal Pain Relief Side Effects Circulatory Dysregulation: Hypotension Nitrate Induced Headache (Vasodilation of the cerebral arteries) Gastroesophageal Reflux Development of Tolerance Cyanide Toxicity Indications Angina Pectoris
Hypertensive Crisis Hypertensive Pulmonary Edema Chronic Heart Failure Contraindications Hypotension
Endocrinology o Lipid Disorders o Cushing Syndrome o Disorders of Sex Development Congenital Adrenal Hyperplasia Androgen Insensitivity Syndrome 5-alpha reductase deficiency Klinefelter Syndrome Turner Syndrome Swyer Syndrome Pure Gonadal Dysgenesis Aromatase Deficiency Ovotesticular Disorder of Sex Development o Hyperprolactinemia Causes hypogonadotrophic hypogonadism o Transplantation** o Primary Hyperaldosteronism o Acromegaly o Inborn Errors of Metabolism o Carcinoid Tumor VIPoma Increases relaxation of gastric and intestinal smooth muscles causing unregulated fluid and electrolyte secretion leading to secretory tea colored diarrhea along with the resulting dehydration and hypokalemia Inhibits gastric acid secretion, increases bone resorption, and stimulates gluconeogenesis leading to achlorhydria/hypochlorhydria o Acute Pancreatitis Diagnostics Most useful initial test – Ultrasound o PCOS Pathophysiology Reduced insulin sensitivity Hyperinsulinemia results in: obesity, epidermal hyperplasia/hyperpigmentation (acanthosis nigricans); increased androgen production in ovarian theca cells (increased LH; Increased androgens; Inhibit production of SHBG in liver)
Clinical Features Menstrual irregularities; Difficulties conceiving or infertility; Obesity; Hirsutism; Androgenic alopecia; Acne vulgaris; Acanthosis nigricans; Premature adrenarche; Diagnostics Hyperandrogenism; Oligo- and/or anovulation; Polycystic ovaries on ultrasound (transvaginal ultrasound) Increased testosterone; Increased LH (LH:FSH >2:1) Differential Pregnancy; Congenital Adrenal Hyperplasia; Cushing’s Disease; Pituitary Adenoma; Hyperprolactinemia Treatment – If treatment for infertility not sought: o If BMI >25 kg/m^2 First Line = Weight Loss Second Line = Combined Oral Contraceptive o If not overweight: combined oral contraceptive therapy If seeking treatment for infertility o First Line: Ovulation induction with clomiphene citrate (inhibits hypothalamic estrogen receptors thereby blocking the normal negative feedback effect of estrogen increased pulsatile secretion of GnRH increased FSH and LH which stimulates ovulation o Second Line: Ovulation induction with oxogenous gonadotropins or laparoscopic ovarian drilling Complications Cardiovascular Events Type II Diabetes Mellitus Endometrial Cancer Increased miscarriage rate o Pituitary Adenoma Can cause hypothyroidism with decreased TSH levels (central hypothyroidism) Diagnostics: Elevated prolactin levels MRI of the Pitutiary o Diabetes Mellitus ** Epidemiology Type 1 o Childhood onset Type 2 o Adult onset Etiology
Type 1: Autoimmune beta cell destruction o Associated with hashimoto thyroiditis, Type A gastritis, Celiac Disease, Primary Adrenal Insufficiency Type 2: Hereditary and environmental factors o Associated with metabolic syndrome o Risk Factors: Obesity, High calorie diet; High waist to hip ratio; Physical inactivity; First degree relative with diabetes; Ethnicity Classification Pathophysiology Clinical Fatures Diagnostics Differential Diagnosis Treatment Algorithm Insulin Therapy Complications HHS o Marked hyperglycemia (>600 mg/dL) increases serum osmolality (>320 mOsm/kg) o Sodium levels low due to extracellular water shifts from the hyperosmolarity (hypertonic hyponatremia) DKA o Cerebral edema is a risk Diabetic Nephropathy Diabetic Retinopathy Diabetic Neuropathy Diabetic Foot Prognosis Special Patient Groups o Metabolic Syndrome Definition Presence of >3 of the following: o Insulin Resistance: Fasting Glucose >100 mg/dL o Elevated BP: >130/85 mmHg o Elevated Triglycerides: >150 mg/dL o Low HDL-C In Men: < 40 mg/dL In Women: <50 mg/dL o Abdominal Obesity > 102 cm (>40 in) in men > 88 cm (>35 in) in women Treatment
o First Line: Lifestyle Modifications Dietary Changes: Calorie Restriction Physical Activity: minimum of 30 minutes moderate exercise per day (2.5 hours per week) which increases insulin sensitivity, lowers blood pressure, and promotes weight loss o Medical Therapy: Treat Hypertension (Ace Inhibitors, Diabetes Mellitus, and Dyslipidemia (Statin) o Bariatric Surgery If BMI >40 with no success with dietary and lifestyle changes Complications o Cardiovascular Disease o Type II Diabetes o Non-Alcoholic Steatohepatitis increased risk of developing liver cirrhosis and hepatocellular carcinoma o Anti-diabetic Drugs Biguanides Mechanism of Action: Enhances effect of insulin o Reduction in insulin resistance via modification of glucose metabolic pathways Inhibits mitochondrial glycerophosphate dehydrogenase Decreases hepatic gluconeogenesis and intestinal glucose absorption Increases peripheral insulin sensitivity o Lowers postprandial and fasting blood glucose levels o Reduces LDL, increases HDL Indications: Type 2 Clinical Characteristics o Glycemic efficacy o Weight Loss of Weight Stabilization o No risk of hypoglycemia Important Side Effects o Metformin Associated Lactic Acidosis GI Prodromal Syndromes: Nausea, vomiting, diarrhea, abdominal pain Severe symptoms: muscle cramps, hyperventilation, apathy, disorientation, coma High risk groups: Elderly; Cardiac or Renal Insufficiency Diagnostics
ABG: Metabolic Acidosis and Anion Gap Increased Serum Lactate o GI Complaints o Vitamin B12 Deficiency o Metallic Taste in the Mouth Contraindications o Renal Failure (GFR <30 mL/min) o Severe Liver Failure o IV Iodinated Contrast Medium o Pause prior to surgery o Ketoacidosis o Heart Failure, Respiratory Failure, Shock, Sepsis o Alcoholism Thiazolidinediones (Pioglitazone, Rosiglitazone) Clinical profile o Mechanism of Action: Activation of the transcription factor PPAR (peroxisome proliferator activated receptor of gamma type) increase transcription of genes involved in glucose and lipid metabolism increased levels of adipokines such as adiponectin increased storage of triglycerides and subsequent reduction of products of lipid metabolism glucose utilization is increased and hepatic glucose production reduced o Clinical Characteristics: Lowers a1c by 1% in 3 months No risk of hypoglycemia o Important Side Effects Fluid Retention and Edema Weight Gain Increased risk of heart failure Increased risk of bone fractures (osteoporosis) o Contraindications CHF Liver Failure Sulfonylureas (Glyburide, Glipizide) Clinical Profile o Mechanism of Action: Block ATP Sensitive potassium channels of the pancreatic beta cells depolarization of the cell membrane calcium influx insulin secretion o Clinical Characteristics: lowers a1c by 1.2% over 3 months Important Side Effects o Life Threatening Hypoglycemia Increased risk in patients with renal failure Weight Gain
Hematological: Granulocytopenia, Hemolytic Anemia Allergic Skin Reactions Alcohol Intolerance Contraindications o Severe Cardiovascular Comorbidity o Obesity o Sulfonamide Allergy o (Beta blockers may mask the warning signs of hypoglycemia and decrease serum glucose levels even further Meglitinides (sulfonylurea analogue – repaglinide, nateglinide) Mechanism of Action: Enhances insulin secretion similar to sulfonylureas Important side effects: o Life threatening hypoglycemia o Weight Gain Contraindications o Severe Liver Failure o Severe Renal Failure Incretin Mimetics (Exenatide, Liraglutide) Mechanism of Action: Food Intake activation of enteroendocrine cells in GI tract release GLP-1 GLP-1 degradation via DPP-4 end of GLP-1 o Incretin mimetic drugs bind to GLP-1 receptors and are resistant to degradation by DPP-4 enzyme insulin secretion increase, decrease glucagon secretion, slow gastric emptying (increased feeling of satiety, decreased weight) Clinical Characteristics o Weight Loss Side Effects o GI Complaints o Increased risk of pancreatitis and potentially pancreatic cancer Contraindications o Symptomatic GI motility disorders o Chronic pancreatitis or family history of pancreatic tumors Dipeptidyl peptidase 4 inhibitors (Sitagliptin, Saxagliptin) Mechanism of action: indirectly increase the endogenous incretin effect by inhibiting the DPP-4 enzyme that breaks down GLP-1 increased insulin secretion, decreased glucagon secretion, delayed gastric emptying
Important Side Effects o GI Complaints: Diarrhea, Constipation o Arthrlagia o Increased risk of pancreatitis o Acute Renal Failure Contraindications o Liver Failure SGLT-2 Inhibitors (Dapaglifozin, Empagliflozin, Canagliflozin) Mechanism of Action: Reversible inhibition of the sodium dependent glucose co-transporter SGLT-2 in the proximal tubule of the kidney reduced glucose reabsorption in the kidney glycosuria and polyuria Clinical Characteristics: Promotes weight loss, reduces blood pressure Important Side Effects: o Urinary Tract Infections, Genital Infections o Dehyhdration o Severe Diabetic Ketoacidosis Contraindications o CKD o Recurrent UTIs Alpha Glucosidase Inhibitors (Acarbose, Miglitol) Mechanism of Action: Inhibits alpha glucosidase decrased intestinal glucose absorption Clinical Characteristics: No risk of hypoglycemia Important Side Effects: GI Complaints (Flatulence, Abdominal Discomfort, Diarrhea) Contraindications o IBS o Malabsorption Conditions o Sever Renal Failure
o Glucagonoma Increased fasting glucagon levels Increases gluconeogenesis and inhibits glycolysis causing hyperglycemia Necrolytic Migratory Erythema Paraneoplastic cutaneous reaction The direct action of glucagon on skin, protein deficiency, and/or a deficiency of zinc and fatty acids due to chronic diarrhea o Acute Adrenal Insufficiency
Symptoms: Fatigue and lack of energy, weight loss, hypotension, loss of appetite, nausea, and vomiting. Dry skin, hyperpigmentation, and abdominal pain Diagnostics Laboratory Findings: Electrolyte disturbances, hyponatremia, hyperkalemia, hypercalcemia, azotemia, anemia, and eosinophilia o Diabetes Insipidus Etiology Central Diabetes Insipidus o Primary: Idiopathic o Secondary: Brain tumors, neurosurgery, TBI, Ppituitary ischemia Nephrogenic Diabetes Insipidus o Medications (lithium, demeclocycline) o Hypokalemia, Hypercalcemia o Renal Disease (ADPKD) o Pregnancy Clinical Features Polyuria; Nocturia; Polydipsia; Dehydration Treatment Central: Desmopressin o Alternative: Chlorpropamide (increases ADH release) Nephrogenic: Thiazide Diuretics; NSAIDs; Amiloride o Thyroid Hypothyroid Can cause an elevated LDL because T4 is required for upregulation of the LDL receptor on cell surfaces Antithyroid Drugs Methimazole – thioamide that interferes with the production of T3 and T4. Inhibits thyroid peroxidase and the oxidation of iodide. Graves Disease Etiology o B and T lymphocyte mediated autoimmune disorder o 50% have family history Pathophysiology o TSH receptor stimulating IgG immunoglobulin hyperthyroid o TRAb stimulate: Orbital fibroblast hyaluronic acid synthesis and differentiation of fibroblasts to adipocytes (opthalmopathy with exophthalmos)
Dermal fibroblasts and deposition of glycosaminoglycans in connective tissue (pretibial myxedema)
o Thyroid Cancer o General Endocrinology Hypothalamic Neuropeptide Y decreased due to an increase in leptin serum concentration = decreased appetite Leptin insensitivity = unopposed appetite Obesity o Subacute Thyroiditis Summary Transient patchy inflammation of the thyroid gland associated with granuloma formation or lymphocytic infiltration Subacute granulomatous thyroiditis = Usually occurs after a viral upper respiratory tract infection Subacute lymphocytic thyroiditis = postpartum period, autoimmune diseases, or side effect of drugs Etiology DeQuervain Thyroidits o Viral Infection: Mumps, Coxsackie, Influenza, Echovirus, Adenovirus, Mycobacterial Infection Subacute Lymphocytic Thyroiditis o Drugs: alpha interferon, lithium, amiodarone, interleukin2, tyrosine kinase inhibitors o Autoimmune disease o Postpartum thyroiditis Pathophysiology Inflammation of the thyroid gland associated with a triphasic response o Thyrotoxic phase (lasts 4-6 weeks): damage to follicular cells and release of pre-formed colloid (stored thyroid hormones) o Hypothyroid phase (4-6 months): depletion of pre-formed colloid and impaired synthesis of new thyroid hormones as a result of damage to follicular cells o Euthyroid phase: Thyroid function recovers and pathological changes are no longer visible in the thyroid gland Clinical Features Subacute Granulomatous Thyroiditis o Possible history of URTI o Painful, diffuse, firm goiter o Fever and/or malaise
o Features of hyperthyroidism followed by features of hypothyroidism Subacute Lymphocytic Thyroiditis o Painless, diffuse, firm goiter o Features of hyperthyroidism followed by features of hypothyroidism Diagnostics o Thyroid Function Test Thyrotoxic phase: Increased T3 and T4; Increased thyroglobulin; Decreased TSH o Confirmatory Test Increased ESR Decreased iodine uptake o Ultrasound: Thyroid with poorly defined hypoechoic regions and decreased vascularity; cobblestone appearance o Histology: Subacute granulomatous thyroiditis: Granulomatous inflammation, multinucleated giant cells Subacute lymphocytic thyroiditis: Absence of germinal follicles, lymphocytic infiltration Treatment o Thyrotoxic phase: Beta Blockers NSAIDs (Granulomatous) Corticosteroids Antithyroid drugs should not be administered o Gastrointestinal Meckel Diverticulum Pathophysiology o Omphalomesenteric duct = connecting yolk sac to the alimentary tract in the embryo o Incomplete obliteration of the omphalomesenteric duct Anatomy o Meckel diverticulum = true diverticulum o 2 types of mucosal lining = native ileal mucosa + heterotopic mucosa o Blood supply: vitelline artery Clinical Features o Asymptomatic o Symptomatic Painless lower GI bleeding
Hematochezia Tarry Stools Currant Jelly Stools
Diagnostics o Imagiang Meckel Scintigraphy Scan (99mTc) CT Angiography Alcoholic Liver Disease Differential Diagnosis o Non-Alcoholic Steatohepatitis Colorectal Cancer Prevention o Asymptomatic men and women >50 years of age o Low risk individuals: Complete colonoscopy = every 10 years if no polyps or carcinomas detected Annual fecal occult blood tet (poor sensitivity) Sigmoidoscopy = every 5 years and FOBT every 3 years Annual Fecal Imunochemical Testing CT Colonography every 5 years o High Risk Individuals Complete colonscopy 10 YEARS EARLIER thant he index patient’s age at diagnosis or NO LATER than 40 years of age o If poly removed: Hyperplastic polyp < 10 mm in size = 10 years Low risk adenoma: 1-2 tubular polyps < 10 mm in size and without intraepithelial neoplasia = 5-10 years High risk adenoma (3-10 tubular polyps; 1 polyp > 10 mm; 1 villous or tubulovillous polyp; 1 tubular polyp = 3 years More than 10 adenomas = <3 years Lynch Syndrome Prevention o Cancer Screening Annual Colonscopy 2-5 years before earliest case of tumor in the family Annual pelvic exam with transvaginal sonography and endometrial biopsy at 30-35 years of age or 35 years before earliest case of tumor in family Annual physical exam and urinalysis
o Total Colectomy Colonic Polyps Classification o Low Malignant Potential Hamartomatous Juvenile Polyposis Syndrome Peutz jeghers Syndrome Cowden Syndrome Cronkhite Canada Syndrome Inflammatory Polyps Ulcerative Colitis Mucosal Polyps Submucosal Polyps o Moderate Malignant Potential Serrated Polyps Hyperplasti Polyps Sessile Serated Polyps Traditional Serrated Adenoma o High Malignant Potential Adenomatous Polyps Tubular Adenoma Tubulovillous Adenoma Villous Adenoma Subtypes and Variants o Hereditary Polyposis Syndrome o Adenomatous Polyposis Syndromes Familial Adenomatous Polyposis Prevention: o Screening begins at 10 years of age = Rectosigmoidoscopy o Upper endoscopy begins at 25 years of age Primary Biliary Cholangitis Pathophysiology o Inflammation and progressive destruction of the small and medium sized intrahepatic bile ducts (progressive ductopenia) defective bile duct regeneration chronic cholestasis secondary hepatocyte damage Clinical Features o Fatigue o Marked generalized pruritis o Hyperpigmentation o Hepatomegaly, Dull Lower Margin, RUQ Discomfort
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o Splenomegaly o Maldigestion o Xanthomas and Xanthelasma Diagnostics o Laboratory Tests Increased Cholestasis (ALP, GGT, Conjugated Bilirubin) Transaminases within normal limits Increased AMA Increased ANA Increased IgM o Liver Biopsy Pathology Treatment o 1st Line = Ursodeoxycholic Acid Inguinal Hernia Indirect Inguinal Hernia Failure of the processus vaginalis to close Pernicious Anemia Increased risk of developing gastric adenocarcinoma 90% have chronic atrophic gastritis Anal Fissures 90% occur at the posterior midline, distal to the pectinate line (dentate line) Inflammatory Bowel Disease Ulcerative Colitis Management o Begin screening colonoscopy 10 years after the initial diagnosis and continue every 2-5 years Crohn’s Disease PPIs The use of PPIs + H2 Receptor Antagonist Vitamin B12 Deficiency Intestinal Ischemia Acute Mesenteric Ischemia Clinical Features o Periumbilical Pain disproportionate to physical findings o Diarrhea o Nausea + Vomiting Diverticulitis Indications for surgery: Generalized peritonitis; Unconfined perforation; Uncontrolled sepsis; Undrainable abscess; Failure of conservative management Irritable Bowel Syndrome
Treatment: Citalopram o Nonalcoholic Fatty Liver Disease Accumulation of fat in hepatocytes Associated with insulin resistance, central adiposity, increased BMI, HTN, Dyslipidemia o Acute Rectal Fissure Treatment: Internal Sphincterotomy; Botulinum toxin injection o Zenker Diverticulum Increased intrapharyngeal pressure on a physiologically weakened area of
the hypopharynx (Killian triangle) causes the local mucosa and submucosa to bulge through the muscularis propria Pressure increase is usually due to esophageal dysmotility (e.g., inadequate relaxation of the upper esophageal sphincter). Pulsion diverticula (due to increased intraluminal pressure), such as Zenker diverticulum or colonic diverticula in diverticulosis, are typically false diverticula, whereas traction diverticula (due to inflammatory processes) are true diverticula.
o Inborn errors of carbohydrate metabolism Glycogen Storage Disorders Type I (Von Gierke) Type II (Pompe) Type III (Cori) Type IV (Anderson) Type V (McArdle) o Myophosphorylase Deficiency (McArdle’s Disease) glycogen storage disease that presents with myalgias, rhabdomyolysis, myoglobinuria, and early fatigue from exercise due to inability to break down glycogen for use as energy in muscle tissues o Second wind phenomenon Type VI (Hers) Galactosemia Most common form is galactose-1-phosphate uridylyltransferase deficiency which leads to the accumulation of galactose-1phospahte and galactitol Accumulation of galactitol causes infantile cataracts Symptoms become apparent when the newborn starts feeding breast milk and/or routine formula Must avoid food containing lactose (cow and breast milk) Disorder of Fructose Metabolism o Rare Neurological Diseases Adrenoleukodystrophy X linked neurological disease caused by an impaired peroxisomal ATP binding cassette transporter protein that leads to an accumulation of very long chain fatty acids in the adrenal glands, testes, and white matter, and subsequent neuron demyelination
o Celiac Disease Associated with Turner Syndrome MSK o Collection of Orthopedic Conditions Popliteal Baker Cyst Bursitis Meniscal Cyst Stress Fracture Genu Valgum Genu Varum Greater Trochanteric Pain Syndrome Forearm Fractures o Insertional Tendinopathies o Dupuytren’s Contracture (Palmar Fibromatosis) Fibromatosis of the palmar fascia leading to overproliferation of fibroblasts and formation of collagen nodules/cords o Reactive Arthritis o Spinal Stenosis o Subacromial Bursitis Subacromial Impingement Syndrome o Orthopedic Shoulder Examination *** o Soft Tissue Lesions of the Shoulder o Patellofemoral Pain Syndrome Peripatellar pain Malalignment of the patella and femoral grove with resultant patellar chondromalacia o Friedreich Ataxia 8-15 years old Etiology Trinucleotide repeat expansion (GAA) in the FXN gene on chromosome 9 intramitochondrial accumulation of iron and dysregulation of cellular antioxidant defense oxidative damage to CNS and CVS cells CNS and CVS degeneration Clinical Features Neurological o Progressive Ataxia Bilateral lower limbs equally affected Wide based steppage gait with dysmetria and frequent falling Torso and Arms Action and intention tremors Choreiform movements
Associated impaired proprioception, vibration sense, and loss of deep tendon reflexes o Dysarthria and dysphagia Skeletal Deformities o Secondary Scoliosis o Foot deformity: foot inversion (pes cavus) with hammer toes Concentric hypertrophic cardiomyopathy Diabetes Mellitus Personality Changes Diagnostics Trinucleotide repeat expansion assay ECG: T wave inversion and ventricular hypertrophy Echocardiography: symmetric, concentric ventricular hypertrophy Nerve conduction studies o Sensory: absent or reduced sensory nerve action potentials o Motor: normal until advanced MRI brain/spinal cord: cervical spine atrophy Treatment None o Paget Disease of Bone o Septic Arthritis Etiology Mechanism of Infection o Hematogenous Spread Distant site Disseminated Infection o Direct Contamination Risk Factors o Prosthetics; Interventions; Immunosuppression; Diabetes Mellitus; Age; Chronic Skin Infections; IV Drug Use Causative Organisms o Most common in adults and children >2 years = staphylococcus aureus o Streptococci o S. epidermidis o H. influenzae o N. gonorrhea o Gram negative rods (E. coli and P. aeruginosa) o M. tuberculosis; Mycobacteria o B. burgdorferi
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X-Ray of the Femur/Hip then CBC and ESR then ultrasonography (highly sensitive for effusion) Treatment Initial Management o Transient Synovitis Polymyositis Proximal muscle involvement Elevation of muscle enzymes CK and Aldolase Treatment = Corticosteroids Ankle Injury Ottawa Ankle Rules Necrotizing Fascitis Group A Streptococcus Treatment Mild Infection = Oral Antibiotics (Pencillin V or Cephalosporin or Dicloxacillin or Clindamycin) Moderate Infection = IV Antibiotics (Penicillin or Ceftriaxone or Cefazolin or Clindamycin Severe Infection = Surgical Debridement + Empiric Antibiotic Treatment (Vancomycin + Piperacillin/Tazobactam) Adehsive Capsulitis Anterosuperior and Anteroinferior Capsular Ligaments Achilles Tendinopathy Physical Examination Muscle Strength 0 = Inability to contract muscle 1 = Contraction without movement 2 = Gravity neutralized 3 = Movement against gravity only 4 = Movement against gravity plus some additional resistance 5 = Movement against substantial resistance Lateral Epicondylitis Degeneration of the extensor carpi radialis muscle tendon Treatment: Conservative Management Patellofemoral Pain Syndrome Anterior knee pain that is worse with running downhill. Apprehension when knee extended with pressure over the patella and patella will sometimes track laterally Treated with exercises to strengthen the quadriceps and hips and by using a knee sleeve with a doughnut type cushion that the patella fits into Osgood Schlatter
Avascular necrosis from overuse of the quadriceps muscle during periods of growth Causes a traction apophysitis at the tibial insetion of the quadriceps tendon Inflammation of the patellar ligament at the tibial tuberosity Clinical: Anterior knee pain that worsens with exercise; Tibial bump may be felt and can often be seen on X-Ray o Progressive Muscular Dystrophies Epidemiology – Only males affected Age of onset: o DMD: 2-5 years o BMD: usually not earlier than 15 years of age Etiology DMD and BMD: X Linked Recessive LGMD: Autosomal Dominant or Autosomal Recessive Chromosomal defects affect the dystrophin gene on the short arm of the X chromosome (Xp21) o Frameshift mutation in DMD o Point mutation in BMD Pathophysiology Dystrophin protein anchors the cytoskeleton of a muscular cell to the extracellular matrix by connecting cytoskeletal actin filaments to membrane bound dystroglycan that is in turn connected to the extracellular laminin Dystrophin gene mutation and subsequent alterations of the protein partial or almost complete impairment of the protein disturbance of numerous cellular signaling pathways necrosis of affected muscle cells and subsequent replacement with connective and fat tissue muscle appears larger (pseudohypertrophy) Clinical Features Duchenne Muscular Dystrophy o Paresis and atrophy starting in the proximal lower limbs o Weak reflexes o Waddling gait (bilateral Trendelenburg Sign) o Gower Maneuver o Calf Pseudohypertrophy o Inability to walk by 12 years of age o Cardiac and respiratory muscle involvement Dilated cardiomyopathy Cardiac arrhythmias Respiratory insufficiency Becker Muscular Dystrophy
o Slower progression Diagnostics Blood tests: Increased creatine kinase Genetic analysis: detect dystrophin gene mutation Muscle biopsy o DMD: Absent dystrophin o BMD: Reduced dystrophin Treatment Medical Therapy o DMD: Glucocorticoids o BMD: Glucocorticoids (efficacy is low) Supportive Therapy o Physiotherapy; Orthopedic assistive devices; Psychological Support; Ventilation Support Prognosis DMD: 30 years (cardiac or pulmonary death) BMD: 40-50 years o Common Peroneal Nerve Injury High stepping gait, weakness of foot eversion and dorsiflexion, and decreased sensation in the anterolateral aspect of the leg and dorsum of the foot Most common peripheral nerve lesion of the lower extremity Susceptible to injury during obstetric procedures Microbiology o Rabies Rhabdoviridae Transmission: Saliva of rabid animal after bite injury Pathophysiology: migrates from bite wound retrograde along microtubules using dynein o Amebiasis Entamoeba histolytica o Helminth Infections Toxocariasis Enterobiasis Ascariasis Trichinellosis Taeniasis Hookworm Infections Strongyloidiasis Diphyllobothriasis o Malaria Epidemiology Tropical Africa
Tropical and Subtropical regions such as Asia and Latin America Etiology Pathogen: Plasmodia Vector: female Anopheles mosquito Partial Resistance against Malaria: o Sickle Cell Trait o Thalassemia, Hb C Species o Plasmodium vivax and Plasmodium ovale (every 2 days fever) o Plasmodium malaria (every 3 days) o Plasmodium falciparum Pathophysiology Developmental Stages of Plasmodium in RBCs o o o
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Immature trophozoite: thick, dark purple ring-shaped inclusions (similar to signet ring cell carcinoma) With Plasmodium falciparum: fine rings Mature trophozoite: ameboid rings With Plasmodium falciparum: finer rings in comparison to immature trophozoites Immature schizont: irregular round, ameboid, almost filling the entire erythrocyte With Plasmodium falciparum: hardly detectable in the blood Mature schizont: conglomerate of 6–24 merozoites (round with central darkening), which develops from an immature schizont With Plasmodium falciparum: hardly detectable in the blood Gametocytes Macrogamete: mature female (sexual) form, visible as a round structure filling almost the entire erythrocyte Microgamete: mature male (sexual) form, visible as a round structure within the erythrocyte. In comparison to macrogametes, it is smaller and has a brighter nucleus.
Clinical Features o Incubation: 7-42 days Relapse in P. ovale or P. vivax Hypnozoites persist within the liver and cause reinfection after lying dormant for months or even years o Flu Like Symptoms o High Fever Tertian Malaria: every 48 hours Quartan malaria: every 72 hours Falciparum malaria: irregular fever spikes with no noticeable rhythm o Weakness, Paleness, Dizziness o Increased bleeding risk
o GI; Diarrhea, Abdominal Pain, Nausea, Vomiting o Liver: Hepatosplenomegaly o Severe Malaria: Most commonly from falciparum malaria Kidneys: hemoglobinuria Cerebral: hallucinations Cardiopulmonary: Heart Failure Diagnostics o History o CBC o Blood Smear Treatment o Tertian malaria P. vivax & ovale = Chloroquine or hydroxychloroquine + Primaquine P. vivax = artemether lumefantrine + primaquine o Quartan Malaria = Chloroquine or Hydroxychloroquine
o Sepsis Staph Aureus o Entamoeba histolytica Cysts or trophozoites ingest phagocytosed erythrocytes Treatment = paramomycin or diloxanide o Campylobacter Treatment – Macrolides (Azithromycin) o Neisseria gonorrhea Treatment – Ceftriaxone + Azithromycin o Community Acquired Pneumonia Diagnostics: CURB-65 Score and SaO2 Treatment – Amoxicillin in children 60 days to 5 years of age for activity against Streptococcus pneumoniae Azithromycin for children 5-16 years old because of its activity against Mycoplasma pneumoniae and Chlamydia pneumoniae o Sepsis Management Respiratory stabilization with oxygen Fluid resuscitation Vasopressors (Dopamine and Norepinephrine) o Croup Clinical:
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Inspiratory stridor, Chest wall retraction, diminished air movement Diagnostics: Steeple Sign Treatment Mild croup: Cool mist inhalation, infant in upright position, Dexamethasone moderate to severe croup: Nebulized epinephrine Tuberculosis Diagnostics Interferon gamma release assay – o Amount of interferon gamma expressed by T cells o Not influenced by prior BCG vaccination Management: Asymptomatic patient with a positive IFN-gamma release assay or TB skin test, treat if high risk factors for TB using Isoniazid for 9 months Asbestosis Diagnosis: Elongated, yellow asbestos body Bilateral infiltrates, Pleural Thickening o Calcified pleural plaques o Bilateral ground glass opacities Increased Alveolar Arterial Gradient o Ventilation-Perfusion mismatch due to impaired diffusion of oxygen across the capillary membrane within the alveoli from inflammation and fibrosis of pleural parenchyma Pertussis Treatment Macrolides Post-Exposure Prophylaxis to all close contacts Influenza Complications Highest risk groups: Children under 2 years old, pregnant women, adults over 65, morbidly obese (BMI > 40 kg/m^2), and Native or Alaskan Americans Streptococcus Group A Treatment: Penicillin Rocky Mountain Spotted Fever Transmission through ticks
Clinical Diagnosis: Fever, hypotension, rash, myalgia, vomiting, and headache (sometimes severe)
o Sepsis >38.3 C; WBC >12,000/mm3; Respiratory Rate >20 min; o Clostridium dificile colitis Severe = Vancomycin oral 500 mg TID o Dengue Clinical Presentation: Retro-orbital pain, fever, malaise, myalgia Treatment o Varicella Zoster Virus Multinucleated giant cells and Cowdry A inclusions via Tzanck test of shingles lesions Immunosuppression is a risk factor for reactivation of VZV after a period of latency in dorsal root ganglia o Shingles Complications Post-herpetic neuralgia o Treatment 1st line: TCAs Relative Contraindictions (heart disease, epilepsy, glaucoma): Glaucoma, Pregabalin nd 2 Line: Topical capsaicin, opioids, intrathecal glucocorticoid injections o Cytomegalovirus (CMV) Immunocompetent patients >90% asymptomatic; <10% CMV mononucleosis Immunocompromised patients: CMV Mononucleosis; CMV Pneumonia; CMV Retinitis; CMV Esophagitis; Adrenal Insufficiency; CMV Encephalitis Psychiatry o Substance-Related and Addictive Disorders Nicotine Use Disorder Varenicline Alcohol Disorder Minor alcohol withdrawal = tremor, anxiety, nausea, vomiting, and/or insomnia Major withdrawal = visual and auditory hallucinations, diaphoresis, tachycardia, and elevated BP Delirium Tremens = Delirim o Anxiety Anxiety, shortness of breath, paresthesia, and carpopedal spasm = hyperventilation o Medications Anti-depressants
SSRIs o Duloxetine Indicated for both depression and chronic pain Unlikely to cause weight gain o Parvovirus B19 Associated with Fifth Disease (nonspecific fever, arthropathy, chronic anemia, and transient aplastic crisis) Parvovirus Arthritis Mild febrile illness, maculopapular rash beginning on the perioral areas of the face several days later and spreading to the extremities from there. Adopts a lacy and reticular pattern. Symmetric polyarthritis in the fingers, hands, knees, and ankles while the rash can be absent Treatment with analgesics and NSAIDs. o Prednisone can also be prescribed OBGYN o Pregnancy Loss Etiology Spontaneous Abortion o Maternal o Fetoplacental o Miscellaneous Stillbirth o Maternal o Fetoplacental o Miscellaneous o Pregnancy*** o Childbirth 40 weeks pregnanncy o Ectopic Pregnancy o Lichen Planus o Lichen Sclerosus o Atrophic Vaginitis o Chorioamnionitis Infection of amniotic fluid, fetal membranes, and placenta Common bacteria: Ureaplasma urealyticum, Mycoplasma hominis, Gardnerella vaginalis, Bacteroides, Group B Streptococcus, E. Coli Risk Factors: Prolonged labor or premature rupture of membranes Pathological bacterial colonization of vaginal tract Multiple digital vaginal exams, invasive procedures Symptoms Maternal
o Fever (>100 F) o Tachycardia (>120 /min) o Uterine tenderness, pelvic pain o Malodorous and purulent amniotic fluid, vaginal discharge o Premature Contractions, PROM Fetal Tachycardia > 160 /min Diagnostics: Clinical Diagnosis Maternal Blood Tests o Leukocytosis >15,000 cells/uL; Elevated CRP Bacterial Cultures o Urogenital secretions o Amniotic fluid Group B Streptococcus screening: cervicovaginal and rectal swabs Management Maternal Antibiotic Therapy o Vaginal Birth: IV Ampicillin + Gentamicin o Cesarean Birth: IV Ampicillin and Gentamicin + Clindamycin Delivery o Swift delivery generally indicated to minimize both maternal and fetal complications Complications Maternal o Uterine atony, postpartum hemorrhage, endometritis o Septic shock, DIC, venous thrombosis, pulmonary embolism, death Fetal/Neonatal o Fetal death, premature birth o Asphyxia, Intraventricular hemorrhage, Cerebral palsy o Neonatal Infection o Neonatal Infection and Sepsis o Omphalitis o Preterm Labor and Birth Definition: Preterm Labor: Regular uterine contractions with cervical effacement, dilation, or both before 37 weeks gestation Preterm Birth: Live birth between 20 0/7 weeks and 36 6/7 weeks of gestation WHO Subcategories o Extremely Preterm (<28 weeks) o Very Preterm (28 to < 32 weeks) o Moderate to Late Preterm (32 to < 37 weeks) Epidemiology
Complications of preterm birth are leading cause of death in children < 5 years of age worldwide Approximately half of patients who deliver prematurely are diagnosed with preterm labor Clinical Features Regular uterine contractions and associated symptoms of labor Cervical dilation >3 cm, effacement, or both Premature Rupture of Membranes Diagnostics Clinical Diagnosis Supportive Tests o Transvaginal Cervical Ultrasound for diagnosis of short cervix o Cervicovaginal fetal fibronectin detection test: a positive test supports diagnosis of preterm labor Treatment Single course of antenatal steroids o Indication: 24-34 weeks gestation with risk of delivery within next 7 days o Improves fetal lung maturity and surfactant production Tocolysis: Administartion of tocolytics to inhibit uterine contractions and prolong pregnancy o Recommended for up to 48 hours to enable administration of antenatal corticosteroids in preterm labor o First Line: Beta adrenergic agonists, NSAIDs, or Calcium Channel Blockers o Second Line: Magnesium Sulfate o Contraindications Maternal drug contraindications Nonreassuring fetal CTG Intrauterine fetal CTG Intrauterine fetal demise Chorioamnionitis Preterm premature rupture of membranes Antepartum hemorrhage with hemodynamic instability Severe pre-eclampsia or eclampsia Lethal fetal anomaly Fetal Neuroprotection: Magnesium sulfate o Indication: If birth < 32 weeks anticipated o Decreases risk and severity of neurological diseases (cerebral palsy)
Antibiotics for Group B Streptococcus prophylaxis is recommended in preterm labor, preterm premature rupture of membranes and when GBS infection is evident Complications o Neonatal respiratory distress syndrome (RDS) o Bronchopulmonary dysplasia (BPD) o Patent ductus arteriosus (PDA) o Retinopathy of prematurity (ROP) o Necrotizing enterocolitis (NEC) o Periventricular leukomalacia (PVL) o Neurological disorders (e.g.,cerebral palsy, learning disabilities, developmental delays, ADHD) o Problems of homeostasis: apnea, bradycardia, hypothermia o Infection and sepsis (e.g., pneumonia) o Anemia of prematurity: impaired ability to produce adequateerythropoietin (EPO); should be suspected in premature infants with low hemoglobin o Intraventricular hemorrhage (IVH) Risk factors Birth weight < 1500 g and delivery before 32 weeks'gestation Maternal chorioamnionitis Hypoxia during or after birth Clinical features Usually occurs within 5 days ofbirth Most infants are asymptomatic, but saltatory (over several days) or, more rarely, catastrophic (over minutes to hours) courses are also possible Lethargy, hypotonia, irregular respirations, seizures, bulginganterior fontanelle Cranial nerve abnormalities (e.g., pupils react sluggishly to light) and changes in eyemovement (e.g., roving eye movements) Diagnosis Cranial ultrasound Since most patients are asymptomatic, screening ultrasounds are routinely performed in infants with a birthweight <
1500 g and delivery before 30 weeks gestation.
Prevention o Avoid modifiable risk factors o Manage cervical insufficiency o Vaginal progesterone supplementation Singleton pregnancy at 16-24 weeks gestation with a prior singleton preterm birth, regardless of cervical length and/or cervical cerclage Women < 24 weeks gestation with a short cervical length (< 25 mm) o Benign Breast Conditions Fibrocystic Changes Mastitis Fat Necrosis of the Breast Benign Breast Neoplasms Fibroadenoma Phyllodes Tumor INtraductal Papilloma Gynecomastia o Breast cancer Overview Noninvasive (in situ) carcinoma o Ductal Carcinoma in Situ o Lobular Carcinoma in Situ Invasive Carcinomas o Invasive Ductal Carcinoma o Invasive Lobular Carcinoma Inflammatory Breast Cancer Clinical Features Subtypes Paget Disease of the Breast Inflammatory Breast Cancer o Congenital TORCH Infections Toxoplasmosis, Other (Varicella-Zoster, Parvovirus, Listeriosis); Rubella; Cytomegalovirus; Herpes Simplex Virus Transplacental transmission occurs following primary infection of a seronegative mother during pregnancy → maternal IgM antibodies (which are unable to cross the placenta) form first, and protective IgG antibodies (which are able to cross the placenta) have not yet been formed → the infant is not protected from infection via the placenta! Congenital Toxoplasmosis
Toxoplasma gondii Transmission o Pregnant women o Fetus Clinical Features o First Trimester Chorioretinitis (form of posterior uveitis) Diffuse intracranial calcifications Signs of hydrocephalus o Second Trimester Subclinical or Mild Toxoplasmosis o Sequelae Epilepsy Diagnosis o Fetus: PCR for T. gondii DNA in amniotic fluid o Newborn: CT/MRI T. gondii specific IgM antibodies; PCR for T. gondii DNA Ophthalmological Evaluation for Chorioretinitis Treatment: o Pregnant Woman: Spiramycin o Fetal Infection: Pyrimethaminel, Sulfadiazine, and Folinic Acid o Newborn Infection: Pyrimethamine, Sulfadiazine, Folinic Acid Congenital Syphilis Pathogen: Treponema pallidum Transmission: Clinical Features o Early Congenital Syphilis (onset prior to 2 years) Hepatomegaly and Jaundice Rhinorrhea Maculopapular Rash on Palms + Soles Skeletal Abnormalities o Late Congenital Syphilis (onset after 2 years age) Facial features: saddle nose, frontal bossing, short maxilla Dental findings: Hutchinson teeth and mulberry molars Eyes and ears: interstitial keratitis, sensorineural hearing loss Skin: Rhagades, Gummas
Skeletal: Saber Shins (Anterior bowing of the tibia); Painless arthritis in knees and other joints Neurological: Cranial Nerve Deficits, ID, Hydrocephalus
Diagnosis o Newborn Initial: RPR or VDRL Confirmatory: Darkfield Microscopy or PCR o Fetus: Repeated Ultrasound Examinations showing placentomegaly, hepatomegaly, ascites, and hydrops fetalis Treatment: IV Penicillin G for both pregnant and newborns Prevention: Maternal screening Congenital and Newborn Listeriosis Pathogen: Listeria monocytogenes Transmission Clinical Features o Intrauterine transmission to the fetus Granulomatosis infatiseptica Severe systemic infection characterized by disseminated abscesses Most common findings: respiratory distress syndrome and skin lesions Signs of meningitis o Transmission during birth Late onset syndrome: Listeria meningitis/encephalitis Diagnosis: Culture from blood or CSF samples (pleocytosis) Treatment: IV Ampicillin and Gentamicin Prevention: Avoid soft cheese Congenital and Perinatal Varicella Infection Pathogen: VZV Transmission o Pregnant Women o Fetus: Vertical transmission during pregnancy or delivery Clinical Features o Congenital Varicella Syndrome (1st and 2nd trimester Hypertrophic scars (cicatricial skin lesions) Limb Defects (hypoplasia Ocular Defects (chorioretinitis, cataracts, microphthalmus) CNS Defects (Cortical atrophy, seizures, intellectual disability)
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o Neonatal Varicella Mild Infection (maternal exanthema > 5 days before birth) Sever Infection (maternal exanthema < 5 days before birth); hemorrhagic exanthema, encephalitis, pneumonia, or congenital varicella syndrome Diagnosis o Newborns: Usually clinical diagnosis based on appearance of skin lesions DFA or PCR of fluid collected from bilsters or CSF Serology o Fetus: PCR for VZV DNA (fetal blood, amniotic fluid) and ultrasound to detect fetal abnormalities Treatment o Acyclovir o Postexposure prophylaxis in newborn infants if the mother displays symptoms of varicella <5 days before delivery IgG antibodies (varicella zoster immune glbulin or VZIG) Hormonal Contraceptives Effects Estrogen o Hypothalamus: Decreased GnRH o Pituitary: Decreased LH inhibit ovulation, decrease FSH prevents ovarian folliculogenesis Progestin o Inhibits GnRH and LH secretion suppresses ovulation; inhibits endometrial proliferation; changes cervical mucus and impairs fallopian tube peristalsis inhibition of sperm ascension and egg implantation o Inhibits follicular maturation Antiprogestin: inhibits or delays ovulation by inhibiting the progesterone receptor The menstrual cycle and menstrual abnormalities Cervical Cancer *** LSIL = repeat pap smear twice at 12 month intervals in patients 21-24 years of age; negative twice patient may return to routine screening If pap smear shows ASC-H, HSIL, AGC colposcopy should be performed Pregnancy Loss Mifepristone = approved for induction of medical abortion Menopause Definitions Perimenopause –
Premonapause – 45-55 years of age Menopause – confirmed after 12 months of amenorrhea; 49-52 years Post menopause – time period beginning 12 months after last menstrual period Pathophysiology Decreased ovarian function Decreased estrogen and progesterone levels loss of negative feedback to gonadotropic hormones increased GnRH levels increased levels of FSH and LH in blood anovulatory cyclesbecome more and more frequent progressive follicular depletion Onset of menopause might be delayed and symptoms might be milder in obese women Clinical Features Irregular Menses Autonomic Symptoms o Increased sweating, hot flashes, heat intolerance o Vertigo; Headache Mental Symptoms o Impaired sleep; Depressed mood or mood swings o Anxiety/Irritability o Loss of Libido Atrophic Features o Breast tenderness and reduced breast size o Vuvlovaginal atrophy Atrophy of the vulva, cervix, vagina Weight Gain and Bloating Subtypes/Variants Surgical Menopause Diagnostics Decreased estrogen/progesterone FSH levels can fluctuate widely in perimenopause Lipid Profile: Increased total cholesterol; Decreased HDL Treatment Lifestyle Modifications o Hot Flashes: Avoid triggers; environmental temperature regulation o Atrophic vaginal symptoms: vaginal estrogen creams, rings, or tablets o Impaired sleep and/or hot flashes: exercise, acupuncture, relaxation techniques o Prevent osteoporosis: Smoking cessation, Adequate Vitamin D Intake
Hormone Replacement Therapy o Types Estrogen Therapy: If hysterectomy Estrogen + Progestin Therapy: If have uterus o Risks Cancer Unopposed estrogen = endometrial hyperplasia increased risk of endometrial cancer Estrogen plus progestin therapy increased risk of breast cancer Cardiovascular Disease: CHD, DVT, PE, Stroke Gallbladder Disease Stress Urinary Incontinence o Contraindications Vaginal Bleeding Pregnancy Breast Cancer/Endometrial Cancer Chronic Liver Disease Hyperlipidemia Recent DVT/Stroke Coronary Artery Disease Premature Menopause = before the age of 40 Ovarian Insufficiency Primary ovarian Insufficiency Secondary Ovarian Insufficiency o Function Disorder (ovarian endometriosis, PCOS, cancer of reproductive organs) o Genetic syndromes (Turner Syndrome, Swyer Syndrome, Androgen Insensitivity Syndrome o Autoimmune Diseases (Autoimmune lymphocytic oophoritis, Hashimoto’s Thyroiditis) o Infection: Measles, mumps, TB of genital tract o Smoking o Post-oophorectomy o Radiation/Chemotherapy o Prolonged GnRH o Induction of multiple ovulation in infertility o Secondary amenorrhea Most common causes = PCOS, Primary Ovarian Failure, Hypothalamic Amenorrhea, Hyperprolactinemia o Postpartum Hemorrhage Definition: Blood loss > 500 mL after vaginal birth; Blood loss > 1000 mL for cesarean section occurring at any time
Primary PPH: Blood loss within 24 hours Secondary PPH: Blood loss from 24 hours to 12 weeks postpartum Etiology Uterine Atony (most common) Abnormal placental separation Maternal injury during birth Bleeding diathesis Clinical Features: Anemia; Hypovolemic Shock Complications: Thromboembolism; Sheehan Syndrome; Uterine Atony Definition: Failure of the uterus to effectively contract and retract after complete or incomplete delivery of the placenta, which can lead to severe postpartum bleeding from the myometrial vessels Epi: responsible for ~80% of PPH Risk Factors: Multiparity, Multiple Pregnancy, Post Term Pregnancy, Instrumental Delivery, Anatomical Abnormalities, Large for gestational age newborn (> 4000 g); Poor myometrial contractions following prolonged or rapid and forceful birth Clinical Findings: Abnormal vaginal bleeding; Soft, enlarged (increased fundal height), boggy ascending uterus Diagnosis: Clinical Treatment: o General measures: Monotirong, adequate large bore IV access (>16 gauge) and an ice pack Fluid therapy (IV crystalloid solutions) Oxygenation o Uterine massage and external compression Bimanual uterine massage: clenched fist inserted into the anterior vaginal fornix and exerts pressure on the anterior wall of the uterus. The other hand is positioned externally and presses against the inner fist, located in the uterine body Tranexamic acid: ASAP to stop fibrinolysis and to reduce mortality Uterotonic agents IV oxytocin IM Carboprost tromethamine (If no asthma, prostaglandin analog) IM Methylergonovine (if no HTN or arterial disease) Prostaglandins such as misoprostol Speculum examination of the vagina and ervix to evaluate possible sources of extrauterine bleeding
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Intracavitary application of prostaglandin Exclude coagulation Uterotonics are first line treatment with decreased uterine tone Methylergonavine should be avoided if hypertensive Pre-Eclampsia Elevated blood pressure and proteinuria after 20 weeks gestation Management 24 hour urine for quantitative measurement of protein or a spot urine protein to creatinine ratio, blood pressure monitoring, and laboratory evaluation (H&H, Platelets, Serum Transaminase, Creatinine, Albumin, LDH, and Uric Acid) Vaccinations Tdap Between 27 and 36 weeks gestation to maximize the maternal antibody response and passive antibody transfer to the infant Pre-Eclampsia Place on magnesium sulfate to prevent seizures and labor should be induced immediately Postmenopausal estrogen plus progesterone Increases the risk for coronary heart disease, stroke, breast cancer, gallbladder disease, dementia, and venous thrombosis Dereased risk of fracture and reduced risk of endometrial cancer Painless Postmenopausal Bleeding Best initial test = transvaginal ultrasonography Endometriosis Diagnosis Definitive = Laparoscopy Treatment Medical Therapy o Mild to moderate: NSAIDs and Hormonal Contraceptives o Severe: GnRH Agonists and Estrogen-Progestin OCPs Surgical Therapy o First Line: Laparoscopic excision and ablation of endometrial implants o Second Line = Hysterectomy w/ or w/o bilateral salpingooophorectomy Precocious Puberty Central vs. Peripheral Differentiate with GnRH stimulation test o Increase in LH levels >5 mIU/mL following GnRH stimulation indicates central precocious puberty o LH levels <5 mIU/mL indicate peripheral precocious puberty
o Nausea and Vomiting in Pregnancy Vitamin B6 Doxylamine o Antepartum Hemorrhage Abruptio Placentae Partial or complete separation of the placenta from the uterus prior to delivery Epidemiology: most often in the third trimester Etiology: o Vascular: HTN; Pre-eclampsia/eclampsia o Abdominal Trauma o Sudden decrease in intrauterine pressure o Previous abruption o Maternal Age o Alcohol and Cigarette Consumption Clinical Features o Continuous, dark, vaginal bleeding of sudden onset o Abdominal pain or back pain; uterine tenderness o Hypertonic contractions; Premature labor o Fetal Distress Decelerations on fetal heart monitor o Vaginal exam contraindicated! Diagnostics: Clinical Diagnosis Treatment: o General Approach: hemodynamic control; correct coagulopathy; RhD Prophylaxis in RhD negative mothers o Specific approach according to severity Normal fetal findings and hemodynamically stable Up to 34th week of pregnancy o Fetal lung maturity induction with corticosteroids o If necessary, tocolysis (slows progression of cervical dilation) with nifedipine or beta 2 adrenergic agonist o Aim for normal delivery 34th to 36th week o Active Uterine contractions present: Vaginal Delivery o No contractions + no signs of fetal distress + bleeding stopped: expectant management After 36th week = deliver!!
Acute symptoms and live fetus = emergency cesarean section Acute symptoms + intrauterine fetal death = vaginal delivery through pharmacological uterine contraction inducers and opening of the amniotic sac Emergency C-section must be performed if maternal risk due to severe bleeding or slow progression of birthing process even in the case of intrauterine fetal death
Complications o Intrauterine Fetal Death (severe hypoxia) o Maternal DIC and hypovolemic shock o Couvelaire uterus Retroplacental hemorrhage may extend through the uterus into the peritoneum Myometreum weakened with possible subsequent uterine rupture during contractions Placenta Previa Definition: presence of the placenta in the lower uterine segment. May lead to partial or full obstruction of the neck of the uterus with high risk of hemorrhage (rupture of placental vessels) and birth complications Etiology o Maternal age >35; Multiparity; Short intervals between pregnancy o Previous curettage or C-section o Previous placenta previa Classification o Low lying Placenta = lower edge of placenta lies less than 2 cm from the internal cervical os o Marginal previa = placenta reaches internal cervical os o Partial previa = placenta partially covers internal cervical os o Complete previa = placenta completely covers the internal cervical os Clinical Features o Sudden painless bright red vaginal bleeding o Usually occurs during the 3rd trimester (before rupture of the membranes) and stops spontaneously after 1-2 hours and recurs during birth Diagnostics o Transvaginal ultrasound
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Treatment o Approach <37 weeks gestational age No active bleeding and no evidence of fetal distress: expectant Active bleeding or evidence of fetal distress: immediate delivery >37 weeks gestational age: immediate delivery o Expectant Management Hospitalization and observation for 48 hours If gestational age <34 weeks: fetal lung maturity induction with corticosteroids (betamethasone) If mild uterine contractions present: tocolysis with magnesium sulfate o Route of Delivery Lower segment cesarean section almost always preferred Ideally scheduled at 36-37 weeks gestation Vaginal birth could cause severe hemorrhage due to rupture of placental vessels Vasa Previa Definition: fetal vessels are located in the membranes near the internal os of the cervix Risk Factors: Placental anomalies; placenta previa; multiparity Clinical Features o Painless vaginal bleeding after rupture of membranes o Fetal distress Diagnostics o Transabdominal or Transvaginal ultrasound with color Doppler Treatment = Emergency Cesarean if signs of fetal distress Chancroid = Haemophilus ducreyi Chancre = primary syphilis Granuloma inguinale Painless nodules Klebsiella granulomatis Vulvar and Vaginal Cancer Screening High Blood Pressure = >40 years old Flexible Sigmoidoscopy = every 5 years Pap smear = every 3 years in women 21-29 years of age Fecal occult blood test = older than 50 years of age DEXA = all women > 65 year of age to screen for osteoporosis
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Colonoscopy = every 10 years starting at 50 years old Lipid profile = 45-75 years old with an ASCVD 10 year risk >10% Blood Glucose Screening = 40-70 years old HIV = 13-64 years Mammography = routine mammograms every 2 years in women 50-74 years of age. Endometriosis – diarrhea, dyschezia, and hematochezia Cervical trauma Postcoital bleeding Childbirth Genital Herpes Painful ulcers on an erythematous base Bilateral tender inguinal lymphadenopathy Ovarian Tumors *** Epithelial Tumors Cystadenoma/Cystadenomcarcinoma o Serous o Mucinous Endometrioid Carcinoma Germ Cell Tumors Teratoma o Mature Dermoid Cyst Struma Ovarii o Immature Dysgerminoma Yolk Sac Tumor of the Ovary Non-Gestational Choriocarcinoma Sex Cord Stromal Tumors of the Ovary Estrogen Producing o Granulosa Cell Tumor o Theca Cell Tumor Androgen Producing o Sertoli-Leydig Cell Tumors Ovarian Fibroma (Meig’s Syndrome) Metastasis Krukenberg Tumor Fetal Death Stillbirth = after 20 weeks gestation Placental abnormalities and obstetric complications were the largest category Breast Conditions Benign
Fibroadenoma o Thyroid and Pregnancy Pregnant woman with Graves Disease, Propylthiouracil is the therapy of choice during the first trimester. Propylthiouracil crosses the placenta less readily and is associated with a lower risk of birth defects when compared with methimazole. T3 and T4 levels should be checked every 3 weeks and the dose of the PTU should be decreased once the mother is euthyroid or only mildy hyperthyroid Methimazole during first trimester associated with congenital defects such as aplasia cutis, choanal atresia, esophageal atresia, and omphalocele During second and third trimester, methimazole is the preferred antithyroid drug because PTU associated with a higher risk of hepatocellular damage and agranulocytosis o Beta Blockers in Pregnancy Propranolol and Metoprolol safe during pregnancy Atenolol associated with an increased risk of fetal growth restriction. o Child Development and Milestones the FDA currently recommends that all exclusively breastfed infants receive 400 international units of vitamin Dsupplementation per day. This supplementation protects against hypocalcemia and rickets, a disease of bone deformities in children due to a deficiency of vitamin D. Rickets is characterized by impaired calcification of the bones, delayed closure of the fontanelles, frontal bossing, prominence of costochondral junctions (“rachitic rosary”), and genu valgum or genu varum. Children with rickets present with varying degrees of pain, poor growth, motor delays, and an increased risk of infections.
o Hypertensive Pregnancy Disorders Before 20 weeks gestation or prior to pregnancy or persisting beyond the 42 postpartum day is known as chronic or pre-existing hypertension Gestational Hypertension – induced after 20 weeks gestation Pre-eclampsia Gestational hypertension with proteinuria, renal insufficiency, thrombocytopenia, evidence of liver damage, and/or cerebral edema HELLP Syndrome = Hemolysis; Elevated Liver Enzymes; Low Platelets o Hemolysis (low hemoglobin; elevated LDH) o Abdominal pain due to stretching of Glisson capsule from hepatic swelling o Schistocytes Eclampsia – severe form of pre-eclampsia with convulsive seizures and/or coma Treatment o Anticonvulsive Therapy
o HPV
Magnesium Sulfate IV Antidote: Calcium Gluconate IV
16 and 18 responsible for the majority of cervical cancers; Facilitate the transcription of proteins that alter tumor suppression upon successful infection of cervical cells. E2F transcription factors that promote G1 to the S phase transition are normally inhibited by the retinoblastoma protein (Rb). High-risk types of HPV induce production of the oncoprotein E7, which binds and inactivates Rb protein, thereby increasing G1to S phase transition and cell proliferation. High-risk HPV also induces the production of the oncoprotein E6, which binds and inactivates the tumor suppressor protein p53.
Oncogenic HPV DNA induces the expression of the E6 protein, which binds and INACTIVATES p53 o Retinopathy of Prematurity Supplemental oxygen at birth Higher arterial oxygen tension in a premature infant inhibits vascularization of the peripheral retina leading to ischemia and production of VEGF leading to neovascularization and formation of new blood vessels that can cause hemorrhages, form fibrovascular membranes, and ultimately lead to retinal detachment or blindness o Prenatal Care Frequency of checkups Until 28th week of pregnancy = monthly 28th to 36th week = every two weeks From 36th week to birth = every week Initial examination (~10 weeks gestation) Personal and family history Gynecological examination Blood pressure Weight Laboratory analysis o CBC o Hemoglobin (anemia) o Blood typing (ABO and rhesus) Rhesus negative mothers receive prophylactic antiD immunoglobulins at 28 weeks to prevent alloimunization o Urine dipstick protein testing = proteinuria o Urine culture (asymptomatic bacteriuria) o Screen for STDs HIV Syphillis Hepatitis B surface antigen Chlamydia
All patients <25 years of age >25 years of age with high risk of infection Rubella and varicella antibody testing o PAP smear o Ultrasound assessment of the estimated gestational age through CROWN RUMP LENGTH General advice o Vaccination against seasonal influenza o Nutritional recommendations o Tdap vaccine during the 3rd trimester Subsequent examinations Weight monitoring Blood pressure monitoring First Trimester screening o Screening of chromosomopathies Physical examination o Fundal height and position of the fetus (identified through the first Leopold’s maneuver) o Fetal heart monitoring Laboratory o Group B Streptococcus screening during 35-37 week gestation (vaginal and rectal swab for culture and gram staining) o Repeat Hb from 24th week of pregnancy o 50 g one hour oral glucose challenge test at 24-28 weeks gestation Positive Screening = 100 g three hour oral glucose tolerance test (oGTT) to confirm diagnosis Glucose would increase transport into adpiocytes via GLUT-4 o Repeat rhesus screening = unsensitized Rh(D) negative women should receive anti(d) immune globulin Prenatal Diagnostics All pregnant women should be offered noninvasive aneuploidy screening tests (before 20 weeks gestation) o Testing maternal serum (specific biomarkers and ultrasound markers ) o Cell free fetal DNA testing All pregnant women should be given the alternative option to undergo invasive genetic testing (amniocentesis or CVS) Non-invasive Screening Test o First Trimester Combined Screening (11-13 weeks gestation)
Sonographic nuchal translucency Subcutaneous area between the skin and cervical spine of the fetus in the sagittal section. Nuchal translucency increases when fluid accumulates in the area.
B-hCG in maternal serum PAPP-A (pregnancy associated protein A Conditions Identified Down Syndrome/Trisomy 21: Increased hCG, decreased PAPP-A; thickened NT Trisomy 18: decreased hCG; Decreased PAPP-A; thickened NT Trisomy 13: Decreased PAPP-A; Increased NT Molar pregnancy: increased hCG Ectopic Pregnancy: decreased hCG Neural Tube Defects: Increased hCG o Quad Screen Test (15-20 weeks gestation) hCG; AFP; Estriol; Inhibin A o Triple Screen (15-20 weks gestation) hCG; AFP; Estriol Conditions identified Trisomy 21: elevated B-hCG; decreased AFP and free estriol; Increased Inhibin A Trisomy 18: decreased b-hCG; decreased AFP and decreased free estriol; Neural Tube Defects: normal B-hCG; Increased AFP; normal free estriol; normal Inhibin A Abdominal Wall Defects o Normal B-hCG; elevated AFP o Sequential Integrated Test (10-13 weeks gestation followed by 15-20 weeks gestation) First trimester combined test plus quad screen test o Cell Free fetal DNA testing (cff-DNA) From 10 weeks gestation onward Fetal DNA isolated from maternal blood specimen for genetic testing Invasive Diagnostic Tests o Chorionic Villus Sampling (10-13 weeks) Transcervical or transabdominal o Amniocentesis (15th week of pregnancy onwards) o Indications Early pregnancy
Sonographic appearance of fetal nuchal edem in 12th to 14th week of pregnancy Maternal age >35 years Suspected toxoplasmosis Late Pregnancy Determination of bilirubin levels in cases of rhesus incompatibility Monitoring of electrolytes in suspected renal failure Estimation of lung maturity in imminent preterm delivery via lecithin-sphingomyelin ratio Determination of insulin levels in gestational diabetes Drainage of excess amniotic fluid in polyhydramnios or amniotic fluid
o Neonatal Jaundice Physiological Jaundice Always unconjugated hyperbilirubinemia Pathological Neonatal Jaundice (conjugated or unconjugated jaundice) Conjugated o Decreased bilirubin excretion Intrahepatic cholestasis Sepsis Hepatitis A Hepatitis B TORCH Infection Cystic Fibrosis Extrahepatic Cholestasis Biliary Atresia Choledochal Cyst o Intrahepatic pathology Infectious Hepatitis Metabolic Diseases Dubin-Johnson Syndrome Rotor Syndrome Galactosemia Alpha-1-Antitrypsin Unconjugated o Hemolytic Infection or Sepsis Hematomas Hemolytic Disease of Newborn
RBC Structural Defects Ineffective Erythropoiesis Glucose-6-Phosphate Dehydrogenase Deficiency o Nonhemolytic Hyperbilirubinemia Syndromes Crigler Najjar Syndrome Gilbert Syndrome Glucuronyl Transferase Deficiency Increased Enterohepatic Circulation Subtypes and Variants Breastfeeding Jaundice o Insufficient breast milk intake lack of calories and inadequate quantities of bowel movements to remove bilirubin from body increased enterohepatic circulation increased reabsorption of bilirubin from the intestines o Clinical Features – within 1 week of birth o Treatment: Increase breastfeeding sessions Breast Milk Jaundice o Pathophysiology: increased concentrations of bglucuronidase in breast milk increased deconjugation and reabsorption of bilirubin persistence of physiologic jaundice o Clinical Features: Onset within 2 weeks after birth o Treatment: Continued breastfeeding and supplementation with formula feeds Phototherapy Indicated in total serum bilirubin >15 mg/dL in a 48 hour old term infant; >20 mg/dL in a 96 hour old infant Contraindicated in increased direct (conjugated) bilirubin Geriatic Medicine o Cachexia = inflammatory response with elevated cytokines + normal appetite in early stages of starvation o Starvation = refeeding causes a reversal of changes Pulmonology o COPD Chronic airway inflammation C: Dyspnea, Productive Cough, Expiratory Wheezing Diagnostics <70% FEV1/FVC Ratio DLCO normal in patients with chronic bronchitis Chronic low blood oxygen levels may lead to hypoxic pulmonary vasoconstriction causing an increase in pulmonary arterial
pressure and increased pulmonary vascular resistance and RVH eventually Right Heart Failure Management Continuous oxygen therapy in patients with severe hypoxemia (oxygen saturation <90% or a PaO2 <60 mmHg) Exacerbation: Prednisone + Albuterol; Macrolide antibiotic can also reduce the duration and severity of the exacerbation o Atelectasis Etiology Obsttuctive Atelectasis: airway obstruction (foreign body, mucus plug, malignancy) nonventilated alveoli reabsorption of gas in the poststenotic space lung collapse Non-obstructive Atelectasis o Compression Atelectasis = external space occupying lesion that compresses the lung forcefully pushes air out of the alveoli o Adhesive atelectasis: surfactant deficiency or dysfunction increases surface tension of alveoli Instability and collapse (ARDs or RDS in premature infants) o Cicatrization atelectasis: parenchymal scarring that leads to contraction of the lung (Chronic Destructive Lung Processes such as TB and fibrosis) o Relaxation atelectasis: loss of contact between parietal and visceral tissue (pneumothorax, pleural effusion) o Replacement atelectasis: all alveoli in entire lobe replaced by tumor (bronchioalveolar cell carcinoma) Post-Operative Atelectasis – most common post operative complications (after chest or abdominal surgery) often occurs within 72 hours of surgery Rounded atelectasis: folding of the atelectacic lung tissue (with fibrous bands and adhesions ) to the pleural (asbestosis) Clinical Features Small number of affected alveoli Asymptomatic Large number of affected alveoli acute dyspnea, chest pain, tachypnea, tachycardia, and cyanosis Dull percussion note, diminished breath sounds, and decreased fremitus over the affected lung Diagnostics ABG: hypoxemia, potential low PaCO2 and respiratory alkalosis o Non ventilated alveoli increased physiologic dead space Chest XR and CT: evidence of lobar collapse o Direc Signs: displacement of fissures and homogenous opacification of collapsed lobe
o Indirect Signs: Elevation of ipsilateral diaphragm Displacement of the hilum and mediastinal structures toward the affected side Loss of volume in the affected side of the chest Increased lucency and overinflation of the unaffected lung; silhouetting of the diaphragm or the heart border Bronchoscopy (diagnostic and therapeutic) o May be performed if the etiology is uncertain despite imaging and mucus plugs can be removed Treatment Analgesia Early mobilization Deep breathing exercises, directed coughing, and incentive spirometry o Pneumonia Pneumocystis pneumonia Etiology o Pathogen: Pneumocystis jirovecii o Risk Factors: HIV Infection CD4 < 200 /uL Primary Immunodeficiency Disorders (SCID) Malignancy (Leukemia, non-Hogdkin Lymphoma) Immunosuppressive Treatment Malnutrition Diagnostics o Laboratory Tests: CD4 count <200 /uL Elevated Beta-D-glucan Confirmatory Test: Microscopic identification of P jirovecii via bronchoalveolar lavage or induced sputum with methenamine silver staining and immunofluorescence Treatment o High Dose o Hospitalization based on CURB-65 score (Confusion, Urea >7, Respiratory Rate >30 min, BP Systolic <90 or Diastolic <60, Age >65; <1 = outpatient; >2 Hospitalization; >3 ICU Care o Pleural Effusion Diagnostics: Blunting of the costophrenic angle
o Bronchiolitis Lower Respiratory Tract Infection in which the bronchioles become inflamed because of a viral infection (RSV). Common during winter months in children <2 y/o Clinical Features URTI symptoms Respiratory distress (in infants) o Tachypnea, prolonged expiration o Nasal flaring, intercostal retractions o Cyanosis Poor feeding in breastfed infants Auscultatory findings: wheezing, crackles Clinical Diagnosis Treatment = Supportive (Hydration, Relief of congestion/obstruction monitoring) Hospitalize if: o Toxic appearance, poor feeding, dehydration, or lethargy o Marked respiratory distress, oxygen saturation <92% o Age <12 and/or history of prematurity o Heart, Lung, or Neurological Condition o Immunodeficiency Increased risk of developing asthma o ARDS o Chronic Cough Patients with chronic cough (>3 months) are treated empirically for UACS, GERD, and asthma. PFT is the first step in management Upper Airway Cough Syndrome Abnormally increased nasal mucus secretion that drips down the back of the throat and can lead to coughing, a feeling of obstruction in the throat, and throat clearing. Causes include allergies, cold temperatures, viral or bacterial infections, dry air, and certain medications. First-line treatment includes first-generation antihistamines (e.g., diphenhydramine). UACS was previously referred to as post-nasal drip syndrome. Obstructive Sleep Apnea
o o Obesity Hypoventilation Syndrome Diurnal alveolar hypoventilation Resulting daytime hypercapnia and respiratory acidosis with metabolic compensation (elevated bicarbonate) o Chronic Pulmonary Aspergillosis Clinical Presentation: Hemoptysis, Weight Loss, Productive Cough Diagnostics:
XRay – Monad Sign (Fungus bal in pre-existing lung cavity). Upper lobe mostly affected because of an increased concentration of oxygen o Moving from supine to prone or lateral recumbent demonstrates mobility of the fungus ball Laboratory Positive Sputum Culture or Positive Aspergillus IgG Serology
o Bronchiectasis Clinical Presentation: chronic cough, dyspnea, hemoptysis, copius amounts of sputum, crackles Exacerbated by acute respiratory tract infections Diagnostics: XRay: Fibrosis of the bronchial walls = tram track lines and increased translucency Confirmed by CT scan o Acute Tonsillitis Diagnostics Gold standard = throat culture for antibiotic sensitivity o Asthma *** Can be triggered by viral respiratory infections and is exacerbated by exercise Treatment Beta-2 agonists Inhaled corticosteroids Leukotriene pathway modifiers Omalizumab o Anti-IgE antibody that binds to serum IgE o Reduces serum levels of IgE to prevent binding of IgE to high affinity IgE Receptors (FCERI) on mast cells and basophils Methylxanthines Mast-Cell Stabilizers o Cancer Nodules on CXR CT Scan o <4 mm Follow up in 12 months o 4-6 mm 6-12 months o 6-8 mm 3-6 months o >8 mm PET scan Biopsy o CT guided transthoracic biopsy o Bronchoscopy with transbronchial biopsy Squamous Cell Carcinoma of the Lung Most common type of lung cancer in smokers Central located cavitary lesions
Associated with paraneoplastic syndromes (Hypercalcemia) Fatigue, Weight Loss, Hemoptysis o Cystic Fibrosis Etiology Defective CFTR protein (most common is DeltaF508 on chromosome 7) Pathophysiology Mutated CTFR misfolded protein retained protein in RER unable to reach cell membrane defective chloride channel inability to transport intracellular chloride ions across the membrane exocrine glands produce hyperviscous secretions accumulation of secretions and blockage of exocrine glands chronic inflammation organ damage Clinical Features Gastrointestinal o Meconium ileus o FTT o Pancreatic Disease Pancreatitis Exocrine Pancreatic Insufficiency Foul smelling steatorrhea Malabsorption Abdominal Distenion Diarrhea ADEK Deficiency o Liver and Bile Duct Abnormalities Cholecytolithiasis, Cholestasis Fatty metamorphosis of the liver eventually progressing to liver cirrhosis Biliary cirrhosis with portal hypertension o Intestinal Obstruction Abdominal distention Respiratory o Obstructive Lung Disease o Chronic Sinusitis – nasal polps may eventually develop o Recurrent or chronic productive cough and pulmonary infections with characteristic microorganisms Dangerous bacteria (Pseudomonas aeruginosa) Expiratory wheezing (obstruction), barrel chest, moist rales (pneumonia), hyperresonance to percussion Signs of chronic respiratory insufficiency: digital clubbing o Airway hyperreactivity Sweat Glands o Salty Tasting Sweat
Musculoskeletal o Kyphoscoliosis Urogenital o Urinary Nephrolithiasis, Nephrocalcinosis Frequent UTIs o Genital Males Obstructive azoospermia Vas deferens may also be absent Female Viscous cervical mucus may obstruct fertilization in females Diagnostics General o Best initial test is the sweat chloride test Diagnostic Criteria Neonatal Screening o Elevated Immunoreactive Trypsinogen (IRT) Detects elevated levels of IRT in heel-prick blood o DNA Assay Laboratory Tests o Quantitatve Pilocarpine Iontophoresis Chloride Levels > 60 mmol/L on two or more occasions are consistent with CF o DNA Analysis Prenatal – Via chorionic villus sampling or amniocentesis Postnatal/adult analysis o Nasal Potential Difference Test Supportive Tests o Stool: Decreased chymotrypsin and pancreatic elastase o Chest XR/CT: Hyperinflation o PFTs: Decreased FEV1:FVC ratio and Increased RV and TLC Treatment Symptomatic Management o Respiratory Hypertonic saline nebulization or dornase alpha (mucolytic agent) Bronchodilator Chest Physiotherapy Chronic Rhinosinusitis = Intranasal glucocorticoids Mucolytics (N-acetylcysteine) Chronic Respiratory Insufficiency Long Term Oxygen Inhalation Therapy
o Diet
Additional Sodium Chloride Intake High energy diet Pancreatic enzyme supplements Oral supplementation of lipophilic vitamins A, D, E, K Pulmonary Infections o Infants Staphylococcus aureus = IV Vancomycin o Adults Pseudomonas aeruginosa = Inhaled tobramycin Preventative Measures o Annual influenza vaccine for all CF patients > 6 months with inactivated influenza vaccine o Pneumococcal vaccine o Palivizumab: antibody for RSV for infants < 24 months Provides passive immunization to RSV infection Indication: infants at risk for severe bronchiolitis Complications Gastrointestinal o Meconium ileus Failure to pass the first stool in neonates CF (90%) Clinical Findings: Distal small bowel obstructions Bilious vomiting Abdominal Distention No passing of meconium or stool Diagnostic Abdominal X-Ray o Dilated small bowel loops, microcolon, Neuhauser Sign Treatment Enema with a contrast agent Respiratory o Hemoptysis o Allergic Bronchopulmonary Aspergillosis o Pulmonary Emphysema Pneumothorax Cor Pulmonale o Interstitial Lung Disease Excess collagen deposition in the extracellular matrix of the lung Diffuse thickening of the alveolar walls result in progressive fibrosis of the lung parenchyma, which in turn causes reduced vital capacity, and the dyspnea, chronic dry cough, and fatigue o Pleural Scarring
Pediatrics o Neonatal Thyrotoxicosis Usually resolves within 12 weeks when maternal TRAbs disappear Treatment includes methimazole and beta blocker Transplacental passage of TSH receptor antibodies o Vaccinations o Tetralogy of Fallot o Puberty Idiopathic Central Precocious Puberty Elevated GnRH levels Treatment = Leuprolide or Buserelin o Growing Pains o Legg-Calve-Perthes Disease o Fever Most common in any child younger than 29 days should undergo a complete sepsis workup and be admitted for observation Most common bacterial organism = Group B Streptococcus and Escherichia coli Broad empiric coverage with ampicillin and cefotaxmine recommended o RSV Bronchiolitis Upper respiratory tract infection followed by cough and signs of respiratory distress (nasal flaring, intercostal retractions, Rhinorrhea, Cough, Wheezing, Mild Tachypnea, Expiratory wheezes) Treatment = Hydration and Supplemental Oxygenation Nebulized hypertonic saline o Acute Otitis Media Treatment = Amoxicillin/Clavulanate Prophylactic antibiotics not recommended o Atopic Dermatitis Clinical Features Infantile AD o Eczema: over the cheeks, face, head, and extensor surfaces of the extremities that usually spares the diaper area (begin as cradle cap) o Dennie-Morgan Fold : increased folds below the eye Childhood AD o Eczema: Flexural creases (antecubital and popliteal fossae), skin folds, extensor surfaces of hands o Lichenified lesions (thickening of the skin with accentuated skin markings Adult AD
o Lichenified lesions and pruritis of flexor surfaces of the extremities o Also: Nummular eczema (coin shaped lesion) st Treatment = 1 line is topical corticosteroids
o Croup Swelling of the larynx causing a barking cough Treatment = Epinephrine then Oral dexamethasone o Whooping Cough Catarrhal stage = Viral URI Paroxysmal stage = severe coughing spells that occur in paroxysms followed by the inspiratory whoop Post-tussive emesis Nasopharyngeal culture and PCR Dermatology o Impetigo Etiology: Staphylococcus aureus: Bullous and nonbullous impetigo Strep pyogenes (GAS) Clinical Features Nonbullous impetigo o Lesions: Papules Small vesicles surrounded by erythema pustules that rupture oozing secretion that dries honey colored crusts heal without scarring Negative nikolsky sign o Localization: Face, especially around the nose and mouth Bullous impetigo Ecthyma Systemic Signs o Staphylococcal Scalded Skin Syndrome Etiology Staphylococcus aureus strains that produce exfoliative toxins o Toxins A and B cleave desmoglein 1 in the granular layer of the epidermis, thereby disrupting keratinocyte attachments o Vitiligo Autoimmune destruction of melanocytes o Psoriasis Epidemiology: Age of onset 20-40 years old Etiology: Polygenetic Infectious (B-hemolytic streptococci, staph, HIV); Mechanical Irritation; Drugs (Beta Blockers, Chloroquine, Lithium, Interferon) Pathophysiology
Increased proliferation of keratinocytes o Acanthosis: thickening of epidermis o Parakeratosis: retention of nucleated keratinocytes in stratum corneum T Cells Clinical Features Course: Relapsing with symptom free intervals Well-demarcated, erythematous lesions and silvery white scaling plaques o Mainly on scalp, back, elbows, and knees (Extensor surfaces) o Pruritis Involvement of nails o Nail pitting o Oil drop sign o Brittle nails o Onycholysis Subtypes o Psoriatic Arthritis Definition: Inflammation of joints Clinical Features Oligoarthritis Enthesitis (where tendons attach to bone) Tenosynovitis Dactylitis (sausage digit) Diagnostics Evidence of psoriasis Psoriatic nail dystrophy Negative rheumatoid factor Dactylitis Radiologic Signs o Pencil in Cup Deformity o Asymmetric Paravertebral Ossification Treatment NSAIDs Moderate to Severe: DMARDs Physical Therapy o Cutaneous Variants Plaque Psoriasis: symmetrically distributed, thick, scaly, erythematous lesions
Guttate psoriasis: size of drops of water; mainly in children and adolescents after streptococcal infection (URTI) Erythrodermic psoriasis: generalized erythematous lesion with diffuse scaling; lead to fever and dehydration Ivnerse psoriasis: may affect skin folds and flexural creases of large joints
Diagnostics o Koebner Phenomenon – skin injury lead to skin lesions typical of underlying condition o Auspitz Sign = small pinpoint bleeding when scales scraped off o Skin Biopsy Parakeratosis Munro microabscesses Acanthosis Spongiotic Dermatitis o Laboratory Tests Elevated ESR & CRP Treatment o Mild to Moderate: First Line: Moisturizers & Topical Medications Steroids; Vitamin D Derivatives (Calcipotriene); Tar Preparations; Retinoids; Vitamin A Derivatives o Moderate to Severe Topical Medications Systemic Agents (Methotrexate, Retinoid, Cyclosporine), Phototherapy o Severe Psoriasis Topical + Systemic Treatment Phototherapy Antiproliferative effects and antiinflammatory effects UVB PUVA (Psoralen + UVA) o Photodermatoses Zinc Oxide o Scabies Treatment: Permethrin
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Binds to voltage gated sodium channels to delay repolarization of neuron cell membranes which causes paralysis and death of the mite Contact Dermatitis Type IV Hypersensitivity Reaction Diagnosis = Patch Test Treatment Mild to Moderate = Topical corticosteroid, oatmeal bath, soothing lotion, wet ressing, topical antihistamine Severe = Systemic corticosteroids, Systemic Antihistamines Pityriasis Rosea Differential Diagnosis = Drug Eruptions, Secondary Syphilis, Guttate Psoriasis, Erythema MIgrans Lichen Simplex Chronicus Treatment Moisturizers and/or calamine lotion Topical glucocorticoids, calcineurin inhibitors, capsaicin, antihistamines Systemic H1 Antihistamines Benign Skin Lesions Vascular Skin Tumors Cherry Hemangioma o Epidemiology: Increases with Age o Pathophysiology: Proliferation of dilated mature capillaries o Clinical Features: Bright cherry red, dome shaped papules or macules Strawberry Angioma = benign vascular tumor of infancy/childhood Pyogenic Granuloma o Definition: Benign vascular tumor o Etiology: Associated with trauma and pregnancy o Clinical Features: soft, round, bright red tumor that bleeds easily o Diagnostics: Clinical o Treatment: Surgical Excision Hypertrophic Scars Definition: High fibroblast proliferation and collagen production as excessive skin tissue response to penetrating trauma; Does not grow beyond the boundaries of the original lesion Etiology: Imbalance in wound healing processes Clinical Features: Raised scar tissue; Pruritis Diagnosis: Clinical Treatment
o Medical Therapy 1st Line: Intralesional Steroid Injection o Surgery: Cryotherapy; Laser; Surgical Excision; Light Therapy Keloid Scars Caused by high fibroblast proliferation collagen production as excessive skin tissue response to typically small skin injuries GROWS BEYOND THE BOUNDARIES OF THE ORIGINAL LESION Does not regress spontaneously Recurs after resection Etiology: Imbalance in wound healing Clinical Features: Scar tissues of varying consistency that may be brownish-red in color; Pruritis; Localization: earlobes, face, neck Diagnostics: Clinical appearance of lesion Treatment: Same as for hypertrophic scars Warts Definition: Hyperkeratosis and hyperplasia of epidermis commonly caused by human papillomavirus Epidemiology: children and young adults Clinical Features o Common Warts (Verruca vulgaris) Localized to elbows, knees, fingers, palsm Appearance: skin colored or whitish, rough, scaly papules or plaques (cauliflower like appearance) o Flat Warts (Verruca Plana) Localized to face, back of hands, legs Appearance: Flesh colored, smooth papules, flat surface o Plantar Wart (verruca Plantaris) Localized to soles of the feet Appearance: Flesh colored, hyperkeratotic surface o Treatment: Salicylic Acid; 5-FU; Topical Retinoic Acid; Cryotherapy or Surgical Excision Seborrheic Keratosis Histology: Immature keratinocytes with small keratin filled cysts (horn cysts) Clinical Features: Multiple darkly pigmented papules/plaques, sharply demarcated and soft o Greasy, wax like stuck on appearance o May be irritated by external trauma or spontaneously o Localization: Trunk, back of hands, face, and neck Diagnosis: Treatment: Not necessary
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Dermatofibroma Definition: Fibroblast proliferation resulting in small, fibrous benign dermal growth Clinical Features: Asymptomatic; Slowly growing skin colored or brownish nodules of ~3-10 mm diameter Localization: lower extremities Diagnostics: Dimple Sign Nevus Lipoma Melasma Acanthosis Nigricans Solar Lentigo Cancerous Lesions Basal Cell Carcinoma Acne Rosacea Treatment = Doxycycline Tinea Capitis Treatment = Oral griseofulvin Intertrigo Skin inflammation caused by skin on skin friction. Facilitated by moisture trapped in deep skinfolds where air circulation is limited Treatment: keep skin clean and dry, evaluate for infection Tinea versicolor Commonly caused by increased growth of Malssezia globose Abnormal pigmentation involving the trunk, back, and/or abdomen following a history of travel to a humid and warm place such as the Caribbean Lesions become more apparent after UV exposure or tanning because the surrounding skin gets darker, which provides greater contrast to the lesions KOH Preparation Epidermoid Cyst Firm, mobile, slow-growing nodule arising from the epidermis Autoimmune Blistering Diseases Pemphigus Vulgaris Autoimmune blistering caused by autoantibodies against desmosomal adhesion proteins including desmoglein 3 and desmoglein 1 Medicatinos such as captopril, glyburide, thiol containing drugs (penicillamine) and phenol containing drugs (cephalosporins, rifampicin, phenobarbital, aspirin) can induce the formation of these autoantibodies
Desmosomal adhesion proteins enable keratinocyte adherence, damage to these proteins causes intraepidermal bullae formation and positive Nikolsky sign Occur first on mucous membranes and an become confluent or erode to form painful ulcers o Collection of Dermatological Disorders Sebaceous and Epidermoid Cysts Cat Scratch Disease Millaria Nummular Eczema Livedo reticularis Xeroderma pigmentosum Pseudofolliculitis barbae Most common in black males Pathophysiology o Extrafollicular penetration: hair enters interfollicular epidermis after it exits the follicular orifice o Transfollicular penetration: hair penetrates the dermis before exiting the follicular orifice Clinical Findings o Firm, hyperpigmented, tender, pruritic papules and pustules on hair growing areas Treatment o Cessation of shaving; alternative hair removal techniques o Adjunctive: Topica (retinoids, corticosteroids, antimicrobials) Albinism Rheumatology o Rheumatoid Arthritis *** Presentation Affects wrists and other extremity joints that have a high ratio of synovium to articular cartilage Diagnostics Anti-CCP antibody (highly specific marker) IgM Autoantibodies targeting Fc region of IgG Imaging o Early: Soft Tissue swelling o Late: Joint Space Narrowing, Erosions of Cartilage and Bone; Treatment Acute Inflammatory Therapy o Indication: Acute Attack o Glucocorticoids
o NSAIDs and COX-2 Inhibitors Long Term o Methotrexate Folic Acid given 24-48 hours after to minimize side effects o Biologic Therapy TNF-alpha inhibitors (adalimumab, infliximab, etanercept) Complications Atlanto-axial Subluxation o Pain/Stiffness of the Neck o Cervical Radiculopathy o Diagnostic: Extension/Flexion X-rays of the Cervical Spine o Ankylosing Spondylitis Etiology 90-95% HLA-B27 Clinical Features Articular symptoms o Back and Neck Pain Morning stiffness that improves with activity o Limited mobility of the spine (especially forward lumbar flexion) o Inflammatory enthesitis Extra-Articular Manifestations o Most common: Unilateral anterior uveitis o GI Symptoms o Prostatitis o Fatigue o Restrictive Pulmonary Disease Diagnostics Differential Diagnosis Treatment NSAIDs TNF-Alpha Inhibitors (Etanercept) Complications Uveitis o Presentation = Painful red eye with conjunctival injection, photophobia, and sluggishly reacting pupil o Treatment = Topical corticosteroids o Sarcoidosis Epidemiology: Bimodal Distribution
Pathophysiology: T Cell Dysfunction and increased B Cell Activity; Formation of non-caseating granulomas commonly within the lungs and lymphatic system Clinical Features Acute Sarcoidosis o High fever, malaise, lack of appetite, weight loss o Pulmonary dyspnea, cough, chest pain o Extrapulmonary: Arthritis, anterior uveitis, erythema nodosum Chronic Sarcoidosis o Pulmonary (Most Common) Dry cough, exertional dyspnea o Extrapulmonary Common Peripheral Lymph Nodes Iridocyclitis Skin: o Lupus pernio o Scar Sarcoidosis o Other Manifestations: MSK, Bone Lesion, Nervous, Heart, Liver, Kidney, Spleen (GRUELING – granulomas, arthritis, uveitis, erythema nodosum, lymphadenopathy, interstitial fibrosis, engative TB, gammaglobulinemia o Granulomatosis with Polyangitis c-ANCA o Drug Induced Lupus SHIPP Hydralazine; Procainamide o Gout Etiology Deposition of urate crystals in the joints Hyperuricemia predisposes to gout (end product of purine metabolism that is renally excreted) o Insufficient excretion or increased production leads to hyperuricemia Primary Hyperuricemia Idiopathic extracellular supersaturation of uric acid Secondary Hyperuricemia Decreased uric acid excretion o Medications (pyrazinamide, aspirin, loop diuretics, thiazides, niacin) o Chronic Renal Insufficiency; Lead nephropathy o Ketoacidosis (starvation, Diabetes mellitus, lactic acidosis) Increased uric acid production
o High cell turnover (Tumor Lysis Syndrome, Hemolytic Anemia, Psoriasis, Myeloproliferative Neoplasms) o Enzyme defects (Lesch Nyhan, PRPP Synthetase overactivity, von Gierke Disease o High Protein Diet o Obesity Combined decreased excretion and overproduction (high alcohol consumption) Pathophysiology Uric acid has poor water solubility Clinical Features Asymptomatic Stage Acute Gouty Arthritis o Usually monoarticular Acute severe pain with overlying erythemia, decreased ROM, swelling, and warmth More likely to occur at night, typically waking the patient Joint may present with desquamation of the overlying skin o Location: Peripheral small joints in the lower extremities Podagra (MTP inflammation) Gonagra (knee) Chiragra (finger joints, especially the thumb) Intercritical Stage Chronic Gouty Arthritis o Progressive joint destruction o Tophi formation Multiple painless hard nodules with possible joint deformities Bone tophi – urate crystal deposition in bones Soft tissue tophi – urate crystal deposition in the pinna of the external ear, subcutis, tendon sheaths, or synovial bursas Diagnostics Arthrocentesis o Needle shaped negatively birefringent monosodium urate crystals o WBC >2000 /uL with >50% neutrophils Laboratory Tests o Elevated serum uric acid o Typical in acute attacks: Increased WBC and ESR Imaging
o Ultrasound – Double contour sign (hyperechoic monosodium urate crystals) o MRI – Excellent to detect tophi formation o CT – bone erosions o XRay – Chronic gout only – punched out lytic bone lesions
Treatment Acute Gout Attack o NSAIDs (Indomethacin, Naproxen, Ibuprofen) Aspirin contraindicated because it inhibits uric acid excretion, thereby delaying the cessation of symptoms o Colchicine Inhibition of microtubule polymerization – inhibits phagocytosis of urate crystals, leukocyte activation and micragion, and cell chemotaxis Use in patients who cannot tolerate NSAIDs (CKS or GI Ulcers) or glucocorticoids Side effects: Diarrhea, Nephrotoxicity, and Myelosuppression o Oral Glucocorticoids Indications: No response or contraindication to NSAIDs and Colchicine o Proton Pump Inhibits should be given to patients being treated with both NSAIDs and Glucocorticoids to avoid gastrointestinal ulcers o Intra-articular corticosteroid Indications: single joint involvement Chronic Gout o General Measures: Weight Loss, Purine Restricted Diet, Reduce Alcohol Consumption; High fluid intake; Consume dairy products, Vitamin C, and Coffee o Medical Therapy Indications Recurrent Gout (more than 2 gout attacks per year) Uric Acid Nephropathy Tophi Development Serum Uric Acid >9 mg/dL General Approach Delay initiation of urate lowering medications until ~2 weeks after an acute attack has resolved
Urate lowering medications may trigger or prolong an acute gout attack st 1 Line Treatment: Xanthine Oxidase Inhibitors (Allopurinol) Mechanism of Action: Reversible inhibitor of xanthine oxidase hypoxanthine and xanthine will not be degraded into uric acid Side Effects: Skin Reaction; TEN; SJS Indications: Chronic Gout and/or hyperuricemia >9 mg/dL; Hyperuricemia Prophylaxis (TLS) Contraindications: Acute Gout Attack Previous hypersensitivity; Kidney Disease (Dose adjustment) Interactions: Increased bone marrow toxicity with purine analog (6mercaptopurine and azathioprine) nd 2 Line Treatment (Benzbromarone, Probenecid, Lesinurad) Mechanism of Action: Inhibition of Uric Acid Reabsorption along renal tubules --. Increased renal elimination Notable side effects: Urolithiasis; GI symptoms; Rash Indication: In combination with allopurinol Contraindications: Acute Gout Attack; Kidney Disease Recombinant Uricase (Rasburicase) Mechanism of Action: Catalyzes the breakdown of uric acid to allantoin (water soluble) Side Effects: Infusion Reactions (premedications administered as prophylaxis e.g. hydrocortisone and antihistamine) Indications: Rapid relief desired; No benefit from 1st and 2nd line Contraindications: Acute Gout Attack; G6PD Deficiency (causes hemolytic crisis due to production of hydrogen peroxide) Allopurinol + Azathioprine leads to INCREASED BONE MARROW TOXICITY
During first 2 weeks of an acute gout attack, treatment with allopurinol should not be initiated or altered can lead to urate crystal mobilization which worsens the symptoms!
Complications o Nephrolithiasis: Uric Acid Stones o Uric Acid Neprhopathy Chronic Tubulointerstitial Nephropathy with Monosodium urate crystal deposition in the stroma of the kidney Inflammatory process Clinical Presentation: Hypertension; Renal Failure (rare) Acute Uric Acid Nephropathy: Possible in TLS
o Pseudogout Paroxysmal joint inflammation due to calcium pyrophosphate crystal deposition (calcium pyrophosphate dehydrate) Epidemiology (Adults >50 y/o) Etiology: mostly idiopathic Secondary form: joint trauma, familial chondrocalcinosis, hyperparathyroidism, hemochromatosis, gout, hypophosphatemia Clinical presentation Often asymptomatic Acute (pseudogout attack): monoarthritis (rarely oligoarthritis), mostly affecting the knees and other large joints (hips, wrists, and ankles) Diagnostics Arthrocentesis: o Polarized light microscopy: detection of rhomboid shaped, positively birefringent CPPD crystals o Synovial fluid: 10,000 – 50,000 WBCs/ uL with >90% neutrophils X-Ray Findings: Cartilage calcification of the affected joint (chondrocalcinosis) o Fibrocartilage (meniscus, annulus fibrosus of IV disc) and hyaline cartilage (joint cartilage) Test for hypercalcemia Treatment Asymptomatic: No treatment Symptomatic Treatment o Best initial treatment: NSAIDs o Alternative: Colchicine or Intra-articular Corticosteroids Arthroscopic Lavage
Possible Joint Replacement o Inflammatory Myopathies Etiology Polymyositis: cell mediated cytotoxicity against unidentified skeletal muscle antigens, chiefly affecting the endomysium Dermatomyositis: idiopathic or paraneoplastic antibody-mediated vasculopathy associated with malignancy (NHL; Lung, Stomach, Colorectal, Ovarian) Clinical Features Proximal Muscle Weakness o Pelvic and Shoulder Girlde muscles most common o Difficulty combing hair, standing up, climbing stairs o Dysphagia Muscle Tenderness Cutaneous Manifestations of Dermatomyositis o Gottron Papules Extensor surface of the hands o Heliotrope rash: erythematous rash on the upper eyelids o Midfacial erythema o Photosensitive poikiloderma Shawl sign V Sign Cutaneous Manifestations of Inclusion Body Myositis o Asymmetric muscle involvement of both proximal and distal muscle groups Diagnostics PM Diagnostic Criteria o Proximal Muscle Involvement o Positive laboratory findings o EMG suggestive of inflammatory myopathy Laboratory Test o Increased muscle enzymes Increased CK and Aldolase Elevated Enzymes: Myoglobin, LDH, AST, ALT o Inflammatory Markers: Increased ESR, CRP, Leukocytosis o Antibodies ANA MSA: Anti-Mi-2; Anti-Jo-1 Other o EMG o Imaging o Muscle Biopsy
PM: Cell Mediated Inflammation, Intrafascicular Infiltration of Cytotoxic CD8+ T cells DM: Antibody Mediated Inflammation involving parafascicular and perivascular infiltration with plasmacytoid dendritic cells and B lymphocytes Inclusion Body Myositis: Endomysial Inflammation + Intramuscular Vacuoles
Infectious Disease o HIV *** Prophylaxis CD4 <200 = Trimethoprim Sulfamethoxazole for Pneumocystis pneumonia CD4 <100 = Toxoplasma gondii CD4 <50 = Mycobacterium avium intracellulare complex Neurosurgery o CSF Rhinorrhea Leakage of CSF from the anterior nares o Meningioma Neurology o Neurocutaneous Syndromes (Phakomatosis – neuro-oculo-cutaneous syndromes = derived from ectoderm) Autosomal Dominant or Spontaneous Neurofibromatosis Type I o Melanocyte Dysfunction Café au lait spots Lisch Nodules Axillary and inguinal Freckling (Hyperpigmentation) o Multiple Neurofibromas Soft Painless Nodules Seizure when CNS involved o Scoliosis o Bone Involvement o Optic Gliomas o Associated with Pheochromocytoma and Wilms Tumor Neurofibromatosis Type II o Bilateral Vestibular Schwannomas (acoustic neuromas) ipsilateral tinnitus, hearing loss, vertigo o Multiple cerebral and spinal tumors o Meningioma Pheochromocytoma o Contraindications Selective beta blockers, Metoprolol Tuberous Sclerosis
o Intellectual Disability o Infantile Spasms or Seizures o Skin Manifestations Adenoma sebaceum Ash leaf spots Shagreen patch o Small Benign Tumor Brain tumors Hamartoma Giant Cell Astrocytoma Cardiac rhabdomyoma Renal cysts of renal angiomyolipoma Ungual fibroma Von Hippel-Lindau Disease o Hemangioblastomas o Bilateral Renal Cell Carcinoma o Pheochromocytoma Autosomal Recessive: Ataxia Telangiectasia Progressive cerebellar ataxia Telangiectasias on the face and conjunctivae Decreased immunocompetence Febrile Seizures Definition: Seizures associated with fever (>100.4 F) in absence of CNS infection, metabolic abnormalities, or history of afebrile seizures Epidemiology: Peak incidence common between 6 months and 5 years of age Clinical Features o Simple Febrile Seizure Generalized, usually tonic-clonic seizures Symmetrical Duration: <15 minutes; Maximum of one seizure within 24 hours Age: 6 months to 5 years Post-Ictal Phase Quick return to normal Confusion and drowsiness may be present for a short period of time Prolonged drowsiness or deviated eyes may be a sign of other etiology o Complex Febrile Seizure Focal onset Pronounced on one side of the body
Transient hemiparesis and speech impairment Duration: > 15 minutes; > 1 seizure within 24 hours Diagnostics o Simple febrile seizures do not require specific diagnostic workup o Focus on identifying the cause of fever o Complex febrile seizures always require specific investigative tests (EEG and imaging) o Determine cause of fever Physical Exam UA and Urine Cultures Blood Tests (CBC w/ diff, CRP, Electrolytes, Blood Glucose) Imaging to locate source of infection (U/S, X-Ray) Toxicology if suspected o Additional diagnostic steps: for complex febrile seizures and/or abnormal neurological exam Lumbar puncture Exclude meningitis and/or herpes encephalitis EEG Imaging Treatment o Uncomplicated seizures resolve after a few minutes spontaneously o Abortive Therapy Treatment of Choice: IV Lorazepam Repeat medication after 5 minutes o Reassure caregivers and provide information o After a febrile seizure, initiate antipyretic therapy (NSAIDs and acetaminophen) at an early stage (temperatures from 100.4 F) as they restore the central thermoregulatory setpoint back to normal by reducing the synthesis of prostaglandin E2 Non-inherited: Sturge Weber Syndrome Port wine stain Vascular malformation of chroic and CNS o Early onset glaucoma o Epilepsy or epileptic spasms in infancy o Intellectual Disability o Myotonic Syndromes Epidemiology: Myotonic Dystrophy Type I: Congenital, Juvenile, or Adult; Myotonic Dystrophy Type II: Usually Adult Onset Clinical Features Myotonic Dystrophy
o Meningitis o Leukocoria “Cat’s eye pupil” All patients with leukocoria should undergo prompt fundoscopic examination to rule out retinoblastoma White mass in the retina on fundoscopy o Retinoblastoma Clinical Features Leukocoria (white fundal reflex Strabismus Painful, red eye Loss of vision Retinal Detachment (later stage) Diagnostics Fundus examination: grayish white, vascularized retinal tumor Molecular genetic testing of leukocytes for mutations in the RB1 gene recommended for all patients with retinoblastomas Differential Diagnosis Leukocoria is considered a retinoblastoma until proven otherwise; a fundus examination of an infant presenting with leukocoria should be conducted as quickly as possible Treatment Low Risk Retinoblastoma: o Cryotherapy; Photocoagulation; Brachytherapy High Risk Retinoblastoma: Chemotherapy If eye not salvageable o Enucleation o Adjuvant systemic chemotherapy Increased risk for osteosarcoma o Parkinson’s Disease Treatment First Line = Pramipexole or Ropinirole o Trigeminal Neuralgia Treatment Conservative Therapy o Drug of Choice: Carbamazepine Surgical Treatment: Microvascular Decompression or Ablative Therapy o Cerebellar Syndromes Etiology Acute o Infarction, TIA o Head Trauma, Edema, Hemorrhage o Infections
Adult: VZV, EBV, Lyme, Tertiary Syphilis, Malaria Children: VZV, Coxsackievirus, Parvo B19, HHV-6, HAV, Enterovirus, Measles, Mumps, Lyme Disease o Medications, toxins, poisons: Barbiturates, benzodiazepines, heavy metals, chemotherapy Subacute/Chronic o Alcoholism o Intracranial tumors o Vitamin Deficiency: Vitamin B12, Vitamin B1 (Wernicke) o Paraneoplastic Cerebellar Degeneration o Genetic: Spinocerebellar Ataxia, Friedrich Ataxia, Ataxia Telangiectasia o Multiple Sclerosis o Wilson Disease Clinical Features Cerebellar Ataxia o Gait Ataxia: Abnormal wide based, and unsteady gait; irregular, uncoorindated movements of the limbs Romberg Test: Unable Unterberger: Positive o Truncal Ataxia: Inability to sit upright and/or stand without support Dysmetria and tremor (postural, action, intention tremor) o Finger to Nose Test: Patient unable to touch tip of nose with index finger o Heel Knee Shin: inability to slide heel of one foot down the shin of the opposite leg; heel will deviate to alternate sides Dysdiadochokinesia o Inability to perform rapidly alternating agonisticantagonistic movements o Rapid alternating movement test: unable to rapidly screw in an imaginary light bulb simultaneously with both hands Rebound phenomenon o Patient bends arm at elbow resisting examiner’s pull on the forearm. Sudden release of arm by examiner results in overshooting movement o Indicates impaired coordination between muscular agonists and antagonists Pronator Drift: Stretch supinated arms out in front of them at shoulder level; arm ipsilateral to the lesion will pronate and drift upwards Dysarthria (Scanning speech): Words are broken down into separate syllables
Oculomotor dysfunction, including nystagmus Acute cerebellar hemorrhage: occipital headache, neck stiffness, vomiting, nystagmus, gait ataxia Muscular hypotonia Vertigo Diagnostics Neuroimaging (CT/MRI) Laboratory Testing: CBC, Electrolytes, B12, B1 Genetic Testing ∂P o Headache Cluster Headache Prevention = Verapamil Vasoconstriction of cranial blood vessels in response to high oxygen concentration and hypocapnea Abortive Therapy o Oxygen o Sumatriptan Migraine Epidemiology o Peak incidence 30-40 years old Etiology o Potential triggers = emotional stress; weather changes; food and beverages; poor sleeping habits Pathophysiology o Not fully understood o Vascular dysregulation (vasodilation and vasospasms); Dysregulation of pain sensitization in trigeminal system o Cortical spreading depression Clinical Features o Recurrent attacks and may occur with aurua o Prodrome (24-48 hours before) Excessive yawning; Difficulties writing or reading o Aura Visual disturbances PHotopsia, Central Scotoma, Flashing Lights, Fortification spectra (star like zig zags) Paresis Impaired sensibility, paresthesia Dizziness Aphasia o Headache Typically unilateral
4-24 hours, rarely lating over 72 hours Progression of pulsating, throbbing, or pounding pain Accompanied by photophobia, phonophobia, and nausea/vomiting o Prodrome Exhaustion/Euphoria Muscle weakness Anorexia or Food Cravings Diagnostics o With aura >2 attacks; without aura >5 attacks o Physical exam to exclude red flag symptoms o Neuroimaging should be used in unusual clinical presentation Treatment o Abortive Therapy Limit stimuli Mild to moderate = NSAIDs Severe = Triptans (sumatriptan) or ergotamine Sumatriptan o 5-HT1 receptor agonist (vasoconstriction of dilated cranial and basilar arteries) o Indicated in migraine and cluster headaches o Contraindicated in coronary artery disease, peripheral artery disease, HTN, and pregnancy/breastfeeding Initial therapy if nausea/vomiting = antiemetics (prochlorperazine, chlorpromazine) o Prophylactic Therapy Non-pharmacological = lifestyle (exercise, avoid triggers) Pharmacological Indications = frequent attacks >3/month; Long lasting (>12-24 hours); Abortive theray fails Agents = o Beta blockers (metoprolol, propranolol, bisoprolol) o Tricyclic antidepressants (amitriptyline) o Anticonvulsants (topiramate or valproate)
o Calcium channel blockers (conflicting study results) o Syncope Aortic Stenosis Vasovagal Orthostatic o Stroke *** May be ischemic or hemorrhagic Transient Ischemic Attack – Temporary, focal cerebral ischemia result in brief neurologic deficits lasting <24 hours Stroke = acute neurologic condition caused by an acute cerebrovascular event Ischemic = cerebral infarction due to insufficient cerebral blood flow (more common) Etiology o Large artery atherosclerosis (secondary to HTN0 o Embolic stroke Cardiac emboli (A Fib) Infectious emboli Ahteroemboli Paradoxical embolism (R->L cardiac shunt) o Small Vessel Occlusion Lipohyalinotic thickening of the small vessels – occlusion of small, penetrating arteries that originate directly from large vessels o Other causes Watershed Coagulopathies Hemorrhagic = Due to hemorrhage (Intracerebral or subarachnoid) Intracerebral = within the brain parenchyma o Hypertension o Cerebral Amyloid Angiopathy – deposition of beta amyloid in vessel walls result in focal damage with formation of microaneurysms and elevated risk of rupture o Ruptured AVM Subarachnoid = into the subarachnoid space o Ruptured aneurysm (usually in circle of Willis) Round saccular aneurysm at major branches in large arteries Clinical Features Sudden onset of focal neurologic deficits and nonspecific symptoms SAH = worst headache of my life, neck stiffness, pupils not reactive to light
By vessel o MCA o ACA o PCA
Contralateral sensory loss and paralysis in the arms, lower half of the face, and lower limbs Gaze deviates TOWARD the side of infarction Contralateral homonymous hemianopia without macular sparing Aphasia Contralateral paralysis in lower limbs >> upper limbs
Visual field defects (Contralateral homonymous hemianopia with macular sparing) Contralateral hemisensory loss (thalamic involvement) Memory deficits o Penetrating Arteries (Lacunar syndromes) o Vertebrobasilar Vertebrobasilar Insufficiency Ipsilateral cranial nerve deficits Vertigo, drop attacks, tinnitus, Gait ataxia Brainstem Wallenberg (Lateral medullary syndrome) Medial medullary syndrome Weber Syndrome Millard Gubler Syndrome Foville Syndrome o Extracranial Arteries Internal Carotid Artery Ipsilateral amaurosis fugax Common carotid artery Horner’s Syndrome Vertebral Artery Wallenberg Syndrome By affected region o Pure motor stroke Most common type of lacunar stroke (Posterior limb or the angle of the internal capsule) Contralateral hemiparesis o Pure sensory stroke Thalamus
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Contralateral numbness and paresthesia of the face, arm, leg Sensoriomotor stroke THalamocapsular area Hemiparesis and ipsilateral sensory impairment Ataxic hemiparesis Corona radiate or the posterior limb of the internal capsule Dysarthria clumsy hand syndrome Base of the pons Dysarthria, dysphagia, contralateral facial and hand weakness Hemiballismus Subthalamic nucleus Contralateral involuntary large and fierce flinging of the arm or leg
Others o Putamenal Stroke Contralateral hemiplegia, hemisensory loss and gaze palsy, ipsilateral deviation of the eyes, stupor, and coma o Cerebellar Stroke Cerebellar signs (ataxia, nystagmus, slurred speech) NO hemiparesis o Thalamic Stroke Contralateral hemiparesis and hemisensory loss Miotic and unreactive pupils, upgaze palsy with gaze deviation away from the side of the lesion (wrong way eyes) o Pontine stroke Decreased level of consciousness or coma, quadriplegia, ocular bobbing, facial palsy, dysarthria Lateral pontine Syndrome Infarction of the lateral pons Descending tracts – corticospinal tract (contralateral hemiparesis) Lateral spinothalamic tract – contralateral loss of pain and temperature sensations Cerebellar tracts – ipsilateral limb and gait ataxia Cranial nerve nuclei
Facial nerve nuclei Descending sympathetic tract o Ipsilateral Horner’s Syndrome
Initial Evaluation o Clinical assessment and history Identify risk factors Signs of the affect vessel or region Onset of symptoms o Rule out other causes of neurologic deficits o Rule out atrial fibrillation via ECG o Laboratory studies (CBC, Coagulation studies, Electrolytes, Serum troponin) Neuroimaging o Noncontrast cranial CT detects acute hemorrhage Cannot reliably identify early ischemia Ischemia Acute Ischemia (6-12 hours after) o Hyperdense occluded vessels o Parenchymal hypodensity o Effacement of the sulci and loss of corticomedullary differentiation 12-24 hours after = hypodense Days after = hyperdense Hemorrhage Hyperacute = Hypodense lesion Acute o Hyperdense lesion o Hpodense perifocal edema o Possible midline shift o MRI Diffusion weighted imaging identifies ischemia earlier than CT (3-30 minutes after onset) Ischemia T1 = Hypointense T2 = Hyperintense Hemorrhage Hyperacute o T1 = Hypointense o T2 = Hyperintense Acute = Hypointense o Other studies o CT, MRA o Digital Subtraction Angiography
o Transcranial Doppler Sonography Lumbar Puncture o Definitive diagnostic test for SAH o Yellowish (Xanthochromia) or red discoloration o Increased RBCs, Increased WBCs, Increased protein Histologic changes in infarcted region o 12-24 hours = red neurons (eosinophilic cytoplasm + pyknotic nucleus) o 1-3 days after = neutrophils = liquefactive necrosis o 3-5 days = macrophages (microglia) o 5-15 days = reactive gliosis (astrocytes) + vascular proliferation o >15 days = Glial scarring Treatment o Acute stabilization/resuscitation and intensive care moitoring Maintain sufficient oxygen supply Maintain blood glucose levels within 140-180 mg/dL o Control elevated ICP and/or cerebral edema; monitor for signs of brain herniation Head elevation to 30 degrees Hyperventilation Administer IV mannitol NO GLUCOCORTICOIDs o Maintain cerebral perfusion Antihypertensive treatment Ischemic Stroke = PERMISSIVE HYPERTENSION; Treat severe hypertension when >220/120 mmHg Hemorrhagic stroke = Maintain blood pressure <160 mmHg NITRATES SHOULD BE AVOIDED MAY INCREASE INTRACRANIAL PRESSURE o Cardiac monitoring for at least 24 hours o Ischemic Stroke Treatment Intravenous rTPA Inclusion criteria = within 3 hours of symptom onset; >18 years old Exclusion criteria o Pre-existing conditions Previous intracranial hemorrhage Head trauma or stroke within the past 3 months
Recent intracranial or intraspinal surgery Intracranial neoplasm o Current Conditions Intracranial bleeding Active internal bleeding Hypertension >185/110 mmHg Anticoagulation (prolonged PTT or INR >1.7) Low platelet count Intra-arterial thrombolysis Intra-arterial administration of tPA close to the vessel occlusion within 6 hours of symptom onset Mechanical thrombectomy Indicated in patients with proximal large artery occlusion in the anterior cerebral circulation Antiplatelet therapy ALL ischemic stroke patients Contraindicated for 24 hours after thrombolytic therapy Drug of Choice = Aspirin o Hemorrhagic Stroke Treatment Intracerebral Hemorrhage Reverse anticoagulation Cranitomy and Clot evacuation o Indications Signs of brain herniation Brainstem compression Obstructive hydrocephalus Hemorrhage extension >3 cm (patients with hemorrhage in basal ganglia or internal capsule should generally not undergo surgical clot removal) Subarachnoid Hemorrhage Reverse Anticoagulation Prevent vasospasm (ischemic stroke) with IV calcium channel blocker (nimodipine)
Neurosurgery = surgical clipping or endovascular coiling
Epilepsy Childhood Absence Epilepsy o Characteristics 5-10 seconds up to 100x per day Brief unresponsiveness without convulsions Amnestic during seizures; Appear to be staring or daydreaming with lip smacking, eye fluttering, or head nodding No postictal phase o EEG = 3 hz spikes and waves in all regions of the brain o Treatment: 1st line: Ethosuximide Inhibition of the low threshold T-type Ca2+ channels in the thalamus that are thought to be responsible for the rhythmic 3 Hz discharge seen nd 2 line: Sodium valproate 3rd line: Lamotrigine Resting Tremor Etiology o Parkinson’s Disease o Drug Induced Parkinsonism o Progressive Supranuclear Palsy Clinical Features o Asymmetric resting tremor (4-6 hz) o Pill rolling of hands that subsides with voluntary movements o Worsens with emotional stress o Reduced with target directed movement Diagnosis: Clinical Treatment: Dopaminergic agents Postural Tremor Essential Tremor o Bimodal distribution (teens and 6th decade of life) o Etiology: Positive family history (AD) o Clinical Features Localization (hands, head) Bilateral postural tremor with 5-10 hz Slowly progressive Worse with voluntary movement Resolves at rest
Improves with alcohol consumption o Diagnosis: Clinical o Treatment 1st Line = Propranolol 2nd Line = AnticonvulsantsPrimidone (anticonvulsant barbituate) Physiologic Tremor o Etiology: Stress, exercise, fatigue Drug Induced (Valproate, Lithium, SSRI, TCAs, Beta2 agonists, Levothyroxine, Immunosuppressants daclizumab, basiliximab; Withdrawal from alcohol benzos, barbituates, marijuana; medical conditions hyperthyroidism pheochromocytoma or Lewy Body Dementia; Magnesium deficiency, hypoglycemia, Wilson’s Disease o Clinical Features Fine bilateral postural tremor in the hands and fingers Occurs while holding a position against gravity o Diagnosis: Underlying disease o Treatment: Reversible once underlying cause is treated Orthostatic Tremor o Etiology o Clinical Features Long periods of standing leading to trembling feeling o Diagnostics: Synchronized shaking; EMG detection of 1318 hz tremor o Treatment: Symptom based; Clonazepam, Gabapentin Intention Tremor Etiology o Cerebellar stroke, tumor or trauma o Multiple Sclerosis o Drug Induced Alcohol/Lithium o Wilson’s Disease Clinical Features o Coarse hand tremor frequency < 5 Hz o Worse with goal directed movemented o Other cerebellar signs dysmetria (abnormal heel to shin and finger to nose testing); Dysdiadochokinesia (inability to perform rapid alternating hand movements); Dysarthria; Nystagmus; Abnormal Gait
Diagnostics o CT/MRI: Cerebellar Lesion o IgG in CSF if Multiple Sclerosis o Screen for alcohol abuse or toxic lithium blood levels Additional Types of Tremors Flapping Tremor (asterixis) o Etiology Metabolic Encephalopathy (alcohol or hepatic) Wilson’s Disease o Clinical Features Irregular, high oscillations when arms and hands are extended o Diagnostics: Determine cause of encephalopathy o Treatment Psychogenic Tremor o Etiology Conversion Disorder o Cilnical Features Mostly postural tremor with sudden onset Worsens under direct observation and diminishes with distraction o Diagnostics: Of exclusion o Treatment: Cognitive Behavioral Therapy o Amyotrophic Lateral Sclerosis Destruction of UMN and LMN in multiple body segments Neurological deficits in cranial nerves progressing to other body segments (weakness, fasciculations, hyperreflexia) o Neurological Examination Upper Motor Neuron Lesion Pronator Drift o Multiple Sclerosis Treatment Interferon Beta o Prevents exacerbations by downregulating expression of MHC molecules on antigen presenting cells, inhibiting T cell proliferation and decreasing the level of proinflammatory cytokines while increasing the level of regulatory cytokines Natalizumab o Increased risk of developing progressive multifocal leukoencephalopathy caused by the JC virus
o Decreases migration of lymphocytes to the CNS and increases the risk of PML o Brain Tumors Primary Brain Tumors Pediatric Primary Brain Tumors: o Most common benign: pilocytic astrocytoma o Most common malignant: medulloblastoma o Pilocytic Astrocytoma o Medulloblastoma o Ependymoma Develop from lining of the ventricular system and if grow large enough, will cause obstruction of CSF flow and consequent dilation of the ventricles proximal to the obstruction (obstructive hydrocephalus) Most common location for ependymoma in children and last ventricle along the CSF pathway and all ventricles become dilated with trapped CSF o Craniopharyngioma o Pinealoma Adult Primary Brain Tumors o Most common benign: meningioma o Most common malignant: glioblastoma multiforme o Glioblastoma multiforme o Meningioma o Hemangioblastoma o Schwannoma o Oligodendroglioma o Pituitary Adenoma Brain f Etiology o Most common: Lung Cancer o Breast Cancer o Malignant melanoma o Renal Cell Carcinoma o Colorectal Carcinoma Clinical Features o Acute or subacute onset of symptoms due to rapid tumor growth Headaches Cognitive Deficits Focal Neurological Deficits Diagnostics: o Neuroimaging
Well circumscribed tumors at the junction of gray and white matter and/or watershed areas of the arterial system
Treatment o Limited Brian Metastases: Surgical resection or stereotactic radiosurgery o Extensive brain metastases: stereotactic radiosurgery, whole brain radiotherapy, or chemotherapy
Urology o Cystoscopy Indications Hematuria o Microhematuria (not grossly visible) o Macrohematuria (grossly visible) o Urinalysis = >3 erythrocytes/HPF or >5 erythrocytes/ uL Recurrent UTIs Suspected Interstitial Cystitis o Infertility Defect in Sertoli cell tight-junction proteins (claudins and occludins) can result in infertility due to impairment of the blood-testis barrier. Spermatozoa enter the bloodstream which are recognized by serum immune cells foreign and thus anti-sperm antibodies are created. o Incontinence Stress Incontinence Etiology o Urethral Hypermobility o Intrinsic Sphincter Deficiency Clinical Features o Loss of urine during physical activity that leads to increased intra-abdominal pressure (laughing, sneezing, coughing, exercising) o No urge to urinate prior to the leakageDe Urge Incontinence Mixed Incontinence Total Incontinence Overflow Incontinence o Nephrolithiasis Calcium Oxalate Stones = Dumbbell Shaped Stones Prevent by adequate hydration o Scrotal Abnormalities Communicating Hydrocele Patent processus vaginalis Increases with crying or Valsalva
Often reducible o Urinary Tract Infections Urinary Tract Infections Nephrology o AKI Acute Interstitial Nephritis Allergic reaction to medications (penicillin, sulfa antibiotics, diuretics, NSAIDs, PPIs) Rash, eosinophilia, and other symptoms o Rhabdoymyolysis Elevated levels of CK or myoglobuin with Dipstick positive for blood but negative for RBCs o End Stage Renal Disease Morphine should be avoided (toxic metabolites morphine-3-glucuronide and morphine-6-glucuronide) causing neuroexcitatory effects (confusion, sedation, respiratory depression, and myclonus) o Renal Artery Stenosis Hyperplasia of juxtaglomerular cells Increased renin from the juxtaglomerular apparatus o Pyelonephritis o Tubulointerstitial Diseases Acute Tubulointerstitial Nephritis Allergic Interstitial Nephritis Crystal Induced Acute Kidney Injury Chronic Tubulointerstitial Nephritis Analgesic Nephropathy Myeloma Kidney Renal Papillary Necrosis o Nephrotic Syndrome Massive Renal Loss of Protein (>3.5 g/day) Hypoalbuminemia Edema Hyperlipidemia Resulting in: Edema, Hypercoaguability (Antithrombin III Deficiency), and an increased risk of infection (loss of immunoglobulin) Laboratory Findings: Hyperlipidemia and Fatty Casts on Urinalysis Most common = Focal Segmental Glomerulosclerosis and Membranous Nephropathy Etiology Minimal Change Disease o Most common cause of nephrotic syndrome in children o Associated with tumors (Hodgkin Lymphoma) o LM: No Change; EM: Effacement of Foot Processes
o Treatment: Responds well to corticosteroids Focal Segmental Glomerulosclerosis o Most common in black people o Associated with heroin, HIV, obesity, and Sickle Cell Disease o LM: Segmental Sclerosis; IM: IgM and C3 inside sclerotic regions; EM: Effacement of foot processes o Treatment: ESRD if untreated; Immunosuppressive treatment Membranous Nephropathy o Most common in white populations o Antibodies to phospholipase A2 receptor o Associated with infections (Hepatitis B and C, SLE, Tumors, and Medications) o LM: Glomerular Capillary Loops and Basement Membrane appear thickened o Treatment: Corticosteroids Membranoproliferative Glomerulonephritis o Immunoglobulin mediated Associated with SLE, Hepatitis C, Monoclonal Gammopathy o Complement Medicated Dense Deposit Disease and C3 Glomerulonephritis o Findings Immunoglobulin Mediated Low serum complement IM: IgG deposits on basement membrane Complement Mediated Low serum C3 levels: patients with dense deposit disease often have IgG antibodies (nephritic factor against C3 convertase, leading to persistent complement activation IM: C3 deposits on basement membrane Both: EM Basement membrane thickening, GBM splitting (tram track appearance) o No single treatment Diabetic Nephropathy o LM: Thickening of the Glomerular Basement Mebrane; Nodules within glomeruli (Kimmelstiel Wilson Nodules) o Treatment is of underlying disease Amyloidosis o Can be associated with multiple myeloma
o LM: Congo red stain shows apple green birefringence under polarized light o Treatment: Melphalan; Corticosteroids Lupus Nephritis o ANA; Anti-DNA Antibodies Pathophysiology
Clinical Features
Structural damage of glomerular filtration barrier → massive renal loss of protein → reactively increased hepatic protein synthesis o Loss of negative charge of GBM → loss of selectivity of barrier (especially for negatively charged albumin) o Podocyte damage and fusion (sign of nephrotic syndrome) → non-selective proteinuria If protein loss exceeds hepatic synthesis (usually with a loss of protein > 3.5 g/24hours) → hypoproteinemia/hypoalbuminemia, initially both normal GFR and creatinine o Decreased serum albumin → ↓ colloid osmotic pressure→ edema (especially if albumin levels < 2.5 g/dl) o Elevated lipoproteins to compensate the loss of albumin→ ↑ cholesterol and triglycerides → lipiduria (fatty casts) o Decreased levels of antithrombin III (AT III) and loss of fluid into the extravascular space (“thickening” of the blood) → hypercoagulability o Loss of IGs → increased risk of infection o Loss of "transport proteins" → vitamin D deficiency, possible thyroxine deficiency, altered pharmacodynamicsof drugs Marked edema: typically starting with periorbital edemaand later pitting edema Weight gain Possibly frothy urine Hypertension Hypercoagulable state with increased risk of thrombosisand embolic events (e.g., pulmonary embolism, renal vein thrombosis) Increased susceptibility to infection Symptoms of hypocalcemia
Diagnostics
Urinalysis o Dipstick (commonly used for screening) : usually shows ≥ 3+ protein o 24-hour urine collection or spot urine (confirmatory tests): Heavy proteinuria (> 3.5 g/24h) While 24-hour urine collection is more precise, a spot urine is usually more practical in a clinical setting. o Urine sediment: Nephrotic sediment Proteinuria Lipiduria, fatty casts (hyaline casts with fat globule inclusions and proteins) appear as “Maltese cross” sign under polarized light Renal tubular epithelial cell casts Blood o ↓ Total serum protein, albumin, IGs, AT III o ↑ Cholesterol, triglycerides
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Protein electrophoresis: ↓ albumin and γ-zone, ↑ α2- and β-zone Possibly ↑ creatinine and/or BUN
Indication: To confirm diagnosis or in patients with nonspecific disease pattern Minimal change disease Because minimal change disease has a very good prognosis, a renal biopsy is generally not performed unless treatment fails. Structural defect of the podocytes Light microscopy: no changes (→ "minimal change") Electron microscopy: effacement of the foot processes Focal segmental glomerulosclerosis (FSGS): damage to the podocytes Electron microscopy: effacement of the foot processes Immunofluorescent microscopy: IgM and C3 insidesclerotic lesions Light microscopy: segmental sclerosis and loss ofpodocytes Membranous nephropathy (MN): deposition of antibodiesbetween podocytes and the basal membrane Electron microscopy: subepithelial dense deposits, also known as "spike and dome" appearance Immunofluorescent microscopy: subepithelial deposits of immune complexes and complement Light microscopy: thickening of glomerular capillary loops and basal membrane Membranoproliferative glomerulonephritis:immunemediated proliferation of the mesangium Electron microscopy: thickening and splitting of the glomerular basement membrane ("traintrack"appearance) Immunofluorescent microscopy: IgG deposits on basement membrane
Treatment General = o Low sodium low protein diet o Start with ACE Inhibitor or Angiotensin II Blockers/Sartans o Diuretics to reduce edema o Treat hypercholesterolemia with statins o Substitute Vitamin D if deficient o Consider thrombosis prophylaxis o AT III Deficiency = Heparin is ineffective Disease Specific o Minimal Change Disease = Glucocorticoids for 12 weeks o Focal Segmental Glomerulosclerosis Glucocorticoids; Cyclosporine or Tacrolimus o Membranous Nephropathy
Glucocortioids + Cyclosporine/Tacrolimus or Cyclophosphamide o Mebranoproliferative Glomerulonephritis No clear recommendation Complications Thrombotic Complications o Deep Vein Thrombosis o Renal Vein Thrombosis Atherosclerotic Complications o Abnormal lipid metabolism in combination with a hypercoagulable state leads to an increased risk of atherosclerotic complications o Presentation: Myocardial Infarction; Stroke End Stage Renal Disease Prognosis o Nephritic Syndrome ** Terminology Diffuse: All glomeruli affected Focal: Only a number of glomeruli affected Global: Entire glomerulus Segmental: only part of the glomerulus affected Proliferative: increased number of cells in the glomerulus Sclerosing: scarring of the glomerulus Necrotizing: cell death within the glomerulus Crescent: Accumulation of cells (macrophages, fibroblasts, epithelial cells) in bowman’s space Presentation Hematuria with acanthocytes RBC casts Proteinuria (<3.5 g/day) Mild to moderate edema Oliguria (500 ml/24 hours) Azotemia (nitrogenous waste) Hypertension Sterile Pyuria (WBCs in urine) Pathophysiology Glomerular filtration barrier o Initial segment – fenestrated glomerular capillary endothelium prevents large proteins from passing through o Second segment – glomerular basement membrane contains a negative charge produced by heparan sulfate
o Final segment – visceral epithelial cells produce/maintain the GBM and contain intercellular junctions created by podocytes that prevent further protein loss Damage to the glomeruli disruption of glomerular filtration barrier nephritic or nephrotic syndrome
Causes Poststreptococcal glomerulonephritis IgA Nephropathy Granulomatosis with polyangiitis (Wegener’s) Microscopic polyangiitis Churg-Strauus Syndrome Goodpasture Syndrome (Anti-GBM) o Autoantibodies gainst noncallagenous domain of the alpha-3 subunits present only in certain tissues (lungs, kidney) Alport Syndrome (Hereditary nephritis) Thin Basement Membrane Disease Rapidly Progressive Glomerulonephritis Lupus Nephritis
Hematology o Hypersensitivity Reactions Type I Anaphylaxis Type II Type III Type IV o Congenital Immunodeficiency Disorders Hyper IgM Syndrome Defect in the CD40 ligand At risk for pneumocystisi o Henoch Schonlein Purpura Tetrad: Palpable Purpura, Arthrlagia, GI Symptoms, Renal Disease Deposition of IgA immune complexes in vascular walls activates complement system, leading to vascular inflammation and damage Involvement of renal capillaries and mesangium often leads to hematuria, often with RBC casts o Chemotherapeutic Agents Vincristine Side Effects: neurotoxicity within 4-5 weeks of therapy o Decreased intestinal motility (constipation) and mixed sensory and motor neuropathy (numbness and tingling then decreased deep tendon reflexes) o Thrombocytopenia
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Purpura Vasculitis causes o Meningococcal Infection o DIC o Henoch Schonlein Purpura (IgA Nephropathy) ITP o IgG antibodies against GpIIb/IIIa receptors on platelets Anemia Microcytic Anemia Iron Deficiency Anemia o Causes: Premenopausal women = Menstrual blood loss o Serum iron and transferrin saturation decreased; TIBC increased; o Clinical Findings: Koilonychia Anemia of Chronic Disease o Serum iron decreased; TIBC and transferrin saturation decreased or normal; Low reticulocytes; Low iron o Normal MCV o Treatment: Oral Prednisone therapy DVT OCPs decrease protein S levels MGUS Serum M protein < 1.5 g/dL Lower back pain, anemia, and M-spike = osteolytic lesion workup ADAMTS13 Treatment = Plasma exchange therapy + Glucocorticoid Thalassemia Alpha thalassemia Determined by the number of missing alleles Cis deletion common in Asian populations Deletion of 3 alleles = causes fetal gamma globin chains to tetramerize and form Bart’s hemoglobin (gamma4) instead of Hemoglobin alpha2, gamma2 Beta Thalassemia Major Frequent blood transfusions = prone to developing secondary iron overload due to high iron content of red blood cells; Decreased transferrin/TIBC levels; elevated transferrin saturation Folate Deficiency Pathophysiology
→ ↓ DNA synthesis → megaloblasticerythropoiesis → megaloblastic anemia (+ ↓ inother cell lines) → ↓ methionine + ↑ homocysteine → endothelial damage (→ ↑ risk of cardiovascular disease +thromboembolic events)
During fetal development: → nucleotide synthesis impairment → neural tube defects → Aberrant DNA methylation → increased risk of cancer
o Hereditary Spherocytosis Defective RBC proteins in the RBC cytoskeleton membrane spectrin/Ankyrin Continuous loss of the outer lipid bilayer and a decrease in erythrocyte surface area, which creates sphere shaped erythrocytes with decreased membrane stability RBCs susceptible to phagocytosis by splenic macrophages, which leads to anemia Bone marrow compensates for RBC loss with increased RBC production which can result in folate deficiency as folate is used up during DNA synthesis Elevated MCHC Jaundice, Splenomegaly Extravascular hemolysis Patients with hemolytic anemia should receive daily folic acid supplementation to prevent megaloblastic anemia Detection with Eosin-5-maleimide binding test specific for hereditary spherocytosis Increased risk of cholecystitis o Lymphoma (Leukopenia WBC <4,500/uL) Non-Hodgkin Lymphoma Types o B Cell Lymphoma Low Grade (CLL) Small Lymphocytic Lymphoma Hairy Cell Leukemia Waldenstrom’s Macroglobulinemia Follicular Lymphoma MALT Lymphoma High Grade Burkitt Lymphoma Diffuse Large B-Cell Lymphoma Precursor B Cell Lymphoblastic Lymphoma Mantle Cell Lymphoma o T Cell Lymphoma Indolent: Mycosis Fungoides Aggressive: Adult T Cell Lymphoma Cutaneous T Cell Lymphoma Precursor T Cell Lymphoblastic Lymphoma
Clinical Features o Painless LAD o Splenomegaly, Hepatomegaly o Extranodal Disease o B Symptoms (Weight Loss, Fever, Night Sweats) o Fatigue; Bone Marrow Involvement (Anemia, Bleeding, Increased susceptibility to infections) Stages o Ann Arbor Staging System o Classification Limited Disease: lymph node involvement limited to one side of the diaphragm Advanced Disease: lymph node involvement on both sides of diaphragm Diagnostics o Blood Tests CBC (WBC, Anemia, Thrombocytopenia) Serum Chemistry (Elevated LDH, Hypercalcemia) Virus Serology o Histology Excisional Lymph Node Biopsy o Imaging X-Ray and CT required for staging o Further Tests IHC: B Cell Lymphomas: CD20 Positive T Cell Lymphomas: CD3 positive Lumbar Puncture with CSF Examination in case of Primary CNS Lymphoma Neurologic Signs/Symptoms HIV-Positive Patients Treatment o Low Grade NHL = Limited Stage Radiation Therapy Advanced Stage Palliative (Polychemotherapy to slow progression) o High Grade NHL Curative Polychemotherapy o CHOP Regimen (Cyclophosphamide, Hydroxydaunorubicin, Oncovin- Vincristine, Prednisolone) If B Cell add Rituximab o Primary CNS Lymphoma = Intrathecal Methotrexate + Chemotherapy
o Hairy Cell Leukemia: Chemotherapy with Cladribine or Pentostatin o Burkitt Lymphoma: Similar to ALL o CLL Hodgkin Lymphoma Categories: o Classical HL (CHL) Nodular Sclerosis Mixed Cellularity Lymphocyte Depleted Lymphocyte Rich o Nodular Lymphocyte Predominant HL (NLPHL) Epidemiology: Bimodal Distribution Etiology o Strong association with EBV o Immunodeficiency o Autoimmune Diseases (RA, Sarcoidosis) Clinical Features o Painless Lymphadenopathy Cervical Lymph Nodes > Axillary Lymph Nodes > Inguinal Lymph Nodes Mediastinal Mass Splenomegaly or Hepatomegaly o B Symptoms Night Sweats, Weight Loss, Fever > 100.4 F o Pel-Ebstein Fever (Intermittent Fever) o Alcohol Induced Pain (highly specific for HL) o Pruritis Stages o Stage 1: 1 lymph node o Stage 2: One side of diaphragm o Stage 3: both sides of diaphragm o Stage 4: Disseminated spread Diagnostics Blood Tests o Elevated or decreased WBCs o Anemia o Eosinophilia Serum Chemistry o Increased LDH o Hypercalcemia Histology o Required diagnostic step
o Lymph Node Excision Reed Sternberg Cells (Pathognomic for HL) Polynuclear Giant Cells (originating from B Cells CD15/CD30 positive) Inflammatory background Granuloma Formation Imaging o Chest XRay or CT Scan o Bone Scintigraphy or PET-CT Pathology Classical Hodgkin Lymphoma (CHL) o Nodular Sclerosing Subtype (Most common; Good Prognosis) o Mixed Cellularity (30% of cases) o Lymphocyte Rich Classical HL (Rare; Good Prognosis) o Lymphocyte Depleted (Very Rare; Bad Prognosis) Nodular Lymphocyte Predominant HL (Rare; Very Good Prognosis) Treatment Early Stage (I and II): Combination of chemotherapy and radiation therapy o Most widely used is ABVD (Adriamycin-Doxorubicin, Bleomycin, Vinblastine, Dacarbazine) Advanced Stage o Threee possible treatments: ABVD Stanford V BEACOPP o Leukemia (increase in premature leukocytes that are subsequently released into the bloodstream) Acute Leukemia (no maturity) Epidemiology o ALL = Peak incidence 2-5 years Most common malignant disease in children 80% are lymphocytic o AML = Peak incidence 65 years 80% during adulthood are myelogenous Etiology o ALL Linked to infection with HTL virus Genetic Down Syndrome Philadelphia Translocation (9;22) NF1
o AML
Ataxia Telangiectasia
Environmental Benzene Ionizing Radiation Tobacco; Chemotherapy Drugs Genetic/Chromosomal Down Syndrome T(15;17) Translocation APML M3 Fanconi Anemia Philadelphia Translocation Myeloproliferative Myelodysplastic Diseases Osteomyelofibrosis Chronic Myelogenous Leukemia
Classification o AML = FAB Classification Based on appearance of cells M3 = APL Auer Rods o ALL (cytogenetic criteria) B Cell ALL Early Pre-B Common Pre-B Mature B T Cell ALL Pre-T Intermediate-T Mature T Pathophysiology o Two hit hypothesis 1st clonal proliferation of a lymphoid or myeloid stem cell 2nd impairs normal hematopoietic differentiation Clinical Features o Fatigue, pallor, weakness (anemia) o Bleeding (petechiae, epistaxis, hematoma – thrombocytopenia) o Hepatomegaly and/or splenomegaly (leukemic infiltration) o Headache, visual field changes, CNS symptoms o Fever o AML Symptoms
Leukemia Cutis (nodular skin lesions with purple or gray-blue color) Gingival Hyperplasia (AML M4 and M5) o ALL Symptoms Painless LAD Fever, Night Sweats, Unexplained Weight Loss Bone Pain Diagnostics o Lab Tests CBC Peripheral Blood Smear Increased Uric Acid and LDH Bone Marrow Aspirate/Biopsy Immunophenotype CSF Analysis o Imaging CXR = Mediastinal Widening Abdominal Ultrasound = Organ Enlargmenet Treatment o Chemotherapy Induction Therapy (reduction of tumor cell count) Re-Induction Therapy (similar to induction) Consolidation Therapy (destruction of remaining tumor cells) Maintenance Therapy (maintaining remission) o Chemotherapeutic Drugs ALL Induction Therapy: Vincristine, Glucocorticoids, Asparaginase In philadelphia chromosome mutation t(9;22) BCR-ABL Tyrosine Kinase Inhibitor (imatinib) AML Induction Therapy: Cytarabine and Anthracyclines (Danorubicin) o AML M3 = All Trans Retinoic Acid t(15;17) o Preventative CNS Treatment o Supportive Therapy o Allogenic Stem Cell Transplant Complications o Tumor Lysis Syndrome Prognosis
Chronic Leukemia (Partial maturity) CML o Definition: Granulocytes = neutrophil, basophil, eosinophil Cells divide too quickly o Epidemiology: 50-60 years o Etiology: Idiopathic; IR; Aromatic Hydrocarbons o Pathophysiology: Philadelphia Chromosome Reciprocal translocation between chromosome 9 and 22 fusion of ABL gene with the BCR gene on chromosome 22 encodes a BCR-ABL non receptor tyrosine kinase Inhibits physiologic apoptosis and increases mitotic rate Genetic Changes o Clinical Features Chronic Phase Persist for up to 10 years Weight Loss, Fever, Night Sweats, Fatigue Splenomegaly No swollen lymph nodes Accelerated Phase Erythrocytopenia: Anemia Thrombocytopenia: Petechial Bleeding Neutropenia: Infection and Fever Extreme Pleocytosis o Infarctions: Splenic and Myocardial Infarctions, Retinal Vessel Occlusion o Leukemic Priapism o Terminal Phase: Myelofibrosis Extreme Splenomegaly Blast Crisis (Terminal Stage of CML) Symptoms resemble acute leukemia Rapid progression to pancytopenia o Diagnostics Peripheral Blood Analysis CBC/Blood Smear o Extreme Leukocytosis (>500,000 /uL) with midstage progenitor cells Basophilia and Eosinophilia Blasts can indicate transition in accelerated phase
Thrombocytosis Cytochemistry: Decreased LAP Cytogenitcs: BCR-ABL fusion gene Bone Marrow Hyperplastic Myelopoiesis Elevated granulocytic precursor cells o Treatment Tyrosine Kinase Inhibitors: Imatinib Binds to active site for ATP on abnormal BCR-ABL tyrosine Kinase inhibits proliferation and induces apoptosis of cells Allogeneic Stem Cell Transplant Cell Count Normalization = Hydroxyurea Blast Phase: Acute Leukemia Treatment
CLL o Definition (lymphocytes B & T Cells) Cells don’t die when they should Chronic Lymphocytic Leukemia: Low Grade B Cell Lymphoma with Lymphocytic Leukocytosis Chronic Lymphocytic T-Cell Leukemia o Epidemiology Median age: 70-72 years o Etiology Advanced Age Environmental Factors: Organic Solvents o Classification Rai Staging System o Pathophysiology Acquired mutations in hematopoietic stem cells Increased proliferation of leukemic B cells with impaired maturation and differentiation in the bone marrow resulting in: Suppression of the proliferation of normal blood cells o Immunosuppression Hypogammaglobulinemia Granulocytopenia o Thrombocytopenia o Anemia Infiltration of the Lymph Nodes, Liver, and Spleen Bruton’s Tyrosine Kinase o Clinical Features
Asymptomatic for long period of time Weight Loss, Fever, Night Sweats, Fatigue Painless LAD Hepatomegaly and/or splenomegaly Repeated infections: Severe bacterial infections; Mycosis; Viral Infections Symptoms of Anemia and Thrombocytopenia Dermatologic: Leukemia Cutis; Chronic Pruritis; Chronic Urticaria o Diagnostic Laboratory CBC o Persisting Lymphocytosis with high percentage of small mature lymphocytes Blood Smear: Smudge Cells Flow Cytometry: Detection of B CLL (CD19, CD20, CD23); Light Chain restriction (kappa or lambda) Serum Antibody Electrophoresis Bone Marrow Aspiration Not necessary to confirm diagnosis Additional Genetics Ultrasound Liver Histology Lymph Node Biopsy o Treatment Principles of Treatment Asymptomatic CLL: Observe and Monitor Symptomatic CLL or Advanced Stage o Chemotherapy o CD20+ = Rituximab o Targeted therapy with ibrutinib Refractory CLL or early recurrence in fit young patients: allogeneic stem cell transplant Treatment Regimens <65-70 o FCR (Fludarabine, Cyclophosphamide, Rituximab) >65-70 o Chlorambucil + monoclonal antibody
o Complications Immunosuppression with subsequent infections Secondary malignancies Hyperviscosity Syndrome Autoimmune Hemolytic Anemia Richter’s Transformation (transformation into a high grade NHL) o AIHA Circulating antibodies (positive direct Coombs test) consistent with autoimmune hemolytic anemia Diagnostics = nucleated RBCs and polychromasia (indicates release of immature RBCs into the circulation as a result of elevated erythropoietic activity o Paroxysmal Nocturnal Hemoglobinuria Clinical Presentation: Fatigue, abdominal pain, jaundice, and dark urine in the morning Pancytopenia, evidence of intravascular hemolysis (unconjugated hyperbilirubinemia, elevated LDH, low haptoglobin) and red urine without RBCs in the sediment (consistent with hemoglobinuria) Decreased CD55 and CD59 in the RBC membrane At risk for venous thrombosis Treatment with oral prednisone o Factor V Leiden (mutation of coagulation factor V) Does not allow activated Protein C (potent anticoagulant) to inhibit the coagulation cascade leading to a procoagulant state by activation of prothrombin into thrombin. o Waldenstrom macroglobulinemia Indolent type of non-Hodgkin lymphoma caused by an abnormal production of IgM antibodies by monoclonal plasma cells. Presents in old age with impaired platelet function (nosebleeds), anemia (Hb < 13.5 g/dL), and mild thrombocytopenia, progressive neuropathy (pain and numbness in feet), and hyperviscosity syndrome (vision and hearing loss) Increased ESR, LDH, and ALP can be seen o Hemolysis Extravascular hemolysis Elevated LDH; Haptoglobin level normal; No hemoglobinuria Intravascular hemolysis Exertional hemoglobinuria o Mechanical destruction of RBCs in the feet during strenuous exercise; o Reticulocytosis; Elevated LDH; Decreased haptoglobin; Hemoglobinuria
o G6PD Deficiency Impaired production of NADPH Impaired regeneration of reduced glutathione (antioxidant that protects the erythrocyte membrane from oxidative damage) Vulnerable to oxidative stress caused by primaquine or antibiotics such as sulfamethoxazole and dapsone Offers resistance against Plasmodium infection o Polycythemia Vera Mutation in JAK2 gene leads to uncontrolled EPO Independent proliferation of the myeloid cell lines, resulting in increased blood cell mass Increased red blood cell mass suppresses secretion of EPO by the kidneys, resulting in low EPO levels Individuals with PV usually have normal arterial O2 saturation and a slightly increased or normal plasma volume o Von Willebrand Disease Deficiency in von Willebrand Factor Hinders the ability of platelets to adhere to subendothelial collagen and inhibits platelet activation which leads to a prolonged bleeding time o Myeloproliferative Neoplasms Overview = All show varying degrees of JAK2 mutations (valine phenylalanine) Primary Myelofibrosis Bone marrow fibrosis, extramedullary hematopoiesis, and splenomegaly Peak incidence between 60-70 years Clinical Features o Weakness, fatigue, weight loss o Splenomegaly: LUQ pain o Thrombocytosis and Leukocytosis o Pancytopenic Phase (Late Phase) Erythrocytopenia anemia Thromboytopenia petechial bleeding Leukopenia increased susceptibility to infections Diagnosis o Elevated LAP, LDH, and Uric Acid o Peripheral Blood Smear: Dacrocytes o Bone Marrow Aspiration: Punctio Sicca Treatment o Curative: Allogenic Stem Cell Transplant o Supportive Hyperproliferative Phase:
Prevent thromboembolisms: antiplatelet drug Control cell count: hydroxyurea, interferon alpha, cladribine Pancytopenic Phase JAK2 Inhibitior: Ruxolitinib Periodic Transfusions Low Dose Thaldiomide + Glucocorticoids Essential Thrombocytopenia Clinical Features o Thromboembolic events o Increased risk of fetal loss o Vasomotor symptoms (headache, visual disturbances, acral paresthesias) o Acute gouty arthritis o Petechial Bleeding Diagnostics o Thrombocytosis (>600,000 /uL) o Increased LDH and Uric Acid o Bone Marrow Aspiration: Hyperplasia of Megakaryocytes Differential Diagnosis o Reactive Thrombocytosis Etiology: Inflammation, Infection; Malignancy; Iron Deficiency Treatment: Prevent thromboembolisms: Low dose aspirin; Reduce thrombocyte count: hydroxyurea or interferon alpha Chronic Eosinophilic Leukemia Description: Leukemia with monoclonal proliferation of eosinophilic granulocytes that causes peripheral eosinophilia and tissue damage Clinical Features o Hepatosplenomegaly o Anemia and/or coagulation disorders Diagnosis o CBC: Elevated eosinophilic granulocytes o Peripheral blood smear and bone marrow aspiration: monoclonal blast cells or cytogenetically abnormal eosinophils o Migratory thrombophlebitis Secondary to an occult malignancy, classically pancreatic cancer Trousseau Syndrome (months to years before a malignant process detected)
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Diarrhea (steatorrhea secondary to exocrine pancreatic insufficiency) and poor appetite and a long smoking history Abdominal CT is the most specific and sensitive diagnostic test for detecting underlying visceral cancer Hemophilia Hemophilic arthropathy Iron deposition causes increased synovial inflammation and recurrent synovitis eventually leading to erosion and loss of cartilage, joint space narrowing, and permanent joint destruction Malabsorption Syndrome Inadequate breakdown and absorption of fats and fat soluble vitamins ADEK, leading to deficiency of II, VII, IX, and X. Inherited hyperbilirbinemia Indirect Gilbert’s Syndrome o Common, inherited hyperbilirubinemia that causes mild excess (<3 mg/dL) of indirect bilirubin (unconjugated hyperbilirubinemia), scleral icterus, and fatigue o Commonly after a period of stress and/or fasting G6PD deficiency o Recent primaquine usage o Blood smear with Heinz bodies Crigler Najjar Syndrome o Type I – affected neonates demonstrate exceptionally high levels of indirect bilirubin and often require liver transplantation o Type II – more mild, intermittent periods of jaundice o Phenobarbital is prescribed to induce the production of the underlying, partially deficienct UDP glucuronosyltransferase enzyme Direct Rotor Syndrome o Increased urinary coproporphyrin and normal liver histology Aplastic Anemia Hyperplasia of adipocytes in bone marrow Causees Medications (carbamazepine, NSAIDs) Radiation Viruses (Parvovirus B19) Inherited (Fanconi anemia) Preleukemia Sickle Cell Anemia **
Transient Aplastic Crisis = reticulocytopenia Treatment Hydroxyurea Family Medicine o Screening Low Dose CT in adults 55-80 y/o with a 30 pack year smoking history and currently smoke or have quit within the past 15 years Genetics o Fragile X Syndrome Mitral Valve Prolapse (Mitral Regurgitation) in ½ of Fragile X patients Toxicology o Metal Toxicity Lead Toxicity Cognitive Deficits Behavioral Problems Fatigue Constipation Abdominal Pain Gingival Hyperpigmentation Microcytic, Hypochromic Anemia o Poisoning