Subjects 0321 Flashcards
How does carotid massage affect HR?
Increases pressure on carotid sinus –> more stretch –> more firing –> increase in AV node refractory period –> decr HR.
What is the Cushing reaction and how does it affect the autonomic system?
Triad: hypertension, bradycardia, respiratory depression
Incr ICP leads to compression of cerebral arterioles –> cerebral ischemia –> incr pCO2 and decr pH –> central reflex sympathetic incr in perfusion pressure (HTN) –> incr stretch –> incr peripheral reflex baroreceptor induced-bradycardia.
What are the blue baby congenital heart diseases? What increasing the shunting?
5T’s: truncus arteriosus, transposition, tricuspid atresia, tetralogy of falot, TAPVR.
The right-to-left shunts cause early hypoxia, so the patients manifest cyanosis in early childhood, or even at birth.
Generally, right-to-left shunts result from a high pulmonary venous resistance and low systemic vascular resistance. Increased pulmonary vascular resistance (PVR) (crying, hypoventilation, and acidosis) or decreased systemic peripheral resistance (SVR) (hypotension, histamine release, sepsis) will increase the shunting and worsen the hypoxia.
Drug induced lupus
SHIPP = Sulfonamides, hydralazine, isoniazid, procainamide, phenytoin
Hypertensive drugs for pregnant mothers?
Hypertensive Moms Love Nifedipine
-Hydralazine, methyldopa, labetalol, nifedipine
What are the two types of arteriolosclerosis?
- Hyaline: thickening of vessel walls in essential HTN or DM. 2. Hyperplastic: onion skinning in severe HTN with proliferation of smooth muscle cells.
How do you characterize temporal arteritis?
Giant cell arteritis–focal granulomatous inflammation (with giant cells) characterize this process. Branches of carotid system are most often involved. Can lead to irreversible blindless if it involves ophthalmic artery.
Maple syrup urine disease is characterized by the defective breakdown of what?
I Love Vermont’s branched chain AAs. Defect in breadown of branched chain AA’s = Leucine, Isoleucine, and Valine. Degradation involves transamination to their respective a-ketoacids, which is then metabolized by branched-chain a-ketoacid dehydrogenase. Mutation in any 4 genes coding for 3 catalytic subunits.
Neurotoxicity results from accumulation of leucine in the serum and tissues. A metabolite of isoleucine gives the urine a sweet odor. MSUD can be life-threatening if untreated.
***Branched chain a-ketoacid dehydrogenase (similar to pyruvate and a-ketoglutarate dehydrogenase) requires the Tender Loving Care For Nobody co-enzymes = Thiamine pyrophosphate, Lipoate, Coenzyme A, FAD, NAD.
Surface ectoderm
Rathke’s pouch (ant pit), lens, cornea, inner ear sensory organs, olfactory epithelium, nasal and oral epithelial linings, epidermis, salivary, sweat, mammary glands.
Neural tube –> ?
Brain and spinal cord, posterior pituitary, pineal gland, retina
Neural crest –> ?
Autonomic, sensory, celiac ganlia, schwann cells, pia and arachnoid mater, aorticopulmonary septum & endocardial cushions, branchial arches (bone and cartilage), skull bones, melanocytes, adrenal medulla.
Fragile X sydrome
Mild to moderate mental retardation, speech/language delay, autistic behavior and ADHD. Long face, prominent jaws, large ears, cleft palate. Macroorchidism. Mitral valve prolapse. Short height, joint laxity, scoliosis, pes cavus, double-jointed thumbs, single palmar crease.
***Increase in number of trinucleotide repeats in FMR1 gene on X-chromosome.
p-ANCA (perinuclear, anti-myeloperoxidase)
Microscopic polyangiitis: lung, kidney, skin (no nasopharyngeal), pauci-immune glomerulonephritis, palpable purpura.
Churg-Strauss (eosinophilic granulomatosis with polyangiitis): asthma, sinusitis, skin nodules or purpura, peripheral neuropathy (wrist/foot drop). Involves heart, GI, kidneys (pauci-immune).
What are the mRNA stop codons?
UGA, UAA, UAG. You go away, you are away, you are gone.
CN- toxicity
Sodium nitratate: promotes methemoglobin formation, which combines with CN- to form cyanmethemoglobin
Sodium thiosulfate: serves as sulfur donor to promote hepatic rhodanese-mediated conversion of CN- to thiocyanate, which is excreted in the urine.
Hydroxocobalamin: cobalt moiety binds to intracellular cyanide ions and forms cyanocobalamin, which is excreted in the urine.
Hep A inactivation
Water chlorination, bleach, formalin, UV irradiation, boiling for 85C for 1 min.
Describe the midgut development.
The midgut herniates through the umbilical ring at the 6th week of embryonic development to allow the rapid growth of the intestine and liver despite the slower growth of the abd cavity. The midgut returns to the cavity at 10th week of fetal life, and completes a 270 degree turn counterclockwise around the SMA.
What are the associated nerve injuries for: carpal tunnel, hook of the hamate, surgical neck of the humerus, head of radius, coracobrachialis?
Carpal tunnel: median nerve compression. Difficulty with fine motor control of thumb.
Hook of hamate: ulner nerve, near Guyon’s canal and pisiform bone in wrist
Medial epicondyle of humerus: ulner nerve
Fracture of surgical neck of humerus: axillary nerve –> paralysis of deltoid and teres minor, loss of sensation of lateral upper arm.
Radial head subluxation: deep branch of radial nerve –> weakness/paralysis of extensor compartment of forearm.
Coracobrachialis: lies deep to biceps brachii and overlies median nerve and brachial artery, innervated by musculocutaneous nerve.
What is Chediak-Higashi syndrome?
Chediak-Higashi syndrome is an autosomal recessive d/o of neutrophil phagosome lysosome fusion. Abnl giant lysosomal inclusions visible on light microscopy of a peripheral blood smear.
- Neurologic abnl (nystagmus, peripheral and cranial neuropathies)
- Partial albinism (abnl melanin storage in melanocytes)
- Immunodeficiency (defective neutrophil function, recurrent pyogenic infxn, staph + strep)
Which bacteria produce IgA protease?
Neisseria meningitidis, N gonorrhoeae, S pneumoniae, H influenzae
Ureters in relation to gonadal vessels and common/external ilaic vessels?
Ureters cross over the common/external iliac vessels and under the gonadal vessels (and uterine vessels in females). They lie anterolateral to the internal iliac vessels and medial to the ovarian vessels within the true pelvis.
What does the thayer-martin selection medium contain?
Chocolate (head blood) agar contains vancomycin (inhibit G+), colistin (polymyxin, inhibit G-), nystatin (inhibit fungi), and trimethoprim (G-, Proteus). Used to ID neisseria.
Alpha-helices are found where in the cell?
Integral membrane proteins contain transmembrane domains composed of alpha helices with hydrophobic AA residues (valine, alanine, isoleucine, methionine, phenylalanine).
Where are the following tumors located?
Craniopharyngioma:
Germ cell tumor:
Meningioma:
Craniopharyngioma: arise from remnants of Rathke’s pouch, located in suprasellar region. Present with hypothalamic or pituitary dysfunction and chnages in vision due to disruption of optic chiasm (bitemporal hemianopia).
Germ cell tumors: arise from pineal gland, located in dorsal midbrain. Cause obstructive hydrocephalus with sx of increased intracranial pressure (HA, vomiting, AMS), and Parinaud syndrome (upward gaze palsy).
Meningioma: falcine/parasagittal region over convexities of cerebral hemispheres. Most are disovered incidentally. Some have seizures, HA, forcal neuro deficits.
Which hormones are secreted from the following structures?
Nucleus cereleus
Raphe nuclei
Nucleus basalis of Meynert
Red nucleus
Caudate nucleus and putamen
Substatia nigra
Nucleus ceruleus: NE-secreting neurons, fight or flight, dorsal pons
Raphe nucleus: Serotonergic relesasing neurons, midbrain, pons, and medulla, axons throughout CNS, sleep-wake cycle, level of arousal. Lesions: insomnia and depression.
Nucleus basalis of Meynert: cholinergic neurons. Alzheimer patient’s neurons here secrete inadequate amounts of acetylcholine.
Red nucleus: anterior midbrain, motor coordination of upper extremities.
Caudate nucleus and putamen: motor activities. Huntington’s–loss of cholinergic and GABA-releasing neurons in striatum.
Substantia nigra: dopaminergic neurons. Parkinson’s–depleted.
Ventromedial hypothalamic nuclei
Satiety. Destruction: hyperphagia. Stimulated by leptin.
Lateral hypothalamic nuclei
Hunger. Destruction: anorexia. Inhibited by leptin.
Anterior hypothalamic nuclei
Heat dissipation via parasympathetics. Destruction: hyperthermia.
Posterior hypothalamic nuclei
Heat conservation via sympathetics. Destruction: hypothermia.
Arcuate hypothalamic nuclei
Secretion of dopamine (inhibits prolactin), growth hormone-releasing hormone and gonadotropin
Paraventricular hypothalamic nuclei
Antidiuretic hormone, corticotropin-releasing hormone, oxytocin and thyrotropin-releasing hormone secretion
Supraoptic hypothalamic nuclei
Secretion of ADH and oxytocin
Suprachiasmatic hypothalamic nuclei
Circadian rhythm regulation and pineal gland function
Leucovorin
Or called folinic acid. Tx methotrexate overdose.
Filgrastim
G-CSF analog used to stimulate proliferation and differentiation of granulocytes in patients with neutropenia post-chemo.
Cyclophosphamide toxicity
Hemorrhagic cystitis–use mesna to bind acrolein in urine.
Fibromyalgia
Chronic d/o with widespread MSS pain, fatigue neuropsychiatric disturbances in W 20-55 yo. Involves abnormal central processing of painful stimuli. Gradual incremental aerobic exercise can reduce pain. Normal acute phase reactants (CRP). Multiple tender points at characteristic locations. No joint or muscle inflammation.
Polymyalgia rheumatica
Inflammatory d/o that affects patients >50yo, causes bilateral pain and morning stiffness in shoulders and hips, weight loss, fever, malaise, elevated ESR. Frequently associated with giant cell (temporal) arteritis.
Red rashes of childhood
- VZV
- Parvovirus B19
- Rubella virus
- Measles virus
- HHV6
- Streptococcus pyogenes
VZV
Chicken pox. Pruritic, vesicular rash on face, trunk and extremities. Lesions in different stages of development.
Parvovirus B19
Erythema infectiosum. Malar rash with slapped cheek appearance (spares nasolabial folds. As rash fades, erythematous rash in reticular (lacelike) pattern appears in trunk and extremities. ***Aplastic crisis in sickle cell and immunocompromised patients.
Rubella
German measles. Togavirus. Maculopapular rash starting on head, progressing to trunk and extremities. Occipital & postauriricular lymphadenopathy. ***Congenital rubella syndrome.
Measles
Rubeola: Maculopapular rash starting on head that progresses to trunk and extremities. Rash preceded by cough, coryza, conjunctivitis, and koplik spots. ***Bronchopneumonia, encephalitits.
HHV6
Roseola infantum: high fever for 3-5 days with rash once fever subsides. Macules & papules first on trunk, spread to extremities. Self limited.
Streptococcus pyogenes
Scarlet fever. Sandpaper-like rash (diffuse erythematous with small papules) that begins on neck, armpits, groin and then generalizes. A/w fever and sore throat. ***Rheumatic fever, glomerulonephritis.
Drugs for BPH and HTN:
Doxazosin, prazosin, terazosin. Also beneficial for CAD, HF patients. A1B1 blockers. SE: first dose effect hypotension.
Axonal reaction
Enlarged, rounded cells with peripherally located nuclei and dispersed finely granular nissle substance. Reflects incresed protein synthesis that facilitates axon repair.
How does botulinum intoxication present?
Descending paralysis that first manifests with cranial nerve abnl (diplopia, dysphagia, difficulty speaking). N/V/abd pain can occur in food-born botulinsm after consumption of contaminated, homemade canned foods. Incubation period is 12-36 hours. Pathophys: botonium toxin inhibits cholinergic nerves (nicotinic and muscarinic motor neurons), prevents binding and fusion of ACh-containing synaptic vesicles with plasma membrane, block relsease of ACh into NM synapse.
Collagen synthesis
Procollagen is made in ER as a central helical structure flanked by globular extensions. Then transported through golgi and released into extracellular space where it’s converted into tropocollagen by procollagen peptidases (N and C terminal propeptides are removed) that remove globular portions of the molecule. The resulting tropocollagen monomers self-assemble into collagen fibrils that are then covalently crosslinked by lysyl oxidase.
Kernicterus
Chorea, cerebral palsy, hearing loss, gaze abnl
Basal ganglia–caudate
Tx hyperbilirubinemia to prevent: phototherapy
Crigler-Najjar syndrome, type II tx
Phenobarbital induces liver enzyme synthesis (UDP-glucuronosyltransferase).
Wilson disease
AR. Defect in ATP7B enzyme: impaired excretion of copper into bile, impaired conversion of copper to ceruloplasmin –> low serum cerloplasmin.
Copper accumulates in liver, brain, cornea, kidneys, joints.
Sx: cirrhosis, Kayser-Fleischer ring, HCC risk, hemolytic anemia, basal ganglia degeneration, Parkinsonian sx, hepatic enceph, dementia, fanconi (PCT defect).
Tx: penicillamine (pennies–copper).
Hemochromatosis
Excess iron deposition.
Triad: cirrhosis, DM, skin pigmentation.
“Bronze DM.” CHF, testicular atrophy, increase risk of HCC.
AR (C282Y on HFE gene) results of transfusions.
Increased ferritin (storage iron). Increased total serum iron, decr total iron binding capacity, incr transferrin saturation.
Prussian blue stain
PBC vs PSC
PBC: +ANA, middle-aged woman, autoimmune
PSC: +pANCA, men > 40yo, a/w UC and cholangiocarcinoma, beads on string
S3 heart sound
Dilated cardiomyopathy
CHF
Mitral regurgitation
L to R shunt: VSD, ASD, PDA
Children (can be normal)
Pregnant woman (can be normal)
S4 heart sound
Late diastole, atrial kick
Stiffened LV wall
Hypertrophic cardiomyopathy
Aortic stenosis
Chronic HTN with LVH
Post-MI
Which thalamic nuclei are the relay station for auditory sensation?
Medial geniculate nucleus
Which thalamic nuclei are the relay station for visual sensation?
Lateral geniculate nucleus
Which thalamic nuclei are the relay station for motor to the body?
Ventral lateral nucleus
Which thalamic nuclei are the relay station for facial sensation?
Ventral posteromedial nuclei
Which thalamic nuclei are the relay station for body sensation?
Ventral posterolateral nuclei
What is PPAR-g? What is it used for?
Peroxisome proliferator-activated receptor gamma.
Nuclear receptors and TF found in adipose tissue. Plays role in adipocyte differentation. TZDs (thiazolidinediones) bind PPAR-g and improve insulin sensitivity.
What are the acute phase cytokines?
IL1, IL6, IFNa
What agents are used in Parkinson’s?
BALSA: Bromocriptine (pramipexole), amantadine, levodopa (carbadopa), selegiline (entacapone), antimuscarinics (benztropine–helps with tremor only)
Where is Meissner’s plexus located?
Submucosa
Where is Auerbach’s plexus located? Also called myenteric plexus?
Outer layer of muscularis externa
What is pulsus paradoxus and what are the causes?
SBP drops 10mmHg during inspiration.
Causes: overinflation of lungs: asthma, COPD, cardiac tamponade.
FQ should not be given to which patients?
Children and pregnant women d/t risk of FQ induced joint toxicity
What is the treatment for diabetes insipidus?
- Hydrochlorothiazide: help body concentrate urine
- Amiloride: closes sodium channel in collecting tubule, which is how lithium get into the cells.
- Indomethacin: reduce RBF
Which corticosteroid do you use for dangerous aldosterone deficiency?
Fludrocortisone: lots of mineralocorticoid activity
What are the 4 tumors that secrete EPO?
Pheochromocytoma, RCC, hemangioblastoma, HCC
What provides blood supply to thyroid and parathyroid glands?
- Superior thyroid artery: branch of external carotid artery
- Inferior thyroid artery: branch of thyrocervial trunk
Varus injury
Bowleg, adduction, LCL
Valgus injury
Knock nee, abduction, MCL
Medial epicondylitis
Golfer’s elbow, repetitive flexion, medial epicondyle pain. (Flexors come from medial side).
Lateral epicondylitis
Tennis elbow. Repetitive extension (backhand), lateral epicondyle pain
Median nerve innervates which hand muscles?
1/2 LOAF: 1, 2 lumbricals, opponens pollicis, abductor pollicis brevis (recurrent branch), flexor pollicis brevis (superficial head)
Ulnar nerve innervates which hand muslces?
3/4 LOAF PAD: 3, 4 lumbricals, opponens digiti minimi, abductor digitis minimi, flexor digiti minimi brevis and deep head of flexor pollicis brevis, PAD, adductor policis, DAB
Lesions of which nerves cause foot drop?
PED = Peroneal Everts and Dorsiflexes. If injured – foot dropPED.
Lesion of which nerves prevent you from standing on tiptoes?
TIP = Tibial Inverts and Plantarflexes. If injured – can’t stand on TIPtoes.
What does sciatic nerve innervate?
L4-S3: posterior thigh, splits into common peroneal and tibial nerves.
What does pudendal nerve innervate?
S2-S4: innervates perineum. Can be blocked with local anesthetic during childbirth using ischial spine as landmark for injection.
Type 1 muscle fibers
1 slow red ox: slow twitch, red fibers. More mitochondria and myoglobin concentration, sustained contraction
Type 2 muscle fibers
Fast twitch, white fibers. Less mitochondria and myoglobin concentration (more anaerobic glycolysis). Weight training results in hypertrophy of fast-twitch muscle fibers.
What are the following types of biological agents?
Rituximab, infliximab, certolizumab, imatinib, etanercept?
Rituximab: CD20 blocker for CD20+ non-Hodgkin’s lymphoma
Infliximab: TNF-a blocker for autoimmune diseases (Crohn’s, RA)
Certolizumab: pegylated humanized monoclonal Ab that targets TNF-a. Lacks Fc region (prevents complement and cell-mediated toxicity), treats autoimmune d/o associated with TNF-a
Imatinib: philadelphia chromosome + CML and kit-positive GI stromal tumors. Small-molecule tyrosine kinase receptor inhibitor.
Etanercept: TNFa inhibitor added to methotrexate for RA. Fusion protein linking soluble TNFa receptor to Fc part of human IgG1. DECOY.
Rituximab
Rituximab: CD20 blocker for CD20+ non-Hodgkin’s lymphoma
Infliximab
Infliximab: TNF-a blocker for autoimmune diseases (Crohn’s, RA)
Certolizumab
Certolizumab: pegylated humanized monoclonal Ab that targets TNF-a. Lacks Fc region (prevents complement and cell-mediated toxicity), treats autoimmune d/o associated with TNF-a
Imatinib
Imatinib: philadelphia chromosome + CML and kit-positive GI stromal tumors. Small-molecule tyrosine kinase receptor inhibitor.
Etanercept
Etanercept: TNFa inhibitor added to methotrexate for RA. Fusion protein linking soluble TNFa receptor to Fc part of human IgG1. DECOY.
cAMP pathway
FLAT ChAMP
FSH
LH
ACTH
TSH
CRH
hCG
ADH (V2 receptor)
MSH
PTH
Also: calcitonin, GHRH, glucagon
cGMP pathway
Think vasodilators
ANP, BNP, NO (EDRF)
IP3 pathway
GOAT HAG
GnRH
Oxytocin
ADH (V1 receptor)
TRH
Histamine (H1 receptor)
Angiotensin II
Gastrin
Intracellular receptor pathway
VETTT CAP
Vitamin D
Estrogen
Testosterone
T3/T4
Cortisol
Aldosterone
Progesterone
Intrinsic tyrosine kinase pathway
MAP kinase pathway, think growth factors
Insulin, IGF-1, FGF, PDGF, EGF
Recetor-associated tyrosine kinase pathway
JAK/STAT pathway, think acidophils and cytokines
PIGGlET
Prolactin
Immunomodulators (cytokines IL2, IL6, IFN)
GH
G-CSF
Erythropoietin
Thrombopoietin
Key features of osteoarthritis
Subchondral cysts, sclerosis, osteophytes (spurs), eburnation, synovitis
Herberden (DIP)
Bouchard (PIP)
No MCP involvement
Knee cartilage loss begins medially –> bowlegged
Noninflammatory, no systemc sx
Tx: acetaminophen, NSAIDs, intraarticular glucocoriticoids
Key features of rheumatoid arthritis
Autoimmmune, inflammatory destruction of synovial joints
Pannus (inflammatory granulation tissue = BV, fibroblasts, myofibroblasts) in MCP and PIP
SQ rheumatoid nodules (fibrinoid necrosis)
Ulnar deviation
Subluxation
Swan neck and boutonniere deformities
No DIP
Baker cyst, vasculitides, interstitial lung fibrosis.
80% have rheumatoid factor (anti-IgG ab), anti-cyclic citrullinated peptide b (more specific)
HLA-DR4
Tx: NSAIDs, glucocorticoids, disease-modifying agents (methotrexate, sulfasalazine), biologics (TNF-a inhibitors)
HLA Subtypes
A3: Hemochormatosis
B27: PAIR (seronegative arthropathies) – Psoriatic arthritis, Ankylosing spondylitis, arthritis of IBD, Reactive arthritis (Reiter)
DQ2/DQ8: celiac disease
DR2: MS, hay fever, SLE, Goodpasture syndrome
DR3: DMTI, SLE, Graves, Hashimoto
DR4: Rheumatoid arthritis (4 walls in rheum “room”), DMTI
DR5: pernicious anemia–>VB12 deficiency, Hashimoto
Positive (upregulated) acute-phase reactants
CRP: opsonin, fixes complement and faciliates phagocytosis. Measures ongoing inflammation.
Ferritin: binds and sequesters iron to inhibit microbial iron scavenging.
Fibrinogen: coagulation factor, promotes endothelial repair, correlates with ESR.
Hepcidin: prevents release of iron bound by ferritin –> anemia of chronic disease.
Serum amyloid A: prolonged elevation –> amyloidosis.
Negative (downregulated) acute-phase reactants
Albumin: reduction conserves Aas for positive reactants.
Transferrin: internalized by MO to sequester iron.
ACEI are contraindicated in patients with a deficiency of what?
C1 esterase inhibitor deficiency. Causes heriditary angioedema. Increases bradykinin.
ACEI are CI in patients with:
- Bilateral renal artery stenosis: ACEI decrease GFR, leading to renal failure
- C1 esterase inhibitor deficiency (hereditary angioedema): icnreased complement activity–>incr bradykinin–>mets by ACE
- Pregnancy: fetal renal damage
Exposure to which organisms require passive immunity?
To Be Healed Very Rapidly
Tetanus toxin, Botulinum toxin, HBV, Varicella, or Rabies
Passive immunity = pre-formed antibodies
What are the live attenuated vaccines?
Measles, mumps, rubella (MMR), polio (Sabin), influenza (intranasal), varicella, yellow fever
*may revert to virulent form
What are the killed vaccines?
RIP Always
Rabies, Influenza (injection), Polio (Salk), hepatitis A
What are the catalase + organisms?
Need PLACESS
Nocardia, Pseudomonas, Listeria, Aspergillus, Candida, E. coli, S. aureus, Serratia
What phase of meiosis is a primary oocyte arrested in until before ovulation? What is it arrested in until fertilization?
Arrested until ovulation: primary oocyte in prophase of meiosis I
Arrested until fertilization: secondary oocyte in metaphase of meiosis II
What drugs are used for pulmonary HTN?
- Endothelin receptor antagonist: bosentan. Decr pulmonary vascuar resistance.
- PDE-5 inhibitors: sildenafil. Inhibit cGMP PDE5, prolong vasodilatory effect of NO.
- Prostacyclin analogs: epoprostenol, iloprost. PGI2 with direct vasodilatory effects on pulmonary and systemic arterial vascular beds. Inhibit platelet aggregation. SE = flushing and jaw pain.
Cytoskeleton:
Actin
Myosin
Tubulin
Kinesin
Dynein
Actin: monomeric units that comprise cytoskeletal structural microfilaments
Myosin: microfilament proteins that are directed toward the + end of filament
Tubulin: monomeric units that comprise MT (necessary for movement of cargo through cell)
Kinesin: motor proteins that move cargo toward the + end of the MT (anterograde)
Dynein: motor protiens that move cargo toward the - end of the MT (retrograde)
Pemphigus vulgaris
Lesions begin in oral mucosa
Acantholysis with intradermal blisters seen
Nikolsky sign +
IgG abs direct against desmoglein (cell-cell adhesion)
Cytotrophoblast
Makes Cells. Inner layer of chorionic villi. Stem cells.
Syncytiotrophoblast
Outer layer of chorionic villi, secretes hCG–similar to LH, stimulates corpus luteum to secrete progesterone during first trimester.
***Lacks MHC-I expression: decrease chance of attack by maternal immune system.
Pathway of sperm during ejaculation
SEVEN UP: seminiferous tubules, epididymis, vas deferens, ejaculatory ducts, (nothing), urethra, penis
Bowen disease
Leukoplakia in penile shaft and scrotum. >35yo, HPV 16, 18.
Erythroplasia of Queyrat
Cancer of glans and prepuce. Presents as erythroplakia. HPV16.
Bowenoid papulosis
Multiple pigmented red/brown papules on external genitalia. Carcinoma in situ of unclear malignant potential.
What is Anserine bursitis?
Pes anserinus bursitis–medial aspect of knee. Results from overuse in atheletes or from chronic trauma in patients with heavy body habitus.
Which muscles contribute to the pes anserinus?
Sergeant FOT: Sartorius, Gracillis, semiTeniosis (medial to lateral), Femoral nerve, Obturator nerve, Tibial nerve
NE is made in _____, increased in _____, decreased in _____.
Locus ceruleus (pons)–stress and panic
Increased in anxiety
Decreased in depression
DA is made in _____, increased in _____, decreased in _____.
Ventra tegmentum and substatia nigra pars compacta (midbrain)
Increased in Huntinton disease
Decreased in Parkinson and depression
5-HT is made in _____, increased in _____, decreased in _____.
Raphe nuclei (pons, medulla, midbrain)
Increased in nothing
Decreased in anxiety and depression
ACh is made in _____, increased in _____, decreased in _____.
Basal nucleus of Meynert
Increased in Parkinson disease
Decreased in Alzheimer and Huntington
GABA is made in _____, increased in _____, decreased in _____.
Nucleus accumbens–reward center, pleasure, addiction, fear
Increased in nothing
Decreased in anxiety and Huntington
***Main inhibitory neuron from glutamate, needs B6
What are some RFs and TXs for pseudotumor cerebri?
RF: woman of childbearing age, vitamin A excess, danazol
Treatment: weight loss, acetazolamide, topiramate (GABA release, antisiezure), invasive procedures for refractory cases
Which muscles close the jaw? Which opens?
Close jaw: Masseter, teMporalis, Medial pterygoid (M’s Munch)
Open jaw: lateral pterygoid (Lateral Lowers)
How does retinal detachment present?
Breaks are most common in patients with high myopia and are often preceded by posterior vitreous detachment (flashes and floaters) and eventual monocular loss of vision like a curtain drawn down. EMERGENCY.
Miosis pathway
1st neuron: Edinger-Westphal nucleus to ciliary ganglion via CN III
2nd neuron: short ciliary nerves to pupillary sphincter muscles
Mydriasis pathway
1st neuron: hypothalamus to ciliospinal center of Budge
2nd neuron: exit at T1 to superior cervical ganglion (travels along cervical sympathetic chain near lung apex, subclavian vessels)
3rd neuron: plexus along internal carotid, thorugh cavernous sinus, enters orbit as long ciliary nerve to pupillary dilator muscles. Sympathetic fibers also innervate smooth muscle of eyelids (minor retractors) and sweat glands of forehead and face.
How do cholinergic agonists affect glaucoma?
Cholinergic agonists (pilocarpine and carbachol) cause miosis by promoting contraction of the sphincter of iris. This causes the anterior chamber angle to become wider, making the trabecular meshwork more accessible to outflow of the aqueous humor.
How do a-agonists treat glaucoma (which kind)?
a-agonists (epinephrine, brimonidine) are used for open angle only.
Decrease aqueous humor synthesis.
***Causes mydriasis (do not use in closed-angle). This would lead to further closing of trabecular meshwork (via narrowing of the uveoscleral outflow tract) –> decreased flow of aqueous humor.
Pure motor hemiparesis
Posterior limb of the internal capsule or basal pons
Pure sensory stroke
VPL or VPM thalamus
Ataxis-hemiplegia syndrome
Posterior limb of the internal capsule or basal pons
Dysarthria-clumsy hand syndrome
Genu of the internal capsule or basal pons
Biofilm-producing organisms
Staphylococcus epidermidis (catheter, prosthetics)
Streptococcus mutans & sanguinis (dental plaques)
Pseudomonas aeruginosa (CF pneumonia, contact lenses)
Viridans group streptococci (endocarditis)
Nontypable H. influenza (otitis media)
Local anesthetics–Esters
Procaine, cocaine, tetracaine
Local anesthetics–Amides
Lidocaine, mepivacain, bupivacaine (all have 2 I’s)
Order of nerve blockade (local anesthetic)
Small-diameter fibers > large
Myelinated fibers > unmyelinated fibers
Order of nerve sensation loss (local anesthetic)
Pain, temp, touch, pressure
Depolarizing NM blocking drugs
Succinylcholine: strong Ach receptor agonist, produces sustained depolarization and prevents muscle contraction.
Reversal of blockage: Phase I–prolonged depolarization/NO ANTIDOTE. Block potentiated by cholinesterase inhibitors. Phase II–repolarized but blocked/ACh receptors are available, but desensitized. Antidote: cholinesterase inhibitors.
Complications: hypercalcemia, hyperkalemia, malignant hyperthermia
Nondepolarizing NM blocking drugs
Tubocurarine, atracurium, mivacurium, pancuronium: all are competitive antagonists and compete with ACh for receptors.
Reversal of blockage: neostigmeine (must be given with atropine to prevent muscarinic effects like bradycardia), edrophonium, other cholinesterase inhibitors.
Therapeutic supplemental O2 for neonatal respiratory distress syndrome can lead to what?
RIB: retinopathy of prematurity, intraventricular hemorrhage, and bronchopulmonary dysplasia
MCC of lobar pneumonia
S. pneumo: CAP
Klebsiella: aspiration, nursing home
Legionella
MCC of bronchopneumonia
Staph aureus: secondary, abscess, empyema
H. influenzae: superimposed on COPD
Pseudomonas: cystic fibrosis
Moraxella catarrhalis: CAP + superimposed on COPD
Legionella: CAP, on COPD, water source, intracellular, silver stain
MCC of interestitial (atypical) pneumonia
Mycoplasma: military or dorm, IgM autoimmune hemolytic anemia, erythema multiforme, no cell wall
Chlamydia: young adults
RSV: infants
CMV: post-transplant immunosuppressive therapy
Influenza virus: immunocompromised, elderly, lung dz, increased secondary bacterial
Coxiella: Q fever, farmer and vets, ricketssial but no vector
Apiration pneumonia
R lower lobe abscess
Alcoholic and comatose
Anaerobes: bacteroides, fusobacterium, peptostreptococcus
S. aureus
Tx: clindamycin
MI myocyte progression
0-4: minimal
4-12: early coagulation necrosis, edema, hemorrhage, wavy fibers
12-24: coagulation necrosis and marginal contraction band necrosis
1-5 days: coagulation necorsis and neutrophilic infiltrate
5-10 days: macrophage phagocytosis of dead cells
10-14 days: granulation tissue and neovascularization
2 weeks to 2 months: collagement deposition/scar formation
Conditions with increased pulse pressure and decreased pulse pressure
Increased PP: hyperthyroidism, aortic regurgitation, aortic stifening (isolated systolic HTN in elderly), OSA (increased sympathetic tone), exercise (transient).
Decreased PP: aortic stenosis, cardiogenic shock, cardiac tamponade, advanced heart failure (HF).
Conditions that increase myocardial O2 demand
Increased: contractility, afterload (proportional to arterial pressure), HR, diameter of ventricle (wall tension)
***Wall tension = (Pressure * radius)/(2 * thickness)
VIPoma
WDHA syndrome: watery diarrhea, hypokalemia, achlorhydria
Somatostatinoma
d-cell, a/w DM, steatorrhea, cholelithiasis, hypochlorhydria
Blocks insulin, gastrin, secretin, CCK, and GI motility
Advance directives
- Living will: specifies end of life wishes–regarding intubation, cardiopulmonary resuscitation, enteral feeding, life-prolonging interventions.
- Health care proxy: individual to make health care decisions, decisions must be made in accordance with patient’s wishes outlined in will.
What are 3 organisms that can undergo transformation?
SHiN: S. pneumo, H. influenzae B, Neisserina
What are 5 bacterial toxins that are encoded in a lysogenic phage?
ShigA-like toxin
Botulinum toxin (certain strains)
Cholera toxin
Diphtheria toxin
Erythrogenic toxin of S. pyogenes
Which drugs have 0-order elimination?
PEA (round, 0): phenytoin, ethanol, aspirin
How do you treat salicylate OD?
How do you treat amphetamine OD?
- Acidic drug OD (salicylate): NaHCO3 to trap acidic drug in basic urine
- Basic drug OD (amphetamines): Na4Cl to trap basic drug in acidic urine
Fanconi syndrome
Generalized resorptive defect in PCT. Increased excretion of all AAs, glucose, HCO3-, PO43-. Results in metabolic acidosis.
Causes: hereditary defects (Wilson, tyrosinemia, glycogen storage dz), ischemia, MM, nephrotoxins/drugs (expired tetracycline, tenofovir), lead poisoning.
Relative concentrations along PCT
PAH > Creatinine > Inulin»_space; Urea > Cl- > K+ > Na+ > osmolarity > Pi»_space; HCO3-»_space; AA > Glucose
Potassium shifts
- Hyperkalemia (shifts K+ out of cell): DO LABS. Digitalis (blocks Na+/K+ ATPase), hyperOsmolarity, Lysis of cells (crush injury, rhabdomyolysis, cancer), Acidosis, B-blocker, high blood Sugar (low insulin). Also K+sparing diuretics, ACEI, digoxin.
- Hypokalemia (shifts K+ into cell): hypo-osmolarity, alkalosis, b-adrenergic agonist (increased Na+/K+ ATPase), insulin (increased Na+/K+ ATPase), INsulin shifts K+ INto cells. Also–Loop diuretics, thiazides.
Renal tubular acidosis–Type 1
Type I/Distal: urine pH > 5.5. Defect in a-intercalated cells to secrete H+ –> no new bicarb generated –> metabolic acidosis. Hypokalemia, incr risk for CaPhos kidney stones (incr urine pH and incr bone turnover).
Causes: amphotericin B, analgesic nephropathy, congenital anomalies (obstruction of UT).
Renal tubular acidosis–Type 2
Type 2/Proximal: urine pH
Renal tubular acidosis–Type 4
Type 4/Hyperkalemic: urine pH hyperkalemia –> decr NH3 synthesis in PCT –> decr NH4 excretion.
Causes: decr aldosterone production (diabetic hyporeninism, ACEI, ARBs, NSAIDs, heparin, cyclosporine, adrenal insufficiency), or aldosterone resistance (K+-sparing diuretics, nephropathy d/t obsturction, TMP/SMX).
Acute Interstitial Nephritis
AKA Drug-induced interstitial nephritis
Classic presentation: fever, rash, eosinophilia, azotemia
MCC: NSAIDs, PCN/cephalosporins, sulfonamides (TMP-SMX, furosemide), ciprofloxacin, cimetidine, allopurinols, PPIs, indinavir, mesalamine.
Diffuse coritcal necrosis
Multiorgan failure, ARDS, DIC
Associated with obstetric catastrophes (abruptio placentae), septic shock
Acute tubular necrosis
Findings: granular casts (necrotic epithelial cells).
Inciting phase. Maintenence phase: oliguric, 1-3 weeks, risk of hyperkalemia, metabolic acidosis, uremia. Recovery phase: risk of hypokalemia during re-epithelization of tubules.
Drugs/toxins: aminoglycosides, cephalosporins, polymyxins, radiograph contrast dye (prevent with fluids, NaHCO3)
Rhabdomyolysis/myoglobinuria (muscle breakdown from seizure d/o, cocaine, or crush injury)–4+ blood in urine, no RBC on urine cell count, renal failure, elevated CPK.
Renal papillary necrosis
SAAD papa with papillary necrosis: sickle cell disease or trait, acute pyelonephritis, analgesics (NSAIDs), Diabetes mellitus
Sloughing of necrotic renal papillae –> gross hematuria and proteinuria. Can be triggered by recent infxn or immune stimulus.
Consequences of renal failure
MADHUNGER
Metabolic Acidosis
Dyslipidemia (increased TG)
Hyperkalemia
Uremia: increased BUN–N/anorexia, pericarditis, asterixis, encephalopathy, platelet dysfunction
Na+/H2O retention (HF, pulmonary edema, hypertension)
Growth retardation and developmental delay
Erythropoietin failure (anemia)
Renal osteodystrophy
Wilms tumor
Nephroblastoma. MC ages 2-4. Embryonic glomerular structures.
Loss of function mutations of WT1/WT2 (tumor suppressors) on chromosome 11.
Beckwith-Widemann: Wilms tumor, macroglossia, organomegaly, hemihypertrophy
WAGR complex: Wilms tumor, Aniridia, GU malformation, mental Retardation
Renal oncocytocytoma
Benign epithelial cell tumor of collecting duct cells
Large eosinophilic cells with abundant mitochondria WITHOUT perinuclear clearing (vs RCC).
RCC
PCT cell tumor–polygonal clear cells with accumulated lipids and carbs. Hematuria, palpable mass, secondary polycythemia, flank pain, fever, weightloss.
Invades renal vein then IVC and spreads, mets to lung and bone.
A/w Von Hippel-Lindau (chr 3)
Paraneoplastic: EPO, ACTH, PTHrP
Acute poststreptococcal glomerulonephritis
IF: granular lumpy-bumpy, IgG, IgM, C3 deposition along GBM and mesangium
EM: subepithelial immune complex (IC) humps
2 weeks after group A strep of pharynx or skin
Type 3 HSN
Peripheral and periorbital edema, cola-colored urine, HTN
Anti-Dnase B titers, decr complement
RPGN
LM and IF: crescent moon shape–fibrin and plasma protein (C3b) with glomerular parietal cells, monocytes, MO.
*Goodpasture: type 2 HSN, anti-GBM and alveolar basement – linear IF
*Granulomatosis with polyangiitis (Wegener) – c-ANCA (PR3)
*Microscopic polyangiitis – p-ANCA (MPO)
Tx: emergent plasmapheresis
DPGN (diffuse proliferative)
Due to SLE or membranoproliferative glomerulonephritis
LM: wire looping
EM: subendothelial, sometimes intramembranous IgG-based Ics with C3 deposition
IF: granular
*MCC of death in SLE (wire lupus)
IgA nephropathy (Berger)
LM: mesangial proliferation
EM: mesangial IC deposits
IF: IgA-based IC deposits in mesangium
Renal pathology of Henoch-Schonlein purpura
*Often presents with renal insufficiency or acute gastroenteritis. Episodic hematuria with RBC casts.
Alport syndrome
Mutation in type IV collagen – thinning and splitting of glomerular BM. X-linked!
*Can’t see, can’t pee, can’t hear a buzzing bee.
*Eye problems (retinopathy, lens dislocation), glomerulonephritis, sensorineural deafness
MPGN (membranoproliferative)
Type I: subendothelial IC deposits with granular IF. Tram-track on PAS from GBM splitting caused by mesangial ingrowth. Hepatitis B/C!!!
Type II: intramembranous IC deposits, dense deposits. C3 neprhitic factor (stabilizes C3 convertase, decr serum C3)!!!
Focal segmental glomerulosclerosis
LM: segmental sclerosis and hyalinosis
IF: nonspecific for focal deposits of IgM, C3, C1
EM: effacement of foot process (like minimal change)
MCC of nephrotic syndrome in AA and Hispanics.
HIV, sickle cell, heroin abuse, obsesity, interferon tx, CKD.
Minimal change disease (lipoid nephrosis)
LM: normal glomeruli
IF: nothing
EM: effacement (fusion) of foot processes.
MCC of nephrotic syndrome in children. Often idiopathic and triggered by recent infection, immunization, immune stimulus, atopic dermatitis.
Membranous nephropathy
LM: diffuse capillary and GMB thickening
IF: granular as a result of IC deposition. Nephrotic presentation of SLE.
EM: spike and dome with subepithelial deposits
MCC of nephrotic syndrome in Caucasians. Can be secondary to drugs (NSAIDs, PCN), infxn (HBV, HCV), SLE, tumors.
Amyloidosis
LM: Congo red stain shows apple-green birefringence under polarized light.
A/w chronic conditions (MM, TB, rheum arthritis)
Diabetic glomerulonephropathy
LM: mesangial expansion, GMB thickening, eosinophilic nodular glomerulosclerosis (Kimmelsiel-Wilson)
Nonenzymatic glycosylation of GBM leads to increased permeability, thickening.
Nonenzymatic glycosylation of efferent arterioles –> increased GFR –> mesangial expansion.
Bartter syndrome
Thick ascending loop–Na/K/Cl cotransporter.
Hypokalemia, metabolic alkalosis, hypercalciuria.
Gitelman syndrome
NaCl in DCT–mimics thiazide diuretic.
Less severe than Bartter.
Hypokalemia, hypomagnesemia, metabolic alkalosis, hypocalciuria.
Muscle weakness, tetany, fatigue (hypoK and Mg)
Liddle syndrome
Gain of function mutation: increased Na reabs in CT (increased ENAC).
Autosomal dominant.
HTN, hypokalemia, metabolic alkalosis, decreased aldosterone.
Tx: amiloride (block Enac)
Syndrome of apparent mineralocorticoid excess = AME
Deficiency of 11b-hydroxysteroid dehydrogenase. Normally converts cortisol into cortisone before cortisol can act on mineralocoritcoid receptors.
Excess coritsol –> HTN, hypokalemia, metabolic alkaosis. Low aldosterone.
Glycyrrhetic acid (licorice).
Chlorpropamide, tolbutamide
First gen sulfonylureas. Close K+ channel in b-cell membrane –> insulin release via calcium influx. SE: disulfiram effects.
Glimepiride, glipizide, glyburide
2nd gen sulfonylureas. SE: hypoglycemia
Pioglitazone, rosiglitazone
Glitazones/thiazolidinedions. Increase insulin sensitivity in peripheral tissue. Binds to PPAR-g nuclear transcription regulator. SE: weight gain, edema, hepatotoxicity, HF, increase risk of fractures.
Exenatide, liraglutide
GLP-1 analogs. Increase insulin, decrease glucagon release. SE: N/V, pancreatitis.
Linagliptin, saxagliptin, sitagliptin
DPP-4 inhibitors. Increase insulin, decrease glucagon release. Mild urinary or respiratory infections.
Pramlintide
Amylin analogs. Decrease gastric emptying, decrease glucagon. Type 1 and type 2 DM. SE: hypoglycemia, N/D.
Canagliflozin
SGLT-2 inhibitors. Block reabs of glucose in PCT. Type 2 DM. SE: Glucosuria, UTIs, vaginal yeast infections.
Acarbose, miglitol
a-glucosidase inhibitors. Inhibit intestinal brush-border a-glucosidases. Delayed carb hydrolysis and glucose abs, decreases post prandial hyperglycemia. SE: GI.
Nimodipine
Subarachnoid hemorrhage (prevents cerebral vasospasm)
Clevidipine
HTN urgency or emergency
Nitroprusside
Releases NO, which generated cGMP in smooth muscle of arteries and veins. Reduces preload and afterload.
Use: HTN emergency, given by IV infusion
SE: rebound HTN, cyanide toxicity (co-admin with nitrates and thiosulfate to decr toxicity).
Refeeding syndrome and hypophosphatemia
Serum phosphate
Narcolepsy
Decreased hypocretin (orexin) production in lateral hypothalamus
FAB GUT
Galactokinase def, classic galactosemia
Fructose is to Aldolase B as Galactose is to UridylTransferase
Target cell–HALT
HALT said the hunter to his target
HbC, Asplenia, Liver disease, Thalassemia
Porphobilinogen deamniase deficiency
Acute intermittent porphyria
5 P’s: Painful abd, Port wine-colored urine, Polyneuropathy, Psychological disturbances, Precipitated by drugs (cytochrom P450 inducers), alcohol, starvation.
Tx: glucose and heme (inhibit ALA synthase)
Uroporphyrinogen decarboxylase deficiency
Porphyria cutanea tarda
Tea-colored urine–uroporphyrin build up
Blistering cutaneous photosensitivity, MC!!
Hypertrichosis, facial hyperpigmentation, hepatitic C, alcoholism, incr LFTs
Lead poisoning
Ferrochelatase and ALA dehydratase
Adults: HA, memory loss, demyelination, foot/wrist drop
Kids: mental deterioation
Colicky abd pain – renal failure
Tx: EDTA or succimer. Severe–dimercaperol and succimer
Potentially Really High Hematocrit
Pheohromocytoma, RCC, HCC, Hemangioblastoma
Orotic aciduria
Deficiency of UMP synthase (pyrimidine synthesis), can’t make UMP
Orotic acid in urine, Megaloblastic anemia
Presentation: FTT, developmental delay, megaloblastic refractory to B12/folate.
No hyperammonemia (vs. ornithine transcarbamylase def)
Tx: uridine monophosphate to bypass mutated enzymme.
Fanconi anemia
DNA repair defect–non-homologous end joining
Causes aplastic anemia
Pyruvate kinase deficiency
Glycolytic enzyme deficiency, can’t make ATP, RBC swelling and hemolysis.
Survive on reticulocytes (still have organelles and can do oxidative phosphorylation, increase 2,3BPG (easier release of O2)
Waldenstrom macroglobulinemia
M spike = IgM –> hyperviscosity syndrome (blurred vision, Raynaud), no CRAB.
Pseudo Pelger Huet anomaly
Neutrophils with bilobed nuclei. Seen after chemotherapy.
Hairy cell leukemia tx
Cladribine–2CDA (adenosine deaminase inhibitor–adenosine accumulates, toxic to B cells), pentostatin
Nerve courses
Median: between humeral and ulner heads of pronator teres muscle, runs between flexor digitorum superficialis and the flexor digitorum profundus within carpal tunnel.
Musculocutaneous: between biceps and coracobrachialis. Injury: bicep and brachilais paralysis.
Ulnar: between olecranon and medial epicondyle of humers (funnybone). Also between flexor carpi ulnaris and flexor digitorum profundus in forearm. Injury: claw hand due to loss of intrinsic muscles of hand.
Radial: through supinator muscle near head of radius. Injury: wrist drop.
