March 15 Flashcards
Anticoag therapy in pregnancy?
Low-molecular-weight heparins
LMWH: enoxaparin
umbilical hernia in a neonate
due to incomplete closure f the umbilical ring & defect at linea alba
associated with:
Down Syndrome
Hypothyroidism
Beckwith-Wiedemann Syndrome
Beckwith-Wiedemann Syndrome
Wilms Tumor
Macroglossia
Umbilical Hernia
Organomegaly
WT2 mutation
Arginase Deficiency
Arginase is a Urea Cycle enzyme - produces UREA and Ornithine form ARGININE
symptoms of deficiency: elevated arginine in plasma and CSF bilateral spastic paresis delayed development (cognitive and motor) growth delay normal or mild ammonemia
Class IB Antiarrhythmics
Lidocaine, Tocainide, Mexiletine
Bind and block sodium channels with the lowest affinity of Class I (dissociate from channels most rapidly)
highest affinity IC>IA>IB
Prolong phase 0 –> decreased AP duration
Increase QT interval
tx: ventricular arrhythmias,
IB is Best for post-MI
Preferentially effects ischemic and depolarized Purkinje and Ventricular tissues
Speed of Cardiac Conduction at various tissues
Purkinje>Atria>Ventricles>AV Node
CXR appears worse than symptoms/patient presents
Mycoplasma pneumonia
Walking pneumonia (you feel fine, CXR looks terrible)
Mitral Regurgitation
mid-systolic click
mid-to-late systolic murmur
@ apex
squatting increases venous return (more volume decreases valve prolapse)
Marfans, Ehler-Danlos, and OI
Chemotactic for Neutrophils
IL-8
Leukotriene B4
C5a
Crohn Disease
Transmural inflammation –> Fistula formation
discontinuous lesions from mouth to anus
Adenoma to Carcinoma Sequence
Normal Colon -1-> proliferative epithelium -2-> Adenoma -3-> Carcinoma
1 = APC inactivation 2 = K-ras activation - uncontrolled proliferation 3= p53 inactivation - malignant transformation
PGI2
inhibits platelet aggregation and adhesion to the vascular endothelium
also vasodilates
PGE2
dilates Afferent Arteriole –> increased RBF and GFR
NSAIDS block PGE2 –> Afferent Arteriole Constriction –> decreased GFR
Retinoblastoma
associated with osteosarcoma
Chromosome 13
Eosinophils mechanism of action
antibody-dependent cell-mediated cytotoxicity
bind Fc of IgE and release Major Basic PRotein and ROS
Parasitic infection –> TH2 differentiation of CD4+ T-cells –> IL-5 release –> recruitment of Eosinophils
Glycogenolysis
breakdown of glycogen, occurs at Liver and Muscle
In Muscle:
Muscle contraction –> increased Ca++ –> activation of Phosphorylase Kinase (PK) –> phosphorylation/activation of Glycogen Phosphorylase –> Glycogenolysis (Glycogen –> Glucose-1-P)
In Liver:
Glucagon/Epinephrine –> increased cAMP –> activation of PK –> activation of Glycogen Phosphorylase –> Glycogenolysis
Allopurinol
blocks Xanthine Oxidase
enhances conversion of Azathioprine –> Active metabolites –> bone marrow suppression
Cryptorchidism
undescended testis
atrophy and necrosis of the seminiferous tubules if left uncorrected
increased risk for testicular cancer
Orchiopexy (moving teste to the scrotal sac) decreases but does not eliminate the risk of cancer
Corynebacterium diphtheriae description
nonmotile gram positive rods with polar granules that stain with aniline dyes (methylene blue)
found in clumps ‘chinese characters’
grown on Cysteine-Tellurite agar (forms black colonies) and Löffler medium
+ Elek test (for toxin)
Toxoid Vaccine
coryne = club shaped
C. diphtheriae toxin
exotoxin - inhibits protein synthesis via ADP-ribosylation of EF-2 (elongation factor)
same mechanism as Exotoxin A from Pseudomonas aeruginosa
Pineal Gland Mass
Obstructive hydrocephalus due to cerebral aqueduct compression
[papilledema, headache, vomiting]
Dorsal Midbrain Syndrome (Parinaud)
[downward gaze preference/limited upward gaze, and bilateral eyelid retraction, and pupils accommodate but don’t react to light]
Most commonly a Germinoma
Lymph Node Anatomy
Cortex
Paracortex
Medullary Sinus
Medullary Cord
Cortex - location of Follicles - B-cells (absent in agammaglobulinemia)
Paracortex - T-cells and Dendritic cells (absent in DiGeorge)
Medullary Sinus - reticular cells and macrophages
Medullary Cord - B-cells, plasma cells, macrophages
Treatment of Obstructive Sleep Apnea
Hypoglossal Nerve Stimulation - causes tongue to move forward and increases anteroposterior airway diameter
Also: weight loss, CPAP, surgery
Invasive Pulmonary Aspergillosis
Patients with profound and prolonged neutropenia
fever, chest pain, dyspnea on exertion, hemoptysis
septate narrow hyphae with acute angle branching
Mitral Stenosis and Hemodynamic Changes
Increased Left Atrial Diastolic Pressure
Increased pulmonary capillary wedge pressure
Pulmonary Hypertension
Decreased Pulmonary Vascular Compliance
Right Ventricular Dilation
Functional Tricuspid Regurgitation
normal diastolic pressure of Left Ventricle
Hepatitis C Immune Evasion?
Antigenic variation of envelope proteins
due to RNA-dependent RNA polymerase with no proofreading
host antibodies (IgG) lag behind, virus stays one step ahead
Neuronal Length Constant
measure of how far along an axon the AP can propagate
decreased with demyelination
Most Common Cause of Cancer Deaths
Lung Cancer
Silicosis
Dx: birefringent silica particles surrounded by fibrous tissue on histology
(eggshell) calcification of the rim of hilar nodes
Impairs macrophage function
Predisposes to TB infection
Marker of Neural Tube Defect and Ventral Wall Defect (omphalocele)
INCREASED AFP
Decreased AFP
Trisomy 18 and 21
dating error (mothers with irregular menses make it difficult to know date of late cycle)
Coagulative Necrosis
Ischemic Injury
Tissue architecture is preserved, cells are anucleated with eosinophilic cytoplasm
Caseous Necrosis
TB infections
also Histoplasma, Cryptococcus, Coccidioides
cheesy tan-white gross appearance
fragmented cells surrounded by macrophages –> granuloma
Fat Necrosis
Acute Pancreatitis
chalky-white deposits due to Saponification (fatty acids + calcium)
“worst headache of my life”
Subarachnoid Hemorrhage
Saccular (berry) aneurysms
usually at Circle of Willis
associated with Ehlers-Danlos and ADPCKD (polycystic kidney disease)
see hyperdensity/blood in the sulci on CT
Bradykinin
Angioedema
Acquired: ACEi (-prils)
Hereditary: C1 esterase inhibitor deficiency (decreased serum C4)
Kallikrein catalyzes Kininogen –> Bradykinin
Ovary Epithelium
simple cuboidal
Fallopian Tube Epithelium
simple columnar
Cervix
Ectocervix
Endocervix
Ectocervix - stratified squamous non-keratinized
Endocervix - simple columnar
Most common cause of Sudden Cardiac Death
Ventricular Fibrillation
70% is related to inadequate tissue perfusion due to coronary artery occlusion
this is also how most people die in the first 48 hours post-MI
Atheroembolism
occurs following an invasive vascular procedure (angiography/angioplasty)
dislodged cholesterol-containing debris is dislodged from large vessels and caught in small vessels
Acute Kidney Injury (oliguria, azotemia) is the most common result
Biopsy shows cholesterol clefts (lost during tissue prep, just see needle-shaped clefts)
MOA of Beta-Blockers for HTN
Reduce cardiac contractility and HR (via beta-1)
Decrease renin release by the kidney
Treatment of Status Epilepticus
IV Benzodiazepines
MOA: increase effects of GABA-A –> increased influx of Cl- –> hyperpolarization
GABA = gamma-aminobutyric acid
Alveolar Hyperventilation
Indicated by hypocapnia (low PCO2)
Caused by V/Q mismatch –> hypoxemia –> increased respiratory drive –> excessive CO2 excretion from lungs
hypoxemia persists because of V/Q mismatch
could be pneumonia or PE
Hypoventilation = Hypercapnia
Plummer-Vinson Syndrome
dysphagia
iron deficiency anemia
koilonychia - spoon shaped nails
shiny red tongue
esophageal web formation
Ivabradine
Inhibits Funny Sodium Channels during Phase 4 (slow depolarization phase)
Decrease Heart Rate
No effect on contractility or relaxation
Xeroderma Pigmentosum
Disorder of Nucleotide Excision Repair (required for repair of DNA damage by UV)
skin cancers seen as early as age 5-6
Disorder of Nucleotide Excision Repair
Xeroderma Pigmentosum
Disorder of DNA Mismatch Repair
Lynch = HNPCC
Disorder of DNA Crosslink Repair/NHEJ
Fanconi anemia
aplastic anemia
short stature
absent thumbs
cafe-au-lait
Acute Graft Rejection
1-4 Weeks post transplant
dense interstitial infiltrate with many mononuclear cells - usually T-cells sensitized for foreign MHC
Very Long Chain Fatty Acid Oxidation Location
Peroxisomes
Peroxisomal Dz
inability to metabolize Very Long Chain Fatty Acids
neurodeficits
improper CNS Myelination
Ataxia-Telangiectasia
autosomal recessive disorder of NHEJ
ataxia
telangiectasias
recurrent sinopulmonary infections
PCP = phencyclidine MOA
NMDA antagonist
NMDA = N-methyl-D-aspartate
hallucinations, violent behavior, vertical nystagmus, ataxia
Thyroid Peroxidase
Thyroglobulin iodination
Iodide oxidation
Coupling of iodized tyrosine residues
antibodies against Thyroid Peroxidase ~90% of Hashimoto Thyroiditis
Niacin B3 Deficiency
Pellagra
Dermatitis (@ sun-exposed areas)
Diarrhea
Dementia
Obtained in diet
Synthesized from Tryptophan
Necessary for NAD+ and NADH synthesis
Also seen in carcinoid syndrome, prolonged INH therapy, Hartnup Dz
Mucociliary Clearance
Remove particulate from the lungs
Particles are trapped in mucus and then swept up to pharynx by ciliated cells that line the trachea –> proximal respiratory bronchioles
Cough Reflex
Afferent carried by Internal Branch of Superior Laryngeal (CNX)
Efferent is also CN X
Internal Branch of Superior Laryngeal can be damaged if things get caught in piriform recess which overlies the N.
Gag Reflex
Afferent: Glossopharyngeal (CN IX)
Efferent: Vagus (CN X)
Vestibulo-ocular Reflex
Afferent: CN VIII - Vestibular component
Efferent: CN III, IV, VI
coordinated compensatory eye movement that allows for image stabilization when head moves
Corneal Reflex
Afferent: Ophthalmic branch of Trigeminal (CN V1)
Efferent: Facial (CN VII)
Cerebral Ischemia 3-5days
Microglia (monocytes) phagocytize myelin breakdown products and become v. fat with lipids
Patellar fracture
inability to extend knee against gravity (patellar tendon deficit)
Culture Media for C. diphtheriae
Cysteine-tellurite agar –> black colonies
Loffler’s medium
Rabies Vaccine
Inactivated Vaccine
Rabies Presentation
Insomnia, Headache, Agitation, Dysphagia
Painful spasm, progressive paralysis, coma, death
EGFR inhibitor therapy resistance
KRAS mutation
normal: EGFR –> KRAS –> cell proliferation
Acute Hep B Infection
incubation of 30-180 days
joint pain, LAD, pruritic uticarial vasculitis rash, RUQ pain, hepatomegaly
elevated AST/ALT, both 10X normal
Vibrio cholerae
Oxidase-positive, gram-negative bacilli
grows well on highly alkaline media (TCBS agar)
increased risk of infection in individuals with PPI therapy - V. cholerae is v. acid sensitive usually
Angiotensin II
systemic vasoconstriction
efferent arteriole constriction
increased aldo secretion
increased GFR
ACE inhibitors
-prils
efferent arteriolar dilation –> decreased GFR
decreased systemic vascular resistant (vasodilation)
Ipratropoium
Anticholinergic (derivative of Atropine)
blocks ACh at muscarinic receptors and prevents bronchoconstriction
less effective than beta2 agonists
also reduces PNS stimulation of tracheobronchial submucosal glands –> decreased mucosal production
Ipratropium: Bronchodilate and decrease mucus production
Medical Therapy to reduce recurrent adenoma of the colon?
COX-2 inhibitors! Aspirin.
decreases polyp formation, colonic adenoma and adenocarcinoma
Cephalosporin
Inhibits Transpeptidases (a form of penicillin-binding protein)
–> cell wall instability and bacterial cell lysis
Resistance: change in protein structure of transpeptidases/penicilliin-binding proteins
Vancomycin
binds D-ala residues of Cell Wall Glycoproteins
prevents transpeptidases from forming cross-links
DRESS Syndrome
Drug Reaction with Eosinophilia and Systemic Symptoms
2-8 weeks after exposure to anticonvulsants (phenytoin and carbamazepine) allopurinol, sulfonamides, vancomycin
symptoms: fever, LAD, facial edema, skin rash
Amniotic Fluid Measurement of Lung Maturity
Phosphatidylcholine aka Lecithin : Sphingomyelin ratio
stays 1:1 until week 30, then Lecithin goes way up
Sphingomyelin - membrane phospholipid
Phosphatidylcholine (Lecithin) - component of pulmonary surfactant - increases at 30 weeks gestation
Phosphatidylglyceral - component of pulmonary surfactant - increases at 36 weeks gestation
Dandy Walker Malformation
hypoplasia/absence of Cerebellar Vermis
Cystic dilation of 4th ventricle
Posterior Fossa Enlargement
patients present with skull enlargement and developmental delay
non-communicating hydrocephalus due to atresia of Luschka and Magendie formania
Duodenal Peptic Ulcer
H. pylori
tx: amoxicillin, clarithromycin, omeprazol
Pulmonary side effect of Methotrexate
Pulmonary Fibrosis
gradually progressive dyspnea
end-inspiratory crackles at the lung base
‘honeycombing’
PFTs increased FEV/FVC decreased lung volumes decreased FEV decreased FVC
patchy interstitial lymphocytic inflammation and fibrosis of the alveolar wall
Parietal Cells
Located in the upper glandular layer of the stomach
Secrete Intrinsic Factor - Binds B12 Cobalamin
Autoimmune Gastritis
Chronic Atrophic Gastritis
autoimmune destruction of parietal cells –> decreased intrinsic factor –> pernicious anemia
histology: lymphocytic and plasma cell infiltration
Pernicious Anemia
CD4+ T-cell mediated destruction of parietal cells –> B12 deficiency
macrocytic megaloblastic anemia
paresthesias and degeneration of dorsal column, lateral corticospinal tract, and spinocerebellar tract - due to abnormal myelin
increase serum homocysteine and methylmalonic acid
West Nile Virus
Flavivirus - ssRNA+ transmitted by mosquito
fever, malaise, headache, myalgia, rash, encephalitis (confusion, altered mental status) and flaccid paralysis
Heparin Overdose
Protamine
fresh frozen plasma contains antithrombin III - enhances the effects of heparin! :(
Warfarin Overdose
short-term: Fresh Frozen Plasma
longer: Vitamin K - takes days to work because requires synthesis of new coag factors
Tetralogy of Fallot
Ventricular septal defect
Overriding aorta
Right ventricular outflow tract obstruction (pulmonary stenosis)
Right ventricular hypertrophy
cyanotic spells that improve with squatting (increases afterload/peripheral systemic vascular resistance)
embryological deviation of the infundibular septum
Dairy products –> Meningitis/Encephalitis
Listeria monocytogenes
intraceullular gram + bacilli
Recombination vs Reassortment
Recombination via crossing over - 2 non-segmented viruses infect same cell
Reassortment with SEGMENTED viruses, mix-n-match - 2 segmented viruses infect same cell
Granuloma in the media of vessels
Giant Cell Temporal Arteritis
Takayasu Arteritis
granulomatous inflammation of the media
Secondary (Acquired) Lactase Deficiency
Inflammatory - Celiac Dz
Infectious - Giardiasis
damage to microvilli –> abd distentsion, cramping, flatulence, diarrhea
Hyperacute Transplant Rejection
Time: Minutes to hours
MOA: preformed antibodies / antibody mediated hypersensitivity (Type II via IgG, @ABO or HLA)
Morphology: Mottling and cyanosis
arterial fibrinoid necrosis
capillary thrombotic occlusion
Acute Transplant Rejection
Time: <6 months
MOA: exposure to donor antigen –> humoral/cellylar activation
Humoral: C4d deposition, neutrophilic infiltrate, necrotizing vasculitis
Cellular: Lymphocytic infiltrate
Chronic Transplant Rejection
Time: months to years
MOA: low-grade immune response refractory to immunosuppressants
Vascular wall thickening and luminal narrowing
interstitial fibrosis with parenchymal atrophy
Substitution of glutamic acid with valine
Sickle Cell! HbS
Pathogenesis of Congestive Heart Failure
1) Decreased CO
2a increased SNS activity
2b increased RAAS activity
2c increased ADH
3a increased heart rate and contractility
3b vasoconstriction
3c increased in extracellular volume
increased hemodynamic stress
increased cardiac remodeling :(
Incidence and Deaths of Breast, Lung and Colon cancer
Highest Incidence:
Breast>Lung>Colon
Highest Death:
Lung>Breast>Colon
Pudendal Nerve
S2-S4
Sensory: external genitalia, skin around anus and perineum
Motor: pelvic floor muscles, external anal and urethral sphincters (#continence)
can be damaged at labor causing
fecal and urinary incontinence
Effects of Ureter Obstruction (on GFR and FF)
Decreased GFR due to increased hydrostatic pressure of Bowman Space
Decreased Filtration Fraction
Filtration Fraction
FF = GFR/RPF - normal=20%
GFR ~ creatinine or inulin clearance
RPF ~ PAH clearance
Clearance = [urine] x urine flow rate / [plasma]
RBF = RPF/(1-Hct)
Tourettes
Motor and Vocal tics for > 1 year
Mycolic Acids and Acid Fast Staining
Mycolic acids @ cell call are the reason that mycobacteria are acid-fast
hold on to carbolfuchsin
Isoniazid inhibits mycolic acid synthesis and decreased staining with acid fast
Cerebral Vessel associated with Wernicke aphasia
Middle Cerebral Artery
supplies Broca and Wernicke area
Wernicke Aphasia
Word Salad
Receptive aphasia
well articulated nonsense speech with lack of comprehension
Broca Aphasia
Broken Boca
comprehension is intact but speech fluency is not
frustrating
Axillary Nerve
C5 and C6
Motor: deltoid and teres minor
Sensory: skin of lateral shoulder
Damage @ proximal humeral fracture
Aortic Stiffening
Age related loss of elastin and increased collagen deposition
Causes decreased compliance and elevated pressures during systole (ex. 180/70)
Neisseria meningitidis meningitis route of infection
pharynx –> blood –> choroid plexus –> meninges
“bean shaped gram negative cocci in pairs”
Hereditary Pancreatitis
Mutation that prevents trypsin from being inactivated –> pancreatitis
ex. SPINK1 gene mutations
Lyme Disease
Borrelia burgdorferi via Ixodes tick in NE USA
early: flu-like symptoms and target rash (erythema chronicum migrans)
middle: facial palsy or AV nodal block
late: asymmetric arthritis (single knee joint) and/or subacute encephalopathy
tx: doxycycline or ceftriaxone
Varenicline
partial agonist of Nicotinic ACh receptors
cessation of tobacco use - decreases withdrawal cravings and reward effects
Type I Hypersensitivity Reaction
Anaphylaxis and Allergies
Humoral: IgE
Cellular: Basophils and Mast Cells
Type II Hypersensitivity Reaction
Autoantibodies
Goodpasture and Autoimmune Hemolytic Anemia
Humoral: IgG and IgM autoantibodies and complement
Cellular: NK cells, Eosinophils, Neutrophils, Macrophages
also: Transfusion reactions, bullous pemphigoid, Graves, Guillain-Barre, Myasthenia gravis, pemphigus vulgaris, pernicious anemia, rheumatic fever
Type III Hypersensitivity Reaction
Immune Complex Deposition
Serum Sickness, Post-Strep Glomerulonephritis, Lupus Nephritis
deposition of antibody-antigen complexes and complement activation
3 things stuck together in type III
Antigen + Antibody + Complement
Type IV Hypersensitivity Reaction
Delayed type
T-cells and Macrophages
contact dermatitis, poison ivy, TB skin test, graft-vs-host Dz.
4 T’s: T-cells, Transplant rejection, TB skin test, and Touching (contact dermatitis)
Medulloblastoma
primitive neuroectodermal tumor
sheets of small cells with deeply basophilic nuclei and scant cytoplasm
small round blue dense cells + abundant mitosis
^this differentiates it from pilocytic astrocytoma
undifferentiated and aggressive
cerebellum
Pilocytic Astrocytoma
most common cerebellar tumor of childhood
Rosenthal fibers and pilocytic astrocytes on histology
low grade and better prog than medulloblastoma
Diphenoxylate
mu opiate receptor agonist in the GI tract
slows motility
tx for diarrhea
Loperamide works this way too!
HER2 Positive breast cancers
worse prognosis - poorly differentiated and rapidly growing tumors
tx: trastuzumab
Non-Cyanotic Congenital Heart Defects
ASD
VSD
PDA
Coarctation of aorta
Ventricular Septal Defects
small VSD –> loud blowing holosytolic murmur at lower left sternal border
present 4-10 days after birth as PVR declines
often close spontaneously
Large VSD –> heart failure, failure to thrive, diaphoresis with feeding
can progress to pulmonary hypertension and cyanosis –> Eisenmenger syndrome
require surg - early close is key to preventing complications
