General knowledge (qbanks, first aid etc) Flashcards
What are the CYP 450 (microsomal monooxygenase) inducers?
carbamazepine, phenobarbital, phenytoin, rifampin, griseofulvin
What are the CYP 450 (microsomal monooxygenase) inhibitors?
Cimetidine, ciprofloxacin, erythromycin, azole antifungals, grapefruit juice, isoniazid, ritonavir (protease inhibitors)
What is HLA-A3?
Hemochromatosis.
What is HLA-B27?
PAIR
Psoriatic arthritis, Ankylosing spondylitis, arthritis of Inflammatory bowel disease, Reactive arthritis (formerly Reiter syndrome)
What is DQ2/DQ8?
Celiac Disease
What is DR2?
Multiple sclerosis, hay fever, SLE, Goodpasture syndrome
What is DR3?
Diabetes mellitus type 1, SLE, Graves disease
What is DR4?
Rheumatoid arthritis, diabetes mellitus type 1.
There are 4 walls in a “rheum”
What is DR5?
Pernicious anemia -> vitamin B12 deficiency, Hashimoto thyroiditis.
where do N-linked and O-linked glycosylation occur?
N-linked: ER (asparagine)
O-linked: Golgi (usually to serines or threonines)
What’s an allergic reaction in blood transfusion?
Type 1 hypersensitivity reaction against plasma proteins in transfused blood.
Urticaria, pruritis, wheezing, fever. Treat with antihistamines.
What is an anaphylactic reaction in blood transfusion?
Severe allergic reaction. IgA deficient individuals must receive blood products that lack IgA.
Dyspnea, bronchospasm, hypotension, respiratory arrest, shock.
What is a febrile non-hemolytic transfusion reaction?
Type II hypersensitivity reaction. Host antibodies against donor HLA antigens and leukocytes.
Fever, headaches, chills, flushing.
What is an acute hemolytic transfusion reaction?
Type II hypersensitivity reaction. Intravascular hemolysis (ABO blood group incompatibility) or extravascular hemolysis (host antibody reaction against foreign antigen on donor RBCs).
Fever hypotension, tachypnea, tachycardia, flank pain, hemoglobinemia (intravascular), jaundice (extravascular hemolysis).
What are the autoantibodies in SLE, antiphospholipid syndrome?
Anti-cardiolipin, lupus anti-coagulant
What are the autoantibodies in Limited scleroderma (CREST)?
anticentromere
What are the autoantibodies in Pemphigus vulgaris?
anti-desmoglein
What are the autoantibodies in SLE?
anti-dsDNA, anti-Smith
What are the autoantibodies in Type 1 diabetes mellitus?
anti-glutamate decarboxylase
What are the autoantibodies in Bullous pemphigoid?
anti-hemidesmosome
What are the autoantibodies in drug-induced lupus?
anti-histone (drugs SHIPP - sulfonamide, hydralizine, isoniazid, phenytoin, procainamide)
What are the autoantibodies in polymyositis, dermatomyositis?
anti-jo-1, anti-SRP, anti-Mi-2
What are the autoantibodies in hashimoto thyroiditis?
anti-microsomal, anti-thyroglobulin
What are the autoantibodies in primary biliary cirrhosis?
anti-mitochondrial
What are the autoantibodies in SLE, nonspecific
anti-nuclear
What are the autoantibodies in scleroderma (diffuse)?
anti-Scl-70 (anti-DNA topisomerase I)
What are the autoantibodies in autoimmune hepatitis?
anti-smooth muscle
What are the autoantibodies in Sjorgen’s syndrome?
anti-SSA, anti-SSB (anti-Ro, anti-La)
What are the autoantibodies in Grave’s disease?
anti-TSH receptor
What are the autoantibodies in Mixed connective tissue disease?
anti-U1 RNP (ribonucleoprotein)
What are the autoantibodies in Granulomatosis with polyangitis (Wegener)?
c-ANCA (PR3-ANCA)
What are the autoantibodies in Celiac disease?
IgA anti-endomysial, IgA anti-tissue transglutaminase
What are the autoantibodies in Microscopic polyangitis, Churg-Strauss?
p-ANCA (MPO-ANCA)
What are the autoantibodies in RA?
Rheumatoid factor (antibody, most commonly IgM, specific to IgG Fc region), anti-CCP
What are you susceptible to in granulocyte deficiency?
Staphylococcus, Burkholderia cepacia, Serratia, Nocardia. Candida and aspergillus too.
What do you get in T cell deficiency?
sepsis from bacteria or CMV, EBV, JCV,VZV, chronic infection with resp/GI viruses. Also candida, PCP
What do you get in B cell deficiency?
SHiNE SKiS - Strep pneumoe, Hemophilus i B, neisseria meningitidis, E. coli, Salmonella, Klebsiella pneumo, strep B. Enteroviral encephalitis, polio virus (dont get live vaccine!) GI giardiasis (no IgA).
What are the three B cell disorders?
X-linked (Bruton) agammaglobulinemia, Selective IgA deficiency, Common variable immunodeficiency
What is X-linked agammaglobulinemia?
Defect in BTK, a tyrosine kinase gene. no B cell maturation. X linked recessive and increased in Boys.
Recurrent bacterial and enteroviral infections after 6 months (decreased maternal IgG).
What is selective IgA deficiency?
unknown but most common primary immunodeficiency.
Majority asymptomatic.
Can see airway and GI infections, Autoimmune disease, Atopy, Anaphylaxis to IgA containing products.
IgA levels low but not IgG or IgM.
What is common variable immunodeficiency?
Defect in B cell differentiation. Many causes.
Can be acquired in 20s-30s; increased risk of autoimmune disease; bronchiectasis, lymphoma, sinopulmonary infections.
Decreased plasma cells, decreased immunoglobulins.
What are the T-cell disorders? four of them
Thymic aplasia (DiGeorge Syndrome), IL-12 receptor deficiency, Autosomal dominant hyper IgE syndrome (Job syndrome), Chronic mucocutaneous candidaisis.
What is thymic aplasia?
Also known as DiGeorge syndrome.
22q11 deletion; failure to develop 3rd and 4th pharyngeal pouches -> absent thymus and parathyroids.
Tetany (hypocalcemia), recurrent viral/fungal infections (T-cell deficiency), conotruncal abnormalities (e.g. tetralogy of Fallot, truncus arteriosus).
Decreased T cells, decreased PTH, decreased Ca+2.
Absent thymic shadow on CXR.
22q11 deletion by FISH.
What is IL-12 receptor deficiency?
Decreased TH1 response. Autosomal recessive.
Disseminated mycobacterial and fungal infections; may present after administration of BCG vaccine.
Decreased IFN-gamma.
What is autosomal dominant hyper-IgE syndrome (job syndrome)?
Deficiency of Th17 cells due to STAT3 mutation -> impaired recruitment of neutrophils to sites of infection.
FATED: coarse Facies, cold (non-inflamed) staphyloccocal Abscesses, retained primary Teeth, increased IgE, Dermatologic problems (eczema).
Increased IgE, decreased IFN-gamma.
What is chronic mucocutaneous candiasis?
T-cell dysfunction. many causes.
Noninvasive Candida albicans infections of skin and mucous membranes.
Absent in vitro T cell proliferation in response to Candida antigens.
Absent cutaneous reaction to Candida antigens.
What are the combined B and T cell disorders? four of them
Severe combined immunodeficiency, Ataxia-telangiectasia, Hyper-IgM syndrome, Wiskott-Aldrich syndrome
What is SCID?
several types including defective IL-2R gamma chain (most common, X-linked), adenosine deaminase deficiency (autosomal recessive).
Failure to thrive, chronic diarrhea, thrush. Recurrent viral, bacterial, fungal, and protozoal infections.
Tx: bone marrow transplant (no concern for rejection).
Decreased T-cell receptor excision circles (TRECs). Absence of thymic shadow (CXR), germinal centers (lymph node biopsy), and T cells (flow cyt)
What is ataxia telangiectasia?
Defects in ATM gene leading to double strand DNA breaks and cell cycle arrest.
Triad: cerebellar defects (Ataxia), spider Angiomas (telangiectasia), IgA deficiency.
Increased AFP and decreased IgA, IgG, and IgE.
Lymphopenia, cerebellar atrophy.
What is hyper IgM syndrome?
Most commonly due to defective CD40L on Th cells = class switching defect. X - linked recessive.
Severe pyogenic infections early in life; opportunistic infection with pneumocystis, Cryptosporidium, CMV.
Increased IgM, decreased IgG, IgA, and IgE.
What is Wiskott-Aldrich syndrome?
Mutation in the WAS gene X-linked recessive. T cells unable to reorganize actin cytoskeleton.
WATER: Wiskott-Aldrich: Thrombocytopenic purpura, Eczema, Recurrent infections. Increased risk of autoimmune disease and malignancy.
Decreased to normal IgG, IgM.
Increased IgE, IgA.
Fewer and smaller platelets.
What are the phagocyte dysfunction disorders? three of them
Leukocyte adhesion deficiency (type 1), Chediak-Higashi syndrome, Chronic granulomatous disease
What is leukocyte adhesion deficiency (type 1)?
Defect in LFA-1 integrin (CD18) protein on phagocytes; impaired migration and chemotaxis; autosomal recessive.
Recurrent bacterial skin and mucosal infections, absent pus formation, impaired wound healing, delayed separation of umbilical cord (greater than 30 days).
Increased neutrophils, absence of neutrophils at infection sites.
What is Chediak-Higashi syndrome?
Defect in lysosomal trafficking regulator gene (LYST). Microtubule dysfunction in phagosome-lysosome fusion; autosomal recessive.
Recurrent pyogenic infections by staphylococci and streptococci, partial albinism, peripheral neuropathy, progressive neurodegeneration, infiltrative lymphohistiocytosis.
Giant granules in neutrophils and platelets. Pancytopenia. Mild coagulation defects.
What is chronic granulomatous disease?
Defect of NADPH oxidase leading to decreased reactive oxygen species (superoxide) and absent respiratory burst in neutrophils; X-linked recessive. Increased susceptibility to catalase positive organisms (PLACESS for your CATS): Pseudomonas, Listeria, Aspergillus, Candida, E. coli, S. aureus, Serratia. Abnormal dihydrorhodamine (flow cyt) test. Nitroblue tetrazolium dye test is negative (test out of favor).
What are the organ specific effects of chronic rejection? heart, lungs, kidneys, liver
T cell and antibody mediated damage that is irreversible.
Heart: atherosclerosis
Lungs: bronchiolitis obliterans.
Liver: vanishing bile ducts
Kidneys: vascular fibrosis, glomerulopathy.
What do you see in graft-vs-host disease?
Maculopapular rash, jaundice, diarrhea, hepatosplenomegaly.
Usually in bone marrow and liver transplants because those are rich in lymphocytes.
What are the afferents and efferents for aortic/carotid baroreceptor response?
Carotid sinus - dilatation of the internal carotid artery just above bifurcation of common artery. Afferent fibers come from Hering’s nerve, which is a branch of the glossopharyngeal nerve (CN IX).
Aortic arch baroreceptors - fibers run within the vagus nerve (CN X).
Both sets of afferents terminate in the solitary nucleus of the medulla.
Remember: aortic arch only senses increase in BP while carotid barorceptors sense increases and decreases in BP. Decreased pressure means less stretch which means less baroreceptor firing and increased efferent sympathetic firing.
Increased pressure means increased stretch and increased baroreceptor firing.
What is a common cause of recurrent lobar hemorrhage?
Cerebral amyloid angiopathy. More benign clinical course than hemorrhagic strokes associated with hypertension (those are oarger and then to involve the basal ganglia vs. being in the lobar areas)
What are the causes of aplastic anemia?
Failure or destruction of myeloid stem cells:
- radiation and drugs (benzene, chloramphenicol, alkylating agents, antimetabolites)
- viral agents (parvovirus B19, EBV, HIV, HCV)
- Fanconi anemia (DNA repair defect)
- idiopathic (immune mediated, primary stem cell defect); may follow acute hepatitis.
What are the common 3 childhood brain tumors?
- Pilocytic astrocytomas are most common. Low grad neoplasms from astrocytomas. Cerebellum is most common location. Cystic with tumor nodule protruding from the wall. On imaging studies, pilocytic astrocytoma appears as a mass with both solid and cystic components on T1. On histo, pilocytic astrocytes and Rosenthal fibers are seen. Good prognosis.
- Medulloblastomas: second most common brain tumor. Most common malignant one. In cerebellum (most commonly vermis). Solid and composed of sheets of blue small blue cells with hyperchromatic nuclei and scant cytoplasm - forming Homer-Wright rosettes. This tumor is highly malignant with poor prognosis.
- Ependymomas: third most common child tumor. Lining of ventricle and can obstruct flow of ventricle. Presents with hydrocephalus. On histo, there is tumor with gland like structures like rosettes (perivascular rosettes).
What is giant cell tumor?
Benign tumor. 20-40 years old. Epiphyseal end of long bones.
Locally aggressive benign tumor often around knee.
“Soap bubble” appearance on x-ray.
Multinucleated giant cells.
What is osteochondroma?
Most common benign tumor. Exostosis.
Males <25 years old.
Mature bone with cartilaginous cap. Rarely transforms to chondrosarcoma.
What is an osteosarcoma?
2nd most common primary malignant bone tumor (after multiple myeloma).
Bimodal distribution: 10-20 years old (primary), > 65 yrs old (secondary).
Predisposing factors: Paget disease of bone, bone infarcts, radiation, familial retinoblastoma, Li-Fraumeni syndrome (germline p53 mutation).
Metaphysis of long bones, often around knee.
Codman triangle (from elevation of periosteum) or sunburst pattern on x-ray. Aggressive. Treat with surgical en bloc resection (with limb salvage) and chemotherapy
What is Ewing sarcoma?
Boys < 15 years old.
Commonly appears in diaphysis of long bones, pelvis, scapula, and ribs.
Anaplastic small blue cell malignant tumor. Extremely aggressive with early metastases, but responsive to chemotherapy.
“Onion skin” appearance in bone.
Associated with t(11;22) translocation.
11 + 22 = 33 (Patrick Ewing’s jersey number)
What is a chondrosarcoma?
Rare, malignant, cartilaginous tumor.
Men 30-60 years old. Usually located in pelvis, spine, humerus, tibia, or femur.
Malignant cartilaginous tumor. May be of primary origin or from osteochondroma. Expansile glistening mass within the medullary cavity.
What are the four W’s of infant deprivation?
Weak, wordless, wanting, wary.
Deprivation for >6 months can lead to irreversible changes.
Severe deprivation can result in infant death.
What is Tourette syndrome?
Onset before age 18.
Sudden, rapid, recurrent, nonrhythmic, stereotyped motor and vocal tics that persist for >1 year.
Coprolalia (involuntary obscene speech) found in only 10-20%.
Associated with OCD and ADHD.
Tx: antipsychotics and behavioral therapy.
What is Rett disorder?
X-linked disorder. Seen almost exclusively in girls (affected males die in utero or shortly after birth).
Symptoms present around 1-4 years of age: regression characterized by loss of development, loss of verbal abilities, intellectual disability, ataxia, and stereotyped hand-wringing.
What are the neurotransmitter changes in the following diseases: Alzheimer's Anxiety Depression Huntington disease Parkinson disease Schizophrenia
Alzheimer’s: Decreased ACh
Anxiety: Increased norepinephrine, Decreased GABA and Serotonin.
Depression: Decreased norepinephrine, serotonin, and dopamine.
Huntington disease: Decreased GABA, ACh. Increased dopamine.
Parkinson disease: Decreased dopamine. Increased serotonin and ACh.
Schizophrenia: increased dopamine.
What is depression like in the elderly?
Depression in the elderly can present like dementia (pseudodementia).
When is tactile sensation seen?
In alcohol withdrawal (e.g. formication - sensation of bugs crawling on one’s skin). Also seen in cocaine abuse.
What is the breakdown of schizophrenia?
Chronic mental disorder with psychosis, disturbed behavior, and thought and decline in functioning that lasts > 6 months. Increased dopamine, decreased dendritic branching.
Brief psychotic disorder - less than 1 month, usually stress related.
Schizophreniform disorder - 1-6 months
Schizoaffective disorder - at least 2 weeks of stable mood with psychotic symptoms, plus a major depressive, manic, or mixed (both) episode.
2 subtypes: bipolar or depressive.
Frequent cannabis use is associated with psychosis/schizophrenia in teens.
Presents early in men (early 20s) vs women (late 20s/early 30s).
What is manic episode?
Lasts at least 1 week. Manics DIG FAST Distractibility Irresponsibility - seeking pleasure no matter what Grandiosity - inflated self-esteem Flight of ideas - racing thoughts Increase in goal-directed Activity/psychomotor Agitation. Decreased need for Sleep. Talkativeness or pressured speech.
What is a hypomanic episode?
Not as severe as manic episode (no social/occupational disruption). Lasts at least 4 consecutive days.
What is a cyclothymic disorder?
dysthymia and hypomania; milder form of bipolar disorder lasting at least 2 years.
What is major depressive disorder?
Must have 6-12 months. at least 5 of the following 12 symptoms for at least 2 weeks during an episode. SIG E CAPS Sleep disturbance Loss of Interest (anhedonia) Guilt or feelings of worthlessness Energy loss and fatigue Concentration problems Appetite/weight changes Psychomotor retardation or agitation. Suicidal ideations.
Patients with depression have the following sleep changes: decreased slow wave sleep, decreased REM latency, Increased REM early in cycle, Increased total REM sleep, repeated nighttime awakenings, early-morning awakening (important screening question).
What is dysthymia?
Persistent depressive disorder
Depression, often milder, lasting at least 2 years.
What is atypical depression?
mood reactivity (can feel briefly happy in response to positive events), reversed vegetative symptoms (hypersomnia and weight gain), leaden paralysis (heavy feeling in arms/legs), and long-standing interpersonal rejection sensitivity. Treatment is MAO inhibitors and SSRIs.
What are the risk factors for suicide completion?
SAD PERSONS Sex (male) age (teenagers or elderly) Depression Previous Attempt Ethanol or drug use loss of Rational thinking Sickness (med illness, 3 or more prescription meds) Organized plan No spouse (divorced, widowed, single...no children) Social Support Lacking.
Women try more often, but men succeed more often
What is general anxiety disorder?
Uncontrollable anxiety for at least 6 months that is unrelated to a specific person. Sleep disturbance, fatigue, GI disturbance, and difficulty concentrating.
Tx: SSRIs, SNRIs, buspirone, cog behavioral therapy.
What are the three clusters of personality disorders?
A, B, and C. Weird, Wild, and Worried
Weird: Paranoid, Schizoid, Schizotypal
Wild: Antisocial, Borderline, Histrionic, Narcissistic
Worried: Avoidant, Obsessive-compulsive, Dependent.
What are the causes of methemoglobinemia and treatment?
Antibiotics (trimethoprim, sulfonamides, and dapsone), local anesthetics (articaine and prilocaine) and others such as aniline dyes, metoclopramide, chlorates, and bromates. Chloroquine, primaquine. Ingestion of compounds containing nitrates.
What are the different types of collagen and where are they found?
Type 1 - skin, bone (made by osteoblasts), tendons, fascia, cornea, and most other organs. late wound repair. bONE. Decreased production in osteogenesis imperfecta type 1.
Type 2- Cartilage (including hyaline) and vitreous humor, nucleus pulposus. carTWOlage.
Type 3 - blood vessels, uterus, and skin. fetal tissue, granulation tissue. Type 3 deficient in the uncommon, vascular type of Ehlers-Danlos syndrome (ThreeE D).
Type 4 - basement membranes, basal lamina, lens. Four under the FLOOR. Efective in Alport syndrome and targeted by autoantibodies in Goodpasture syndrome.
Type 5 - minor component of interstitial tissues and blood vessels.
What does sonic hedgehog gene do?
Produced at base of limbs in zone of polarizing activity. Involved in patterning along anterior-posterior axis. Involved in CNS development; mutation can cause holoprosencephaly.
What does Wnt-7 gene do?
Produced at apical ectodermal ridge (thickened ectoderm at distal end of each developing limb). Necessary for proper organization along dorsal-ventral axis.
What does FGF do?
Produced at apical ectodermal ridge. Stimulates mitosis of underlying mesoderm, providing for lengthening of limbs.
What does Homeobox (Hox) genes do ?
Involved in segmental organization of embryo in a craniocaudal direction. Hox mutations -> appendages in wrong locations.
Describe progression of Early fetal development at the following times: Day 0 Within week 1 Within week 2 Within week 3 Weeks 3-8 (embryonic period) Week 4 Week 6 Week 10
Day 0: Fertilization and initiating embryogenesis
Within week 1: hCG secretion begins around time of implantation of blastocyst
Within week 2: bilaminar disc (epiblast, hypoblast). 2 weeks = 2 layers
Within week 3: Trilaminar disk. 3 weeks = 3 layers. Gastrulation (establishing of the ectoderm, mesoderm, endoderm. Primitive streak formation begins this process)
Weeks 3-8 (embryonic period): Neural tube forms by neuroectoderm and closes by week 4. Organogenesis and extremely susceptible to teratogens.
Week 4: Heart begins to beat. Upper and lower limb buds begin to form.
Week 6: Fetal cardiac activity visible by transvaginal ultrasound.
Week 10: Genitalia have male/female characteristics.
What is derived from surface ectoderm?
Adenohypophysis (from Rathke pouch and where craniopharyngioma comes from- tumor with cholesterol crystals and calcifications); lens of eye; epithelial linings of oral cavity, sensory organs of ear, and olfactory epithelium; epidermis; anal canal below pectinate line; parotid, sweat, and mammary glands.
What is derived from the neuroectoderm?
Brain (neurohypophysis, CNS neurons, oligodendrocytes, astrocytes, ependymal cells, pineal glands), retina and optic nerve, spinal cord.
Think CNS.
What is derived from neural crest cells?
PNS (dorsal root ganglia, cranial nerves, celiac ganglion, Schwann cells, ANS), melanocytes, chromaffin cells of adrenal medulla, parafollicular cells (C) cells of thyroid, pia and arachnoid, bones of skull, odontoblasts (cells that produce dentin in the dental pulp), aorticopulmonary septum.
Think PNS and non-neural structures nearby.
what is derived from mesoderm?
Muscle, bone, connective tissue, serous linings of body cavities (e.g. peritoneum), spleen (derived from foregut mesentery), cardiovascular structures, lymphatics, blood, wall of gut tube, vagina, kidneys, adrenal cortex, vagina, kidneys, adrenal cortex, dermis, testes, ovaries.
Notochord induces ectoderm to form neuroectoderm (neural plate). Its only postnatal derivative is the nucleus pulposus of the intervertebral disc.
What are the mesodermal defects?
VACTERL Vertebral defects Anal Atresia Cardiac Defects Tracheo-Esophageal fistula Renal defects Limb defects (bone and muscle)
What is derived from endoderm?
Gut tube epithelium (including anal canal above the pectinate line), most of the urethra (derived from urogenital sinus), luminal epithelial derivatives (e.g. lungs, liver, gall bladder, pancreas, eustachian tube, thymus, parathryoid, thyroid follicular cells).
Agenesis vs aplasia?
Agenesis: absent organ due to lack of primordial tissue.
Aplasia: absent organ despite presence of primordial tissue. `
Hypoplasia vs deformation vs disruption vs malformation?
Hypoplasia: incomplete organ development; primordial tissue present.
Deformation: extrinsic disruption; occurs after the embryonic period.
Disruption: secondary breakdown of a previously normal tissue or structure (e.g. amniotic band syndrome).
Malformation: Intrinsic disruption; occurs during the embryonic period (weeks 3-8).
Breakdown of teratogen effects.
before 3 week
3-8 weeks
after 8 weeks
Before 3 weeks: all or none effects
3-8 week: most susceptible here because it is the embryonic period(organogenesis)
after 8 weeks: growth and function affected.
What do ace inhibitors do as a teratogen?
renal damage
What do alkylating agents do as a teratogen?
absence of digits, multiple anomalies.
What do aminoglycosides do as a teratogen?
CN VIII toxicity.
A MEAN GUY hit the baby in the car.
What do carbamazepine do as a teratogen?
Neural tube defects, craniofacial defects, fingernail hypoplasia, developmental delay, IUGR
What do diethylsilbestrol (DES) do as a teratogen?
vaginal clear cell adenocarcinoma, congenital mullerian anomalies.
What do folate antagonists do as a teratogen?
Neural tube defects
What do lithium do as a teratogen?
Ebstein anomaly (atrialized right ventricle)
What do methimazole do as a teratogen?
Aplasia cutis congenita - focal absence of epidermis
What do phenytoin do as a teratogen?
Fetal hydantoin syndrome: microcephaly, dysmorphic craniofacial features, hypoplastic nails and distal phalanges, cardiac defects, IUGR, intellectual disability.
What do tetracyclines do as a teratogen?
Discolored teeth.
TEETHracyclines
What do thalidomide do as a teratogen?
Limb defects (phocomelia, micromelia - "flipper" limbs) LIMB defects with tha-LIMB-domide
What do valproate do as a teratogen?
Inhibition of maternal folate absorption -> neural tube defects.
valproATE inhibits folATE absorption
What does warfarin do as a teratogen?
Bone deformities, fetal hemorrhage, abortion, ophthalmologic abnormalities.
do not wage WARFARE on the baby; keep it HEPpy with HEParin (does not cross placenta).
What does alcohol do as a teratogen?
Common cause of birth defects and intellectual disability; fetal alcohol syndrome: CNS damage, facial abnormalities like long philtrum and maxillary hypoplasia. Problem with cell migration.
What’s the breakdown for mental retardation?
As in most common genetic, inherited, and congenital causes.
Genetic: Down’s syndrome
Inherited: Fragile X
Congenital: Alcohol
What does cocaine do as a teratogen?
Abnormal fetal growth and fetal addiction; placental abruption.
What does smoking (nicotine, CO) do as a teratogen?
A leading cause of low birth weight in developed countries; associated with preterm labor, placental problems, IUGR, ADHD
What does iodine do as a teratogen (lack or excess)?
Congenital goiter or hypothyroidism (cretinism)
What does maternal diabetes do as a teratogen?
Caudal regression syndrome (anal atresia to sirenomelia (legs are fused together)), congenital heart defects (transposition of the great vessels), neural tube defects (anencephaly).
What does Vitamin A excess do as a teratogen?
Extremely high risk for spontaneous abortions and birth defects (cleft palate, cardiac abnormalities).
What does x-rays do as a teratogen?
Microcephaly, intellectual disability.
What is fetal alcohol syndrome?
One of the leading causes of congenital malformations in the US. Intellectual disability, pre- and postnatal developmental retardation, microcephaly, holoprosencephaly, facial abnormalities (smooth philtrum, thin upper lip, small palpebral fissures (distance under eye), hypertelorism (distance between eyes increased)), limb dislocation, and heart defects (ventricular septal defects - cell migration problem).
Give the breakdown on the number of chorions/amnions depending on timing of separation.
0-4 days - cleavage between 2 cell and morula. Dichorionic, diamniotic (placenta may be fused).
4-8 days - cleavage between morula and blastocyst. Monochorionic diamniotic.
8-12 days - cleavage between blastocyst formed embryonic disc. Monochorionic monoamniotic.
> 13 days - monochorionic monoamniotic conjoined twins.
What does failure of the urachus to obliterate cause? three things
Forms at 3rd week. Duct between fetal bladder and yolk sac (allantois which becomes the urachus)
patent urachus - urine discharge from umbilicus
urachal cyst - partial failure of urachus to obliterate; fluid-filled cavity lined with uro-epithelium, between umbilicus and bladder. Can lead to infection and adenocarcinoma.
vesicourachal diverticulum - outpouching of bladder.
What does failure of vitelline duct cause? two things
normally obliterates at 7th week. Normally connects yolk salk to mid-gut lumen.
Vitelline fistula - meconium discharge from umbilicus
Meckel diverticulum - partial closure, with patent portion attached to ileum (true diverticulum). May have ectopic gastric mucosa and/or pancreatic tissue -> melana, periumbilical pain, and ulcers.
Can also get a cyst here if closed on both ends.
What are the aortic arch derivatives?
1st, 2nd, 3rd, 4th, and 6th
Develop into the arterial system.
1st: part of MAXillary artery (branch of external carotid). 1st arch is MAXimal
2nd: Stapedial artery and hyoid artery. Second is Stapedial
3rd: Common Carotid artery and proximal part of internal Carotid artery. C is 3rd letter of alphabet.
4th: On left, aortic arch; on right, proximal part of subclavian artery. 4th arch (4 limbs) = systemic.
6th: Proximal part of pulmonary arteries and (on left only) ductus arteriosus. 6th arch is pulmonary and the pulmonary-to-systemic shunt (ductus arteriosus).
What are the embryological origins of the branchial apparatus (pharyngeal apparatus)? clefts, arches, and pouches
Branchial clefts (or grooves) are derived from ectoderm. Branchial arches - derived from mesoderm (muscles, arteries) and neural crest (bone, cartilage). Branchial pouches - derived from endoderm
CAP covers from outside to inside - Clefts, arches, pouches (ectoderm, mesoderm, endoderm).
What are the branchial cleft derivatives?
1st cleft develops into external auditory meatus.
2nd through 4th clefts form temporary cervical sinuses, which are obliterated by proliferation of 2nd arch mesenchyme.
Persistent cervical sinus -> branchial cleft cyst within lateral neck.
What are the 1st branchial arch derivatives? there is cartilage, muscles and nerves. List associated abnormalities too
Think of all the M’s. Chew
Cartilage: Meckel cartilage: Mandible, Malleus, incus, spheno-Mandibular ligament.
Muscles: Muscles of Mastication (temporalis, Masseter, lateral and Medial pterygoids), Mylohyoid, anterior belly of diagastric, tensor tympani (attaches to malleus), tensor veli palatani (only muscle of the palate not innervated by the vagus nerve)
Nerves: CN V2 and V3. Chews
Abnormality: Teacher Collins syndrome - 1st arch neural crest fails to migrate -> mandibular hypoplasia, facial abnormalities
When at the restaurant of golden ARCHES, children tend to first CHEW (1), then SMILE (2), then SWALLOW STYLishly (3) or simple swallow (4), and then SPEAK (6)
What are the 2nd branchial arch derivatives? there is cartilage, muscles and nerves. List associated abnormalities too
Think of all the Ss. Smile
Cartilage: Reichert cartilage - Stapes, Styloid process, lesser horn of hyoid, Stylohyoid ligament.
Muscle: Muscles of facial expression - Stapedius, Stylohyoid, platySma, belly of digastric
Nerve: CNVII (facial expression). SMILE
Abnormality: Congenital pharyngo-cutaneous fistula - persistance of cleft and pouch -> fistula between tonsillar area and lateral neck
When at the restaurant of golden ARCHES, children tend to first CHEW (1), then SMILE (2), then SWALLOW STYLishly (3) or simple swallow (4), and then SPEAK (6)
What are the 3rd branchial arch derivatives? there is cartilage, muscles and nerves. List associated abnormalities too
SWALLOW STYLishly
Cartilage: greater horn of hyoid
Muscles: Stylopharyngeus (think of stylopharyngeus innervated by glossopharyngeal nerve)
Nerve: CN IX (stylo-pharyngeus). swallow STYLishly
When at the restaurant of golden ARCHES, children tend to first CHEW (1), then SMILE (2), then SWALLOW STYLishly (3) or simple swallow (4), and then SPEAK (6)
What are the 4th-6th branchial arch derivatives? there is cartilage, muscles and nerves. List associated abnormalities too
Cartilages: thyroid, cricoid, arytenoids, corniculate, cuneiform.
Muscles: 4th arch - most pharyngeal constrictors; cricothyroid; levator veli palatini. 6th - arch all intrinsic muscles of the larynx except cricothyroid.
Nerves: 4th arch- CN X (superior laryngeal branch) simply swallow. 6th arch - CN X (recurrent laryngeal branch. speak.
Notes: Arches 3 and 4 form posterior 1/3 of tongue;
Arch 5 makes no major contributions.
What are the 1st branchial pouch derivatives?
Develops into middle ear cavity, eustachian tube, mastoid air cells.
1st pouch contributes to endoderm-lined structures of ear.
Ear, tonsils, bottom-to-top: 1 (ear), 2 (tonsils), 3 (dorsal - bottom for inferior parathyroids…ventral- to for thymus), 4 (top = superior parathyroids)
What are the 2nd branchial pouch derivatives?
Develops into epithelial lining of palatine tonsil.
Ear, tonsils, bottom-to-top: 1 (ear), 2 (tonsils), 3 (dorsal - bottom for inferior parathyroids…ventral- to for thymus), 4 (top = superior parathyroids)
What are the 3rd branchial pouch derivatives?
Dorsal wings - develops into inferior parathyroids.
Ventral wings - develops into thymus.
3rd pouch contributes to 3 structures (thymus, left and right inferior parathyroids). 3rd pouch structures end up below 4th pouch structures.
Ear, tonsils, bottom-to-top: 1 (ear), 2 (tonsils), 3 (dorsal - bottom for inferior parathyroids…ventral- to for thymus), 4 (top = superior parathyroids)
What are the 4th branchial pouch derivatives?
Dorsal wings - develops into superior parathyroids.
Ear, tonsils, bottom-to-top: 1 (ear), 2 (tonsils), 3 (dorsal - bottom for inferior parathyroids…ventral- to for thymus), 4 (top = superior parathyroids)
What is MEN 2A?
Mutation of germline RET (neural crest cells): Adrenal medulla (pheochromocytoma), parathyroid tumors (3rd/4th pharyngeal pouch), parafollicular cells (medullary thyroid cancer which is derived from neural crest cells; associated with 4th and 5th pharyngeal pouches)
What are cleft lip and cleft palate?
Cleft lip - failure of fusion of the maxillary and medial nasal processes (formation of primary palate).
Cleft palate - failure of fusion of the two lateral palatine processes or failure of fusion of lateral palatine processes with the nasal septum and/or median palatine process (formation of secondary palate).
Cleft lip and cleft palate have two distinct etiologies, but often occur together.
How does male development occur?
SRY gene on Y chromosome - produces testis determining factor (testes development).
Sertoli cells secrete Mullerian inhibitor factor (MIF) that suppresses development of paramesonephric ducts.
Leydig cells secrete androgens that stimulate the development of mesonephric ducts.
What is a bicornuate uterus?
Results from incomplete fusion of the paramesonephric ducts (vs complete failure of fusion, resulting in double uterus and vagina). Can lead to autonomic defects -> recurrent miscarriages.
What does the genital tubercle become? in males and female
Males: DHT causes formation of glans penis and corpus cavernosum and spongiosum.
Females: estrogen causes formation of glans clitoris and vestibular bulbs.
What does the urogenital sinus become? in males and female
Males: DHT causes formation of bulbo urethral glands (of Cowper) and prostate gland.
Females: Estrogen causes formation of greater vestibular glands (of Bartholin), urethral and para-urethral glands (of Skene).
What does the urogenital folds become? in males and female
Males: DHT causes ventral shaft of penis (penile urethra).
Females: estrogen causes labia minora to form.
What does the labioscrotal swelling become? in males and female
Males: DHT causes scrotum to form.
Females: Estrogen causes labia majora to form.
What is exstrophy of the bladder associated with?
Epispadias (when opening of penile urethra is on the superior side of penis due to faulty positioning of the genital tubercle vs hypospadias which is on the inferior side due to failure of the urethral folds to close).
What is the gubernaculum in males and females?
Band of Fibrous tissue.
Male remnant anchors testes within scrotum.
Female remnant becomes Ovarian Ligament + Round Ligament of Uterus
What is the processus vaginalis?
Evagination of peritoneum.
Male remnant is the tunica vaginalis (structure that surrounds testis and reaches back to peritoneum through inguinal canal).
Female remnant is obliterated.
More info: During fetal development, an extension of the peritoneum migrates distally through the inguinal canal with the gubernaculum in the first trimester. Normally, this thin membrane that extends through the inguinal canal and descends into the scrotum (processus vaginalis) is obliterated proximally at the internal inguinal ring, and the distal portion forms the tunica vaginalis.
In the majority of cases, the processus vaginalis closes within the first year of life. If it is not obliterated at the internal ring, it is referred to as a patent processus vaginalis, and the tunica vaginalis communicates with the peritoneum, so that peritoneal fluid flows freely between both structures and a communicating hydrocele forms.
See here for more: https://online.epocrates.com/u/29241104/Hydrocele/Basics/Etiology
What is the lymphatic drainage for the gonads?
Ovaries/testis - para-aortic lymph nodes
Distal vagina/vulva/scrotum - superficial inguinal nodes
Proximal vagina/uterus - obturator, external iliac, and hypogastric nodes.
Note: uterine vessels drain by internal illiac to external illiac
Describe the female reproductive ligaments?
Infundibulopelvic ligament (suspensory ligament of ovaries) - ovaries to lateral pelvic wall. Contains ovarian vessels. Must ligate during oophorectomy to avoid bleeding. Ureter courses retroperitoneally close to gonadal vessels. At risk of injury during ligation of ovarian vessels.
Cardinal ligmanet - cervix to side wall of pelvis. Contains uterine vessels. Ureter at risk of injury during ligation of uterine vessels in hysterectomy.
Round ligament of the uterus - uterine fundus to labia majora. Derivative of gubernaculum. Travels through round inguinal canal; above the artery of Sampson.
Broad ligament: mesosalpinx (superior to ovaries reaching around falopian tubes), mesovarium (surrounding ovary), mesometrium (inferior to ovary and reaching towards uterine surface). Connects uterus, fallopian tubes, and ovaries to pelvic side wall. Contains ovaries, fallopian tubes, and round ligaments of uterus.
Ovarian ligament (connects ovary to superior portion/fundal portion of uterus) - medial pole of ovary to lateral uterus. A derivative of guvernaculum.
Uterosacral ligament - connects at cervical area of uterus.
What is the type of tissue for the following female areas? Vagina Ectocervix Endocervix Transformation zone Uterus Fallopian Tube Ovary, outer surface
Vagina: Stratified squamous epithelium, nonkeratinized
Ectocervix: Stratified squamous epithelium, nonkeratinized
Endocervix: Simple columnar epithelium
Transformation zone: squamocolumnar junction (most common area for cervical cancer)
Uterus: simple columnar epithelium with long tubular glands
Fallopian tubes: Simple columnar epithelium, many ciliated cells, a few secretory (peg) cells
Ovary, outer surface: Simple cuboidal epithelium (germinal epithelium covering surface of ovary).
What are the processes involved in male sexual response? and what never is part of the erectile reflex?
Erection - Parasympathetic nervous system (pelvic nerve):
NO -> increased cGMP and smooth muscle relaxation -> vasodilation -> proerectile
Norepinephrine - increased Ca+2 -> smooth muscle contraction -> vasoconstriction -> antierectile
Emission: Sympathetic nervous system (hypogastric nerve)
Ejaculation: visceral and somatic nerve (pudendal nerve).
Erectile nerve involves S2-24 (i.e. the pudendal nerve).
Describe seminiferous tubules?
From outer to inner: Spermatogonia, primary spermatocytes, secondary spermatocytes, spermatids.
Sertoli cells line seminiferous tubules
What do Sertoli cells do?
secrete inhibin -> inhibit FSH.
Secrete androgen binding protein -> maintain local levels of testosterone
Tight junctions between adjacent Sertoli cells form blood blood-testis barrier -> isolate gametes from autoimmune attack.
Support and nourish developing spermatozoa. Regulate spermatogenesis. Produce MIF.
Temperature sensitive; decreased sperm production and decreased inhibin with increased temperature.
Increased temperature seen in varicocele, cryptoorchidism.
Convert testosterone and androstenedione to estrogen via aromatase.
What do Leydig cells do?
Secrete testosterone in the presence of LH; testosterone production unaffected by temperature.
Located in the Interstitium.
Also contain aromatase.
What are the different types of estrogen and where do they act?
Ovary makes 17beta-estradiol
Placenta makes estriol
Adipose tissue makes estrone via aromatization.
Potency: estradiol > estrone > estriol
In pregnancy: there is a 50 fold increase in estradiol and estrone
1000 fold increase in estriol (indicator of fetal well-being).
Estrogen receptors expressed in cytoplasm; translocate to the nucleus when bound by ligand. `
Describe the stages of boys external genitalia?
Stage 1: prepubertal
Stage 2: enlargement of scrotum and testes; scrotal skin reddens and changes in textures.
Stage 3: enlargement of penis (length at first); further growth of testes
Stage 4: Increased size of penis with growth in breadth and development of glans; testes and scrotum larger, scrotal skin darker.
Stage 5: adult genitalia.
Describe the stages of Girls Breast development
Stage 1: prepubertal
Stage 2: breast bud stage with elevation of breast and papilla; enlargement of areola.
Stage 3: Further enlargement of breast and areola; no separation of their contour.
Stage 4: Areola and papilla from a secondary mound above level of breast.
Stage 5: Mature stage: projection of papilla only, related to recession of areola
Describe the pubic hair development of boys and girls?
Stage 1: Prepubertal (the pubic area may have vellus hair, similar to that of forearms)
Stage 2: Sparse growth of long, slightly pigmented hair, straight or curled, at base of penis or along labia.
Stage 3: Darker, coarser and more curled hair, spreading sparsely over junction of pubes.
Stage 4: Hair adult in type, but covering smaller area than in adult; no spread to medial surface of thighs.
Stage 5: Adult female in type and quantity, with horizontal upper border.
Describe female ovulation
Increased estrogen, increased GnRH receptors on anterior pituitary. Estrogen surge then stimulates LH release -> ovulation (rupture of follicle).
Increased temperature (progesterone induced).
Mittelschmerz: refers to transient mid-cycle ovulatory pain; classically associated with peritoneal irritation (e.g. follicular swelling/rupture, fallopian tube contraction). Can mimic appendicitis.
Why is breastmilke useful?
Good for infants < 6 months old. Contains maternal IgA, macrophages, and lymphocytes. Breast milk reduces infant infections and is associated with decreased risk for the child to develop asthma, allergies, diabetes mellitus, and obesity. Exclusively breast fed infants require vitamin D supplementation. Breast feeding also decreases maternal risk of breast and ovarian cancer, and facilitates mother-child bonding.
Describe the source and function of hCG?
Source: synctiotrophoblast of placenta
Function: Maintains the corpus luteum (and thus progesterone) for the 1st trimester by acting like LH (otherwise no luteal cell stimulation, and abortion results). In the 2nd and 3rd semesters, the placenta synthesizes its own estriol and progesterone and the corpus luteum degenerates.
alpha subunit structurally identical to alpha subunits of LH, FSH, and TSH. Beta subunit is unique (pregnancy tests detect Beta subunit). hCG is increased in multiple gestations and pathological states (e.g. hydatidiform mole, choriocarcinoma).
Describe the androgens
DHT, testosterone, AnDrostenedione
DHT and testosterone (testis); AnDrostenedione (ADrenal).
Potency: DHT > testosterone > androstenedione
testosterone: differentiation of genitalia except prostate (epididymis, vas deferens, seminal vesicles)
Growth spurt: penis, seminal vesicles, sperm, muscle, RBCs.
Deepening of voice
Closing of epiphyseal plates (via estrogen converted from testosterone)
Libido
DHT: early - differentiation of penis, scrotum, prostate
Late - prostate growth, balding, sebaceous gland activity (androgen receptors in these hair follicle areas stimulating this gland and this is why men get acne more).
DHT comes from testosterone through 5alpha-reductase (finasteride inhibits this).
Androgens converted to estrogen by cytochrome P-450 aromatase (primarily in adipose tissue and testis).
Exogenous testosterone causes inhibition of hypothal-pituitary-gonadal axis and causes less testoterone intratesticularly -> decreased testicular size -> azoospermia.
What is Klinefelter syndrome?
seen in males with XXY, 1:850
Dysgenesis of seminiferous tubules -> decreased inhibin -> increased FSH
Abnormal Leydig cell function -> decreased testosterone -> increased LH -> increased estrogen.
Testicular atrophy, eunuchoid body shape, tall, long extremeties, gynecomastia, female hair distribution.
May present with developmental delay. Presence of inactivated X chromosome (Barr body). Common cause of hypogonadism in infertility workups.
What is Turner syndrome ?
seen in females with XO.
“Hugs and Kisses” XO from Tina Turner
Menopause before menarche. Decreased estrogen leads to increased LH and FSH.
Can result from mitotic or meiotic error.
Can be complete monosomy (45,XO) or mosaicism (e.g. 45,XO/46,XX).
Pregnancy is possible in some cases (oocyte donation, exogenous estradiol-17B and progesterone).
Short stature (if untreated), ovarian dysgenesis (streak ovary), shield chest, bicuspid aortic valve, preductal coarctation (femoral < brachial pulse, notched ribs), lymphatic defects (results in webbed neck or cystic hygroma; lymphedema in feet, hands), horseshoe kidney (gets stuck on IMA). Most common cause of primary amenorrhea. No Barr Body.
What are double Y males?
XYY, 1:1000
Phenotypically normal, very tall, severe acne, antisocial behavior (seen in 1-2% of XYY males). Normal fertility. Small percentage diagnosed with autism spectrum disorders.
What is true hermaphroditism?
46,XX or 47XXY
Also called ovotesticular disorder of sex development. BOth ovary and testicular tissue present (ovotestis_; ambiguous genitalia. Very rare.
What’s the difference between complete mole and partial mole.
Complete Mole: 46,XX; 46,XY. hCG very very increased, with large uterine size, 2% chance of converting to choriocarcinmoa, no fetal parts, enucleated egg + single sperm (with duplicated paternal DNA) or 2 different sperm, 15-20% malignant disease, vaginal bleeding/enlarged uterus/hyperemesis/pre-eclampsia/hyperthyroidism, honeycombed uterus or clusters of grapes on imaging. Otherwise known as snowstorm on ultrasound.
Partial Mole: 69, XXX or XXY or XYY. slightly increased hCG, fetal parts present, uterine size not increased, low risk of malignancy, 2 sperm + 1 egg, vaginal bleeding/abdominal pain. Fetal parts seen on imaging.
Tx: dilation and curretage and methotrexate.
What is the treatment for pre-eclampsia?
remember if before 20 weeks it might be molar pregnancy. Otherwise need to have hypertension (>140/90) and proteinuria (>300mg/24hr).
Treat with antihypertensives (alpha-methyldopa, labetolol, nifedipine, hydralazine). Deliver at 37 wks if mild or more severe at 34 weeks. Use Magnesium sulfate to prevent seizure.
NOTE: don’t forget about HELLP
What is placental abruption?
Define it, risk factors, and presentation
Abruptio placentae. Premature separation (partial or complete) of placenta from uterine wall before delivery of infant. Risk factors: trauma (e.g. motor vehicle accident), smoking, hypertension, pre-eclampsia, cocaine abuse.
Concealed is towards uterine fundus (i.e. no blood coming out through cervix). Apparent would show hemorrhage out of cervix.
Presentation: abrupt, painful bleeding (concealed or apparent) in third trimester; possible DIC, maternal shock, fetal distress. Life threatening for mother and fetus.
What is placenta acreta/increta/percreta?
Define, risk factors, and presentation
Defective decidual layer -> abnormal attachment and separation after delivery.
Risk factors: prior C-section, inflammation, placenta previa.
Types are determined by depth of penetration:
Placenta accreta: placenta ATTACHES to myometrium without penetrating it; most common type.
Placenta increta - placenta penetrates INTO myometrium.
Placenta percreta - placenta penetrates (“PERFORATES”) through the myometrium and into uterine serosa (invades entire uterine wall); can result in placental attachment to rectum or bladder.
Presentation: no separation of placenta after delivery -> massive bleeding. Life threatening for mother.
What is placenta previa? define and risk factors.
Attachment of placenta to lower uterine segment. Lies near (marginal), partially covers (partial), or completely covers internal cervical os.
Risk factors: multiparity, prior C-section.
What is ectopic pregnancy and the risk factors?
Most often in amupulla of fallopian tube. Suspect with history of amenorrhea, lower-than-expected rise in hCG based on dates, and sudden lower abdominal pain; confirm with ultrasound. Often clinically mistaken for appendicitis.
Pain with or without bleeding.
Risk factors: history of infertility, salpinigits (PID), ruptured appendix, prior tubal surgery.
what is polyhydraminios associated with?
fetal malformations (esophageal/duodenal atresia, anencephaly; both result in inability to swallow amniotic fluid), maternal diabetes, fetal anemia, multiple gestations
What is oligohydramnios associated with?
associated with placental insufficiency, bilateral renal agenesis, or posterior urethral valves (in males) and resultant inability to excrete urine. Any profound oligohydramnios can cause Potter sequence.
What is Potter sequence?
Atypical physical appearance of fetus due to oligohydramnios experience in womb. Also associated with ARPKD because this presents with infants and significant renal failure in utero can lead to this. Can be caused by ARPKD, posterior urethral valves, bilaterial renal agenesis.
Oligohydramnios leads to compression of developing fetus -> limb deformities, facial anomalies (low-set ears and retrognathia), and compression of chest -> pulmonary hypoplasia (cause of death).
Clubbed feet, pulmonary hypoplasia, and cranial abnormalities.
Babies who cant PEE get POTTER syndrome.
POTTER associated with:
Pulmonary hypoplasia (less amniotic fluid leads to less stretch of the lungs)
Oligohydramnios (trigger)
Twisted face (flat face from less fluid so face pushed up against wall)
Twisted skin
Extremity defects
Renal failure (in utero)
What are the risk factors for dysplasia and carcinoma in situ (cervical) and how is invasive carcinoma dealt with? risk factors, diagnosis, and potential outcomes
HPV 16/18 (the E6/E7 variant with p53/RB involvement, respectively)
Usually pap smear or bleeding post coital.
risk factors: multiple sexual partners (#1), early sex, smoking, or HIV infection.
Invasive carcinoma is usually found on pap smear which shows koilocytes (raisinoid nuclei with perinuclear halo clearing). Catches it before progression to invasive carcinoma. Lateral invasion can block ureters causing renal failure.
How is endometritis caused and treatment?
Inflammation of endometrium (plasma cells/lymphocytes) associated with retained products (vagina/C-section/miscarriage/abortion or foreign body like IUD). Retained material promotes bacterial invasion from vagina or intestinal tract.
Tx: gentamicin+clindamycin with/without ampicillin.
What is endometriosis and treatment for it?
Remember: it’s non-neoplastic endometrial glands/stroma outside of endometrial cavity (ovary, pelvis, peritoneum). Blood filled chocolate cyst in ovary.
Cyclic pelvic pain and pain on bleeding, urinating, and defecating. Dysmenorrhea, infertility and NORMAL SIZED UTERUS.
Tx: NSAIDs, OCP, progestins, GnRH agonists, surgery.
What is adenomyosis?
Extension of endometrial tissue (glandular) into the uterine myometrium.
Caused by hyperplasia of the basalis layer of the endometrium.
Dysmenorrhea, menorrhagia.
Uniformly, ENLARGED AND SOFT globular uterus.
Tx: hysterectomy
Describe the layers of the uterus?
Outer to inner: Endometrium (epithelium, Stratum functionalis with the stratum basalis below it touchign myometrium), myometrium, perimetrium.
What is endometrial hyperplasia? define and risk factors
Abnormal endometrial gland proliferation usually caused by excess estrogen stimulation. Increased risk for endometrial carcinoma.
Manifests as postmenopasual vaginal bleeding.
Risk factors: anovulatory cycles, hormone replacement therapy, PCOS, granulosa cell tumor.
What is endometrial carcinoma? define and risk factors.
Most common gynecologic malignancy.
Peak occurrence at 55-65 years old.
Clinically presents with vaginal bleeding and preceded by endometrial hyperplasia.
Risk factors include prolonged use of estrogen without progestins, obesity, diabetes, hypertension, nulliparity, and late menopause. Increased myometrial invasion and decreased prognosis.
What is leiomyoma? give presentation and define
Most common tumors in females.
Presents with multiple discrete tumors. Increased incidence inblacks. Benign smooth muscle tumor; malignant transformation is rare. Estrogen sensitive - tumor size increases with pregnancy and decreases after menopause. Peak occurence at 20-40 years old. May be asymptomatic, cause abnormal uterine bleeding, or result in miscarriage. Severe bleeding can lead to iron deficiency anemia. Does not go to leiomyosarcoma though.
Whorled pattern of smooth muscle with well-demarcated borders .
What is the epidemiology of gynecologic tumors?
Incidence: endometrial > ovarian > cervical (data in the US…cervical cancer is most common worldwide).
Worst prognosis: Ovarian > cervical > endometrial.
What are common causes of anovulation?
Pregnancy, PCOS, obesity, HPO axis abnormalities, premature ovarian failure, hyperprolactinemia, thyroid disorders, eating disorders, female athletes, Cushing syndrome, adrenal insufficiency.
What is a follicular cyst?
Distention of unruptured graafian follicle. May be associated with hyperestrogenism and endometrial hyperplasia. Most common ovarian mass in young women.
What is a corpus luteum cyst?
Hemorrhage into persistent corpus luteum. Commonly regresses spontaneously.
What is a theca-lutein cyst?
Often bilateral/multiple. Due to gonadotropin stimulation. Associated with choriocarcinoma and moles.
What is a hemorrhagic cyst?
Blood vessel rupture in cyst wall. Cyst grows with increased blood retention; usually self-resolves.
What is a dermoid cyst?
Mature teratoma. Cystic growths filled with various types of tissue such as fat, hair, teeth, bits of bone, and cartilage.
What is a endometrioid cyst?
Endometriosis within ovary with cyst formation. Varies with menstrual cycle. When filled with dark, reddish-brown blood it is called a chocolate cyst.
What are the most common ovarian tumors and risk factors? define, risk factors, and presentation
Most common adnexal mass in women > 55 years old. Can be benign or malignant. Arises from surface epithelium, germ cells, and sex cord stromal cells.
Majority of malignant tumors are from epithelial cells. Majority (95%) are epithelial (serous cystadenocarcinoma most common).
Risk increases with advanced age, infertility, endometriosis, PCOS, genetic predisposition (BRCA-1 or BRCA-2 mutation, HNPCC, strong family history)..
Risk decreases with previous pregnancy, history of breastfeeding, OCPs, tubal ligation.
Presents with adnexal mass, abdominal distention, bowel obstruction, pleural effusion. Diagnose surgically. Monitor progression by measuring CA-125 levels (not good for screening).
What is serous cystadenoma?
Most common ovarian neoplasm. It is benign. Thin-walled, uni- or multilocular. Lined with fallopian-like epithelium. Often bilateral.
What is a mucinous cystadenoma?
Benign ovarian neoplasm.
Multiloculated, large. Lined by mucus-secreting epithelium.
What is endometrioma?
Benign ovarian neoplasm
Mass arising from growth of ectopic endometrial tissue. Complex mass on ultrasound. Presents with pelvic pain, dysmenorrhea, dyspareunia.
What is a mature cystic teratoma (dermoid cyst).
Benign ovarian neoplasm.
Germ cell tumor, most common ovarian tumor in women 20-30 years old. Can contain elements from all 3 germ layers; teeth, hair, sebum are common components. Can present with pain secondary to ovarian enlargement or torsion. Can also contain functional thyroid tissue and present as hyperthyroidism (struma ovarii).
What is a Brenner tumor?
Benign ovarian neoplasm. Think B’s for Brenner.
Looks like Bladder. Solid tumor that is pale yellow-tan in color and appears encapsulated. “Coffee Bean’ nuclei on H&E stain.
What is a fibroma tumor?
Benign ovarian neoplasm
Bundles of spindle-shaped fibroblasts.
Meigs syndrome - triad of ovarian fibroma, ascites, and hydrothorax. Pulling sensation in groin.
What is a thecoma tumor?
Benign ovarian neoplasm.
Like granulosa cell tumors, may produce estrogen. Usually present as abnormal uterine bleeding in a postmenopausal woman (perhaps due to estrogen stimulation and endometrial hyperplasia?).
What is an immature teratoma?
Malignant ovarian neoplasm
Aggressive, contains fetal tissue, neuroectoderm. Immature teratoma is mostly typically represented by immature/embryonic-like neural tissue. Mature teratoma are more likely to contain thyroid tissue.
What is granulosa cell tumor?
Most common sex cord stromal tumor. Malignant ovarian neoplasm.
Predominantly women in their 50s. Often produce estrogen and/or progesterone and present with abnormal uterine bleeding, sexual precocity (in pre-adolescents), breast tenderness. Histology shows Call-Exner bodies (resemble primordial follicles).
What is a serous cystadenocarcinoma?
Malignant ovarian neoplasm
Most common ovarian neoplasm, frequently bilateral. Psammoma bodies.
What is a mucinous cystadenocarcinoma?
Malignant ovarian neoplasm
Pseudomyxoma peritonei-intraperitoneal accumulation of mucinous material from ovarian or appendiceal tumor.
What is a dysgerminoma tumor?
Malignant ovarian neoplasm
Most common in adolescents. Equivalent to male seminoma but rarer. 1% of all ovarian tumors; 30% of germ cell tumors. Sheets of uniform “fried egg” cells. hCG and LDH are tumor markers.
What is a choriocarcinoma tumor?
Malignant ovarian neoplasm.
Rare; can develop during or after pregnancy in mother or baby. Malignancy of trophoblastic tissue (cytotrophoblasts, syncytiotrophoblasts); no chorionic villi present. Increased frequency of theca-lutein cysts. Presents with abnormal B-hCG, shortness of breath, hemoptysis.
Hematogenous spread to lungs. Very responsive to chemotherapy.
What is a yolk sac tumor?
Endodermal sinus. Malignant ovarian neoplasm
Aggressive, in ovaries or testes and sacrococcygeal area in young children. Most common tumor in male infants. Yellow, friable (hemorrhagic), solid mass. 50% have Schiller-Duval bodies (resemble glomeruli). AFP = tumor marker.
What is a Krukenberg tumor?
Malignant ovarian neoplasm
GI malignancy that metastasizes to the ovaries, causing a mucin secreting signet cell adenocarcinoma (usually from diffuse stomach adenocarcinoma).
What are the three vaginal tumors?
Squamous cell carcinoma - usually secondary to cervical SCC; primary vaginal carcinoma rare.
Clear cell adenocarcinoma - Affects women who had exposure to DES in utero.
Sarcoma botryoides (rhabdomyosarcoma variant) - affects girls < 4 years old; spindle-shaped tumor cells that are desmin.
What are the IHC stains for intermediate filaments? Connective tissue Muscle Epithelial Cells Neuroglia Neurons
Connective tissue - Vimentin Muscle - DesMin Epithelial Cells - Cytokeratin Neuroglia - GFAP Neurons - Neurofilaments
Name which tumors lie along the breast ducts? Nipple Lactiferous sinus Major duct Terminal duct Lobules Stroma
Nipple - Paget disease, breast abscess.
Lactiferous sinus - intraductal papilloma, abscess/mastitis
Major duct - fibrocystic change, DCIS, invasive ductal carcinoma.
Terminal duct - tubular carcinoma.
Lobules - lobular carcinoma.
What is a fibroadenoma?
Benign breast tumor.
Stromal.
Small mobile firm mass with sharp edges.
Most common tumor in those <35 years old.
Increased size and tenderness with increased estrogen (e.g. pregnancy, prior to menstruation). Not a precursor to breast cancer.
What is an intraductal papilloma?
Benign breast tumor.
Lactiferous sinus.
Small tumor that grows in lacterifous ducts. Typically beneath areola.
Serous or bloody nipple discharge. Slight (1.5-2x) increased risk for carcinoma.
What is a Phyllodes tumor?
Benign breast tumor. Stromal. Large bulky mass of connective tissue and cysts. "Leaf-like" projections. most common in 6th decade. Some may become malignant.
What are common characteristics of malignant breast tumors? and risk factors
Commonly postmenopausal. Usually arise from terminal duct lobular unit.
Overexpression of estrogen/progesterone receptors or c-erbB2 (HER2, an EGF receptor) is common; triple negative (ER neg, PR neg, and Her2/Neu neg) more aggressive.
Type affects therapy and prognosis.
Axillary lymph node involvement indicating metastasis is the single most important prognostic factor. Most often located in the upper outer quadrant of breast.
Risk factors: increased estrogen exposure, increased total number of menstrual cycles, older age at first live birth, obesity (increased estrogen exposure as adipose tissue converts androstenedione to estrone), BRCA1 and BRCA2 gene mutations, African American ethnicity (increased risk for triple neg breast cancer).
What is a breast DCIS?
noninvasive malignant breast tumor
Major duct.
Fills duct lumen. Arises from ductal atypia. Often seen as microcalcfications on mammography.
Early malignancy without basement membrane penetration.
What is a comedocarcinoma?
noninvasive malignant breast tumor
Ductual, caseous necrosis. Subtype of DCIS.
What is Paget disease of the breast?
noninvasive malignant breast tumor
Nipple
Results from underlying DCIS. Eczematous patches on nipple. Paget cells = large cells in epidermis with clear halo on histology.
Suggests underlying DCIS. Also seen on vulva, though does not suggest underlying malignancy.
What is invasive ductal carcinoma?
invasive malignant breast tumor
Major duct.
Firm, fibrous, “rock-hard” mass with sharp margins and small, glandular, duct-like cells. Grossly, see classic “stellate” infiltration.
Worst and most invasive. Most common (76% of all breast cancers).
What is invasive lobular carcinoma?
invasive malignant breast tumor
Lobules
Orderly row of cells (“Indian file”).
Often bilateral with multiple lesions in the same location.
What is medullary carcinoma?
invasive malignant breast tumor
Fleshy, cellular, lymphocytic infiltrate. Good prognosis.
What is inflammatory carcinoma?
invasive malignant breast tumor
Dermal lymphatic invasion by breast carcinoma. Peau d’orange (breast skin resembles orange peel); neoplastic cells block lymphatic drainage.
50% survival at 5 years.
Describe the types of proliferative breast changes? Fibrosis Cystic Sclerosing adenosis Epithelial hyperplasia
common cause of breast lumps from age 25 to menopause. Presents with pre-menstrual breast pain and multiple lesions, often bilateral. Fluctuation in size of mass. Usually does not indicate increased risk of carcinoma.
Types:
Fibrosis: hyperplasia of breast stroma.
Cystic - fluid filled, blue dome. Ductal dilation.
Sclerosing adenosis - increased acini and intralobular fibrosis. Associated with calcifications. Often confused with cancer. increased risk (1.5-2x) of developing cancer.
Epithelial hyperplasia - increase in number of epithelial cell layers in terminal duct lobule. Increased risk of carcinoma with atypical cells. Occurs in women > 30 years old.
What is acute mastitis and treatment?
breast abscess; during breast-feeding increased risk of bacterial infection through cracks in the nipple. S. aureus is the most common pathogen. Treat with dicloxacillin and continued breast-feeding.
What is fat necrosis of the breast?
A benign, usually painless lump; forms as a result of injury to breast tissue. Abnormal calcification on mammography; biopsy shows necrotic fat, giant cells. Up to 50% of patients may not report trauma.
What are the causes of gynecomastia?
Occurs in males.
Results from hyperestrogenism (cirrhosis, testicular tumor, puberty, old age).
Klinefelter
drugs: Spironolactone, marijuana [Dope], Digitalis, Estrogen, Cimetidine, Alcohol, Heroin, Dopamine D2 antagonists, Ketoconazole.
Some Dope Drugs Easily Create Awkward Hairy DD Knockers.
Describe benign prostatic hyperplasia and treatment
men > 50 years old
Smooth, elastic, firm nodular enlargement of the periurethral lobes (lateral and middle), compressing urethra into vertical slit.
PResents with increased frequency of urination, nocturia, difficulty starting and stopping the stream of urine and dysuria. May lead to distention and hypertrophy of the bladder, hydronephrosis, and UTIs. Increased PSA.
Tx: alpha1-antagonists (terazosin, tamsulosin), which cause relaxation of smooth muscle; finasteride (reduces DHT production)
Where does prostatic adenocarcinoma metastasize?
In late disease it can become osteoblastic mets in bone result in lower back pain and increase in serum ALP and PSA.
Remember total PSA is increased in disease and there is a decrease in fraction of free PSA. Prostatic acid phosphatase (PAP) can also be increased.
What is a varicocele?
Dilated veins in pampiniform plexus as a result of increased venous pressure; most common cause of scrotal enlargement in adult males; most often on the left side because of increased resistance to flow from left gonadal vein drainage into the left renal vein; can cause infertility because of increased temperature; “bag of worms” appearance . Diagnose by ultrasound.
Tx: varicocelectomy, embolization by interventional radiologist.
What are risk factors for testicular germ cell tumors? and diagnosis?
95% of all testicular tumors.
Young men.
Risk factors: cryptorchidism, Klinefelter.
Can present as a mixed germ cell tumor.
Testicular mass that does not transilluminate!
what is a seminoma?
male Germ cell tumor
Malignant; painless, homogenous testicular enlargement; most common testicular tumor, most common in 3rd decade, never in infancy. Large cells in lobules with watery cytoplasm and a “fried egg” appearance.
Increased placental ALP. Radiosensitive. Late metastasis, excellent prognosis.
What is a yolk salk tumor in male?
male Germ cell tumor
Yellow, mucinous. Aggressive malignancy of testes, analogous to ovarian yolk sac tumor. Schiller Duval bodies resemble primitive glomeruli. Most common testicular tumor in boys <3 years old.
What is a choriocarcinoma in men?
male Germ cell tumor
Malignant, increased hCG. Disordered syncytiotrophoblastic and cytotrophoblastic elements. Hematogenous metastases to lungs and brain (may present with “hemorrhagic stroke” due to bleeding into the metastasis. May produce gynecomastia or symptoms of hyperthyroidism (hCG is an LH and TSH analog).
What is a teratoma in men?
male Germ cell tumor
Unlike in females, mature teratoma in adult males may be malignant. Benign in children.
increased hCG and/or AFP in 50% of cases.
What is embryonal carcinoma?
male Germ cell tumor
Malignant, hemorrhagic mass with necrosis; painful; worse prognosis than seminoma. Often glandular/papillary morphology. “Pure” embryonal carcinoma is rare; most commonly mixed with other tumor types. May be associated with increased hCG and normal AFP levels when pure (increased AFP when mixed)
What is a leydig cell tumor?
male non-germ cell tumor
Contains Reinke crystals; usually androgen producing, gynecomastia in men, precocious puberty in boys. Golden brown in color.
What is a sertoli cell tumor?
male non-germ cell tumor
androblastoma from sex cord stroma.
What is testicular lymphoma?
male non-germ cell tumor
most common testicular cancer in older men. Not a primary cancer, arises from lymphoma mets to testes. Agressive.
What are the two tunica vaginalis lesions?
Lesions in the serous covering of testis present as testicular masses that can be transilluminated (vs cancers)
Hydrocele - increased fluid secondary to incomplete obliteration of processus vaginalis
Spermatocele - dilated epididymal duct.
What are the precursors for squamous cell carcinoma in penis?
More common in Asia, Africa, and South America
Percursor in situ lesions: Bowen disease (in penile shaft, presents as leukoplakia), erythroplasia of Queyrat (cancer of glans, presents as erythroplakia), Bowenoid papulosis (presents as a reddish papules). Associated with HPV, lack of circumcision.
What are causes of priapism?
Trauma, sickle cell disease (sickled RBCs get trapped in vascular channels), medications (anticoagulants, PDE-5 inhibitors, antidepressants, alpha-blockers, cocaine).
Describe what the half life is and the formula? how long does it take to reach steady state?
Property of first order elimination. Drug infused at steady rate takes 4-5 half lives to reach steady state. It takes 3.3 half-lives to reach 90%
half life time = 0.693 * Vd / CL.
What is the clearance equation?
CL = rate of elimination of drug / Plasma drug concentration = Vd * Ke (elimination constant).
How do you calculate loading dose?
Loading dose = Cp * Vd / F.
Cp = Target plasma concentration at steady state.
How do you calculate maintenance dose?
Cp * CL * tau / F.
where Cp is target plasma concentration at steady state.
tau is the dosage interval (time between doses), if not administered continuously.
How do you adjust loading dose and maintenance dose in renal or liver disease?
Decrease maintenance dose but loading does is usually unchanged.
What is drug stead state dependent on?
Only on half life. Little dependence on loading or maintenance doses!
difference between zero order and first order elimination? examples of zero order?
Zero order: constant amount of drug eliminated per unit time. Linear relationship with time.
Examples: Phenytoin, Ethanol, and Aspirin (PEA, which is round like a ZERO-order).
First order: Rate of elimination is directly proportional to the drug concentration (constant fraction of drug eliminated per unit time). Cp decreases exponentially with time.
What are examples of weak acid drugs and what happens to them in the urine?
Ionized species are trapped in urine and eliminated. Neutral forms are reabsorbed.
Examples: phenobarbital, aspirin, methotrexate. PAM
These get trapped in basic environments so can treat overdose with bicarbonate.
What are examples of weak base drugs and what happens to them in the urine?
Ionized species are trapped in urine and eliminated. Neutral forms are reabsorbed.
Examples: amphetamines.
Trapped in acidic environments so use ammonium chloride for overdose.
What are examples of Phase 1 drug metabolism?
Reduction, oxidation, hydrolysis with cytochrome P450 usually yield slightly polar, water-soluble metabolites (often still active).
Geriatric patients lose phase 1 first.
What are examples of Phase 2 drug metabolism?
Conjugation (Glucuronidation, Acetylation, Sulfation) usually yields very polar, inactive metabolites (renally excreted).
Geriatric patients have GAS (phase II).
Patients who are slow acetylators have greater side effects from certain drugs because of decreased metabolism.
