High yield notes on micro midterm spring quarter

HSV-1, HSV-2, VZV (alpha group)

Cowdry Type A inclusions, multinucleated giant cells (like parainfluenza, RSV, giant cell pneumonia in measles too), broad host range, latency in DRG.

CMV (beta group, along with HHV-6 the cause of exanthem subitum)

Infects leukocytes; retinitis, encephalitis in AIDS patients; interstitial pneumonitis in transplant patients; enteritis in both; mononucleosis in transfusion patients; most common cause of congenital abnormalities -- deafness, mental retardation, blueberry muffin baby, seizures, periventricular calcifications; transmitted by any contact with bodily fluids; treat with first line ganciclovir (bone marrow suppression, nephrotoxicity), backup foscarnet (nephrotoxicity).

EBV (gamma group, along with HHV-8 the cause of Kaposi's)

Infects oropharynx epithelial cells and B cells. Transmitted by saliva. Causes infectious mononucleosis. Associated with endemic form of Burkitt's lymphoma in Africa (affects jaw). Associated with 20% of Burkitt's (predominantly abdominal) in this country. In immunocompromised associated with other lymphomas, both Hodgkin's and non-Hodgkin's. Also associated with nasopharyngeal carcinoma (especially in southern China). Can see reactive T lymphocytes (not themselves infected) in peripheral blood smear, called atypical lymphocytes or Downey cells. Associated with positive heterophile antibody test, where nonspecific antibodies agglutinate sheep or horse RBCs. A rise in EBV-specific antibodies is diagnostic. To diagnose mononucleosis: fever, sore throat, cervical lymphadenopathy, enlarged liver and spleen. Like other members of herpesviridae, establish latency -- in B cells. No vaccine or effective treatment. Anti-EBNA antibodies appear late, 3-4 weeks after onset. IgG anti-VCA and IgM anti-VCA are present at clinical presentation; IgM disappear by 4-8 weeks, IgG are lifelong.

Adenovirus

Cause of pharyngitis, pneumonia, colds (5 most common causes of colds are coxsackie, rhinovirus, coronavirus, adenovirus, and influenza C), conjunctivitis, gastroenteritis, cystitis. Doesn't cause meningitis (3 most common causes of aseptic meningitis are coxsackie, echovirus, mumps). Adenovirus prevents transport of MHC Class I to cell surface -- thus protecting itself against one arm of cell-mediated immunity, the CD8 cytotoxic T cell, but exposing itself to another, the natural killer cell. Adenovirus has taken a page from human papilloma virus' playbook: it has proteins E1A, and E1B, that knock out Rb and p53, respectively.

Poxvirus

Need to bring a DNA-dependent RNA polymerase in the virion and encode a DNA-dependent DNA polymerase, because it replicates in the cytoplasm, unlike other DNA viruses.

Latent infections

Herpesviridae and Papilloma/Polyoma family viruses tend to be latent.

Micro winter lecture final

Chloramphenicol works against everything but unfortunately it causes aplastic anemia in 1 out of about every 24,000 to 40,000 patients. It's still good enough for government work though -- in third world countries (it helps that it can be given orally). In the US, chloramphenicol is only first line for meningitis when there are known severe allergies to penicillins AND cephalosporins; and for Rickettsial diseases (think Rocky Mountain Spotted Fever) in children or pregnant women.

Imipenem also works against everything, with the notable exception of MRSA. It is degraded renally by dihydropeptidase I (co-administer cilastatin) and excreted renally (reduce dose in renal failure). Meropenem is an improved version that is resistant to dihydropeptidase. Unfortunately, the carbepenems are limited in their use by CNS toxicity: they can cause seizures, though meropenem is better in this respect. They are also cross-allergenic with penicillin. They are first-line therapy for Enterobacter. Ertapenem, a newer carbepenem that only requires once daily I.V. administration, is the drug of choice for severe, polymicrobic diabetic foot infections.

Vancomycin works against all gram positive organisms, with the notable exception of VRE (resistance when D-ala D-ala becomes D-ala D-lac). The main indications for use are endocarditis, line sepsis, and meningitis -- think severe, nosocomial infections where MRSA coverage is crucial. Vancomycin is generally well tolerated (some nephrotoxicity, ototoxicity, thrombophlebitis, IgE-mediated "red man syndrome" if administered by I.V. too fast) but these side effects pale in comparison to the severe situations that actually warrant its use. Vancomycin could be used more broadly, but it's generally held in reserve as an ace card to prevent development of more widespread resistance.

Aztreonam, a monobactam, works against all gram negative organisms, with the notable exception of gram-negative anaerobes. Like other beta lactam antibiotics, they are synergistic with aminoglycosides. However, they are less nephrotoxic than aminoglycosides and can be used as a solo alternative in severe gram negative rod infections. They can also be used if the patient is allergic to penicillins, as unlike cephalosporins and carbepenems, monobactams are not cross-allergenic with penicillin. Monobactams are generally well-tolerated: the only main side effect is occasional GI upset.

Penicillin is first line for beta-hemolytic strep (long-acting IM benzathine penicillin for strep pharyngitis) and syphilis; less high yield -- Actinomyces israelii, and Leptospira interrogans. Penicillin may also be useful against alpha-hemolytic strep like Viridans strep and pneumococcus (latter now displays intermediate-level resistance to penicillin).

Penicillinase-resistant penicillins. Methicillin is no longer used due to interstial nephritis. Use nafcillin for MSSA; use "naf" for staph. Use dicloxacillin (can be given orally) for outpatient empiric treatment of infected skin wound.

Aminopenicillins are penicillinase-sensitive and therefore administered with clavulanic acid. Amoxicillin (oral) is used for outpatient treatment of bronchitis, otitis media, and sinusitis. Ampicillin combined with gentamicin is a combo used for broad empiric coverage (surgery, serious urinary tract infections). Amp-gent also treats enterococcal infections, which are resistant to most penicillin and cephalosporins. Ampicillin also covers Listeria, and is added empirically in meningitis for neonates, the elderly, and the immunocompromised.

Anti-pseudomonals: ticarcillin, carbenecillin, piperacillin.

Actinomyces is resistant to metronidazole; use penicillin. Use TMP-SMX for Nocardia.

First line therapy for meningitis is ceftriaxone and Vancomycin.

Normal flora: Candida; Viridans, Enteroccoci, GBS in women; S. epidermidis; Acinetobacter (only gram negative skin flora), Bacteroides, Fusobacterium, Actinomyces, Pseudomonas, a lot of other Enterobactericiae

Psychiatry final notes

The unique therapeutic actions of clozapine are attributed to 5HT2 receptors. This is also true of the other atypical antipsychotics: olanzapine, quetiapine, risperidone, aripiprazole, ziprasidone.

Risperidone, unlike most antipsychotics, actually increases salivation.

Schizophrenia has a high genetic component. Psychotic symptoms are influenced by life stresses. Intrauterine and perinatal insult is associated with higher risk for schizophrenia. There is no gender or racial difference in schizophrenia incidence. Abuse of hallucinogenic drugs, does NOT lead to schizophrenia. Negative symptoms are least likely to respond to drug therapy; paranoid type schizophrenia (no thought disorder, disorganized behavior, or affective flattening) has best prognosis. Schizotypal is the personality disorder most associated with schizophrenia.

Unipolar disease is more common than bipolar in both sexes. Bipolar disease has more genetic components. Bipolar patients tend to have shorter episodes of untreated illness than unipolar patients. Postpartum disorders are more common in bipolar than unipolar disorder.

Buproprion: less risk of rebound mania.

Therapy of depression. After first major episode: 6-9 months of taking antidepressants. If repeated episodes: at least several years and then re-evaluation.

Cognitive behavioral therapy (CBT): corrects distortions in thinking about oneself and their life; negative triad -- towards oneself, the present world, the future

Interpersonal therapy (IPT): Concentrates on relationships, role transitions; suggests depression often occurs in the context of interpersonal conflict, anger turned inward, loss of a loved one.

Psychodynamic psychotherapy (psychoanalysis-lite): Concentrates on unconscious drives

Panic disorder and generalized anxiety disorder are often comorbid with depression.

Micro lab final notes

M. bovis (TB complex) and M. kansasii cause TB-like respiratory illness in humans -- they are also INH-sensitive. Remember that M. avium-intracellulare and most other nontuberculous mycobacterium are INH-resistant.

Photochromogens (yellow-orange pigment in light): M. kansasii and M. marinum (swimming pool granuloma). It's sunny in Kansas, and over the ocean.

Scotochromogens (pigment in dark and in light): M. scrofulaceum (scrofula, granulomatous cervical lymphadenitis). It's dark where your scrotum is.

Nonchromogens (no pigment): M. avium-intracellulare.

-----------

Rapid death in stationary phase: Strep pneumo, Neisseria.

Klebsiella - butanediol; E. coli -- mixed acids (lactic, formic, acetic acids)

Both Mycoplasma and all fungi have sterols in their cell membranes.

Normal flora: Haemophilus influenza, Candida albicans,

-----------

Isoniazid is activated by catalase and inhibits cell wall synthesis by binding to an enoyl-acyl carrier protein reductase involved in mycolic acid synthesis. Isoniazid resistance is mediated by mutations that knock out catalase or the reductase.

Clavulanic acid is not effective against all beta lactamases, including Class I chromosomally encoded ones (Pseudomonas, Enterobacter, Citrobacter, Serratia).

Metronidazole: intrinsic resistance in Actinomyces; must be reduced to active toxic metabolites in the cell -- these damage DNA.

Quinolones: Both stepwise chromosomal (altered gyrase, reduced uptake) and plasmid-mediated resistance.

Streptomycin binds to single site (S12 protein) on 30S ribosome and is susceptible to single base pair change mutation. Other aminoglycosides bind to multiple sites and are less susceptible. Main mechanism of resistance to aminoglycosides, however, is plasmid- or chromosomally-encoded enzyme inactivation.

Tetracycline: increase efflux of drug (plasmid encoded), or modify ribosome (plasmid encoded).

Path lab exam notes I

Basal cell carcinoma -- arises from basal cell layer of epidermis; multifocal nests of intensely basophilic cells, palisading at the borders; invasion into the dermis -- hence malignant. Like locations: upper lip, inner canthus of the eye.

Psoriasis -- red plaques with white scales; symmetric distribution, frequently on elbows and knees, scalp, genitalia, in general extensor surfaces (in contrast to eczema); acanthosis (thickening of the stratum spinosum), hyperkeratosis (thickening of stratum corneum), perikeratosis (retention of nuclei in stratum corneum); tall dermal papillae.

Herpes zoster -- intraepidermal blisters; at borders of blisters, can see eosinophilic intranuclear inclusions with clear border and then round rim of basophilic marginated chromatin; "dew drop on a rose petal" -- small blister on a red macule; Tzanck stain detects multinucleated epidermal giant cells.

Eczematous dermatitis -- spongiosus.

Melanoma -- brown melanin pigment

Squamous cell carcinoma -- Scaly to nodular lesions, often ulcerated; lower lip, dorsum of hand, or earlobe are common locations (contrast basal cell).

Acne -- hair follicle with keratin and sebum in dermis; foci of inflammation in adjacent wall.

Lupus -- lymphocytic infiltrates in dermis and dermal-epidermal junction; follicular plugging in epidermis; forehead, ear lesions, wolf rash

------------

Eosinophil -- bilobed nucleus, red granules (look like they have rods or long scrolls in them on EM).

Type II pneumocytes also have distinctive lamellar bodies.

Peritoneal inflammation -- opaque rather than glistening peritoneal surface, petechial hemorrhages,

Alveolar inflammation -- first pass is neutrophils, second pass is macrophages; foamy quality due to lipids in cell walls of phagocytosed bacteria. Macrophages are like a diagnosis of exclusion: not particularly distinctive -- renniform (kidney-shaped) nucleus (not lobulated like neutrophils), more cytoplasm and larger than neutrophils, not really any distinctive granules.

Plasma cell -- eccentric and clockface nucleus, perinuclear clear space; large cell like macrophage, but reddish purple (darker) cytoplasm due to large amount of RER.

Bone tumors

Giant cell tumor: Epiphysis -- benign -- female 20-40 -- distal femur, proximal tibia (knee) -- giant cell formation, in reaction to spindle-shaped mononuclear neoplastic cells. "Soap bubble" appearance on X-ray.

Osteochondroma: Metaphysis -- benign -- men 10-25 -- long bones -- exostosis, bone with cartilage cap. Transformation to chondrosarcoma is rare.

Osteosarcoma: Metaphysis -- malignant -- men 10-20 -- distal femur, proximal tibia (knee) -- has predisposing factors including Paget's, fibrous dysplasia, familial retinoblastoma, radiation, bone infarcts -- Codman's triangle due to elevation of periosteum. Poor prognosis.

Osteoid osteoma: Diaphysis-- benign -- men 10-20 -- Interlacing trabeculae of woven bone surrounded by osteoblasts -- less than 2cm and found in proximal femur and tibia.

Ewing's sarcoma: Diaphysis -- malignant -- men 10-20 -- anaplastic small blue cell tumor -- extremely aggressive with early mets but resposne to chemo -- "onion-skin" appearance on X-ray due to periosteal reaction -- 11:22 translocation -- long bones, pelvis, scapula, and ribs.

Enchondroma: Intramedullary -- benign -- men 20-50 -- cartilaginous -- usually in distal extremities.

Chondrosarcoma: Intramedullary -- malignant -- men 30-60 -- cartilaginous -- usually in pelvis, spine, scapula, humerus, tibia, or femur -- may be primary or develop from a osteochondroma (exostosis).

QBank notes: 2/26/2010 [48]

Parathyroid hormone acts on bone, kidney, and intestine via kidney. PTH binds osteoblasts in bone, makes them present RANKL to RANK on osteoclast precursors, which fuse to form osteoclasts that resorb bone, increasing serum calcium. PTH causes increased reabsorption of calcium, and increased excretion of phosphate in the kidney. Finally, PTH causes increased calcium absorption in the GI via its activation of 1-alpha hydroxylation of 25-OH D3 in the kidney.

Calcitonin is less important for daily calcium homeostasis. Calcitonin decrease calcium absorption in the gut, but conserves calcium in the kidney. It causes increased excretion of phosphate in the kidney. In the bone, calcitonin decreases the activity of osteoclasts, therefore depressing serum calcium levels (opposite of PTH). Calcitonin is stimulated by an increase in serum calcium, gastrin, and pentagastrin.

QBank notes: 2/26/2010 [48]

Damaged periosteum can form new bone fragments that interfere with joint movement (heterotopic ossification) following fracture.

Growth hormone and ACTH cause an increase in insulin sensitivity. TSH causes increased glucose absorption from small intestine. They all cause increased blood glucose.

Pleural exudate, not transudate, if PF protein / serum protein over 0.5, PF LDH / serum LDH over 0.6, or absolute LDH over 200 U/L. Exudate indicates pneumonia, infarction or malignancy.

At altitude, partial pressure of oxygen in blood, and saturation of hemoglobin, are lower, but hematocrit is higher (60-65, instead of ~45).

Strawberry tongue diseases: Kawasaki disease, Scarlet fever (and toxic shock syndrome). Both also have rashes, but Kawasaki is mostly hand and feet, and has redness of lips and oral mucosa. Scarlet fever tends to spare the oral region, the rash starts in the chest, arm pits, and behind the ears. Both rashes are desquamative.

Measles: Rash starts on head and spreads to rest of body. Remember the three C's -- cough, coryza, and conjunctivitis -- as well as Koplik's spots, which are pathognomonic but not always seen since they are transient.

Elevated alkaline phosphatase is seen in many disease states of the liver, bone, and bone marrow. Liver: cholestasis, cirrhosis, hepatitis, many liver disease. Bone: Paget's disease, primary hyperparathyroidism and secondary hyperparathyroidism, bone metastases of prostatic cancer, bone fracture, bone fracture in multiple myeloma. Bone marrow: PV, ET, MF, but NOT chronic myelogenous leukemia (in fact you see lowered leukocyte alkaline phosphatase in CML).

QBank notes: 2/25/2010 [48]

Carcinoid syndrome of heart: flushing, nausea/vomiting, diarrhea, TIPS -- tricuspid insufficiency pulmonary stenosis, if carcinoid tumor is in liver. If in lung, can cause left heart problems. Due to serotonin causing fibrosis of endocardium.

Putamen is brave, it's on outside; pallidum pales in comparison, it hides on the inside.

Caudate is a C-shaped nucleus comprising part of the lateral wall of the lateral ventricle.

Salicylate poisoning: You get both metabolic acidosis and respiratory alkalosis. The respiratory alkalosis is due to a direct stimulation of the respiratory center in the medulla. The metabolic acidosis is due to interference with the Krebs cycle, causing reversion to anaerobic glycolysis, which produces lactic acidosis. This gives metabolic acidosis with high-anion gap, due to depletion of bicarbonate. (Anion gap = [Na+ plus K+] - [HCO3- plus Cl-]).

Common causes of high-anion gap metabolic acidosis: lactic acidosis (i.e. metformin, INH, alcohol), ketoacidosis (Type I diabetes -- no insulin, alcohol).

Common causes of normal-anion gap metabolic acidosis: GI or renal loss of bicarbonate, acetazolamide.

Acetaminophen poisoning: liver failure, given N-acetylcysteine. Also nausea, vomiting, abdominal pain.

Carbon monoxide: hypoxemia, cherry-red lips.

Acute mercury poisoning: necrosis of renal tubules, GI epithelium. Chronic mercury poisoning: CNS atrophy, gingivitis, gastritis, renal tubular changes.

Lead poisoning (chronic): neuropathy, abdominal pain, anemia with basophilic stippling.

Potter's syndrome: Babies who can't Pee in utero develop Potter's. Caused by malformation of uretic buds, so bilateral renal agenesis. Face and limb deformities, hypoplastic lung. Oligohydramnios.

Molluscum contagiosum: caused by poxvirus (dsDNA), replicates in cytoplasmic in inclusion bodies, causes umbilicated papules, transmitted by sexual or nonsexual contact (wrestling); chronic infection in HIV positive patients.

Tuberoglomerular feedback. Furosemide doesn't cause afferent arteriole constrict because although it increase osmotic diuresis, it inhibits the same NKCC transporter that's on the macula densa cells of the distal tubule.

Mast cells: cytoplasmic granules with "scroll-like" content.

Terazosin: Treats both benign prostatic hyperplasia and hypertension in one fell swoop.

Celiac sprue involves the proximal small bowel; at this point the gliadin has not yet been digested.

Cimetidine: P450 inhibitor (increases warfarin), antiandrogenic effects, crosses blood brain barrier (confusion, dizziness, headaches), along with ranitidine decreases renal excretion of creatinine.

QBank notes: 2/23/2010 [48]

Psoas major attaches to lesser trochanter. Glut medius and Glut minimus attach to greater trochanter. Glut max attaches to gluteal tuberosity. A sudden strain can cause reflex contraction of psoas major causing avulsion of lesser trochanter.

Human papilloma virus (6 and 11); infects stratum basale. Make it grow out, thicken, and keratinize. Enlarged nucleus with perinuclear vacuolization: koilocytes.

Negri bodies -- Rabies.

Owl eyes -- CMV.

Cowdry type inclusions -- Herpesviruses.

Guarnieri bodies -- small pox.

--------------

CCK -- stimulates blood flow to intestines after fatty meal, makes food stay in stomach longer, decreases gastrin (by promoting stomach antral secretion of somatostatin) and gastric acid, stimulates secretion from pancreas and gall bladder.

GIP -- at physiological dose, secretion of insulin; at pharmcological dose, inhibition of stomach acid secretion and gastric motility.

Secretin -- secretion of bicarb from pancreas and biliary ducts

Vasoactive intestinal polypeptide -- stimulates gut secretion of water and electrolytes; relaxes smooth muscle. Overall promotes gastric motility.

Common causes of otitis media, in descending order of probability: Strep pneumo (~30%), Haemophilus (~25%), Moraxella catarrhalis (15-20%).

Wiskott-Aldrich syndrome: triad of thombocytopenia, infections, and eczema (TIE). Associated with low IgM and high IgE, IgA. Due to defect in response to polysaccharide antigens due to cytoskeletal problems -- defective binding of T cells to B cells, progressive deletion of B and T cells. X-linked recessive.

Pre-eclampsia: pregnancy-induced hypertension, proteinuria, edema (+seizure = eclampsia)

HELLP: Hemolytic anemia, elevated liver enzymes, low platelet count.

Supraclavicular node -- Virchow's node. Enlarged left supraclavicular node a classic finding in gastric carcinoma.

The most common cause of chorioretinitis in infants is congenital toxoplasmosis, which is acquired by maternal exposure to cat litter. The classic triad of toxoplasmosis is chorioretinitis, hydrocephalus, and intracranial calcifications. Toxoplasma gondii is an obligate intracellular protozoan. It can be treated with the folate blocking combo, pyrimethamine and sulfadiazine.

Exemestane is an aromatase inhibitor. It blocks the androstenedione to estrone and testosterone to estradiol conversion in the granulosa cells of the ovary. Leuprolide is a GnRH analogue used in advanced prostate cancer.

Dumping syndrome is a complication of gastric bypass surgery. The food reaches the small intestine too quickly, the osmotic load draws water into the intestine, causing motility and diarrhea. The fluid loss and release of "vasoactive substances" also causes hypotension and reflex tachycardia and sympathetic activation. Treat by advising smaller meals higher in fat.

Pyridoxine (active form -- pyridoxal phosphate): transamination reactions (ALT, AST), decarboxylation reactions, glycogen phosphorylase, cystathionine synthesis, heme synthesis. Required for synthesis of niacin from tryptophan. Deficiency: Convulsions, irritability, peripheral neuropathy (deficiency can be induced by INH and oral contraceptives); also, can cause sideroblastic anemias.

Campylobacter jejuni: Think microaerophilic, grows BEST at 42c, comma-shaped organism with polar flagella (looks like Vibrio; also oxidase positive like Vibrio; unlike Vibrio, can cause bloody diarrhea in addition to watery). Usually get it fecal-orally by eating poultry, due to its zoonotic nature.

WAGR complex: Wilms tumor, Aniridia, Genitourinary malformation, mental Retardation. Wilms tumor usually presents as large abdominal mass at 2 years of age.

Glioblastoma multiforme: pseudopalisading necrosis, butterfly glioma, grave IV astrocytoma.

Seborrheic keratosis: usually dark like melanoma, histologically resembles both basal and squamous cells with basaloid apperance and pseudo-horn cysts. Can be "peeled" with dull side of scapel.

QBank notes: 2/22/2010 [48]

Rhabdomyomas (present with signs of cardiac outflow obstruction) are associated with tuberous sclerosis: cortical tubers, adenoma sebaceum, epilepsy, mental retardation.

Chediak-Higashi: infection susceptibility, albinism.

Neural ectoderm: oligodendrocytes, astrocytes, epndymal cells.

Yersinia enterocolitica: pediatric diarrhea with blood and pus "mini epidemics;" mimics appendicitis, mesenteric lymphadenitis; Yersinia can grow at 4C, so common in cold climes.

Bordetella pertussis secretes 4 toxins: (1) Pertussis toxin -- in addition to causing the whooping cough, inactivates the inactivator of cAMP (Gi) resulting in lymphocytosis, increased insulin secretion (hypoglycemia), and increased sensitivity to histamine; (2) extracellular adenylate cyclase -- somehow weakens neutrophils, lymphocytes, and monocytes; (3) filamentous hemagglutinin -- better binding to ciliated epithelial cells; (4) tracheal cytotoxin -- kills ciliated epithelial cells.

Middle third of esophagus: contains both striated AND smooth muscle.

VIPoma: diarrhea due to excess Na, Cl secretion; lowered stomach acid secretion.

Drug-induced lupus: antihistone antibody. It's not HIPP to have lupus. Hydralazine, INH, Phenytoin, Procainamide.

Posterior mediastinum -- DATES: descending aorta, azygos and hemiazygos vein, thoracic duct, esophagus, sympathetic trunk.

Draining of colorectal cancer. Below the pectineal line: superficial inguinal. Above the pectineal line: internal iliac.

Cerebral aqueduct of Sylvius -- mesencephalon.

Steroids and thyroxine promote surfactant production. Insulin suppresses (maternal diabetes a risk factor for RDS).

Ionic effects on heart

Hyperkalemia: Tall T waves

Hypercalcemia: Shorter QT interval, almost absent ST; elevated BP, vomiting

Hypermagnesemia: Prolonged PR, QT; hypotension, respiratory depression; impaired Ach release (muscle weakness)

Fungi III - Yeasts

CRYPTOCOCCUS NEOFORMANS

Cryptococcus neoformans is an encapsulated yeast (non-dimorphic) in pigeon droppings that causes meningoencephalitis, especially in AIDS patients; characteristic halos on India ink stain. Diagnosis is based on two things: cryptococcal antigen (use latex agglutination test to detect capsular polysaccharide antigen); culture on Sabouraud's agar. Treat with Amphotericin B and flucytosine, 2 weeks, followed by fluconazole, 8 weeks.

It produces phenol oxidase, producing melanin and neutralizing neutrophil-released peroxides.

CANDIDA ALBICANS

Candida is normal flora (normal host defense: normal flora, T-cell function). Candida forms pseudohyphae at 20C, and germ tubes at 37C.

Non-immunocompromised.

Oral thrush. Treatment: Imidazole lollipop, nystatin (which can only be given orally).

Vaginitis (pruritus, copious discharge, cottage cheese on vaginal wall). Treatment: Single dose oral fluconazole Risk factors: High pH, diabetes, antibiotic use

Diaper rash in babies, or other warm, moist areas (under breasts).

Immunocompromised.

Esophagitis (risk factors: neonate, steroids AIDS, diabetes).

Disseminated disease (any organ). If you see Candida in blood (always abnormal), look for it on retina (white fluffy patches). There's no good antigen (though beta-D-glucan is sometimes used) or antibody test, but you can diagnose by culture.

**Mucocutaneous candidiasis: lack of dectin, a receptor for glucan that stimulates immune response to fungi. Get granulomatous lesions of fingers, toes, mouth.

Fungi II - Primary pathogenic fungi

Primary pathogenic fungi are dimorphic. At 37C they grow as yeast. They are very similar to TB. Like TB, they require cell-mediated immunity to clear (Type IV) -- they even have equivalent antigen skin tests, like PPD for TB.

Coccidiodes immitis

Forms alternating arthroconidia in mycelia; these are infectious when inhaled. In tissue grow as large spherules filled with endospores within caseating granulomas. Endemic to Southwestern United States and Northern Mexico. San Joaquin Valley fever. Anything that disturbs soil (earthquakes) can cause increase in cases. Disseminated disease only in 5% of infections, more likely in immunocompromised: skin granulomas, lytic bone granulomas, meningitis (the worst). High titer of antibody associated with poor prognosis -- indicates disseminated disease. Black or Filipino population at higher risk for disseminated disease. Diagnosis: culture, antibody test, skin test.

Histoplasma capsulatum

Associated with bird and bat droppings (at risk if cleaning chicken cage, spelunking). Endemic to Mississippi and Ohio River valleys. Not that pathogenic: often asymptomatic, or mild pneumonia. Microconidia or tuberculate macroconidia (pathognomonic). Doesn't have true capsule; called capsulatum because of histological apperance -- clear space around the yeast. Hide out in macrophages as intracellular parasites. Small, so can see many inside one macrophage. Disseminated disease in immunocompromised, may be mistaken for cancer due to wasting, possibly associated with TNF inhibitors. Antibody level is not a useful prognostic sign; antigen test, skin test, and culture used for diagnosis.

Blastomyces dermatitidis
Hardest to get (rarest, get it from rotten wood and soil) and hardest to have (often disseminated, even in non-immunocompromised). Endemic to states east of Mississippi and Central America. Inflammatory lung disease, and commonly disseminates to skin and bone where it forms granulomatous nodules. Broad-based bud (as opposed to Histoplasma, with narrow neck). No antibody test. Culture for diagnosis.

Sporothrix schenckii

Also known as rose gardener's disease. Inoculated by trauma to skin (rose thorn for instance). Local pustule or ulcer, with ascending lymphangitis. Dimoprhic fungus, cigar-shaped yeast at 37C.

Fungi I -- Aspergillus and Mucor

Fungal cell membrane has ergosterol. Amphotericin B and nystatin bind to ergosterol; imidazoles inhibit synthesis of ergosterol.

Fungal cell walls are thick and formed by carbohydrate units of glucan, mannan, and chitin.

Asexual reproduction. Yeasts (i.e., Candida) divide by budding. Molds divide by elongation, and are fuzzy because aerial mycelia grow up into air (and eventually form spores). Molds do not form spores in tissue. Hence you cannot identify fungi by spore arrangement on tissue biopsy; furthermore, since spores are the infectious form, you can only get infected from the environment, not another human.

Aspergillus. A. fumigatus causes 90% of human disease due to molds; also, flavus is similar; A. niger is black. Acute branching septate hyphae. Ubiquitous in environment -- we all inhale hundreds of fumigatus spores (they are very aerodynamic) daily!

Invasive aspergillosis is typically seen only in immunocompromised (chemo, high dose steroids, CGD, AIDS) patients. Most commonly starts in lung, but can disseminate to other organs. The organism likes to invade blood vessel walls, causing infarction and hemoptysis. Definitive diagnosis difficult, since difficult to grow mold; serum antigen assay for galactomannan (specific to Aspergillus) is best: specific but not that sensitive. Can't look for antibody since most patients are immunocompromised! CT: "halo sign" -- air crescents around infiltrate. Treatment: Voriconazole.

Allergic aspergillosis. IgE-mediated, eosinophilia. Can look for precipitating antibody. Responds to corticosteroids like asthma.

Aspergilloma. Usually grows in previous cavity, like old TB cavitary lesion. Ball has minimal contact with tissue, so will move dependent on patient position. Surgery is an option.

Mucormycosis. Mucor, Rhizopus species. Non septate "empty looking" hyphae, 90 degree angle branching. Disease mostly in ketoacidotic diabetes (low pH: causes dissociation of iron from hemoglobin, interferes with PMN function, promtoes fungal growth) and leukemia patients (low PMNs). Also proliferate in blood vessel walls, causing infarction of distal tissue. Rhinocerebral, frontal lobe abscesses -- may require disfiguring surgery.

QBank notes: 2/21/2010 [48]

Metformin contraindicated in renal failure due to its lactic acidosis effect.

Metformin (a biguanide) and sulfonylureas (i.e. glipizide) are 1st line treatments for diabetes.

Japanese at higher risk for gastric carcinoma due to polycyclic hydrocarbons in their diet (smoked fish, etc).

Changes in sleep in elderly: less sleep, less REM percentage after 80, gradual decrease and disappearance on Stage 4, then Stage 3, sleep.

Low cortisol: nausea, vomiting, anorexia, fatigability, weakness, low blood pressure and orthostatic hypotension (due to decreased response to catecholamines).

You have to be 18 before you can decide to take yourself off the ventilator. A parent cannot decide to take someone off the ventilator, even if the child agrees.

How to see if respiratory acidosis is compensated. pH = 6.1 + log(bicarb/(0.03*PaCO2))

Viruses that can't complete life cycle without their own polymerase: all negative sense RNA, double stranded RNA (reovirus), dsDNA that replicates in cytoplasm (poxvirus), retroviruses.

Amyloid angiopathy can cause lobar hemorrhage encompassing entire hemisphere.

FSH, LH responsible for initial increase in estrogen. Above certain threshold, feedback inhibition switches and estrogen actually promotes more FSH, LH release. This promotes higher levels of estrogen. Also LH surge results in ovulation. Estrogen levels and increased before and during ovulation, and depressed right after. The corpus luteum results in second rise in estrogen.

Angiosarcoma: arsenic, vinyl chloride

Hepatocellular carcinoma: cirrhosis, hepatitis B

Liver cell adenoma: oral contraceptive use

Hypospadias: cryptorchidism, ascending urinary tract infections (secondary to urinary retention if narrow opening), sterility (ejaculation compromised)

Pemphigus vulgaris versus bullous pemphigoid. Pemphigus vulgaris: classically oral lesions first, positive Nikolsky sign (separation of epidermis from dermis on pressure), intraepidermal acantholysis (tombstoning). Bullous pemphigoid: not oral first though possible later, negative Nikolsky, subepidermal blisters.

Neoplastic lung disease

Cancer that has metastasized to the lungs is more common than primary lung cancer. That said, most primary lung cancer is has metastasized (Stage 4) by time of diagnosis.

Most primary lung cancer (~95 percent) is bronchogenic carcinoma; 5 percent is bronchial carcinoid and miscellaneous tumors.

Bronchogenic carcinoma is most frequently diagnosed cancer, and the most frequent cause of death from cancer.

Smoking is the main risk factor for small cell and squamous cell lung cancer. Polycyclic aromatic hydrocarbons cause DNA damage are are "initators" of cancer.

Mediastinal symptoms: hoarseness (recurrent laryngeal nerve injury), dysphagia (compression on esophagus), Horner's syndrome (usually squamous cell tumor at extreme apex of lung destroying the superior cervical sympathetic ganglion: ptosis, miosis, anhydrosis), SVC syndrome, hemorrhagic pericarditis.

Paraneoplastic syndromes: Small cell secrete ADH, ACTH, also associated with Eaton-Lambert syndrome; squamous secretes PTH and cause hypercalcemia; adenocarcinomas associated with hypertrophic pulmonary osteoarthropathy (associated with clubbing) and migratory thrombophlebitis (also seen in pancreatic adenocarcinoma); carcinoid tumor associated with carcinoid syndrome (excess serotonin gives flushing, diarrhea, salivation, wheezing).

Mesothelioma has Psammoma bodies and results in hemorrhagic pleural effusions and pleural thickening.

Common areas of metastasis: Sometimes Cancer Penetrates Benign Liver, Lots of Bad Stuff Kill Glia, PT Barnum Likes (lytic) Kids. Also adrenals and contralateral lung.

Small cell versus non-small cell. Small cell usually metastatic at presentation; surgery contraindicated.

SQUAMOUS CELL CARCINOMA

Preceded by squamous metaplasia, dysplasia, carcinoma in situ, finally breaks through basement membrane. Squamous, Sentral, Smoking; associated with cavitation; hilar mass arising from bronchus, keratin pearls, intracellular bridges.

ADENOCARCINOMA

Associated with women, nonsmokers. Peripheral, associated with scarring or site of previous injury or inflammation. Glandular histology (Clara cell derived, produces mucin -- blue and foamy) and papillary growth pattern.

Bronchioloalveolar carcinoma subtype: in situ growth pattern, no evidence of stromal, vascular, or pleural invasiveness. Much better prognosis.

LARGE CELL TUMOR

Peripheral. Highly anaplastic, pleomorphic tumor. Poor prognosis. Removed surgically.

CARCINOID TUMOR

Carcinoid syndrome.

Environmental lung disease

COAL

Pulmonary anthracosis is asymptomatic -- see anthracotic deposits in interstitium and hilar lymph nodes, dust cells. Don't have to work in a coal mine to get this, living in Chicago will do it.

Simple coal worker's pneumoconiosis (CWP) is characterized by small fibrotic (less than 1cm) lesions in the lung, mostly in upper lobes and upper parts of lower lobes. This can lead to centriacinar emphysema (not just a restrictive disease, but also obstructive).

Complicated CWP is characterized by large fibrotic (greater than 1cm) lesions in the lung, and in its severe form is called black lung disease. This can lead to right heart failure (cor pulmonale), and Caplan syndrome (large, cavitating rheumatoid nodules), but there is no increased risk for TB or cancer.

SILICOSIS

Quartz is highly fibrogenic because it activates macrophages to secrete cytokines. Acute exposure leads to "ground glass" appearance in all lung fields. Chronic exposure leads to formation of nodular opacities (on CXR) of quartz and concentric layers of collagen in upper lung lobes, with or without central cavitation, as well as "egg-shell" dystrophic calcification of hilar lymph nodes. Silicosis is associated with cor pulmonale, Caplan syndrome, and higher TB and cancer incidence.

ASBESTOSIS

Asbestos fibers come in two types: the curly, flexible serpentine type; the straight, stiff, amphibole type, which is the worst type and the type that causes mesothelioma. Asbestos is found in insulation materials, as well as roofing, ceiling and floor tiles. Exposure causes macrophages to coat fibers with ferritin. Pathologies associated with asbestos: (1) benign pleural plaques, not associated with cancer; (2) diffuse interstitial fibrosis with or without pleural effusions -- lower lobe preference, unlike CWP or silicosis; (3) bronchogenic carcinoma ~20 years post exposure; (4) mesothelioma (pleural effusion, pleuritic chest pain, dyspnea due to compression) ~25-40 years post exposure. There is no risk for TB, but cor pulmonale and Caplan syndrome are possible complications, as with the other pneumoconioses. Mesothelioma risk is not affected by smoking. Synergistic effect of smoking and asbestos on lung carcinoma, however.

BERYLLIOSIS

Nuclear and aerospace industries. Diffuse interstitial fibrosis with noncaseating granulomas. No additional risk for TB, but primary lung cancer risk is increased. Cor pulmonale risk.

HYPERSENSITIVITY PNEUMONITIS

Organic antigens. Both Type III (IgG immune complexes form in response to inhaled antigen, causing inflammatory damage in lung) and type IV hypersensitivities (dysfunctional granulomatous response that causes widespread fibrosis; diffuse lymphocytic interstitial infiltrate) involved.

Farmer's lung -- thermophilic actinomycetes

Silo filler's disease -- oxides of nitrogen

Byssinosis -- bacterial endotoxin of gram negative bacteria growing in cotton, linen, hemp; cause "Monday morning blues"

Treatment: face mask, dust removal, corticosteroids

DRUG-INDUCED INTERSTITIAL FIBROSIS

Amiodarone, methotrexate, cyclophosphamide, bleomycin.

RADIATION-INDUCED LUNG DISEASE

Occurs 1-6 months after treatment. Fever, dyspnea, pleural effusions, infiltrates on CXR.

Infectious Lung Disease

Smoking can damage the mucociliary apparatus. Alcoholic stupor can interfere with epiglottic and cough reflexes (leads to aspiration pneumonia).

Community-acquired bacterial pneumonia

Sudden onset high fever with productive cough. Signs of consolidation: dullness to percussion, increased vocal tactile fremitus, egophony, lobar or patchy radiodensities on CXR. Alveolae filled with exudate, mostly PMNs.

Pneumococcus is classic lobar pneumonia: congestion, red hepatization, gray hepatization, resolution. Resolution can result in fibrosis, organizing pneumonia.

Haemophilus influenza is classic bronchopneumonia: usually lower lobes or right middle lobe, patchy in distribution, begins as bronchitis and spreads locally into lungs.

Community-acquired atypical pneumonia

Insidious onset with low-grade fever, nonproductive cough, flu-like symptoms: pharyngitis, laryngitis, myalgias, headache; no signs of consolidation on physical exam. Patchy interstitial infiltrate on CXR. Alveolae clear, interstitial mononuclear infiltrate. May see hyaline membrane as in ARDS.

Mycoplasma pneumoniae

Viruses: Respiratory syncytial virus, Influenza A and B

Influenzaviruses (RNA genome) have two major virulence factors: (1) hemagglutinin -- binds virus to cell receptors in nasal passages; (2) neuraminadase -- dissolves mucus, promotes release and dissemination of virus particles. Antigenic drift and antigen shift: latter requires new vaccine. Use of aspirin as treatment associated with Reye syndrome. Also associated with Guillain-Barre (not just C. jejuni).

Nosocomial pneumonia

Staph aureus, Gram negative rods (Enterobacteriaceae, Pseudomonas)

Aspiration pneumonia

Anaerobes from oral cavity (Bacteroides, Prevotella, Fusobacterium, Peptostreptococcus); aspiration of gastric acid part of pathology; right lobe usually affected and depends on position (upright -- posterobasal lower lobe; supine -- superior lower lobe; right-sided -- middle lobe and posterior upper lobe).

Abscess

Usually a complication of (1) aspiration (mostly oral anaerobes); (2) bacterial pneumonia (most commonly, Staph aureus and Klebsiella pneumoniae), (3) septic embolism (from bacterial endocarditis), or (4) obstructive cancer (bronchogenic carcinoma). Foul-smelling sputum since usually have mixed aerobic/anaerobic infection. Cavitary lesions on CXR with air-fluid levels.

HIV-specific pneumonias

Cytomegalovirus -- basophilic inclusions in nuclei of alveolar macrophages, endothelial cells, epithelial cells look like owl's eyes

Pneumocystis pneumonia -- "intra-alveolar foamy exudate," yeast that looks like "flattened ping-pong balls," require CD4 levels lower than 200, an AIDS defining infection, treat with TMP-SMX.

Aspergillus -- acute-angled branching septated hyphae (45 degrees), forms aspergillomas in cavitary lesions (e.g., TB) and cause hemoptysis, allergic aspergillosis (Type I and Type III hypersensitivities) causes interstitial lung disease and bronchiectasis, invasive aspergillosis of vessel walls causing hemorrhagic infarctions and necrotizing bronchopneumonia. Treat with voriconazole.

Bronchiectasis

Permanent fibrotic dilatation of bronchi and bronchioles caused by inflammatory destruction of muscle and elastic tissue, resulting from chronic necrotizing infections. Associated with cystic fibrosis, primary ciliary dyskinesia, and obstruction (cancer). Dilation all the way out to pleural surface (usually can't see 2-3cm from surface). Severe, persistent cough with bloody and/or foul-smelling sputum (coughing only way to get mucus out).

QBank notes: 2/19/2010 [48]

Nutmeg liver: think CHF.

Antibiotic that inhibits CYP3A4 -- macrolides, boosts levels of theophylline, warfarin. Antibiotic that boosts CYP3A4 -- rifampin, lowers levels of theophylline, warfarin.

Anterior to the anterior scalene: phrenic nerve. Between anterior and middle scalenes: lower trunk of brachial plexus and subclavian artery. Compression due to muscle or bone overgrowth results in thoracic outlet syndrome: atrophy of hypothenar, thenar eminences; atrophy of interosseus muscles; paresthesias of medial side of hand and arm; weak radial pulse.

Superior laryngeal nerve: cricothyroid muscle, laryngeal mucosa above the vocal folds; recurrent laryngeal nerve: rest of the laryngeal muscles, laryngeal mucosa below the vocal folds.

You drive CARS with your hands and feet: Coxsackie A, RMSF, Syphilis (secondary).

Radiolucency means dark area on chest X-ray (the rays pass through). Opaque means white area (rays are absorbed).

Infantile hypothyroidism: difficulty feeding, somnolence, constipation, failure to thrive. Can lead to cretinism if untreated. Maternal transfer of thyroxine may initially mask the condition.

Nulliparity is protective against cervical carcinoma but a risk factor for breast cancer. Risk factors for cervical carcinoma: young age at first coitus, multiple sexual partners, HPV infection, smoking, multiparity.

Deep inguinal ring: 0.5 inch above the midpoint of the inguinal ligament.

Tuberculosis (Fierer)

Mode of transmission: aerosolized droplets from infected people. Transmission in a previously uninfected person leads to primary foci of TB in the lung (Ghon focus granuloma, or Ghon complex if accompanied by perihilar lymph node calcified granulomas) and other organs to which it has spread hematogenously; in 5% of cases, reactivation in first two years, and an addition 5% lifetime risk. Reactivation risk is higher in the young, the elderly, and the immunocompromised. In AIDS patients, reactivation risk is 10% per year!

TB is known as consumption due to weight loss; as in cancer, cachexia is caused by chronic hypersecretion of tumor necrosis factor.

Isoniazid led to drastic decline of TB incidence in the U.S., 1950s-present.

Mycobacterium tuberculosis is a slow growing, acid-fast, obligate aerobe (that nevertheless can survive anaerobically, if not grow, inside granulomas). Virulence factors include mycosides, cord factor (inhibit neutrophil chemotaxis, damages mitochondria and triggers TNF release), Wax D (actually an adjuvant to our immune response), and sulfatides (inhibit phagosome-lysosome fusion).

IFN-gamma, secreted by TH1 CD4 cells, is required for macrophages to kill intracellular TB. If you put patient on TNF inhibitors, you predispose to miliary TB. IL-12 is also important to prevent disseminated TB infection.

Diagnosis of TB: sputum stain (not sensitive and not specific), culture (slow, 4-6 weeks), nucleic acid methods (not sensitive but very specific), skin test (anergy can give false negative, BCG can give false positive); IFN-gamma test (gold standard).

Positive PPD: treat with INH (inhibits mycolic acid synthesis), 9 months; Rifampin, 4months. Other drugs: ethambutol (inhibits arabinogalactan synthesis); pyrazinamide.

Pulmonary vascular disease

Physical exam of lung

Rales, crackles, crepitations: Usually inspiratory. Early to mid are due to secretions in large to medium airways (e.g., bronchitis) and clear with coughing. Late are due to opening of small airways and do not clear with coughing. Causes: pneumonia, pulmonary edema, interstitial fibrosis (e.g., sarcoidosis). Fine crackles (like rubbing strands of hair together) are more indicative of interstitial pathology, such as CHF or fibrosis; coarse, airway bronchiectasis.

Wheezing: Usually expiratory, high-pitched musical sound. Caused by narrowing of small airways and segmental bronchi by inflammation (e.g., asthma, bronchitis); peribronchiolar pulmonary edema (e.g., cardiac asthma), or pulmonary embolism/infarct (platelets release TXA2, a bronchoconstrictor).

Rhonchi: Both inspiratory and expiratory, low-pitched snoring sound. Causing by secretions in large airways (e.g., bronchitis); clear with coughing.

-----

These lung findings are less reliable in vascular diseases like pulmonary embolism.

Pulmonary embolism is often caused by deep vein thrombosis (main risk factor: stasis, hypercoagulable states -- e.g., Factor V Leiden, which is not degraded by Protein C).

In PE you have V/Q mismatch because the blood goes preferentially to upper lobes, but there is less ventilation there. You also get pulmonary hypertension since the same amount of blood has to go through less parallel circuits.

The main problem in PE is not losing part of the lung, or hypoxemia, but hemodynamic instability, since the RV is a poor pump and can't deal with pulmonary hypertension. As RV pressures increase, coronary artery driving pressure (BP - P in muscle of RV) decreases, as this leads to right ventricular ischemia. Hence, giving a systemic pressor like phenylephrine can paradoxically increase cardiac output by improving RV oxygenation.

Pulmonary hypertension: compensation, then decompensation (dyspnea, dizziness, syncope). Can be due to large vessel obstruction (Chronic Thromboembolic Pulmonary Hypertension -- basically scarring from PE); small vessel obstruction (idiopathic, collagen vascular disease); congenital heart disease giving left to right shunts

Respiratory failure

Dead space ventilation versus shunt: A shunt does not respond to 100% oxygen administration.

There are two types of respiratory failure: (1) Hypoxemia without hypercapnia; (2) Hypoxemia with hypercapnia

Type 1 respiratory failure is characterized by low PaO2, normal or low PaCO2, and increased arterial-alveolar gradient. This caused by perfusion, ventilation, or diffusion defect, or right-to-left shunt (i.e. Tetralogy of Fallot).

Type 2 respiratory failure is characterized by low PaO2, hypercapnia, and normal arterial-alveolar gradient. This can be caused by hypoventilation due to drugs (for example, barbiturates depress respiratory center in medulla), upper airway obstruction (epiglottitis, croup), chest bellows dysfunction (polio, ALS, Guillain-Barre), or skeletal deformities (kyphoscoliosis, pectus excavatum).

Pulmonary Edema (John West lecture)

Blood gas barrier (endothelium, ECM, Type I pneumocyte) is polarized. The thinner side is for gas exchange and the thicker side is for fluid exchange. The strength of the barrier derives from Type IV collagen in the ECM. The endothelium has looser junctions and is more permeable to ions, fluid, and proteins than the epithelial layer.

Starling forces apply. What's normal: small amount of fluid always leaving pulmonary capillaries (through thick side), and this is drained by lymphatics. Increased hydrostatic pressure (left heart failure -- most common cause, often secondary to MI, volume overload, mitral stenosis) and decreased oncotic pressure (nephrotic syndrome, cirrhosis) lead to transudate pulmonary edema. Other causes of pulmonary edema. Rapid re-expansion of collapsed lung. Lymphatic insufficiency from silicosis.

Reflection coefficient is 0.7, because some osmotic elements escape from capillary. Factors that reduce reflection coefficient (increase capillary permeability) include endotoxins (sepsis), radiation (breast carcinoma radiation -- localized pulmonary edema), and toxins (chloride gas, chronic exposure to oxygen gas) and high-altitude (uneven hypoxic pulmonary vasoconstriction). This leads to exudative (protein-rich) pulmonary edema.

If the amount of fluid leaving increases, then you get interstitial edema and then alveolar edema (alveolar epithelium becomes pathologically permeable). Interstitial edema manifests itself in perivascular and peribronchiolar spaces; septal lines (horizontal white lines) on CXR are only sign -- subtle. Alveolar edema results in shunting. Easy to see (butterfly shadow, symmetrical) on CXR.

Signs of pulmonary edema: Dyspnea, orthopnea, paroxysmal nocturnal dyspnea; pink, frothy sputum from RBCs and surfactant.

QBank notes: 2/17/2010 [48]

Trisomy 16 -- most common chromosomal defect in spontaneous abortion. Turner Syndrome (45,XO) also produces spontaneous abortion, but live birth is also possible.

Trisomy 13 (Puberty) -- Patau -- Microcephaly, HoloProsencephaly, Polydactyly, cleft lip / Palate, mental retardation, rocker-bottom feet, congenital heart disease. Death within 1 year of birth.

Trisomy 18 (Election age) -- Edwards' -- clenched hands, micrognathia, low-set ears, prominent occiput, severe mental retardation, rocker-bottom feet, congenital heart disease. Most common after Down syndrome. Death within 1 year of birth.

Trisomy 21 -- Down syndrome -- flat facies, prominent epicanthal folds, simian crease, large 1st web space (between 1st and 2nd toes), duodenal atresia, congenital heart disease (septum primum type ASD), increased risk of ALL Alzheimer's disease.

Myoepithelial cell -- can contract, associated with glandular epithelium

Myofibroblast -- can contract, associated with wound contraction, Dupuytren contracture

Aortic coarctation -- Turner's syndrome; Aneurysms of proximal aorta -- tertiary syphilis; Cardiac septal defects -- Fetal alcohol syndrome, Trisomy 18 and 21; Mitral valve prolapse and aortic root dilation -- Fetal alcohol syndrome

Ehler-Danlos versus Marfan versus homocystinuria

EDS triad: skin (hyperextensible, easily bruised), joints (hypermobile), cardiovascular (MVP, AAA, berry aneurysms)

Marfan triad: skeletal (eunuchoid habitus, arachnodactyly), eye (superotemporal ectopia lentis), cardiovascular (MVP, AAA)

Homocystinuria: skeletal (Marfanoid habitus -- can even get pectus excavatum, carinatum as in Marfan), eye (inferonasal ectopia lentis), mental retardation, atherosclerosis (stroke, MI, vessel thrombosis)

Normally carotid occlusion effect at carotid sinus (IX) is attenuated by aortic arch baroreceptors (X). Vagotomy potentiates effect, leading to greater increase of heart rate and mean arterial pressure.

Trimethaphan will decrease tone. This means vasodilation of vessels and MAP decrease (vessels: SNS dominant) and increase in heart rate (heart: PNS dominant)

Peutz-Jeghers syndrome: widespread freckles especially of lips and oral mucosa, and palms and soles, associated with increased potential for GI cancers (pancreas, colon, stomach, small intestine) and other carcinomas (breast, ovary, uterus, cervix, and lung)

Intense exercise leads to VEGF production, but not bFGF production; both cause angiogenesis.

Pigmented bile stones (calcium bilirubinate): biliary tract infections, hemolytic anemia, advanced age, alcoholic cirrhosis.

Increasing tidal volume is a more effective way of increasing alveolar ventilation than increasing breathing rate (due to dead space fixed costs).

ARDS and Pneumothorax

ARDS

Type II pneumocytes: (1) surfactant -- prevents atelectasis; (2) repair

There are more Type II pneumocytes than Type I pneumocytes

Type II pneumocytes proliferate in repair phase post-ARDS

The three main causes of acute respiratory distress syndrome: (1) gram negative sepsis; (2) gastric aspiration; (3) severe trauma

Findings in ARDS: (1) Severe hypoxemia (PaO2 less than 50) not relieved by 100 percent oxygen; (2) Pulmonary wedge pressure less than 18, ruling out cardiogenic pulmonary edema

What causes hypoxemia in ARDS? (1) Shunting (perfusion but no ventilation due to atelectasis caused by injury to Type II pneumocytes); (2) Diffusion defect (hyaline membrane formation due to alveolar capillary and Type I pneumocyte damage)

Late complications of ARDS: chronic interstitial fibrosis --> restrictive lung disease

Pneumothorax

The critical distinction is between spontaneous pneumothorax and a tension pneumothorax. A spontaneous pneumothorax is caused most commonly by bursting of a subpleural bleb (underlying condition may be emphysema), causes a minimal or ipsilateral mediastinal shift, and is benign since the air in the pleural space will slowly be reabsorbed (atmospheric pressure > arterial pressure). Treat by observation if mild (less than 15%)

OTOH, a tension pneumothorax is usually due to penetrating wound (knife, shrapnel) and involves a check valve, where can get into the pleural space with inspiration but not out with expiration; this causes GREATER THAN ATMOSPHERIC pressure in the pleural space. Hence there is contralateral mediastinal shift and since pressure buildup can cause compression atelectasis in the contralateral and only remaining lung, this is a medical emergency. Treat by inserting a needle at the 2nd intercostal space on the midclavicular line

Common findings in both types of pneumothorax is pleuritic chest pain, tympanitic percussion and absent breath sounds.

QBank notes: 2/15/2010 [48]

Fatty change of the liver is reversible.

Histoplasma capsulatum -- despite the name, a 2-5um yeast with no true capsule. Regional to Mississippi/Ohio river valleys. Causes tuberculous illness with calcifying lung lesions.

CN IV lesion: Can be caused by trauma to frontal bone; diplopia worse on downgaze; can be ameliorated by tucking chin in ("pathetic nerve palsy").

Punishment is using a stick. Positive reinforcement is using a carrot. Extinction is taking away a carrot. Negative reinforcement is taking away a stick.

Metabolic acidosis triggers hyperkalemia (potassium shift from inside cell to outside). This causes depolarized cells, possibly culminating in ventricular fibrillation.

Listeriosis causes spontaneous abortion. Avoid unpasteurized soft cheese (i.e. Brie) and deli meats during pregnancy.

In primary hypothyroidism, TRH and TSH are already high. Injection of TRH leads to exaggerated response (surprising to me). In hypothalamic hypothyroidism, there is a delayed rise in TSH.

Epstein-Barr virus: mononucleosis, nasopharyngeal carcinoma, Burkitt's lymphoma, primary CNS lymphoma.

"Double-bubble" sign: duodenal atresia, annular pancreas. Duodenal atresia more common in Down syndrome.

Diagnosis of syphilis. Primary syphilis: chanchroid biopsy and darkfield microscopy; Secondary syphilis (bronze maculopapular rash over entire body, including mucous membranes, soles, and palms; also condylomata lata -- flat warty growth on perineum): non-specific serologic tests (VRDL -- cheap, so use first) and specific (FTA-ABS, microhemoagglutinin); Tertiary syphilis (gummas in nervous system and vasculature): specific serologic tests (nonspecific may be negative).

Hypocalcemia: Muscle cramps, perioral and extremity tingling, carpopedal spasm (Trousseau's sign of hypocalcemia), Chvostek's sign.

Gastroschisis versus omphacele: both are abdominal herniations with elevated alpha-feto protein. Gastroschisis will not be covered by peritoneum.

Retroperitoneal organs: SAD PUCKER

Suprarenal glands (as in adrenal glands)

Aorta/IVC

Duodenum (not first part)

Pancreas (except tail, in splenorenal ligament)

Ureters

Colon (only ascending/cecum and descending)

Kidneys
Esophagus
Rectum

Embryonic factoids
Mullerian duct forms ovaries, Fallopian tubes, uterus, and proximal 2/3 of vagina. In males, Sertoli cells secrete Mullerian inhibiting factor.

The falciform ligament / round ligament of the liver is the remnant of the umbilical vein.

The ligamentum arteriosum is the remnant of the ductus arteriosus.

The ligamentum venosum is the remnant of the ductus venosum, which shunts blood from the umbilical vein to the inferior vena cava, bypassing the liver.

The median umbilical ligament is the remnant of the urachus, the connection between the embryonic urinary bladder and the allantois.

The medial umbilical ligaments (lateral to median) are the remnant of the umbilical arteries.

The lateral umbilical ligament is not important to embryology but is an important landmark to use to differentiate direct (medial to ligament) from indirect (lateral to ligament) inguinal hernias, since it overlies the inferior epigastric artery, which arises from the external iliac (not to be confused with the superficial epigastric artery, which arises from the femoral artery).

Meckel's diverticulum is the remnant of the vitelline or omphalomesenteric duct. It may become inflamed (appendicitis-like), present as lower GI bleeding, or act as a nidus for intussusception and volvulus.

Median nerve injury at wrist (suicide attempt for example): denervation of thenar muscles -- flexor pollicis brevis (MP flexion); abductor pollicis brevis; opponens pollicis. Adduction of thumb is controlled by adductor pollicis (ulnar nerve) and thumb flexion at IP joint is controlled by flexor pollicis longus (median nerve proximal to injury site).

Rickettsia and friends

The triad of Rickettsial disease: fever, headache, and rash. "Undifferentiated febrile illness" or "flu-like illness." Rickettsiae grow intracellularly, like inside endothelial cells (this includes all of genus Rickettsia, Coxiella burnetii, and Ehrlichia, but NOT Bartonella, which can be cultured on agar). Need to T-mediated cellular immunity to clear these infections. Go from cell to cell (using actin tail); part of its adaptation to evade host response by always being intracellular.

Epidemic typhus -- Rickettsia prowazekii -- vector: louse -- fever, headache, delayed rash: small pink macules on trunk, sparing palms, soles, and face; increased risk of vessel thrombosis, gangrene of feet or hands. Can be fatal. Flying squirrels a reservoir in southern U.S. Has a latent form, which can cause Brill-Zinsser disease, characterized by fever and headache (no rash) and early rise in IgG titer specific for Rickettsia prowakezii.

Endemic typhus -- Rickettsia typhi -- vector: rat flea, associated with rodents (duh) -- fever, headache, maculopapular rash. Milder than epidemic typhus. Don't want to just kill rats, but both rats and fleas.

Rocky Mountain Spotted fever -- Rickettsia rickettsiae -- vector: wood tick (Dermacentor andersoni), dog tick (Dermacentor variabilis) -- fever, headache, rash on palms, soles, wrists, ankles and later on trunk; conjunctivitis; vessel thrombosis: edema. Early removal of tick will prevent infection. Reservoir in southeastern U.S.

** Vessel thrombosis characteristic of both Rocky Mountain Spotted fever and epidemic typhus (most severe, can cause gangrene).

Scrub typhus (walking through scrub in Thailand) -- Rickettsia tsutsugamushi -- vector: chiggers (larvae of mites) -- fever, headache, scab at bite site, maculopapular rash.

** Treat all rickettsial diseases with doxycycline and chloramphenicol (only latter for pregnant women, slight risk of aplastic anemia, versus bone development insult with tetracylines).

Human ehrlichiosis -- tick-borne, "Rocky Mountain SPOTLESS Fever."

Human Monocytic Ehrlichiosis -- Ehrlichia chaffeensis -- vector: tick-borne (Lone Star tick), carried on white-tailed deer -- think hunters in Missouri. Morula in monocytes with replicating bacteria -- can see on blood smear. Perivascular lymphohistiocytic infiltrates WITHOUT vasculitis (distinguishes from Rickettsia), noncaseating granulomas.

Human Granulocytic Anaplasmosis -- Anaplasma phagocytophilum -- vector: tick-borne (Ixodes tick), carried on white-footed mice (small mammals). Morula in PMNs. Clinically indistinguishable from human monocytic ehrlichiosis -- need PCR.

** Ixodes tick also transmits Borrelia burgdorferi (Lyme disease), Babesia (parasite) and Francisella tularensis, and human granulocytic anaplasmosis.

Q fever -- Coxiella burnetii -- endospore form found in non-pasteurized milk products, cow hides, dried placental remnants (no arthropod vector!) -- can be inhaled into lungs, caused a pneumonia similar to Mycoplasma. Can be asymptomatic, cause granulomatous hepatitis "donut hole granuloma" -- lipid droplet in middle, or "culture negative" subacute endocarditis. Only rickettsial disease with pneumonia AND no rash. Obligate intracellular and steals ATP like Rickettsia, Chlamydia.

Cat scratch disease -- Bartonella hensalae -- Local lymphadenopathy, low-grade fever malaise, self-limited disease; associated with bacillary angiomatosis (proliferation of small blood vessels in skin and organs of AIDS patients -- can also be caused by B. quintana), also may be complicated by bacteremia and "culture-negative" subacute endocarditis.

Trench fever -- Bartonella quintana -- vector: lice-born like Rickettsia prowakezii, causes high fevers, headache, back and leg pains; characterized by multiple relapses (quintana -- every 5 days); usually resolves, not fatal.

Oroya fever -- B. bacilliformis -- severe hemolytic anemia, vascular skin warts called verruga peruana (related to bacillary angiomatosis -- something about Bartonella). Transmitted by sand fly, which also transmits Leishmaniasis. Organisms adherent to blood cells (very small gram negative rods).

Leptospira interrogans -- long, thin, aerobic spirochete -- found in urine of animals, can penetrate abraded skin and mucous membranes, especially if you swim in contaminated water. Biphasic illness: (1) leptospiremic phase, invades blood and CSF, causing fever, headache, malaise, and severe muscle aches, red conjunctiva, and photophobia; resembles Rickettsial symptoms; followed by 1 week afebrile period; (2) immune phase correlates with IgM antibodies, can now culture from urine, meningismus, elevated CSF white blood count. Can also cause Weil's disease: hepatitis with jaundice (but normal transaminases!), renal failure, mental status changes, hemorrhage in many organs.

Endocarditis

Aortic and mitral > tricuspid (IV drug users) >> pulmonic. Bacteremia characteristic, and predisposes to. Regurgitant jet damage (mitral valve prolapse WITH regurgitation) will predispose, as will pre-existing valvular damage from rheumatic fever.

Acute: Staph aureus, beta-hemolytic strep -- Group A, Group B, Group G, S. pneumoniae (in context of pneumonia, developing world), N. gonorrhea (rare). Subacute: strep. viridans, Enterococcus, Group D strep -- onset over weeks to months, low grade fever, night sweats, weight loss.

HACEK organisms: slow-growing causes of endocarditis. Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella.

Pathogenesis. Initial injury, get thrombus, bacteria grows in fibrin-platelet matrices (hence gram negative endocarditis is rare, because they don't stick as well as gram positives). Build-up over time, "cauliflower" forms. Need long course of antibiotics to "clear away layers." Need BACTERICIDAL drugs.

FROM JANE:

Fever
Roth's spots, white spots on retina, surrounded by hemorrhage, due to immune complex vasculitis
Osler's nodes, immune complex related, tender
Murmur

Janeway lesions, immune complex related, painless erythematous lesions on palm or sole
Anemia (of chronic disease)

Nail-bed splinter hemorrhages
Emboli, can be septic pulmonary emboli if right-sided

Treatment: Penicillin G, Ceftriaxone +/- gentamicin (aminoglycoside synergistic) is 1st line. Synergy is especially for important for enterococcus because it is intrinsically resistant to penicillin. Vancomycin if allergic to above. For VRE, need to treat with daptomycin or linezolid +/- gentamicin.

S. bovis -- also think colon cancer.

Complications of acute endocarditis: brain abscesses, abscess going into conduction system -- heart block and death. Treatment for acute: nafcillin/cefazolin + gentamicin for MSSA; vancomycin + gentamicin for MRSA (also consider rifampin, daptomycin, linezolid as needed); penicillin G / ceftriaxone for beta-hemolytic strep.

Prophylaxis a good idea for some high risk groups post dental procedures.

Whipple's disease (Tropheryma whipplei) can cause endocarditis. Looks for PAS-positive macrophages on histology.

QBank notes: 2/14/2010 [48]

When volume depleted, the drive to maintain intravascular volume supersedes the drive to maintain osmolality. Therefore you can get ADH secretion and profound hyponatremia.

Free water clearance is the amount of solute-free water that needs to be removed to make the urine osmolality the same as plasma osmolality. Negative free water clearance is the amount of solute-free water that needs to be added to make the urine osmolality the same as plasma osmolality.

Positive skew means the tail of the distribution is on the right. In other words, mean > median. The opposite applies for negative skew. For skewed distributions, median is the better representation of central tendency.

Beta blockers. A through M are beta1-selective, including atenolol, esmolol, and metoprolol. Exception: carvedilol, labetalol are nonselective. Acebutalol, carteolol, pindolol have intrinsic sympathomimetic activity.

Femoral nerve. Anterior compartment. Quadriceps femoris, sartorius "check bottom of foot for gum", pectineus. Obturator nerve. Medial compartment (gracilis, adductor longus, adductor brevis, anterior portion of adductor magnus). Adduct thigh, medially rotate thing. Tibial nerve. Posterior compartment of thigh (semimembranosus, semitendinosus, long head of biceps femoris, posterior portion of adductor magnus). Flex the knee, extend the thigh. Posterior compartment of leg (gastrocnemius, soleus, flexor digitorum longus, flexor hallucis longus, tibialis posterior). Plantarflexion, flex digits, inversion. Common peroneal nerve. Short head of biceps femoris. Flex knee. Superficial peroneal nerve. Lateral compartment of leg (peroneus longus, peroneus brevis). Eversion. Deep peroneal nerve. Anterior compartment of leg (tibialis anterior, extensor hallucis longus, extensor digitorum). Dorsiflexion, extend digits, inversion.

Muscle contraction velocity is determined by "myosin ATPase activity" -- however myosin ATPase activity does not affect maximum load that can be lifted. Conversely, increasing frequency of contraction, muscle hypertrophy, and increased motor unit recruitment will affect amount of weight that can be lifted but not the contraction velocity.

During pregnancy, increased estrogen stimulates more thyroid binding globulin (TBG). This can cause elevated serum thyroxine (T4). However, free serum thyroxine remains normal because of intact feedback mechanisms. During pregnancy, thyroid enlargement, tenderness, heat intolerance, and palpitations are normal. Do not interpret the woman as being in a hyperthyroid condition based on the symptoms and high total serum T4 levels; all these changes are normal.

Pemphigus vulgaris versus bullous pemphigoid. Pemphigus vulgaris: positive Nikolsky's sign (epidermis exfoliates on rubbing); lesions of oral mucosa; bad prognosis -- most die within a year without treatment. Bullous pemphigoid: negative Nikolsky's sign, no oral mucosal lesions, usually do quite well.

Mental retardation versus autism. Mental retardation: even decrease in all skills, still communicative with people, 1:1 male:female ratio, most common causes are fetal alcohol syndrome, fragile-X syndrome, and Down syndrome. Autism: uneven performance in skills, not communicative, 4:1 male:female ratio, association with chromosome 15. ADHD: 10:1 male to female ratio.

Prolactinomas suppress the HPTA axis.

N. gonorrhoeae arthritis: petechial rash, tenosynovitis, antigenic variation and phase variation of the pili allow reinfections. Especially susceptible to complement mediated killing. Treat with ceftriaxone.

Ascaris lumbricoides. Giant roundworm. Can cause small bowel obstruction. "Tinkly" sounds on auscultation; distended abdomen.

It seems infantile polycystic kidney disease is distinguished from adult polycystic kidney disease by mode of inheritance. The infantile disease is also known as ARPKD. The adult form is now known as ADPKD. ARPKD: presents in infancy with renal (and often hepatic) cysts, progressive renal failure, bilateral enlarged kidneys with smooth surfaces; spongelike appearance with multiple small cysts in cortex and medulla.

Strep pyogenes -- non immunogenic hyaluronic acid capsule.

Renal insufficiency can cause decreased calcium (decreased synthesis of 1,25(OH)2-D3) and increased phosphate (decreased excretion). Increased calcium and phosphate suggests Vit D intoxication. Decreased calcium and phosphate suggest Vit D deficiency (rickets in kids, osteomalacia in adults). Increase in calcium and alkaline phosphatase, and decrease in phosphate, suggest hyperparathyroidism.

Ketotifen: opthalmic selective, noncompetitive H1 antagonist. Limited systemic absorption. Stabilizes mast cells. Good for IgE-mediated conjunctivitis.

Intrinsic factor is degraded at alkaline pH. It allows B12 absorption. It exerts negative feedback on gastrin.

QBank notes: 2/13/2010 [48]

UTI DDx: Gram negative rod -- E. coli, causes cystitis, can develop bacteremia and acute respiratory distress syndrome (ARDS). Gram negative diplococci - Neisseria gonorrhea, can cause symptomatic urethritis most commonly in young, sexually active males; Moraxella catarrhalis, usually not UTI, but COPD exacerbation (along with H. influenza, Legionella pneumophila) as well as otitis media (along with H. influenza, S. pneumoniae). Gram positive cocci -- Staph saprophyticus -- UTI in young, sexually active women; Enterococcus - nosocomial patients with indwelling catheters, can be complicated by bacteremia and subacute endocarditis but not ARDS. Gram-positive diplococci - Strep pneumo, most common cause of community acquired pneumonia; not associated with UTI.

Left adrenal vein and left gonadal vein drain into left renal vein (think cross). Right adrenal vein and right gonadal vein drain directly into the inferior vena cava.

Latent (primary) TB is asymptomatic and lesions are in lower upper lobe or upper lower lobe as well as hilar node involvement. Active (re-infection) TB is symptomatic, with fever, night sweats, weight loss and cough, and lesions in the apex of the lung.

Niacin: positive effect on all blood lipids. Facial flushing, hyperglycemia, hyperuricemia. (Contrast red man syndrome, Vancomycin reaction).

Seizure pharm. Treat tonic-clonic (grand mal) seizures with phenytoin, valproic acid, and carbamazepine (1st line therapy). Treat absence seizures (petit mal) with ethosuximide (1st line) and valproic acid. Treat status epilepticus with benzos -- diazepam and lorazapem -- (1st line for acute) and phenytoin (1st line for prophylaxis). Valproic acid (everything but status epilepticus) and phenytoin (everything but absence) are the most versatile anticonvulsants. On the other end of the spectrum, ethosuximide is only used for absence seizures.

The great saphenous vein passes anterior to the medial malleolus at the ankle and posterior to the medial side of the knee. It then passes through the saphenous hiatus of the fascia lata to empty into the femoral vein slightly below the inguinal ligament.

Type I collagen in skin, bone, tendon, and most organs. Type II in cartilage, vitreous humor. Type III in skin, blood vessels, uterus. Type IV in basement membranes.

Anterior to tonsils: palatoglossus. Posterior: palatopharyngeus. Both are innervated by the vagus nerve.

QBank notes: 2/12/09 [48]

The penis, vagina, and anal canal drain to the medial side of the horizontal chain of superficial inguinal lymph nodes. Stomach cancers go to Virchow's nodes (left supraclavicular).

Pre-eclampsia = hypertension, proteinuria, edema; eclampsia: +seizures.

Since transplanted hearts are de-innervated, chest pain does not occur with progressive graft arteriosclerosis (intimal thickening without atheroma formation or significant inflammation). Immunosuppresants do not prevent graft arteriosclerosis.

Superior oblique. SO LID. Lateral rotation (abduction), intorsion, depression. Works with inferior rectus (which tends to extort and depress). Inferior oblique: adduction, extorsion, elevation. Works with superior rectus, which tends to intort and elevate.

In female patient with IUD, think Actinomyces israelii. Can cause lumpy jaw, female reproductive, or gastrointestinal mycetomas with sulfur granules.

South American immigrant with megaesophagus. Chagas disease, Trypanosoma cruzi. Presents with cardiac failure, megaesophagus, megacolon.

Haptoglobin binds free hemoglobin serum. Decreased haptoglobin, high bilirubin -- mostly indirect: intravascular hemolysis. Normal haptoglobin, high bilirubin -- mostly direct: obstructive jaundice. Normal haptoglobin, high bilirubin -- mostly indirect: Crigler-Najjar.

Catecholamine metabolites, important in pheochromocytoma (episodic or chronic hypertension, palpitations, sweating, headache, vomiting; 10% extra-adrenal, 10% bilateral, 10% malignant): VMA - vanillylmandelic acid; HVA - homovanillic acid. 5-HIAA - serotonin syndrome, i.e. carcinoid syndrome: diarrhea, flushing, wheezing (from bronchoconstriction).

Defecation: relaxation of internal anal sphincter, tensing of external anal sphincter, conscious urge to defecate. Pudendal nerve -- external sphincter; pelvic nerve -- internal sphincter.

Diabetes can overload loop of Henle with increased fluid and electrolytes, interfering with establishment of medullar osmotic gradient. This causes functional resistance to ADH.

Transudative edema -- liver cirrhosis. Exudative edema -- inflammation, lymphatic blockage.

AML. M1 = no differentiation, mostly myeloblasts. M2 = some differential, blasts and some promyelocytes. M3 = APL, lots of faggot cells (promyelocytes with Auer rods). M5 = promonocytes with nonspecific esterases. M7 = promegakaryocytes.

Left-sided neglect is a lesion of right parietal lobe. Also associated with extinguishing to double simultaneous stimuli of the stimuli on neglected side.

Pneumonia

Pleurisy is inflammation of the pleura, it may be infectious or non-infectious. Empyema is infection of the pleural space.

Classical bacterial pneumonias
Pneumococcus
Staphylococcus

Streptococcal (beta-hemolytic)
Klebsiella

Pneumococcus
Disease of the elderly, commonly follow upper respiratory infection. Most common pneumonia. Abrupt onset of fever, shaking chills, purulent sputum. Leukocytosis, hypoxia. Lobar pneumonia on X-ray. Rx: penicillin, third generation cephalosporin. Classically, axillary lobar segment.

Staphylococcus
In community, see it postviral, for instance after post-influenza. Also common nosocomial. Can get cavitations, unlike pneumococcus. Variable presentation on X-ray: looks lobar is inhaled, cavities if hematogenous. Acute presentation, leukocytosis.

Streptococcus
Pleural effusions early in infection, can lead to empyema. Use penicillins and clindamycin if severe infection to stop toxin production early.

Klebsiella

In alcoholics, diabetes, people with underlying lung disease. Red currant jelly sputum: due to necrotizing nature of Klebsiella, there is blood in sputum. Leukopenia. Bulging fissure (infection expands the affected lobe). Rx: Cephalosporins, quinolones.

Haemophilus
Usually non-typeable, common cause of bronchitis and sometimes pneumonia in patients COPD. Other organisms that can cause similar disease: Legionella pneumophila, Moraxella catarrhalis. Rx: Ampicillin, cephalosporins.

Atypical pneumonias: Mycoplasma pneumoniae, Legionella pneumophila, Chlamydia pneumoniae

Mycoplasma Pneumonia

Classic walking pneumonia, second-most cause of community-acquired pneumonia after pneumococcus. Younger population (young adults especially). Spread by droplets; average incubation 3weeks versus a day or two for pneumococcus. Symptoms: low-grade fever, malaise, headache, non-productive cough, ear pain with bullous myringitis. Diagnosis: PCR, EIA, bedside "cold agglutinin" test. Rx: Tetracyclines, macrolides, quinolones. Extra-pulmonary manifestations: Can cause IgM antibodies to red cell I antigen, Stevens-Johnson syndrome, CNS disease. X-ray: interstitial pattern, also what Chlamydia looks like.

Chlamydia pneumonia (and psittaci -- zoonosis)
No peptidoglycan like mycoplasma, though it does have a cell wall; obligate intracellular organism. Resembles Mycoplasma. Tx: Tetracyclines or macrolides.

Legionella pneumophila
Small, fastidious, aerobic gram negative that multiplies inside macrophages (DOT and ICM virulence factors prevent phagosome-lysosome fusion). If you have impaired macrophage function as in COPD, you are more susceptible. You need TH1/IFN-gamma to activate macrophages to kill the organism. Legionella can hide inside amoeba in water, as well as enter a low metabolic state inside biofilm. Symptoms: high fever but relative bradycardia (pulse-temperature dissociation), nonproductive cough, diarrhea and abdominal pain, hyponatremia. Diagnosis: culture on charcoal yeast extract agar with cysteine; urinary antigen, serology; patchy, nodular infiltrates -- pleural or perihilar based on X-ray. Rx: quinolones or macrolides.

Aspiration pneumonia
Associated with anaerobes. Chronic infection, low grade fever, putrid foul smelling sputum. Cavitary lesions and abscesses in dependent lung segments.

Nosocomial pneumonia
Staph aureus, enteric gram-negative rods.

Septic shock

Meningococcemia case history: fever, low blood pressure, compensatory tachy, diffuse petechiae; prolonged PT, PTT, low platelets, D-dimer present (indicating DIC); cardiac output high, systemic vascular resistance low; mild renal failure.

LPS can give septic shock: O-specific side chain is antigenic but not toxic; core region; Lipid A part is toxic. Basically an exaggerated, maladaptive inflammatory response. LPS activates macrophages via CD14; it also activates coagulation system -- hence DIC.

TLRs: family of 11 proteins; distinct extracellular domains, but similar intracellular domains; form heterodimers when activated. Activated by things like peptidoglycan, lipoteichoic acid, fungal glucan, viral RNA, LPS, oxLDL, flagellin, bacterial CpG DNA. Not just bacterial products but fungal and viral and even parasites! Bacterial TLRs on outer membrane, but also intracellular receptors for viral infections. Macrophages are primary responders to bacterial products.

Cytokines and other mediators. Macrophages release a lot of shit. Endothelial cells produce a lot of cytokines, plus NO (contributes to vasodilation, reduction in systemic vascular resistance, shock).

Tachypnea (respiratory alkalosis), fever --> compensated metabolic acidosis, hypotension, DIC --> ARDS, renal failure, hepatic damage. DIC: Consumption of platelets and coagulation factors. Microinfarcts. Hemorrhage due to consumption. DIC is major contributor to renal failure in septic shock. ARDS: Lungs fill up with fluid due to endothelial damage, may require intubation.

Can be gram positive, gram negative, mixed, or fungal, even viral in kids.

Risks factors: central venous catheter, malignancy causing neutropenia, HIV infection, old age, patients post-op for GI problem.

Treatment: First priority is keeping blood pressure up: fluid replacement, and pressors to keep BP above 90; start broad spectrum antibiotics promptly. Anti-inflammatory drugs don't work. Activated Protein C somewhat effective: reduces clotting, general anti-inflammatory effect.

Matching questions (on test?)

TLR2 -- peptidoglycan, glucan

TLR4 -- LPS

TLR5 -- Flagellin

CD14 -- LPS

Dectin -- Glucan (fungal)

Emerging problems with antibiotic resistance

How to treat bullous impetigo due to MRSA?

TMP-SMX (oral); Vancomycin (IV, needs hospitalization); Clindamycin (oral, works against most community strains); Linezolid (oral, expensive); Daptomycin

Due to MSSA?

Dicloxacillin (penicillinase-resistant penicillin); cephalexin (1st gen cephalosporin)

Strep pneumoniae

Intermediate- and high-level resistance to penicillins. Treat with ceftriaxone (3rd gen cephalosporin) because resistance is due to changes in penicillin binding protein. You can overcome PBP changes, but not beta lactamase production, with increased dose of drug.

VRE
Created by widespread use of oral vancomycin for C. difficiles infections in the '90s.

UTIs: TMP-SMX, then ciprofloxacin used to be standard treatment. Resistance cropping up.

Otitis media: Empirical amoxicillin. Usually it's Pneumococcus, Moraxella, or H. influenza. Can overcome pneumococcal resistance with higher dose. Moraxella and H. influenza get better anyway -- don't actually need antibiotic. Difficult to culture middle ear and figure out causative bug. If doesn't get better use ampicillin/clavulanic acid combo, or 2nd/3rd gen cephalosporin to overcome beta-lactamase resistance. Ace card is ceftriaxone.

Community-acquired pneumonia: Macrolide or doxycycline; if recent antibiotic treatment, advanced macrolide or quinolone AND amoxicillin/clavulanic acid.