UWorld Questions 2 Flashcards
Bloom Syndrome?
mutation in the BLM gene which codes for helicase; defective helicase results in chromosome instability and breakage and results in growth retardation, facial anomalies, photosensitive rash, immunodeficiencies, small stature and infertility
Fabry (XR)?
deficiency in alpha-galactosidase and globotriaosylceramide (ceramide trihexoside) accumulates
angiokeratomas, peripheral neuropathy, and hypohidrosis
Adulthood - renal and CV complications, and cerebral vascular accident
Gaucher?
Most common in Ashkenazi Jews (founder effect)
hepatosplenomegaly, pancytopenia, osteopenia/bone pain; delayed puberty and birth
Difference between Krabbe and Metachromatic leukodystrophy?
Krabbe - def in galactocerebrosidase, acc galactocerebroside; peripheral neuropathy, CNS, OPTIC ATROPHY
McL - def in arylsulfatase A, acc cerebroside sulfate; peripheral neuropathy, CNS
What gene defects is Tuberous Sclerosis associated with?
defective tumor suppressor genes - hamartin (TSC1) and tuberin (TSC2) - characterized by cutaneous angiofibromas, brain hamartomas, and cardiac rhabdomyomas
How will individual units of Hemoglobin act?
Like myoglobin - high affinity for oxygen
What is carnitine synthesized from? what cofactor?
- responsible for transporting FA into the mitochondria for beta-oxidation; made from LYSINE and METHIONINE vitamin C is essential
Autoantibody of lupus?
anti Smith Ab
small nuclear RNA (snRNA) synthesized by RNA polymerase II complexes with certain proteins (Smith proteins) to form snRNP (small nuclear ribonuclear proteins)
Activity of leptin
leptin is a protein hormone produced by adipocytes - it acts on the arcuate nucleus of the hypothalamus inhibiting production of neuropeptide Y (decreasing appetite) and stimulate production of alpha-MSH (increasing satiety)
Effects of ionizing radiation as a cancer therapy? Characteristic cell death curve?
Ionizing radiation can cause:
- double-stranded DNA breaks
- free radical formation - reactive oxygen species are formed by the ionization of water
Characteristic cell death curve shows a nearly flat line on initial exposure, followed by a steep increase in cell death as radiation dose decreases
compare with UV radiation which is non-ionizing and can cause pyrimidine dimers
Hemoglobin curve shifts? What is 2,3 DPG?
Left (less available to tissues)- decrease H+, temperature, 2,3-DPG
Right (more available to tissues) - increase H+, temperature, 2,3-DPG
2,3 DPG is an organophosphate created in erythrocytes during glycolysis; the production of 2,3DPG is increased when oxygen availability is reduced (chronic lung disease, heart failure, high altitudes)
2,3 DPG is negatively charged and binds strongly in HbA where the binding pocket has positively charged residues of lysine and histidine; FAMILIAL ERYTHROCYTOSIS results from defective binding to 2,3 DPG
Patau Syndrome - cause and defects?
compare with phenytoin exposure in utero?
GI issue associated with Edwards?
valproate (medication for epilepsy or bipolar disorder)?
Gi issue associated with Down’s Syndrome?
defect in the fusion of the prechordal mesoderm and integral embryonic structure affecting growth of the midbrain, eyes, and forebrain
holoprosencephaly, microopthalmia, cleft lip/palate, omphalocele, polydactlyly, cutis aplasia, cardiac defects
phenytoin exposure: cardiac defects, hypoplastic nails, cleft lip/palate
- Meckel’s diverticulum - incomplete closure of the vitelline duct (normally connects the midgut and the yolk sac, also called omphalomesenteric duct); can present with bleeding due to ectopic gastric mucosa
- can cause neural tube defects because you have impaired folate metabolism
- UMBILICAL HERNIA - incomplete closure of the umbilical ring; normally it forms the linea alba
nicotine exposure during childbirth
secondhand smoke?
placenta previa, abruption, prematurity, low birth weight
SIDS, asthma, respiratory tract infections, otitis media, decreased GFR (reduced renal function)
decreased estriol during pregnancy - causes fetal growth restriction
How would you distinguish Cori with von Gierke?
Both have hepatic involvement, but Cori also has muscle involvement (muscle weakness and hypotonia)
VG does not have muscle involvement but you have hyperlipidemia, hyperuricemia, and hepatic steatosis
Pathogenesis of pigment gallstones
pigment gallstones are soft and dark brown to black
composed of calcium salts of unconjugated bilirubin and arise secondary to bacterial or helminthic infections of the biliary tract; Clonorchis sinensis has a high prevalence in Asian countries (BROWN)
beta-glucuronidase released by injured hepatocytes and bacteria hydrolyzes bilirubin glucuronides to unconjugated bilirubin
BLACK - due to hemolysis; radioopaque because unconjugated combines with calcium
Chediak-Higashi Syndrome is characterized by
disorder of phagosome-lysosome formation (abnormal lysosomal inclusions seen under the microscope) –> neurological abnormalities, albinism, and immunodeficiency
Henoch-Schonlein purpura is characterized by
IgA mediated Type III hypersensitivity that follows infection - deposition of IgA containing immune complexes in small vessels results in vasculitis
purpura, arthralgias, abdominal pain, hematuria
Tests for chronic granulomatous disease (NAPDH oxidase)
nitroblue tetrazolium dye - add NBT to patient’s neutrophils; properly functioning neutrophils produced ROS that can reduce the yellow NBT to dark blue formazan that precipitates within cells
Dihydrorhodamine - assesses the production of superoxide radicals by measuring the conversion of DHR to rhodamine which is a fluorescent green
catalase positive organism - Burkholderia cepacia
How you do prevent hemolytic disease of the newborn in a Rh+ fetus with an Rh- mother?
Anti-Rh immune globulin consists of IgG anti-D antibodies that opsonize fetal Rh+ erythrocytes promoting clearance by maternal reticuloendothelial macrophages and preventing maternal Rh sensitization; routinely administered to Rh negative women 28 weeks gestation and immediately postpartum
Name the autoimmune disease
- anti-mitochondrial
- anti-centromere, anti-topoisomerase (Scl-70), anti-RNA Polymerase III
- anti-phospholipase A2 receptor
- anti-smooth muscle
- anti Jo-1 (anti tRNA-histidyl synthetase)
- primary biliary cirrhosis (this can lead to hyperlipidemia causing xanthomas on the eyelid, tendons etc. under a microscope - foam-laden macrophages)
- CREST syndrome (calcifications, raynauds, esophageal dysmotility, schlerodactyly, telangiectastia)
- primary membranous nephropathy
- autoimmune hepatitis
- polymyositis (increased creatine kinase and aldolase; associated complications are myocarditis and interstitial lung disease; can indicate an underlying malignancy - adenocarcinoma)
Anti-phospholipid syndrome?
Autoimmune condition (against CARDIOLIPIN) - antiphospholipid antibody syndrome causes hyper-coagulability, paradoxical PTT prolongation, and recurrent miscarriages (spontaneous abortions)
Reactive arthritis
the classic triad is urethritis, conjunctivitis, and arthritis; HLA-B27 associated; several weeks after a genitourinary or enteric infection
can present with sacroilitis, keratoderma blennorrhagium (hyperkeratotic vesicles on the palms and soles), and circinate balanitis (annular dermatitis of the glans penis)
Major way to prevent reinfection with influenza
antibodies against hemagglutinin in the inactivated vaccine
Bortezomib mechanism of action ()
binds and inhibits the 26S proteasome; in multiple myeloma, it can facilitate the apoptosis of neoplastic cells by preventing degradation of pro-apoptotic metabolites
What does mutation of the TTR gene cause? non-mutated TTR?
results in misfolding and extracellular deposition of transthyretin protein (prealbumin) which can cause familial amyloid polyneuropathy or familial amyloid cardiomyopathy
senile cardiac amyloidosis - non-mutated transthyretin deposits in the heart
How does HIV get into the cell?
What are the functions of Nef and Tat?
The HIV virus uses CD4 protein as a primary receptor and the CCR5 chemokine receptor serves as a co-receptor. Both CD4 and CCR5 are bound by the HIV viral outer envelope protein gp120. HIV virus enters by fusion with the cell membrane
Tat plays a role in viral replication
Nef decreases expression of MHC Class I proteins on the surfaces of infected cells
Cause of splenomegaly in a patient with hemolytic anemia
increased work of the splenic parenchyma which must remove the deformed erythrocytes from the circulation - red pulp hyperplasia
Homocystinuria
marfanoid body habitus and hypercoagulable state
- Translocation for B-cell lymphoma
- Translocation for chronic myelogenous leukemia
- t(14,18) – Bcl2 overexpression which has an antiapoptotic effect
- t(9,22) - philadelphia chromosome, bcr-abl - constitutively active tyrosine kinase
Overexpressed in Burkitt’s lymphoma?
Overexpressed in breast cancer?
the c-myc gene (on chr 8); can be coupled with the heavy chain promotor on chromosome 14
HER-2-neu and Erb-B2 overexpression which are both epidermal growth factor receptors
3 things that are messed up in the brain due to hepatic encephalopathy due to hyperammonemia
what is oxindole?
- increased levels of ammonia result in depletion of alpha-keto-glutarate causing inhibition of the Krebs cycle
- depletes glutamate an excitatory NT
- causes an increase of glutamine which results in astrocyte swelling and dysfunction
Oxindole is produced by bacteria in the gut from tryptophan and normally cleared by the liver; elevated levels have been found in patient with hepatic encephalopathy
Marker of anaphylaxis?
Anaphylaxis is the result of widespread mast cell and basophil degranulation and the release of pre-formed inflammatory mediators including histamine and tryptase. Tryptase is relatively specific to mast cells and can be used as a marker for mast cell activation
mastocytosis - abnormal proliferation of mast cells; KIT gene
5-hydroxyindoleacetic acid is a breakdown product of serotonin used as a marker for what?
Carcinoid syndrome (diarrhea and flushing)
histo - salt and pepper chromatin
Findings in serum sickness
Type III hypersensitivity reaction to non-human proteins characterized by vasculitis resulting from tissue deposition of circulating immune complexes; fever, pruritic skin rash, arthalgias, and low complement levels; presents ~1-2weeks after exposure
reaction can be to chimeric monoclonal antibodies (-iximab), venom antitoxins, and certain non-protein drugs like penicillin and TMP-SMX
How long can vitamins A, D, and K be stored in the body?
A - 6 months in the liver (in the perisinusoidal stellate Ito cells)
D - over the course of several months, stored in adipose tissue
K - small amount stored in the liver that can last for 1-3 weeks, however the gut bacteria produce enough functional Vit K
most water-soluble vitamins are excreted quickly
Components of telomerase
TERT - telomerase reverse transcriptase
TERC - telomerase RNA component
TERC is a built-in RNA template that is repeatedly read by the TERT subunit to add TTAGGG DNA sequence repeats to telomeres
What are the most dependent locations of the lungs in supine individuals?
superior part of lower lobe and posterior part of upper lobe; commonly seen in aspiration pneumonia
Primary method of renal acid excretion in chronic acidotic states
- increase bicarb absorption
- increase H secretion
- increase secretion of titratable acids
Acidosis stimulates renal ammoniagenesis, a process by which renal tubular epithelial cells metabolize glutamine to glutamate generating ammonia which is excreted in the urine and bicarbonate which is absorbed into the blood
also increase secretion of titratable acids
glutamine is the most abundant AA in the blood
How does glucokinase faciliate the release of insulin from pancreatic beta cells?
mutations in GK lead to MODY
glucose –> glucose-6-phosphate via glucokinase
glucose-6-phosphate –> increase in the ATP/ADP ratio
this causes closure of the ATP-sensitive potassium channels, causes depolarization of the cell, Ca floods the cell and insulin granules are released
What microorganisms have IgA-proteases?
S. aureus, Neisseria species, H. influenza
cleaves at the hinge region rendering it ineffective
Role of the NF1 gene (codes for neurofibromin)
NF2 (codes for merlin a tumor supressor)
mutation in RB causes?
suppresses Ras
bilateral acoustic Schwannomas
retinoblastoma and osteosarcoma
What is unusual about arginase deficiency?
Presents WITHOUT hyperammonemia
symptoms - spastic diplegia, growth delay, abnormal movements
How would you treat acute gouty arthritis?
NSAIDs - inhibit COX and exert a broad anti-inflammatory event that includes inhibition of neutrophils
When NSAIDs are contraindicated - used colchicine - inhibits neutrophil chemotaxis and phagocytosis by impaired microtubule formation
Electrolyte imbalances after administration of a thiazide diuretic?
Thiazide diuretics inhibit the Na/Cl co-transporter in the distal tubule leading to increased excretion of Na, Cl, and H2O as well as K+ and H+ ions
They also increase the absorption of Ca
What is a lecithinase? Which organism uses it?
How does coagulase help bacteria?
C. perfringens, also known as alpha-toxin; an enzyme with phospholipase activity which increases platelet aggregation and adherence molecule expression on platelets and leukocytes resulting in vasoocclusion and ischemic disease
Activates coagulation cascade, gets coated in fibrin - difficult to phagocytose
- Bevacizumab
- Alemtuzumab
- Interferon-gamma
- Aldesleukin (IL-2)
- VEGF –> inhibits angiogenesis, RCC, CRectal
- CLL, CD-52 receptor- fixes complement and has a cytotoxic effect through ADCC
- increases expression of MHC I and II, improves antigen presentation
- stimulates CD4, CD8, B-cells, monocytes, and NK cells - used for metastatic melanoma and renal cell carcinoma
2 cells that CANNOT use ketone bodies for energy
- erythrocytes - no mitochondria
- the liver - lacks the enyzme thiophorase which converts acetoacetate into acetoacetylCoA (and ultimately into acetyl CoA)
what molecules is flavin incorporated into?
FMN - flavin mononucleotide (complex I)
FAD - flavin dinucleotide (complex II of ETC = succinate dehydrogenase which is part of TCA)
What compound inhibits the process of beta-oxidation?
malonyl-CoA
cytosolic acetyl-CoA carboylase converts acetyl CoA to malonyl CoA which is the rate limiting step of fatty-acid synthesis; malonyl-CoA also inhibits the action of mitochondrial carnitine acyltransferase inhibiting beta-oxidation of newly formed fatty acids
Fungus most likely associated with catheter use?
Candida - psuedohyphae with blastoconidia
associated with intertrigo - well-defined erythematous plaques or satellite vessels in warm, moist skin areas
Trysinogen activated by what enzyme? What does it catalyze?
Role of secretin?
Duodenal enteropeptidase activates trypsinogen to trypsin; degrades peptides and activates other proteases such as carboxypeptidase, elastase, and chymotrypsin; NOT LIPASE however - lipase is secreted in its active form; once it leaks from the damaged acini can cause fat necrosis
stimulates S-cells of the duodenum to make bicarbonate (from pancreas and gallbladder) in response to low duodenal pH; also reduces gastrin secretion
secretory fluid is isotonic with plasma with respect to Na and K; increased HCO3, decreased Cl
Difference between aspiration pneumonia and aspiration pneumonitis?
PNEUMONIA - lung parenchyma INFECTION, aspiration of ORAL cavity anaerobes, presents DAYS after the aspiration event, FEVER, can process to ABSCESSES (air-fluid; usually as a result of impaired consciousness or decreased ability to swallow), give antibiotics to manage
PNEUMONITIS - lung parenchyma INFLAMMATION, aspiration of GASTRIC contents, present HOURS after, supportive treatment
Function of the D-arm and the T-arm in tRNA
D-arm has dihydrouridine residues which facilitate binding to the correct tRNA sythetase
T-arm - modified bases (ribothymidine, pseudouridine, cytidine) –> binds the tRNA to the ribosome
In prokaryotes, DNA polymerase I vs III?
III - the main polymerase with 5’–> 3’ synthesis activity and 3’–>5’ exonuclease activity, leading and lagging strand synthesis
I - has 5’ to 3’ exonuclease activity - involved in removing RNA primers on the lagging strand and DNA repair
Heart defect in Freidrich ataxia?
The neurologic symptoms of FA can mimic what vitamin deficiency?
hypertrophic cardiomyopathy
Vitamin E deficiency - increase of free radicals causes degeneration of the dorsal columns, peripheral nerves, and spinocerebellar tracts
Other than Toxo, what other pathology has ring-enhancing lesions?
glioblastoma - but usually a single, butterfly-shaped lesion; most common brain tumor in adults, presents with necrosis and hemorrhage and shift of the midline structures
Precaution for C. diff?
When do you need a respirator vs a face-mask for airborne pathogens?
proper hand-washing (alcohol based ones do not kill spores), gown, nonsterile gloves
respirator - if pathogen is 5 microns; bordetella, Neisseria meningitis, influenza, mycoplasma pneumo, RSV
Common medical conditions with polygenic inheritance?
androgenetic alopecia (determined by circulating androgen and genetic factors), HTN, DMII, epilepsy, glaucoma, schizophrenia
Moraxella catarrhalis?
normal flora of the upper respiratory tract - causes otitis media and sinusitis in healthy individuals; exacerbates COPD
Most common source of hematogenously spread osteomyelitis after S. aureus?
3 ways that osteomyelitis is caused?
Strep pyogenes
- bacteremia - hematogenously spread
- contiguous infection (DM or spread from recumbent ulcers)
- direct inoculation
Cytokines involved in granulomatous inflammation
IL-12, IFN-gamma, and TNF-alpha (induces and maintains granuloma formation)
Platelet activating factor?
platelet aggregation, bronchoconstriction, vasoconstriction, increased leukocytes adhesion to the endothelium; at low concentrations causes vasodilation and increases the permeability of venules
Ataxia-telangiectasia?
cerebellar atrophy, telangiectasias, recurrent sinopulmonary infections; sensitivity to ionizing radiation
Fanconi anemia is also caused by non-homologous end-joining - increased susceptibility to alkylating agents
Primary carnitine defiency?
What other disorder has hypoketotic hypoglycemia?
Muscle weakness (myopathy, increased CK; lack of ATP from TCA), cardiomegaly, hypoketotic hypoglycemia
medium (or very long chain)-chain acyl-CoA dehydrogenase deficiency
Ristocetin test results if there is a vWF deficency? How can this be treated?
GP Ib deficiency (Bernard-Soulier)?
Risocetin activates GPIb receptors on platelets and makes them available for binding with vWF
decreased aggregation if vWF def; but yes aggregation if you add normal plasma; desmopressin stimulates vWF release from endothelium
decreased aggregation if GP Ib def; still negative if you add normal plasma
What sort of supercoiling does topoisomerase II produce?
negative supercoiling to reduce the strain of unwinding which produces positive supercoiling
Microscopic finding to distinguish Herpes simplex I/II and Klebsiella granulomatosis? H. ducreyi?
Herpes - lesions are initially painful; Cowdry bodies - intranuclear inclusions, multinucleated Giant cells
Klebsiella - painless initially, deeply staining intracytoplasmic donovan bodies
H. ducreyi: organisms often clump in long strands; “schools of fish”
How does M-protein help Strep?
helps the bacteria evade phagocytosis by preventing activation of the alternate complement pathway
Virulence factors for Pseudomonas that contribute to Ecthyma gangrenosum?
occurs from perivascular invasion and release of skin destructive exotoxins causing vascular damage and insufficient blood flow to patches of skin that become edematous and necrotic
exotoxins include - exotoxin A (protein synthesis inhibitor), phospholipase C (cell membrane disruptor), elastase (blood vessel destruction), pyocyanin (makes reactive oxygen species)
treatment for PID?
Should include ceftriaxone for N.gonorrhea and azithromycin and doxycylcine for Chylamydia
Genetic association with early onset Alzheimer’s and late-onset Alzheimer’s?
hypertrophic cardiomyopathy?
early - Alzheimer’s precursor protein (21), presenilin 1 (14) and presenilin 2 (1) –> all though to promote the production of beta-amyloid
late-Apolipoprotein E4
HCM: beta-myosin heavy chain
Bordetella pertussis toxin?
ADP-ribosylated the Gi protein causing increased cAMP production:
- increased insulin
- lymphocyte and neutrophil dysfunction
- increased sensitivity to histamine
Winged scapula is caused by?
damage to the LONG THORACIC NERVE (C5-C7) that innervates the SERRATUS ANTERIOR - the SA muscle attaches the medial anterior end of the scapula against the rib cage; typically injured during axillary lymphadenopathy surgery
you hit the serratus if you make an incision at the 4th/5th intercostal space at the midaxillary line; pectoralis major anterior and latissmus dorsi posterior, external oblique inferior
What are the subdivisions of the parietal pleura? which parts of the pleura carry pain via the phrenic nerve and referred to the C3-C5 distribution (base of neck and over the shoulder)?
costal, mediastinal, diaphragm, cervical
sensory innervation of the rest of the pleura is carried by the intercostal nerves and more locally referred
What does the lingual nerve innervate?
Branch of the mandibular portion of the trigeminal nerve and provides sensory innervation to the tongue
Underlying pathology behind obstructive sleep apnea?
What happens to the blood gases?
Complication?
neuromuscular weakness - only occurs during sleep when the muscles are relaxed; the upper airway dilator muscles weaken during the transition from wake–>sleep and lead to airway narrowing and ultimately collapse
when the airway is occluded, PO2 declines and PCO2 increases until the receptors in the carotid body and brainstem trigger arousal and pharyngeal tone returns - wake up often
pulmonary hypertension is a complication, right heart failure, and increased risk for CV events
Where is the piriform recess? What nerve runs through it? Disrupting that nerve can cause what?
- lie on either side of the laryngeal orifice between the thyroid cartilage; bound medially by the aryoepiglottic folds and laterally by the thyroid cartilage
- internal laryngeal branch of the superior laryngeal nerve (sensory from the larynx and epiglottis)
- can cause disruption of the afferent portion of the COUGH reflex
When does dipalmitylphosphotidylcholine [] increase during gestation?
What happens to the concentration of albumin during gestation in the amniotic fluid?
what is the lecithin/sphingomyelin ratio indicate?
- sharply increases at 30 weeks, phosphatidylGLYCEROL (another component of surfactant) increases at 36 weeks
- decreases by 50%
- produced in same quantities until 30 weeks; a L/S ration > 1.9 indicates mature lungs
Injury of what artery can cause hoarseness?
inferior thyroid artery (courses behind the carotid artery and jugular vein and arises from the thyrocervical trunk) because it supplies the recurrent laryngeal nerve
What muscles does the ansa cervicalis innervate?
What muscles are paralyzed with an interscalene nerve block?
-sternohyoid, omohyoid, sternothyroid
suspect injury if penetrating wound is above cricoid cartilage
the nerve block blocks the brachial plexus an also affects the DIAPHRAGM
Where does the carotid bifurcate?
at C4 below the hyoid bone
Where should you perform thoracentesis at the midclavicular, midaxillary, and paraventebral lines?
What do you risk injuring?
- midclavicular - above 8th rib (recess is between 6-8)
- midaxillary - above 10th rib (8-10)
- paracentricular - above 12th rib (10-12)
the rationale is that you want to get fluid from the costodiaphragmatic recess - the space between the visceral pleura and the parietal pleura (the p.pleura extends 2 ribs below the parenchyma)
neurovascular bundle if you puncture below the ribs; and abdominal structures if you hit lower than these structures
What does the azygous vein drain?
Lies in the posterior mediastinum and drains blood from the posterior intercostals to the SVC; lies right of the midline
Match the fetal structures to the adult counterparts
- umbilical vein
- ductus venosus (bypasses hepatic circulation and dumps into IVC)
- foramen ovale
- ductus arteriosus
- umbilical artery
- common cardinal vein
- vitelline vein
- ligamentum teres
- ligamentum venosus
- fossa ovale
- ligamentum arteriosum
- medial umbilical ligaments
- systemic venous circulation
- portal vein
When to suspect a pulmonary embolism? What causes the hypoxemia?
How is this different than a fat embolism?
- immobile and postoperative patients are at risk for PE; tachypnea, tachycardia, and pleuritic chest pain; the resulting ischemic injury also causes inflammation –> surfactant defiency –> atelectasis –> poorly ventilated and poorly perfused
- causes hypoxemia by a ventilation/perfusion mismatch (impaired perfusion); the hyperventilation causes decreased CO2 and respiratory alkalosis
- FAT EMBOLISM - triad of respiratory distress (blocks the pulmonary vasculature also release of the FFA can cause toxic injury to the endothelium), neurological symptoms, petechiae, thrombocytopenia (fat globules covered in platelets), and anemia (RBC aggregation or pulmonary hemorrhage); stains black with osmium tetroxide
What is a normal A-a gradient? Due to what?
In what hypoxemic states is a normal A-a gradient maintained?
PAO2 (104) - PaO2(100) = 4 mmHg; due to deoxygenated blood from the bronchial circulation and Thebesian veins of the heart; normal is from 5 mmHg-15 mmHg; increases as you get older due to poor diffusing capacity with age
- HYPOVENTILATION - either due to suppressed central respiratory drive (opiate overdose) or with diseases that restrict inspiratory capacity (obesity, MG)
Describe airway resistance along the bronchial tree
Resistance is determined by both flow (turbulent>laminar) and radius
Half of the resistance is in the upper respiratory tract (nasal passages, mouth, pharynx, larynx)
- resistance in the trachea and bronchus is relatively high (turbulent flow)
- it increases in the medium sized airways because of increased turbulence in the airflow
- greatly drops in the smaller airways because the velocity decreases because the total cross-sectional area increases; v = Q/A; flow becomes laminar
Where is pulmonary vascular resistance the lowest? Relation to COPD?
at the functional reserve capacity
at high volume: the extra-alveolar vessels have a low resistance (radial forces pulling outward), but the alveolar vessels have a high resistance (the diameter is reduced at the vessel lengthens)
at low volumes: the extra-alveolar vessels have a high resistance (they collapse inward); the alveolar vessels have a low resistance
the result is a U-curve
With COPD patients try to maintain the least airway resistance (that is why they are in a hyperinflated state)
Mechanisms of clearance depending on particle size
10-15 micrometers - upper airway - coughing, sneezing
2.5-10 micrometers - mucociliary clearance
pneumoconioses
From apex to base, how do these values change? V, Q, V/Q ratio
V: increases apex to base
Q: increases apex to base (to a greater extant)
V/Q ratio: decreases from apex (3) to base (0.6)
Zones of the lung
Zone 1: PA>Pa>Pv (no blood flow)
Zone 2:Pa>PA>Pv (pulsatile flow during systole)
Zone 3: Pa>Pv>PA (continuous blood flow; all zones are Zone 3 when the patient is supine)
FEV1/FEV ratio in obstructive and restrictive (explain why) diseases
FVC decreased in both
FEV1/FVC is DECREASED in OBSTRUCTIVE
FEV1/FVC is INCREASED in RESTRICTIVE; this is because there is increased elastic recoil caused by the fibrotic interstitial tissue; this results in increased radial traction (outward pulling) leading to increased expiratory flow rates
How does carbon-dioxide affect cerebral blood flow? Oxygen?
How is this used in the lowering pressures in a patient with cerebral edema?
hypercapnia causes vasodilation
hypocapnia causes vasoconstriction
hypoxia causes vasodilation, but CO2 is a more potent mediator
edema = high pressure –> hyperventilate = low CO2 = vasoconstriction (increase resistance)/reduce cerebral blood flow = reduced pressure; the other way to reduce pressure is to reduce the systemic pressure
Relative vs Hypoxic erythrocytosis?
Hematocrit is increased in both
Relative - the volume of RBCs is normal; probably due to dehydration (plasma volume contraction)
Hypoxic - increased mass of RBCs; stimulated by erythropoetin (from renal peritubular cells)
What is contraction alkalosis?
What else can excess aldosterone cause?
What is aldosterone escape?
you take a diuretic and lose a lot of volume, body increases production of aldosterone, leads to increased absorption of Na and H2O and increased EXCRETION of K and H
hypokalemia - muscle weakness and parasthesias
the increased blood volume increases renal blood flow which increases ANP and Na excretion
cyanide poisoning - oxygen values? venous oxygen content? treatment?
normal PaO2, SaO2, oxygen content
venous O2 increased because oxygen is not being used by the peripheral tissues because oxidative phosphorylation is being blocked
methylene blue; or amyl nitrate to make methemoglobin (binds to oxygen tightly)
What type of channels are the CFTR involved in CF
ATP-gated
Where are the following sensory receptors and what do they sense?
central chemoreceptors - in the medulla and stimulated by decreased in pH (CO2) of the CSF; excess CO2 diffuses into the CSF to lower the pH
carotid and aortic body - stimulated by HYPOXEMIA
pulmonary stretch receptors - regulate the duration of inspiration, protect lung from hyperinflammation
- in healthy people CO2 is the major stimulator of respiration; in patients with COPD, response to Co2 becomes blunted and hypoxemia becomes the major drive
Acute Humoral vs Acute Cellular transplant rejection
Acute Humoral - neutrophilic infiltrate, necrotizing vasculitis
Acute Cellular - lymphocytic infiltrate
Clinical features of Turner’s Syndrome?
lymphadema and cystic hygroma (abnormalities of lymphatic outflow; dilated lymphatic space lined by endothelial cells); cystic hygroma also seen in patients with Downs Syndrome
Androgen insensitivity?
lack the androgen receptors - have an XY karyotype - present with amenorrhea due to the absence of the female reproductive tract and the presence of testes
What is cord factor?
virulence factor of TB - it is a part of the cell wall to prevent fusion with phagolysosomes
Cryptogenic organizing pneumonia?
causes obliterative lower airway inflammation - inflammation causes granulation tissue proliferation that proceeds to obstruct small bronchioles and airways and consolidate the alveoli; typically resolves with corticosteroids
Most common sub-type of Hodgkin’s lymphoma?
Nodular sclerosis - nodular growth pattern, surrounding fibrous bands, lacunar-variant Reed-Sternberg cells
constitutional symptoms and enlarged lymph nodes
What type of sweat is produced in patients with cystic fibrosis? in normal patients?
what bowel abnormality is associated with CF?
normal - hypotonic sweat; CFTR resorbs Cl- and Na+ follows; loss of free water causes hyperosmotic volume contraction
CF - CFTR is defective, so the sweat has high sodium and chloride content
rectal prolapse
Different breathing patterns and associations?
- Kussmaul
- Cheyne-Stokes
- obstructive sleep apnea
- hypothyroidism
- metabolic acidosis - especially Diabetes Ketoacidosis, deep labored breathing
- congestive heart failure - apnea is followed by gradually increasing and decreasing tidal volumes until the next apneic period; caused by increased levels for CO2 which spur the breathing and once CO2 gets below a certain threshold you have apneic breathing again
- reductions of airflow during sleep due to airway obstruction despite adequate respiratory effort
- hypoventilation from respiratory weakness
Where are Club (Clara) cells found and what is their role?
nonciliated, secretory cells found in the terminal portion of the bronchioles
regenerative source of ciliated cells in the broncioles and help to detoxify tobacco smoke via a P450 mechanism
Describe the interaction between the CFTR channel and the ENaC channel in CF in respiratory/gastric mucosa and sweat glands.
Respiratory/Gastric - impaired CFTR reduces luminal Cl secretion and also increases ENaC absorption (decreased Na in the lumen, more within the cell); causes dehydrated mucus and NEGATIVE transepithelial difference
Sweat glands - impaired Cl- absorption and Na+ absorption by the ENaC causes hypertonic sweat with increased Cl and Na
What is large cell carcinoma of the lung associated with?
galactorrhea and gynecomastia; large polygonal cells in sheets or nests, located peripherally
Wegener’s granulomatosis - what antibody? which systems affected?
What is p-ANCA associated with?
c-ANCA (neutrophils), vasculitis of small and medium sized arteries
- upper respiratory tract - epistaxis, otitis, sinusitis
- lungs - hemoptysis
- kidneys - rapidly progressing glomerulonepritis
p-ANCA = neutrophil myeloperoxidase; churg-strauss
Stages of Sarcoidosis using CXR and other clinical manifestations, microscopic?
Stage 1 - bilateral hilar lymphadenopathy
2 - bilateral hilar lymphadenopathy + pulmonary infiltrates in the upper lbes
3 - pulmonary infiltrates
Stage 4 - pulmonary fibrosis
also can present with uveitis and cutaneous findings including erythema nodosum
non-caseating granuloma; asteroid body in macrophage
What stains can be used for iron?
Prussian blue - stains blue
hemotoyxlin or eosin stain - stain brown
CXR findings in someone with COPD (on the spectrum between bronchitis and emphysema)?
What affect does COPD have on the diffusing capacity of CO?
- hyper-inflated lungs and a flattened diaphragm
- decreased diffusing capacity in emphysema b/c the surface area of the alveolar-capillary interface is reduced due to alveolar destruction; asthma and bronchitis are normal
Stages of a lobar pneumonia
- congestion - red, heavy boggy, vascular dilation, mostly bacteria
- red hepatization - red, firm –> RBCs, neutrophils, fibrin
- gray hepatization - pale, gray –> FRAGMENTED RBCs, neutrophils, fibrin
- resolution - enzymatic degradation of the exudate
Cause of pulmonary fibrosis (autoimmune disease)? drugs?
CXR shows?
rheumatoid arthritis
methotrexate, bleomycin, amiodarone
RETICULONODULAR PATTERN
How does sepsis cause ARDS? CXR finding?
as cytokines circulate in response to an infection, they activate the pulmonary epithelium and provoke an inflammatory response mediated by neutrophils –> capillary damage and leakage of proteins into the alveolar space; presents within 24 hours of the inciting risk factor
white-out on CXR
X-Ray findings in a PE?
- Hamptons Hump - wedge shaped opacity adjacent to pleura
2. Westermark sign - area of lucency due to reduced perfusion
Mainstem bronchus lesion - CXR?
a lesion in the mainstem bronchus can prevent ventilation to the lung leading to obstructive lung collapse and complete atelactasis
unilateral pulmonary opacification and deviation of the mediastinum toward the opacified side
Histology and clinical presentation of mesothelioma?
-hemorrhagic pleural effusions and thickening of the pleura
numerous, slender, long villi and tonofilaments
Pulmonary hemorrhage syndromes?
- anti-glomerular membrane antibody disease
- vasculitis associated hemorrhage
- idiopathic pulmonary hemosiderosis
Anterior mediastinal masses?
- thymoma (increased risk of with M. Gravis), teratoma, thyroid cancer, and lymphoma
Where is the superior sulcus? If there is a tumor there (Pancoast - non-small cell carcinoma), what can it cause?
- groove formed by the subclavian vessels
- ipsilateral Horner syndrome (miosis, anhydrosis, ptosis), shoulder pain in the C8, T1, T2 distribution, hand muscle atrophy (involvement of the brachial plexus), rib destruction
What is Beck’s triad? What does it indicate?
pathophysiology behind pulsus paradoxus (can also see this in constrictive pericarditis, COPD, asthma, and PE )
- JVP (compression of the RA and decreasing venous return)
- muffled heart sounds
- hypotension (decreased CO from the LV)
TAMPONADE
normally, blood pressure is lower during inspiration than expiration - this is b/c negative intrathoracic pressure draws blood into the right side of the heart and causes the capillaries in the lung to fill with blood –> less return to the L side of the heart
during tamponade, the heart chambers are smaller because of the effusion; when the RV fills up it pushes the IV septum and reduces the size of the LV –> DECREASED PRESSURE OF MORE THAN 10 MMHG
asbestos on a CXR?
silicosis?
pleural plaques affecting the parietal pleura, ferruginous bodies on histo
eggshell calcifications, birefringent silica
which receptor antagonists provide significant relief in the treatment of asthma?
anti-leukotriene and anti-muscarinic
Puncture wound at the left sternal border goes through what layers?
- skin
- pectoralis major
- external intercostal
- internal intercostal
- internal thoracic artery and veins
- transverse thoracis muscle
- parietal pleura
- pericardium
- right ventricular myocardium
What vein is routinely used for a graft if the LAD alone is occluded?
If multiple coronary vessels other than the LAD? where does that vessel run?
- left internal thoracic artery
- great saphenous vein (located superficially in the leg and the longest vein in the body - arises inferolateral of the pubic tubercle, joins femoral vein in the saphenous opening, runs medial side of leg)
Major peripheral artery aneurysm? what nerve runs here?
popliteal artery aneurysm
tibial nerve
vein on the lateral side of the foot?
small saphenous vein
The path that a clot takes to result in retinal artery occlusion?
internal carotid –> ophthalmic artery –> retinal artery
Why do children with Tetrology of Fallot squat? what is the anomaly caused by?
when you are running 2 things happen:
- you decrease the O2 content of the veins - less oxygenated blood being pumped through the systemic circulation
- the arteries of your lower extremities are vasodilated - less resistance for the aorta to push against
when you squat:
1. using less O2
2 increase resistance in the systemic vasculature and blood is diverted preferentially to the pulmonary trunk vs the aorta
3. increased return to the heart
deviation of the infundibular septum
anomalous pulmonary venous return?
blood from both the pulmonary (oxygenated) and systemic (deoxygenated) flow into the right atrium; patients have obligatory right to left atrial shunting
Ideal site for vascular access to the lower extremity during cardiac catherization? What happens if you miss?
in the common femoral artery BELOW in the inguinal ligament
if you puncture above, increase risk of RETROPERITONEAL hemorrhage
Where are the paracolic gutters and what are they used for?
space between the ascending or descending colon and the abdominal wall; blood, bile, or pus accumulates here from pathology involving the GI organs
What level do the renal veins join the IVC?
The common iliac veins join the IVC at?
L1/L2
L4
ST elevations mean an acute MI
- Leads I and avL, V5-V6
- Leads V1-V4
- Leads avF, II, III
- lateral - left circumflex
- anterior - LAD (RUPTURE OF LV FREE WALL IS A CATASTROPHIC COMPLICATION, leads to cardiac tamponade and death)
(if combined leads then left coronary) - inferior - R coronary artery
Anterior and posterior to the esophagus?
Branches of the pulmonary trunk?
anterior - LA
posterior - descending aorta
R side - horizontally under the aortic arch and posterior to the SVC
L side - superiorly over the left main bronchus
CXR in decompenated heart failure - increased atrial and ventricular pressures are transferred to the pulmonary vasculature causing fluid transudation into pulmonary interstitial and alveolar spaces?
how does the body compensate?
cephalization of the pulmonary vessels, perihilar alveolar edema (batwing), blunting of costophrenic angles due to pleural effusions, Kerley B lines (short horizontal lines representing interlobar septa)
activate the RAAS and sympathetic nervous system to increase CO –> however this leads to deleterious remodeling, increased afterload, and excess fluid retention
Borders of the Heart?
right - SVC, RA, IVC
inferior/anterior - RV (seen best on lateral view)
left - left auricle, LV
What does the Valsalva maneuver do?
decreased preload
decreases intensity of aortic stenosis, pulmonary stenosis, tricuspid regurgitation
increases intensity of HOCM (vasodilators and diuretics contraindicated), mitral prolapse
Most common site of thrombus formation in the heart?
left atrial appendage
What artery is injured if you have trauma to the pterion - the place where the frontal, parietal, temporal, and sphenoid bones meet?
What is the terminal branch of the artery that this artery comes off of?
Middle meningeal artery (epidural hematoma) - branch of the maxillary artery and enters through the foramen spinosum
the sphenopalatine is the terminal branch of the maxillary artery - supplies much of the nasal mucosa; Kiesselbach’s plexus (sphenopalatine, superior labial artery, anterior ethmoidal artery)
SUPERIOR MEATUS - drains posterior ethmoid and sphenoid
MIDDLE MEATUS - frontal, maxillary, posterior ethmoid (nasal polyps most often found here)
INFERIOR MEATUS (nasolacrimal)
Describe the branches of the common iliac artery
Common iliac splits into internal and external.
External splits into inferior epigastric (proximal to the inguinal ligament; runs superior and medially) and the deep circumflex iliac; the external iliac becomes the femoral artery as it crosses the inguinal ligament; the medial circumflex femoral artery branches off the deep femoral artery and supplies the femoral neck
Internal iliac branches off (S to I) superior gluteal, inferior gluteal, obturator (supplies ligamentum teres, important in children because it supplies area proximal to wpiphyseal growth plate)
What artery does the Posterior Descending Branch (supplies the SA and AV nodes) come off of in right-dominant? in L dominant?
R - right coronary
L - left circumflex (branch of left coronary)
What happens to cardiac output and venous return in chronic anemia and anaphylaxis?
anemia: increased CO, slightly increased VR (decreased viscosity)
anaphylaxis: increased CO to compensate for lower blood volume; decreased VR
What does atrial natriuretic peptide do? Where does it act? What drug increased levels by preventing its degradation?
senses when blood pressure is high and lowers it via action of cGMP
- restricts aldosterone secretion
- vasodilates
- in kidney dilates afferent arterioles –> increases GFR and sodium secretion, inhibits sodium and renin secretion
NEPRILYSIN INHIBITOR (normally neprilysin degrades peptide hormones; ie sacubitril)
What causes isolated systolic hypertension? SBP>140, DBP
age-related stiffness and reduced compliance of the aorta and the major peripheral arteries - endothelial cell dysfunction - change in ECM composition (more collagen, less elastin)
can also occur due to aortic regurg (increase in stroke volume), anemia, or hyperthyroidism
Sudden onset of palpitations and rapid regular tachycardia?
paroxysmal supraventricular tachycardia - usually due to a recurrent impulse traveling between the slowly and rapidly conducting systems of the AV node
can be relieved by Valsalva (using rectus muscles) or vagal stimulation
Most frequent mechanism of sudden cardiac death?
Ventricular fibrillation in the first 48 hours after an acute MI, related to electric instability in the ischemic myocardium
AV fistula - how does it affect preload and afterload?
preload - increases preload because arterial blood is going into the venous system
afterload - decreases afterload because blood is by passing the arterioles (major site of resistance)
Describe excitation-contraction coupling in the cardiac myocyte
During Phase 2, there is a calcium influx into the myocyte (due to the voltage gated L-type calcium)
The calcium influx is sensed by the ryanodine receptors on the sarcoplasmic reticulum which open (calcium induced calcium release) to release more calcium
calcium binds to troponin and moves tropomyosin and the cardiac muscle contraction occurs
When is pulsus alternas seen?
electrical alternans?
pulsus parvus et tardus?
beat-to-beat variation in pulse amplitude due to changes in systolic blood pressure - usually due to LV dysfunction
beat to beat variation in the QRS complex - occurs with severe cardiac tamponade (heart swinging in the percardial fluid)
slow-rising low amplitude, prolonged LV ejection time; seen with aortic stenosis; also with aortic stenosis S2 is diminished due to reduced mobility of the leaflets; also radiates to neck
Pressures in the RA, RV, and PA?
RA - 1-6 mm Hg
RV - systolic is between 15-30 (strength of right ventricular contraction)
diastolic - lower than the RA pressure
PA - systolic - around the same as the RV
diastolic - due to pulmonary capillary resistance and backward transmission of left atrial pressure
Why does verapamil (L-type channel calcium blocker) not work on skeletal muscle cells?
In skeletal muscles, L-type calcium channels interact directly with the ryanodine receptors - the calcium influx does NOT cause the ryanodine receptor to open (no calcium induced calcium release)
How to adenosine and Ach slow the sinus rate and increase the AV node conduction delay?
Difference between L-type and T-type channels?
affect phase 4 - activates potassium channels increasing conductance causing the membrane potential to be negative for longer; also inhibit L-type calcium channels
L-Type (long-lasting) - responsible for the upstroke in Phase 0, opens when membrane potential is -40 mV
T-type (transient) - opens when membrane potential is at -50 mV
what is permissiveness? describe the interplay between NE and cortisol?
additive?
synergistic?
when one hormone allows another to exert its maximal effect; cortisol on it own has no vasoactive properties, however it does upregulate the expression of alpha-1-adrenergic receptors on smooth muscle allowing NE to bind more; also increases glucose release by the liver in response to glucagon
additive - sum of the effects of 2 drugs is equal
synergistic - sum of the effects of 2 drugs is greater than them individually
Where is S3 best heard?
occurs during early diastole and best heard with the BELL of the stethoscope in the left lateral decubitis position during EXPIRATION (decreasing lung volume and bringing heart closer to the chest wall); indicates increased left ventricular end-systolic volume
not always pathologic if seen in younger patients; contrast with S4 which is pathologic in children
Most deoxygenated blood in the body?
coronary sinus - the myocardium has the greatest oxygen demand
Role of prostacyclin (Prostaglandin I2)?
Protein C?
Kallikrein?
Serotonin?
- antagonizes effects of thromboxane; inhibits platelet aggregation, vasodilates, increases vascular permeability
- inactivates factors Va and VIIIa; vitamin K depedent
- converts kininogen into bradykinin in the lung (ACE break down bradykinin; ACEI cause accumulation of bradykinin and subsequent cough); bradykinin is made in the kidneys and vasodilates the renal vasculature, implicated in angioedema
- regulates mood in the CNS; secreted by gut chromaffin cells and increases peristalsis and nausea; also vasodilates and increases vascular permeability
Organ susceptibility to ischemic injury - worst prognosis to best?
- brain, myocardium, spleen, kidney, liver (dual blood supply)
Pathology behind varicose veins? What does it cause?
What are claudications caused by?
result from the impairment of venous valves and reflux of venous blood - leads to stasis, congestion, edema, skin ulcers, and SUPERFICIAL thromboembolism; (DEEP VEIN THROMBOSIS can cause pulmonary embolism)
-pain and weakness associated with exertion; most frequently due to peripheral arterial disease
Phlegmasia alba dolens?
Painful, white leg is a consequence of iliofemoral venous thrombosis occurring in peripartum women
Describe fibrinolytic therapy and the major complication
Altepase can bind to fibrin and convert plasmin to plasminogen which can dissolve the clot
Hemorrhage
Difference between nitroprusside and nitroglycerin?
Nitroprusside decreases preload and afteload
Nitroglycerin just reduces preload
Murmur in hypertrophy cardiomyopathy? What is the obstruction caused by?
decreases when preload or afterload is increased (handgrip, passive leg raise, squatting) –> the left ventricular outflow tract is attenuated
increases when preload decreases (valsalva, nitroglycerin, abrupt standing)
anterior displace of the MITRAL VALVE LEAFLET and INTERVENTRICULAR SEPTUM
Clopidogrel mechanism of action?
irreversibly blocks the PGY component of ADP on the platelet surface and prevents platelet aggregation
What are the signs of a TCA overdose? what do you treat it with?
CNS (seizure, coma), Cardiovascular (hypotension, tachycardia, prolonged PR/QRS/QT intervals; arrythmias), anti-Cholinergic effects (hyperthermia, urinary retention, dry mouth)
these symptoms are caused by blockage of cardiac fast sodium channels; treat with SODIUM BICARBONATE - it makes the serum pH higher which favors the non-ionized form of drug (less able to bind to the sodium channels); also increases the sodium concentration and helps overcomes the competitive inhibition of the fast sodium channels
How do you treat acetominophen overdose?
opiate overdose?
benzo overdose?
N-acetylcysteine - reduces hepatic injury by restoring liver glutathione stores
naloxone
flumazenil
Congenital Syndromes that cause QT-prolongation and predispose to torsades de pointes
2 types of K+ channels in normal cardiac muscle
both cause unprovoked syncope in a previously asymptomatic person; mutation in the K+ channel in the cardiac action potential
- Romano-Ward (autosomal dominant; NO deafness)
- Jervell and Lange-Nielsen Syndrome (autosomal dominant, sensorineural deafness)
- in Phase 1: transient outward potassium channel
- in Phase 3 - delayed rectifier potassium channel
Arrythmogenic Right Ventricular Cardiomyopathy
progressive fibrofatty replacement of the right ventricle
What is Kussmaul’s sign?
pericardial knock?
- Normally, JVP decreases upon inspiration
- Kussmaul’s sign is when JVP increases upon inspiration; found in patient’s with chronic constrictive pericarditis/restrictive cardiomyopathy
a brief, high-pitched sound heard in early diastole after S2 and before S3 – in chronic (constrictive) pericarditis
another sign of constrictive pericarditis is pulsus paradoxis
Release of what cytokine by what cells cause recruitment of a major component of the atheroschlerotic plaque?
Most common location for formation?
platelet-derived growth factor released by platelets, endothelial cells, and macrophages promotes the migration of smooth muscle from the media into the intima
then the smooth muscle synthesizes collagen and extracellular matrix
CORONARY ARTERIES and ABDOMINAL AORTA
Role of TGF-beta
transforming growth factor
- angiogensis
- inhibition of the cell cycle
- stimulate fibroblasts to lay down ECM proteins
Action of the superior oblique? How does a lesion present?How do people compensate?
- intort when abducted; depress when adducted
- vertical diplopia; unable to read or walk down stairs
- compensate by tucking in chin and tilting head away from the affected side
What part of the brain is atrophied in Huntingtons?
caudate; but PET scan shows reduced activity in the caudate and the putamen (collectively called the striatum)
What do the anterior and posterior limbs of the internal capsule separate? What is the function of this structure?
what do UMN lesions cause?
Anterior - separate GP/Put FROM caudate; carries thalmocortical fibers
Posterior - separate GP/Put FROM thalamus; carries corticospinal motor, somatic sensory, visual and auditory fibers
and the “genu” you have corticobulbar fibers
CLASP KNIFE SPASTICITY, hyperreflexia, motor weakness on the contralateral side; present in newborn because of incomplete myelination
Describe the sympathetic pathway to the eye
First Order neuron starts in the hypothalamus and descend down through the brainstem to the spinal cord where they synapse on the lateral horns in the spinal cord (T1-L2)
Second Order Neurons exit the spinal cord via the ventral root and enter the sympathetic ganglia via the white communicating rami
The neurons ascends and then synapses with third order neurons in the superior cervical ganglion where it follows the branches of the carotid artery to innervate its target
Where does the suprachiasmatic nucleus receive input from?
How to the levels of melatonin and cortisol change throughout the day?
receives input from specialized photosensitive ganglion cells from the retina via the retinohypothalamic tract
melatonin - high at night, low in the morning
cortisol - high in the morning, low at night
easier to lengthen the sleep-wake cycle (westward travel) than to shorten it (eastward travel)
Anatomy of the macula?
Difference between wet and dry macular degeneration?
densely packed cones, each synapses with a single bipolar cell and a single ganglion cell and then goes to a separate section of the occipital cortex that is different than peripheral vision- this is why you have macular sparing with lesions of the occipital cortex
Dry - fatty deposits of drusen; gradual vision loss
Wet - neovascularization as a result of hypoxia; acute vision loss and metamorphosphia; greyish-green subretinal membrane; VEGF inhibitor therapy (ranibizumab, bevacizumab)
Both benefit from antioxidant therapy and smoking cessation
What is Wilson’s Disease characterized by?
caused by a defect in the ATP7B transporter - decreased formation of ceruloplasmin (low serum ceruloplasmin is diagnostic) and decreased excretion of copper into the bile so that copper builds up in the body
- hepatitis, cirrhosis
- atrophy of lentiform nucleus (putamen and GP)
- psychiatric symptoms - depression, personality changes
- neurologic - movement disorder, disarthria
- Keyser-Fleisher rings deposited in Descement membrane of the cornea
What is the descending aorta derived from?
Trunctus arteriosus is partitioned into aorta and pulmonary trunk by which cells?
fusion of the right and left embryonal dorsal aorta
neural crest
- Lesion of the lower roots of the brachial plexus (C8-T1)
- shoulder dislocation or fracture of the surgical neck of the humerus causing injury of the axillary nerve
- injury of musculocutaneous nerve
- supracondylar fracture
- injury to the suprascapular nerve
- Klumpke’s palsy - dysfunction of the intrinsic muscles of the hand (thenar, hypothenar, lumbricals, interosseus), sparing of the extensors and flexors of the hands leads to claw hand deformity
- weakness of the deltoid (important for abduction of the arm below the horizontal plane) and teres minor, loss of sensation over the lateral shoulder
- weak elbow flexion due to impaired biceps, coracobrachialis, loss of lateral sensation to the FOREARM
- damages the median nerve (nerve travels through the ulnar and humeral heads of pronator teres) - lose sensation in the first 3.5 digits; impaired motor function in thumb; wrist flexion impaired (innervates flexor digitorum profundus and superficialis); impaired flexion of 2nd and 3rd digit
- supraspinatus - impaired abduction
infraspinatus - impaired lateral rotation of the arm
Infarct at the anterior pons can cause
- corticomotor/corticobulbar issues
- Babinski
- you also get cerebellar issues - pontinocerebellar fibers arise from the pons and then decussate and enter the contralateral cerebellum via the middle cerebellar peduncle
motor portion of TRIGEMINAL NERVE arises here (lateral aspect of mid-pons)
Lithium during pregnancy is associated with?
What adult organ systems?
Ebstein abnormality - tricuspid valves are abnormally formed; RA is large and RV is hypoplastic; right to left ASD
renal and thyroid
Superior gluteal nerve injury?
Inferior gluteal nerve injury?
Femoral nerve (L2-L4)?
Sciatic nerve (L4-S3; test with straight leg raise)?
superolateral is the safest place; actually ANTEROLATERAL
normally innervates the gluteus medius and minimus (HIP ABDUCTION); when you stand on the affected foot, hip tilt to the contralateral side; when you walk lean to the ipsilateral side to maintain a level pelvis; exits through GREATER SCIATIC FORAMEN above the piriformis; risk of INJURY if injection in the SUPEROMEDIAL quadrant
Innervates the gluteus maximus which helps EXTEND THE THIGH at the hip; you can’t get up from a sitting position or climb stairs; exits the GREATER SCIATIC FORAMEN below the piriformis
Femoral nerve helps FLEX THE HIP (illiacus and sartorius (and psoas which is innervated by the lumbar plexus)); also helps extend the knee (quads); injury results in knee buckling and loss of patellar reflex; loss of sensation on anterior and medial thigh and medial leg
innervates the hamstrings; and splits into the tibial and common peroneal nerve; tibial nerve courses along the posterior calf and involved in PLANTAR FLEXION and INVERSION; the common peroneal nerve crosses the lateral head of the fibula and splits in the deep and superficial peroneal nerve; deep enters the anterior compartment and involved in DORSIFLEXION; superficial courses on the lateral side of the foot and is involved in EVERSION
Where do you put the 3 leads of a pacemaker into the heart and how do you access them?
- RA
- RV
- LV
accessed by left subclavian vein –> SVC –> RA/RV –> coronary sinus (atrioventricular groove) –> LV
What is the length constant? How does it change in MS?
a measure of how far along the axon and electrical impulse can propagate; myelination INCREASES the length constant and decreases the time constant
demyelination DECREASES the length constant and increases the time constant
Neural crest derivatives?
P. SANAM
Pia Matar Schwann cells Arachnoid Matar PNeuronS (DRG, sympathetic ganglia) Adrenal Medulla Melanocytes
also aorticopulmonary septum
Mesoderm derivatives
Endoderm derivatives
muscles, bones, blood, connective tissues, kidney/ureter, dermis, *vertebrae are derived from the paraxial mesoderm, spleen
thyroid follicular cells (derived from primitive tongue), thymus, parathyroids, lungs, the GI tract, middle ear, bladder, urethra
How does morphine (opioid agonist) decrease pain sensation?
what are some endogenous opioids and how are they made?
Binds to mu receptor (G-protein) and causes an efflux of potassium; this causes hyperpolarization effectively blocking pain transmission
enkephalin, beta-endorphin is made from POMC (proopiomelanocortin) which is a peptide that undergoes enzymatic cleavage to form beta-endorphin, ACTH, and MSH
Common complications of premature babies
respiratory distress necrotizing enterocolitis intraventricular hemorrhage (of the GERMINAL MATRIX - a highly vascular and cellular layer under the ventricle from where neurons and glial cells migrate out during development; this area has thin-walled vessels that lack glial cells for support) PDA retinopathy of prematurity bronchopulmonary dysplasia
Course of the radial nerve
- Posterior cord of the brachial plexus (CRUTCH PALSY - COMPRESSION IN THE AXILLA causes impairment of everything downstream)
- travels through the radial groove to innervate triceps (LESION HERE SPARES TRICEPS)
- Enters the forearm anterior to the lateral epicondyle
- Splits into the deep and superficial branches
- Superficial branches provide sensory innervation to the back of the forearm and dorsum of the hand
- Deep branch supplies the extensor compartment of the wrist
- travels through the supinator canal to become the posterior interosseus nerve which innervates finger and thumb extension (INJURY DUE TO EXCESSIVE PRONATION AND SUPINATION CAN CAUSE FINGER DROP)
What nerve travels through the hook of the hamate and pisiform?
Ulnar nerve through Guyon’s Canal
ulnar nerve provides sensory innervation to the 4th and 5th digit; you can also have ULNAR CLAW deformity where you are unable to flex the 4th and 5th digit; also is responsible for WRIST ADDUCTION and FINGER ABDUCTION AND ADDUCTION (dorsal and palmar interossei)
innervates what?
dorsal scapular
thoracodorsal (C6-C8)
innervated by?
playsma
rhomboid (retract scapula), levator scapulae (elevate scapula)
latissmus dorsi (shoulder extension, ADDUCTION, internal rotation)
platysma is innervated by the facial nerve
Occlusion of the anterior cerebral artery (can occur from SUBFALCARINE herniation)
posterior cerebral artery?
anterior choroidal artery?
-loss of motor/sensory of the lower extremities, urinary incontinence, behavior changes
cranial nerves III and IV and other dorsal midbrain structures and thalamus (deep branch called the PERCHERON), median temporal lobe, and occipital cortex
branch of the INTERNAL CAROTID - supplies posterior limb of internal capsule, optic tract, lateral geniculate body, uncus, amygdala
What are the pharyngeal arches associated with?
1st - trigeminal nerve; muscles of mastication; maxilla, zygomatica, mandible, malleus, incus
2nd - facial nerve; styloid process of the temporal bone, stapes, lesser part of the hyoid bone, muscles of facial expression
TREACHER-COLLINS SYNDROME - hypoplasia of the mandibular and zygomatic bones; dysfunction of the 1st and 2nd arches, also have conductive hearing loss
3rd - glossopharyngeal nerve; if damaged, impaired taste perception and absent gag reflex, styloparyngeus muscle, greater horn of the hyoid
4/6th - vagus nerve, cartilaginous structures of the larynx,; dysfunction leads to laryngeal and pharyngeal dysfunction and autonomic dysfunction (impaired gastric acid secretion, esophageal motility, heart rate variability)
Injury to the trapezius (classically in the posterior triangle of the neck)
- drooping of the shoulder
- raising arm above the horizontal
Fracture of the orbit floor can cause?
What is Battle’s sign?
commonly arise from direct frontal trauma to the orbit; INFRAORBITAL nerve runs here and if damaged there is impaired sensation to the upper lip, gingiva, and upper cheek; inferior rectus can also be entrapped
the most susceptible parts to damage are the medial wall and floor of the orbit (ethmoid and maxillary sinuses)
hematoma over the mastoid process, periorbital bruising, otorrhea are clear signs of basilar skull fracture
Iliohypogastric (L1)?
genitofemoral (L1-L2)?
Ilioinguinal (L1)?
obturator is also L2-L4
motor function to anterolateral abdominal muscles, sensation to suprapubic and gluteal regions; can be damaged during APPENDECTOMY
sensation to upper anterior thigh, motor function to genitalia (cremasteric reflex)
sensation to upper and medial thigh and some parts of genitalia, accompanies spermatic cord through superficial inguinal ring
Fastest to Slowest (conduction systems of the heart)
Purkinje FIbers (2.2 m/s)
atria (1.1 m/s)
ventricles (0.3 m/s)
AV node (0.05 m/s)
What can uncal herniation cause?
- dilated pupils
- progresses to third nerve palsy (down and out)
- ipsilateral posterior cerebral artery compression (contralateral homonymous hemianopsia)
- pons and midbrain (Duret hemorrhages) from basilar artery
Timeline for ischemic cell injury in the heart?
loss of myocyte contractility occurs after 30 seconds after the onset of total ischemia
when ischemia lasts less than 30 minutes, restoration of blood leads to reversible contractile dysfunction
however, after 30 minutes injury becomes irreversible
Mechanism of action of ivabradine
-inhibits the funny sodium channels and prolongs Phase 4 and slows the SA node firing rate
negative chronotropic effect with no effect on contractility
Formation of peripheral edema in cor pulmonale is compensated by what?
lymphatic drainage
Best way to prevent doxorubicin toxicity in the heart
Give dexrazoxane - iron chelating agent that decreases the formation of free radicals from -rubicins
Divisions of the spinothalamic tract? Where is the lesion from a syrinx?
Lateral spinothalamic tract (pain, temperature)
Anterior spinothalamic tract (crude touch, pressure)
- first order neuron body is in the DRG
- synapses with second order neuron at the dorsal horn and the fibers of the lateral spinothalamic tract decussate in the VENTRAL WHITE COMMISSURE and then ascend on the contralateral side
syrinx usually forms lesion in the ventral white commissure and in later stages can expand to the ventral horns causing LMN signs
How are craniopharyngeomas formed and what do they look like grossly and histologically?
anterior pituitary - Rathke’s pouch, evagination of surface ectoderm
posterior pituitary - neuroectoderm
craniopharyngeoma arise from remnants of Rathke’s pouch and are composed of calcified cysts containing cholesterol crystals- cystic-filled with viscous fluid that resembles machine oil; look like wet keratin under the microscope
Migraine headache
Cluster headache
unilateral, localized to frontotemporal and ocular area, progressively posteriorly and becomes diffuse; lasts from several hours to an entire day, photophobia, nausea
recurrent attacks of sudden, severe, unilateral periorbital pain, ipsilateral rhinorrhea and watering of the eyes
Cerebral amyloid angiopathy?
brain AV malformation?
Charcot-Bouchard aneurysm?
hypertensive encephalopathy?
GRADUALLY worsening symptoms are indicative of a hemorrhagic stroke
consequence of beta-amyloid deposition in the walls of small to medium sized cerebral arteries; spontaneous LOBAR HEMORRHAGE
most common cause of intracranial hemorrhage in children, tends to be a SINGLE lesion
complication of HTN and involves DEEP BRAIN STRUCTURES
PROGRESSIVE headache + nausea/vomiting + NONLOCALIZED symptoms (the non-localized nature of symptoms also common in subarachnoid hemorrhage)
Decerbrate vs Decorticate posture?
Injury to cervical spinal cord?
lesion to dorsal midbrain?
DecerEbrate posture (Extensor) = lesion is below the red nucleus of the midbrain (disrupts signal to the flexors) and the extensor signal from the vestibulospinal tract predominates
DecORticate posture (flexOR) = lesion is above the red nucleus; loss of descending inhibition from the red nucleus leads to flexor response
Quadriplegia
vertical gaze palsy (Parinauds)
Associated signs with NEUROBLASTOMA (not to be confused with medulloblastoma)
- non-rhythmic conjugated eye movements
- myoclonus
- most common EXTRACRANIAL childhood cancer
can be found in adrenal medulla
Communicating hydrocephalus is caused by?
decreased absorption of CSF; secondary to dysfunction or obliteration of the subarachnoid villi which is a sequelae of a meningeal infection
all ventricles are SYMMETRICALLY enlarged as opposed to in a non-communicating hydrocephalus
you can also get this presentation if you have a choroid plexus papilloma but that is less likely
acute intermittent porphyria?
lead poisoning?
abdominal pain and peripheral neuropathy; can be managed with dextrose or heme infusion that blocks ALA synthase; can be exacerbated with CYP450 inducers
irritability, loss of developmental milestones in infants, and learning problems in older children
in adults - constipation, peripheral neuropathy, anemia, lead lines on the gum
Difference between nerve compression and nerve ischemic pertaining to the oculomotor nerve?
in a nerve fiber, the core has the fibers that innervate the extraocular muscles; the peripheral part of the fiber has the parasympathetic fibers involved in pupil constriction
Nerve compression - early sign is loss of parasympathetic function (dilated pupil) and loss of accomodation
Nerve ischemia - “down and out” pupil + ptosis, pupil is reactive however and accomodation is spared
optic neuritis
pain on ocular movement and decreased vision = sign of MS
Lesions to the cerebellar vermis
cause truncal and gait ataxia due to impaired modulation of the medial-descending motor systems (corticospinal, reticulospinal, vestibulospinal, tectospinal)
can also cause nystagmus and vertigo due to involvement of the flocculonodular node
Webers syndrome?
stroke characterized by oculomotor nerve palsy and contralateral hemiparesis
Charcot-Marie Tooth
presents with weakness of foot dorsiflexion due to involvement of common peroneal nerve
PARKINSONS DRUGS
dopamine agonists (can also be used to treat RESTLESS LEG SYNDROME)?
COMT inhibitors? (prevents methylation of DOPA)
what does carbidopa do?
amantidine?
bromocriptine (ergot), pramipexole, ropinirole
tolcapone (central and peripheral), entacapone (peripheral)
prevent conversion of L-dopa to dopamine
increase endogenous dopamine synthesis and release
SEIZURE MEDICATIONS
for an absence seizure? absence seizure + tonic-clonic seizure?
phenytoin used for? mech of action?
carbamazepine used for? bad side effect?
how goes gabapentin work?
just absence use ETHOSUXIMIDE (blocks T-type Ca channels in the thalamus), if both use VALPROATE (blocks NMDA receptors and increases GABA concentration, blocks Na receptors)
phenytoin is used for generalized tonic-clonic and status epilepticus; blocks Na channels
blocks Na channels; used for partial complex and partial simple seizures, trigeminal neuralgia; agranulocytosis and aplastic anemia, hepatotoxic, and SIADH
blocks calcium channels in the axon terminal preventing the release of excitatory neurotransmitters
Stepwise process for treating Statis Epilepticus
- give lorezepam - benzos are first-line acute treatment because of their fast onset of action
- give phenytoin at the same time (to prevent recurrence of seizures)
- if still seizing give phenobarbitol
- no improvement, give anesthetics (thiopental, midazolam, ketamine, propofol, opiates)
ANESTHETICS
anesthetics that are highly soluble in the blood have a longer onset of action
a high AV gradient means that the body’s tissues have absorbed a lot of the drug –> slow onset of action because this increases the time for the blood to be saturated
minimal alveolar [] (MAC) is a measure of potency - what dose is needed to knock 50% of the people out?
Halothane can cause Hepatotoxicity, can also cause onset of neuroleptic malignant syndrome
thiopental is a short acting barbituate, high lipid solubility, rapid entry into the brain, after equilibration with the brain rapidly redistributes into adipose tissue and skeletal muscle
bupropion is used for?
antidepressant and for smoking cessation
treating insomnia in the elderly?
raMELTeon - a melatonin agonist with few side effects
Neuroleptic malignant syndrome is caused by what?
abnormal ryanodine receptor releases large amounts of calcium into the muscle cytoplasm when exposed to halothane or succinylcholine; ATP-dependent mechanism to transport the calcium back into the sarcoplasmic reticulum
this generates heat from using ATP
loss of ATP causes muscle damage = rhabdomyolysis
treat with dantrolene
What should juvenile myoclonic epilepsy be treated with?
A broad spectrum anticonvulsant like VALPROIC ACID, topiramide, lamotrigine, levetiracetam
DO NOT give a more narrow spectrum anticonvulsant such as a carbamazepine, phenytoin, or phenobarbital (favored for focal onset seizures, not generalized syndromes)
Symptoms of serotonin syndrome?
can be treated with?
confusion, agitation, tremor, tachycardia, hypertension, clonus, hyperreflexia, hyperclonus (abnormal mental status, autonomic hyperactivity, muscular rigidity with hyperreflexia)
CYPROHEPTADINE (first gen anti-histamine with anti-serotinergic properties)
These AA are precursors to what?
phenylalanine
tryptophan
glycine
glutamate
arginine
phenylalanine (need BH4) –> tyrosine (need BH4)–> DOPA –>NE, Epi, dopamine, thyroxine, melanin
(need BH4)serotonin, NAD
heme
glutathione, GABA
urea, NO, creatinine
How does left sided heart failure cause pulmonary hypertension?
primary pulmonary hypertension?
left sided heart disease can increase the pulmonary venous pressure and cause congestion; this results in passive increase of pulmonary artery pressure which is made worse by NO depletion and increased endothelin causing vasoconstriction and pulmonary remodeling (smooth muscle proliferation + intimal thickening and fibrosis)
follows a 2-hit hypothesis; mutation in BMPR2 (pro-apoptotic) gene acts as the first insult and predisposes to excessive endothelial and smooth muscle proliferation; a second insult is then thought to activate the disease process resulting in vascular remodeling and elevated pulmonary HTN; plexiform lesion
treat with BOSENAN - endothelin receptor antagonist
Nursemaid’s elbow (radial subluxation)?
- occurs commonly in children 1-4
- injury is from a sharp pull on the forearm when the forearm is pronated and the elbow is extended
- the ANULAR ligament tears and is displaced
- can reduce the injury by supinating forearm and flexing elbow
what is caudal regression syndrome? what can it be caused by?
Vitamin A overuse doing pregnancy can cause?
Cocaine use?
patients are born with agenesis of the sacrum and lower lumbar area and experience flaccid paralysis of the legs, dorsiflexed contractures of the feet, and urinary incontinence; associated with maternal diabetes
craniofacial abnormality, posterior fossa CNS issues, auditory defects, abnormalities of the great vessels (similar to DiGeorge Syndrome)
causes vasoconstriction and limits blood supply to the fetus
Anatomy of the sciatic foramen
what is the coccygeus muscle part of?
Split into the greater sciatic foramen and lesser sciatic foramen by the sacrospinous ligament; piriformis is part of the greater notch and involved in EXTERNAL HIP ROTATION
part of the pelvic diaphragm (+levator ani), anterior to the sacrospinous ligament
Psoas major muscle?
Erector spinae?
ligamentum flavia?
originates from the anterior surface of the transverse processes and lateral surfaces of the vertebral bodies of T12-L5; acts to flex thigh at hip; psoas abcesses are a complication (presents with flank pain, inguinal mass and difficulty walking, elicits pain on PSOAS sign when the hip is extended - to minimize muscle stretching patients are in a flexed, lumbar lordosis postion)
large muscle of the back that courses longitudinally along the spinous processes; bilateral contraction causes spine extension
paired elastic ligaments that connect the vertebral laminae; help from the posterior wall of the spinal canal
Lateral epicondylitis is caused by what?
DeQuervain tenosynovitis?
overuse of the extensor muscles and characterized by angiofibroblastic tendinosis
overuse of abductor pollicus longus and brevis; causes thumb and wrist pain
Describe the muscle spindle feedback system (connected in parallel; myotatic reflex)
Golgi Tendon (connected in series with the skeletal muscle fibers)
The muscle spindle is a proprioceptor. a sense organ that receives information from muscle, that senses STRETCH and the SPEED of the stretch. When you stretch and feel the message that you are at the end of your stretch the spindle is sending a reflex arc signal to your spinal column telling you not to stretch any further and CONTRACT. This sense organ protects you from overstretching.
The golgi tendon organ is a proprioceptor, sense organ that receives information from the tendon, that senses TENSION. When you lift weights, the golgi tendon organ is the sense organ that tells you how much tension the muscle is exerting. If there is too much muscle tension the golgi tendon organ will inhibit the muscle from creating any force (via an inhibitory interneuron) and causing relaxation
Markers of osteoblastic activity?
Osteoclastic activity?
Osteoblastic - bone-specific alkaline phosphatase; ALP is also made by the liver and intestine in addition to the bone; you can differentiate by this test - bone ALP is unstable in heat (bone = boil) or by monoclonal antibodies
Osteoclastic - tartrate-resistant acid phosphatase and degradation products in urine including hydroxyproline and deoxypyridinoline(most reliable; pyridinoline links collagen fibers)
in a muscle sarcomere
H-band
A-band
I-band
H-band contains only thick filaments (shrinks with muscle contraction)
A-band (stays the same size)
I-band only contains thin filaments and decreases in length during contraction
risk factors for osteoporosis?
bone mass is determined by peak bone mass as an adult and subsequent bone loss
- race (African Americans have higher bone mass than Asians)
- smoking
- low BMI (low BMI –> increased risk of fractures)
- early menopause (estrogen is protective - increases osteoblast activity, decrease osteoclast activity)
- glucocorticoid use (prevents intestinal absorption of calcium, decreases collagen synthesis, decrease gonadotropin releasing hormone)
characterized by trabecular thinning; common sites are vertebral bodies and head of the femur
Hyperparathyroidism involves loss of cortical bone - characterized by subperiosteal resorption with cystic degeneration
NORMAL Ca, PO4, and PTH
Pharyngeal pouches
1 - epithelium of middle ear and auditory tube; pharyngeal membrane - tympanic membrane; pharyngeal groove - epithelium of external ear canal
2 - palatine tonsils
3 - inferior parathyroid, thymus
4 - superior parathyroid glands, ultimobranchial gland (calcitonin producing C-cells of the thyroid)
Supracondylar fracture of the humerus - what nerves and arteries are likely to be injured (common pediatric hyperextension injury)?
if ANTEROMEDIAL median nerve and brachial artery
if ANTEROLATERAL radial nerve; basilic vein does run anteromedially, but is unlikely to be injured due to its superficial course
ULNAR nerve is likely to be injured if the fall is on a hyperflexed elbow and the bone is displaced posteriorly
Pes anserinus?
biceps femoris?
semimembranosis?
all attach at anteromedial tibia - gracilis, sartorius, semitendinosis
attaches at styloid process of the fibula
attaches at medial condyle of the tibia (most medial hamstring)
Ankle ligaments
what can forced eversion cause?
What 2 muscles join to create Achilles tendon?
LATERAL - anterior talofibular (most commonly injured), posterior talofibular, and calcaneofibular
MEDIAL - anterior tibiotalar, posterior tibiotalar, tibiocalcaneal, tibionavicular
aversion of the medial malleolus
gastrocnemius and soleus
action of teres minor and major
Minor -externally rotates and adduction
major - internally rotates
Lymph of the lower extremity
superficial lymph nodes - drain veins and subcutaneous
deep - arteries and muscles
medial and lateral tracts
medial - drains to superficial inguinal lymph nodes, bypassing popliteal
lateral - drains popliteal AND inguinal nodes
Cilostazol mechanism of action?
used in the management of peripheral arterial disease - phosphodiesterase inhibitor that inhibits platelet aggregation and acts as a direct arteriolar vasodilator
increasing cAMP levels prevents platelet shape change and granule release
Acrochordons (skin tags)
cavernous angioma
superficial angioma
actinic keratosis?
dermatofibromas?
ecchymosis (>1 cm) > purpura (5 mm-1 cm) > petechiae (
pedunculated outgrowths of normal skin seen in areas of friction
dilated vascular space with thin-walled epithelial cells, can be found on skin, deep tissue, and viscera; cavernous hemangioma on brain and viscera associated with VHL; CAVERNOUS HEMANGIOMA IS THE MOST COMMON BENIGN LIVER TUMOR
also known as infantile hemangioma, strawberry hemangioma
small, scaly epidermal lesions; histologic findings include keratinocyte atypia, hyperkeratosis, and parakeratosis (retention of nucleus); can progress to squamous cell carcinoma
benign proliferation of fibroblasts
purpura are a sign of leukocytoclastic vaculitis (Type 3 hypersensitivity reaction)
What condition can chronic lymphedema predispose to?
Chronic lymphadema is caused by lymph node dissection during a masectomy
Predisposes to the development of angiosarcoma (Stewart-Treves Syndrome)
difference between solar lentigines and freckles (ephilides)?
Lentigo malinga?
solar lentingines = increase in melanocytes
freckles = increase in melanosomes
multinucleated, giant melanocytes; common finding in elderly patients; considered as “melanoma in situ”
malignant breast cancer is commonly found in which quadrant? skin dimpling is caused by invasion of what?
- outer upper quadrant
- invasion of suspensory ligament
Types of exocrine glands
MEROCRINE - cells secrete via exocytosis; salivary glands, eccrine sweat gland, apocrine sweat gland
APOCRINE - by membrane-bound vesicles; mammary glands
HOLOCRINE - by cell lysis; sebaceous glands; Meibomian glands of the eyelid
acanthosis?
dyskeratosis?
spongiosis?
thickening of the SPINOSUM layer - seen in psoriasis, seborrheic dermatitis (characterized by KERATIN PSEUDOCYSTS)
premature keratinization of individual keratinocytes, see basophilic nuclear remnants
intercellular epidermal edema that appears as an increase in width of the space between cells; eczema
Function of Th17 cells?
recruit neutrophils and secrete antimicrobial peptides; improves host defense against fungi and parasites at epithelial and mucosal surfaces
Mutation associated with melanoma
in the BRAF gene - substitution of valine for glutamic acid; involved in the signaling pathway for melanocyte proliferation
What can cause IgE-independent mast cell degranulation?
opioids, vancomycin, radiocontrast agents
activate protein kinase A
Junctional nevu vs compound vs intradermal
junctional - at dermo-epidermal jxn (flat macule, deeply pigemented )
compound - at jxn and in dermis
intradermal - only in dermis (skin, tan color; may be pedunculated)
How to differentiate M. Gravis from Eaton-Lambert?
They both can have ocular involvement, but patients with LEMS also have hypo or areflexia, autonomic symptoms, and classic incremental response to stimuli with continued stimulation
Late-term complications of ankylosing spondylitis (not associated with rheumatoid factor)
characterized by stiffness and fusion of the axial joints and inflammation of the site of tendon insertion into bone
involvement of thoracic spine, costovertebral, and costosternal junctions can limit chest wall expansion leading to hypoventilation
ascending aortitis can cause AR
anterior uveitis
McCune-Albright Syndrome?
Legg-Calve-Perthe disease?
somatic mosaicis mutation; due to overactivation of G-protein signaling cascade; leads to triad of - cafe au lait spots, endocrine abnormalities (precocious puberty), and osteolytic bone lesions (increased activation of fibroblasts and osteoclasts)
presents in children, osteonecrosis of the hip
Findings in:
Giant Cell Arteritis
Takayasu Arteritis
Polyarteritis Nodosa
granulomatous vasculitis involving branches of the carotid, polymyalgia rheumatica, T-cell mediated inflammatory process in the media
same histology as GCA; involves aortic acrches
nectrotizing vasculitis involved many organs (lungs are spared); transmural inflammation with fibrinoid necrosis; beads on a string appearance
How can lymphoma and thyrotoxicosis cause hypercalcemia?
lymphoma and granulomatous diseases (sarcoid) increase conversion of 25-hydroxyVitamin D to 1,25-hydroxyvitamin D
thyrotoxicosis causes mild hypercalcemia due to increased bone turnover
Role of excess metalloprotease activity (requires zinc as a cofactor)
ulceration of a wound results from?
encourages both myofibroblast accumulation at the wound edges and scar tissue remodeling resulting in contracture, also degradation of collagen and other components of the ECM
peripheral artery disease; inadequate blood supply
What are some issues that can arise with the urachus?
gastroschisis?
congenital diaphragmatic hernia?
inguinal hernia is caused by?
cryptorchism has to be pulled through what if caught in the inguinal canal?
at 3 weeks of gestation, the yolk sac forms a protrusion (ALLANTOIS) that extends into the urogenital tract - the upper part of the urogenital sinus develops into the bladder, allantois becomes the urachus (a duct between the bladder and the yolk sac); normally regresses and forms medial umbilical ligament
If the urachus fails to close you can get
- patent urachus - straw-colored urine discharge from the umbilicus
- urachal sinus (failure to close the distal portion) - periumbilical tenderness and recurrent purulent infection
- urachal cyst - failure of central portion to obliterate
viscera protrude through an abdominal wall defect next to the umbilicus
abdominal content enter the chest cavity and prevent lungs from developing properly
when the processes vaginalis, an outpouching of the peritoneum, fails to obliterate; leaves a path to allow bowel contents into the inguinal canal;
the deep inguinal canal is made by an opening in the transverse fascia; superficial inguinal canal is made by an opening in the external abdominal oblique (if testes is stuck in the canal, has to be pulled through the opening in the external oblique)
Potassium absorption in the nephron
how does increased fluid flow have an effect on K excretion?
Most of the K+ filtered by the kidney gets resorbed in the PCT (35% of original filtered amount) and the loop of Henle.(10% of original amount)
If HYPOkalemic - H+/K+ pump in the alpha-intercalated cells increases sodium resorption (collecting duct can end up with 1%)
If HYPERkalemic - increased activity of the apical K+ channels in the principal cells and secretion of potassium (can end up with 110%)
the increased flow quickly flushes away secreted K+, this helps maintain a high concentration gradient allowing more intracellular K to enter the tubular fluid (more K is excreted)
Mutation in what gene causes ARPKD
posterior urethral valve?
What are the VACTERL association?
most common place for UNILATERAL fetal hydronephrosis?
fibrocystin - a component of epithelial cells in both the renal tubule and the bile duct
abnormality of the urethral outflow, impedes flow - can cause oligohydramnois during gestation; persistent urogenital membrane; bilateral hydronephrosis
non-random co-occurence of birth defects - vertebral, anal atresia, cardiac defects, tracheoesophageal fistula, esophageal atresia, renal anomalies, limb defects
urteropelvic jxn (incomplete canalization)
Injury at 12th rib can damage?
9th, 10th, and 11th?
2nd lumbar body
damage of ribs 1-6
8th-11th ribs?
kidney
spleen
pancreas
visceral pleura of the lungs
overlie posterior surface of the liver
Where does the majority of water absorption occur in the nephron?
proximal convoluted tubule regardless of the patient’s hydration status (>60%)
Filtration Fraction
GFR/RPF (renal plasma flow)
RBF = RPF/(1-hematocrit)
RPF = (1-hematocrit)*RBF
Ureteral anatomy and blood supply
inferior phrenic artery supplies?
In the retroperitoneum ureters pass posterior to the gonadal (ovary or testicalar) vessels and anterior to the psoas muscle; at the pelvic inlet passes anterior to common iliac artery and then continues to be anterior to the internal iliac artery in the true pelvis
In the true pelvis, ureter is medial to the ovarian artery and posterior to the uterine artery; testicular artery does not enter pelvic brim
PROXIMAL URETER - renal artery
DISTAL URETER - superior vesicular
MIDDLE - anastomoses between the common, internal iliac; gonadal and uterine
-diaphragm and suprarenal vessels
What does bradykinin do?
Prostaglandins?
Leukotrienes?
–
With regard to asthma therapy
Methylxantines?
Magnesium sulfate?
vasodilate, increase vascular permeability, pain
vasodilate at arterioles, increase vascular permeability at post-capillary venules
(late acting) vasoconstriction, bronchospasm, increase vascular permeability
phosphodiesterase inhibitor - increased levels of cAMP cause vasodilation
inhibits calcium influx into smooth muscle causing vasodilation; also stabilizes mast cells preventing degranulation
Where is osmolarity the lowest in the nephron? The highest?
In the PCT - 300 mOsm/L (isosmotic to plasma)
becomes concentrated as you descend; *highest at the bottom of the LoH
becomes less concentrated as you ascend (permeable to electrolytes, not permeable to water); LOWEST in the DCT
*highest at the end of the collecting duct where aquaporins mediate water absorption
What happens when you constrict the efferent arteriole?
What happens when you are hypovolemic to RPF and GFR?
At first you increase the GFR because you are in increasing the hydrostatic pressure in the glomerulus
However as you continue to increase the constriction, the oncotic pressure increases and you reduce GFR
FF still increases
RPF goes down because of hypovolemia and because the low volume triggers vasoconstriction; GFR also goes down but less so because of constriction on the efferent arteriole –> FF increases
Relationship between serum creatinine and GFR?
Where is PAH secreted back into the nephron?
at normal GFR, decreases produce small increase in creatinine
at decreased GFR, decreases produce large increase in creatinine
as GFR halves, creatinine doubles
PAH is secreted at the PCT
Different types of incontinence: stress, overflow, urge
Stress - loss of pelvic floor support (in post-menopausal women - lack of estrogen causes laxity and weakness of the pelvic floor or damage of pudendal nerve during childbirth) and urethral sphincter incontinence; increased abdominal pressure (coughing, sneezing) greater than urethral pressure cause leakage
Urge - detrusor overactivity; can be due to hand-washing, running water - loss of CNS inhibitory input to the bladder
Overflow - due to impaired detrusor muscle (diabetic autonomic) or outflow obstruction (tumor); bladder is not completely emptied and involuntarily spill when pressure inside exceeds that of the sphincters
Systolic heart failure vs diastolic heart failure?
diastolic - decreased ventricular compliance, characterized by normal SV, ejection fraction, and LV end diastolic volume; elevated LV filling pressure
systolic - reduced ejection fraction because of impaired contractility, increased LV end diastolic volume with elevated end diastolic pressure, dilated ventricles
Most common cause of bloody nipple discharge?
Intraductal papilloma - proliferation of papillary cells around a fibrovascular core in a cyst wall or duct that may contain focal atypia; bloody discharge - twisting of the vascular stalk of the papilloma in the duct
not accompanied with breast masses or skin changes
What is the vasovagal reflex?
majority of the external ear receives sensory innervation from the mandibular division of the trigeminal nerve
The POSTERIOR part of the ear is innervated by the small auricular branch of the vagus nerve; stimulation to this nerve causes increased parasympathetic output resulting in decreased heart rate and syncope
Where are somatostatinomas found and what effect do they have?
somatostatin is formed by the delta-cells of the pancreas
results in decreased secretion of: gastrin - hypochlorhydria secretin - steatorrhea (decreased bile) cholecystokinin - gall stones insulin and glucagon, but I>G --> hyperglycemia
somatostatin is also secreted by the hypothalmus and inhibits growth hormone production
PORPHYRIAS
- Acute intermittent porphyria?
- Cutanea porphyria tarda?
- lead poisoning?
- deficiency in porphobilinogen deAminase or increased induction of ALA synthase (either via drugs - griseofulvin, phenytoin, phenobarbital; low calorie diet; progesterone); leads to an increase in ALA and porphobilinogen; treat with glucose or heme which inhibit ALA synthase; ABDOMINAL PAIN AND NEUROLOGICAL ISSUES, port wine urine
- deficiency in uroporphyrinogen deCarboxylase; leads to increase in uroporphyrinogen; presents with tea-colored urine and blistering photosensitivity
- inhibits ferrochelatase and ALA dehydratase; increase in ALA and protoporphyrin; microcytic anemia with basophilic stippling
DRESS syndrome? (drug reaction with eosinophilia and systemic symptoms) - likely involves drug-induced reactivation of herpesvirus
what drugs can induce antineutrophil cytoplasmic antibodies?
what is cryoglobulinemia?
anticonvulsants (phenytoin, carbamazepine), allopurinal, sulfasalazine, vancomycin can precipitate; develop fever, generalized LAD, facial edema, skin rash, eosinophilia, internal organ dysfunction
hyperthyroid medications and hydralazine
small to medium vessel vasculitis, circulating Ig-complement complexes that precipitate on refrigeration during states of chronic inflammation - hepatitis; SLE
What can Crohn’s disease cause in the urine?
why can a high protein diet cause stones?
high sodium?
low calcium diet?
hyperoxaluria - bowel resection can increase the amount of oxalate absorbed from foods which can increase the amount of oxalate excreted in urine; can TREAT WITH B6 - decreases the production of endogenous oxalate
increased protein raises acid production from sulfur-containing AA; the acids are buffered with bone salts
–>increased calcium excretion; the acidosis also causes increased citrate reabsorption in PCT causing HYPOCITRATURIA (citrate is protective against stone formation)
less sodium is reabsorbed; calcium follows sodium so there is more calcium in the urine
low calcium in the diet does not bind with all the oxalate to make excretable calcium-oxalate; the unbound oxalate ends up in the urine
What cells undergo hypertrophy in renal stenosis?
significant artery stenosis causes renal hypoperfusion and activation of the RAAS initiated by the JGA (the smooth muscles of the afferent arteriole)
renal artery stenosis on an XRay shows one atrophic kidney; patient will either be an older man with atheroschlerosis (pain after eating insinuates intestinal ischemia caused by the atheroschlerosis) or a young woman with fibrouscular dysplasia (both narrow the vessels); abdominal bruit is usually present
Shapes of calcium stones under the microscope?
cystine - hexagonal
struvite - coffin
uric acid - rhomboid
calcium oxalate - envelope
hepatorenal syndrome?
findings of ethylene glycol ingestion?
hemorrhagic cystitis?
advanced liver disease with portal hypertension can cause renal failure due to vasoconstriction; kidneys are histologically normal and resume function with liver transplant
toxic, acute tubular necrosis with vacuolar degeneration and ballooning of the PCT cells, increased anion gap, calcium oxalate crystals in urine
common adverse side effect from cyclophosphamide; acrolein a metabolite irritates the bladder mucosa and causes hematuria
Causes of metabolic alkalosis; volume status and urine chloride in each?
vomiting - lose H and Cl from gastric contents; cannot excrete HCO3 due to Cl loss and this contributes to the alkalemia; volume-depleted state that is SALINE RESPONSIVE
loop diuretics and thiazides - prevent absorption of Na and Cl in the proximal parts of the tubule; the volume depletion stimulates aldosterone which increases Na absorption and wastes H and K (alkalosis); high urine chloride; SALINE-RESPONSIVE
mineralocorticoid excess state - SALINE UNRESPONSIVE (hypervolemic state) high urine chloride due to pressure natriuresis
Myeloma kidney?
- easy fatigability
- constipation (hypercalcemia)
- back pain (bone lysis due to production of osteoclast-activating factor by the myeloma cells)
- elevated serum protein
- renal failure - Bence-Jones proteins - excess excretion of light chains that precipitate with Tamm Horsfall proteins - tubular obstruction and epithelial damage; GLASSY EOSINOPHILIC CASTS; can also get light chains deposited in the mesangium = AL amyloidosis
Lower urinary tract infection cause vs upper UTI?
In patients with a catheter, what is the most common predisposing factor to developing a UTI?
upper - vesicoureteral reflex
lower - suppression of endogenous flora, colonization of distal urethra by pathogenic gram negative rods, attachment of those organisms to the bladder mucosa via virulence factors (fimbrae)
avoiding unnecessary catheterization, sterile technique when inserting, and removing ASAP
What is a complication of invasive vascular procedures?
atheroembolic disease which can affect the kidneys, GI tract, CNS, and skin - signs of embolism include blue toe and livedo reticularis
microscopy shows partially or completely obstructed lumen with cholesterol clefts
Findings and treatment of DKA?
dehydration, mental status changes, abdominal pain, tachypnea, increased anion gap acidosis, hyponatremia (sodium follows water), hyperkalemia, increased plasma osmolarity, ketosis
INSULIN (intracellular shift of potassium because of the sodium-potassium increased glucose utilization preventing lipolysis) AND HYDRATION
(in viruses) what is phenotype mixing?
can occur when a host cell is infected with 2 strains of a virus; the progeny contain parental genome from one strain but may contain nucelocapsid from the other strain (can acquire the ability to infect new host cells)
however, as the genome is unchanged, subsequent progeny do not retain these traits
Development of the female reproductive tract
what happens when you have a failed fusion of the paramesonephric ducts with the urogenital sinus?
What happens in males?
mesonephric ducts degenerates
paramesonephric ducts fuse to form the cervix, fallopian tubes, uterus, and upper vagina; failure to fuse laterally can lead to a variety of mullerian and combined renal abnormalities
transverse vaginal septum - retained menses in the uterus
bicornate uterus is an example (indentation at the center of the fundus)
In males:
- SRY gene on the Y-chromosome - testes-determining factor
- Sertoli cells make Mullerian inhibiting factor
- Leydig cells make androgen to stimulate the mesonephric duct (aka Wolffian duct)
BREAST CANCER TREATMENTS
aromatase inhibitors - anastrozole, letrozole; decrease the conversion of androgen into estrogen; slows the progression of ER-positive tumors; in postmenopausal women, you have degradation of the granulosa cells so you have decreased conversion of A to E anyway but you have extraovarian aromatase in the adrenal cortex
continuous-stimulation of GnRH (as opposed to pulsatile) decreases production of LH and FSH leading to decreased levels of estrogen (goserelin)
tamoxifen binds to the Estrogen receptor itself
If the breast cancer is HER-2 neu positive, treat with trastuzumab; inhibits MAPK signaling pathways, increases degradation of HER2, and facilitates antibody-mediated degradation of tumor cells
Voltage-gated sodium channel toxins
Block depolarization - parasthesias, weakness, dizziness, nausea, hypotension and respiratory distress
- tetrodotoxin (pufferfish)
- saxitoxin (dinoflagellates; red tide)
Persistant depolarization
- ciguatoxin (exotic fish, Moray eel)
- batrachotoxin (South American frog)
Diseases with X-linked dominant inheritance?
what is the inheritance pattern of hereditary spherocytosis?
Alport syndrome, Rett Syndrome, Fragile X, hypophosphatemic (vitamin D resistant) rickets
AD; also has osmotic fragility
Acute lymphblastic leukemia is the most common leukemia of childhood. What is the difference between the B-type and the T-type?
T-type - presents with a mediastinal mass that can cause respiratory symptoms, dysphagia, and super vena cava syndrome
Different AML subtypes
AML 4/5 - monocyte
AML 6 - erythroid precursors and affects elderly patients
AML 7 - megakaryoblasts, Down syndrome in children
What is the function of carboxylation of the clotting factors?
it allows for the creation of calcium-binding sites; the calcium attracts the clotting factors to the negatively charged phospholipids on platelet membranes
Triad for paroxysmal nocturnal hemoglobinuria?
deficiency in GPI which impairs adhesion of CD55(DAF) and CD59(MAC complex inhibitor)
- hemolytic anemia
- pancytopenia (the mutation is in a stem cell)
- hypercoagulability - release of free hemoglobin and other prothrombotic factors
Von Hippel Lindau associated with which 3 cancers?
Li-Fraumeni?
APC?
Lynch (MSH, MLH)?
- RCC
- cerebellar hemangioblastoma
- pheochromocytoma
- sarcoma
- breast
- brain
- leukemia
- colorectal
- osteoma
- fibroma
- brain tumors
- colorectal
- endometrial
- ovary
Pure Red Cell Aplasia is associated with what?
severe hypoplasia of erythroid elements in the bone marrow in the setting of normal granulopoesis and thrombopoiesis
associated with THYMOMA and PARVOVIRUS
How does hepatitis B increase the risk of HCC?
the virus has a revere transcriptase and incorporates into the host cell genome; disrupts cell cycle control by inactivating p53 tumor suppressor protein
also the chronic liver cell injury causes regenerative hyperplasia increasing the number of mutations
acanthocytes are characteristic of
abetalipoproteinemia; cholesterol accumulates in the RBCs
BRCA1/BRCA2 (associated in an autosomal dominant mode with incomplete penetrance)
associated with repair of double-stranded DNA breaks
Side-effects of mu-opioid analgesics?
- constipation (binds to mu receptors in the gut)
- causes histamine release and vasodilation and itching (should be avoided with people with hypotension)
- cause contraction of smooth muscle in the Spinchter of Oddi leading to spasm and increased common bile duct pressures; also pressures in the gallbladder can increase leading to biliary colic (pain in upper right quadrant)
Breast milk lacks which vitamins?
Vitamin K (given at birth intramuscularly to prevent hemorrhagic disease of the newborn) and D (exacerbated if the baby is exclusively breastfed, dark-skinned, and not exposed to sunlight)
supplement with IRON if the baby is pre-term and low birth weight; althought breast milk has low iron, it is sufficient until 4 months after which time supplementation is required
Ribavirin - mechanism of action?
Ribavirin is a nucleoside analog of guanosine
- when incorporated into viral RNA, it can pair equally well with uracil and cytosine - disrupts RNA-dependent RNA replication which is lethal to RNA viruses
- direct inactivation for viral RNA polymerase
- inhibits the conversion of IMP to GMP (inosine monophosphate dehydrogenase); depletes intracellular GTP
- inhibits formation of the 5’ GTP cap - inefficient translation from mRNA
- enhances Th1 immunity and suppresses Th2 cytokines
How is a gastrojejunostomy performed (to treat peptic ulcer disease)? What nutrients may not able to be absorbed?
removing antrum of the stomach (to decrease gastrin production) and connecting it to the jejunum; blind loop is created involving the proximal jejunum and the duodenum
folate, B12, calcium, iron, and vitamin D
The great majority of ulcers occur where on the stomach?
Most likely to cause bleeding if eroded into?
arise along the lesser curvature of the stomach at the border of the acid secreting and gastrin secreting mucosa
right and left gastric artery
Vitelline duct (omphalomesenteric) abnormalities; usually obliterates at 7 weeks?
Imperforate anus?
- persistent vitelline duct - meconium from the umbilicus
- Meckel’s diverticulum
- vitelline sinus - partial closure of the vitelline duct with the patent portion open at the umbilicus
- vitelline duct cyst - peripheral portions (those attached to the umbilicus and the ileum) are obliterated (fibrous); area in the middle remains
abnormal development of anorectal structures; infants fail to pass meconium
acute interstitial pancreatitis vs acute hemorrhage pancreatitis
caused by duct obstruction - lipase digests adipose tissue; pancreas is grossly edematous; fat necrosis; calcium deposition
blood flow is disrupted to the pancreas, acinar cells are damaged and causes activation of trypsin; chalky-white areas of fat necrosis interspersed with hemorrhage due to autolysis of pancreatic tissue
pulsion vs traction diverticulum
pulsion - due to increased pressure (pseudo); diverticula in colon (mucosa and submucosa) and Zenker’s
traction - inflammation and scarring of the gut wall resulting in the pulling of the gut wall layers - (true); usually in midesophagus after TB or fungal infection
How does Shigella sonnei get into the body?
What are Paneth cells?
exhibits specificity for the M (microfold)-cell at the base of mucosal villi of a Peyer’s patch in the terminal ileum; passes through the M-cell via endocytosis; lyses the endosome, multiplies and then spreads laterally
lie at the base of the intestinal crypt - they are secretory (lysozymes and defensins) and phagocytic
What can precipitate hepatic encephalopathy?
How does it cause neurological symptoms?
ammonia is normally produced by the GI tract from catabolism of glutamine or bacteria catabolism of protein; in a patient with liver failure increased nitrogen from GI bleeding or increased dietary intake leads to an increase in ammonia that cannot be metabolized by the liver into urea; in liver disease DECREASED BUN
impairs excitatory NT
increases inhibitory NT
Hepatitis histology
ballooning degeneration, Councilman bodies - eosinophilic apoptotic hepatocytes, and mononuclear cell infiltrates
hepatoblastoma
most common liver neoplasm in children; associated with Beckwith-Wiedemann and FAP
also, liver is the second most common organ of metastatic spread after the lymph nodes
how is stool osmotic gap calculated?
290 - 2*(stool Na + stool K)
plasma osmolarity - electrolytes in stool
high gap - osmotic diarrhea (lactase def, Whipples)
low gap - secretory diarrhea (cholera, VIPoma, laxative abuse)
What affect does maternal diabetes have on the fetus?
effect of antenatal magnesium sulfate in preterm?
hyperinsulinemia in the fetus (beta cell hyperplasia); the increased insulin inhibits the maturational effects of cortisol and can cause decreased surfactant production; increased insulin also contributes to increased fat deposition causing macrosomnia; after birth, at risk for HYPOGLYCEMIA
decrease risk of cerebral palsy
Different types of DCIS and Invasive DC (most common type)?
What happens if the sinuses in the breast get blocked?
- see calcifications on mammogram with central necrosis
- DCIS can progress to Paget’s disease of the breast; erythema and ulceration of the nipple
- tubular type - lack myoepithelial cells in a desmoplastic stroma
- mucinous carcinoma - occurs in older women
- medullary - inflammatory infiltrate; mimics fibroadenoma; associated with BRCA1
- inflammatory - in dermal lymphatics; worst prognosis
GALACTOCELE that can lead to breast abcess
Pathogenesis of secondary hyperparathyroidism?
What is the fxn of 24,25-Vitamin D?
kidneys not working -> increased phosphate retention -> hypocalcemia –> increased PTH secretion, can’t produce 1,25-Vit D –> bone and muscle pain, decreased bone mineralization
inactive form of Vit D produced by the kidneys when excess 1,25 Vit-D activity
Parabasal cells on a Pap Smear?
round cells with basophilic cytoplasm; “fried eggs” appearance; high nuclear to cytoplasm ratio; normal finding in post-menopausal and post-partum women
anastamosis between SMA and IMA
MAIN: marginal artery (of Drummonad) and arc of Riolan (meandering mesenteric artery)
classic presentation of pernicious anemia?
Vit C overdose?
Vit E overdose?
older, mentally slow woman of European descent; “lemon-like” - icteric and anemic; smooth, shiny tongue; shuffling gait
diarrhea, abdominal bloating; false-negative stool guaiac results
hemorrhagic stroke in adults; necrotizing enterocolitis in newborns
Which are calcineurin inhibitors? What side-effect can they cause?
Grapefruit’s affect on this?
tacrolimus and cyclosporine inhibit calcineurin; elevated levels can cause nephrotoxicity
grapefruit (furocoumarins) inhibits P450 3A and increases levels of the drug
Cocaine withdrawal?
Alcohol withdrawal?
Cannibis?
hyperphagia, hypersomnia, depression, fatigue, vivid dreams
- tremor, agitation, anxiety, tachycardia
- seizures
- hallucinations
- DELIRIUM TREMENS (shaking, confusion, hallucinations, HTN), SEIZURE; treat with benzos; if liver function is impaired, treat with lorazepam, oxazepam, or temazepam (LOT)
irritation, anxiety, depressed mood, insomnia, decreased appetite
Why do pregnant women and women on OCPs susceptible to gallstones?
estrogen - cholesterol hypersecretion (upregulating HMG-CoA reductase)
progesterone - gallbladder hypomotility
Thrombin activates which coag factors?
conversion of fibrinogen to fibrin and conversion of V, VIII, and XIII to active forms
What drug competitively inhibits the Na-I co-transporter in the thyroid follicle?
perchlorate and pertechetate
propothiourahil and methimazole inhibit iodine organification and iodotyrosinase coupling
Appendix cannot be palpated, how do you identify it?
Follow the teniae coli (3 separate smooth muscle ribbons)
pathogenesis of abdominal aortic aneurysm?
TRANSMURAL aortic wall inflammation, abnormal collagen remodeling and cross-linking, loss of elastin and smooth muscle cells
Steps in Collagen Synthesis
- pre-pro-collagen transported to RER and the signal sequence is cleaved
- hydroxylation of proline and lysine residues (need Vit C)
- glycosylation of hydroxylysine
- form triple helix via disulfide bonds - defective in osteogenesis imperfecta
- exocytosis
- proteolytic processing cleavage of N and C terminals to make insoluble tropocollagen (defective in Ehlers-Danlos)
- Lysyl-oxidase links tropocollagen strands together; need Copper; defective in Menkes
Anovulation treatment; what mimics FSH? LH?
FSH - menotropin (human menopausal gonadotropin)
LH - hCG (alpha subunits are the same)
Factors the decrease incidence of epithelial ovarian cancer (CA-125 raised)?
The pathogenesis of ovarian cancer is linked to the frequency of trauma and repair at the ovarian surface; oral contraceptives, breast feeding, and multiparity are protective by decreasing the frequency of ovulation
risk factors - nulliparity, BRCA, infertilier
Drugs for neuropathic pain
tricyclic antidepressants (amitryptine, nortryptiline) - decrease S and N re-uptake
anticonvulsants (gabapentin) - decreased depolarization of neurons in the CNS
opioids - activation of central opioid receptors
capsaicin - causes release and subsequent depletion of substance P; causes build-up of intracellular calcium that leads to neuron dysfunction
lidocaine - decreased depolarization of peripheral neurons
When would the murmur of aortic stenosis be heard the loudest?
intensity of the murmur is proportional to the magnitude of left ventricle to aorta pressure gradient during systole
Elderly patient keeps falling - what do you do?
re-evaluate medications
antipsychotics, antidepressants, and benzos have increased fall risk
On an MRI, how do you locate the medial knee?
insertion of the sartorious, gracilis, and semitendinosus
composition of Thayer-Martin media
vancomycin - for gram positive organisms
colistin - for gram negative organisms
nystatin - for yeast
trimethoprim - for Proteus
Treatment for spasticity in MS?
baclofen - GABA agonist
tizanidine
What does the human multidrug resistance code for and how can it prevent the action of chemotherapeutic drugs?
codes for P-glycoprotein; a transmembrane ATP-dependent efflux pump; decreases influx and efflux of hydrophobic compounds
Difference between schizoaffective disorder and bipolar/MDD with psychotic symptoms?
PCP overdose?
methamphetamine overdose?
SAD - psychosis must occur in the absence of mood symptoms for >2 weeks; but also mood disorders must be present for most of the illness
with psychotic symptoms: psychotic symptoms occur exclusively during mood episodes
psychosis, dissociative and anesthetic events, severe agitation leading to violent trauma, *nystagmus, ataxia, delirium, AMNESIA; NMDA-ANTAGONIST
stimulant - tooth decay, tachycardia, diaphoresis, violent behavior, psychosis, NO NYSTAGMUS
Pathogenesis of IBD?
abnormal immune response to intestinal microorganims
Crohns disease shows mutations in NOD2 (encodes an intracellular microbial receptor helps to recognize bacterial LPS and contributes to innate immune response) leading to decreased activation of NF-kB –> decreased pro-inflammatory cytokines
side effects of antipsychotics
clopazine - AGRANULOCYTOSIS, myocarditis, seizure, metabolic syndrome
ziprasidone - prolonged QT interval
risperidone - increased prolactin levels
Local cutaneous effects of applying corticosteroids
atrophy/thinning of the dermis; loss of dermal collagen, drying, cracking and tightening of the skin, telangectasias, and ecchymoses
Pelvic floor muscles
perineal body - fibromuscular tissue between urogenital triangle and anal triangle; damaged in MIDLINE EPISIOTOMY
transverse perineal muscles - arises from ischial rami and tuberosities and inserts into perineal body; injured during MEDIOLATERAL EPISIOTOMY
levator ani - part of anal triangle and supports pelvic floor; can be torn during crowning
ischiocavernosus - urogenital triangle; forces blood into clitoris
Peyronie disease?
excess collagen formation in the tunica albuginea (fibrous tissue overlying the testicles); can cause significant pain and curvature of the penis
Cell junctions
Gap - conexin (upregulated during childbirth in the myometrium along with oxytocin receptors)
desmosomes - intermediate filaments + cadherins (desmoglein)
adherens junction - cadherin
tight - claudin (affected by C. perfringens) and occludin
hemidesmosomes - integrins
Insurance companies
Health Maintenance Organization $; PCP referral before specialized visits, may not go outside provider network
Point of service $$, can go outside provider network but with a fee, PCP referral before specialist
Preferred provider organization $$$
Treatment for panic disorder
long term - SSRI
immediate relief - benzos (have high abuse potential because of their rapid onset of action)
Treatment for an ectopic pregnancy?
What can be used to counter the effects of MTX chemotoxicity?
methotrexate - folate antagonist
folinic acid; competes with MTX for DHF binding sites (leucovorin)
Skeletal findings in primary hyperthyroidism?
sub-periosteal erosions affected phalanges of the hand, salt and pepper skull, osteitis fibrosa cystica
CP450 inducer
CP450 inhibitor
inducers: phenytoin, carbamazepine, phenobarbital, griseofulvin, rifampin
inhibitors: erythromycin, ciprofloxacin, azole, isoniazid, grapefruit juice, cimetidine, protease inhibitors, cyclosporine, amiodarone
all statins are metabolized by P450 except pravastatin
Aspirin overdose
triad: tinnitis, tachypnea, fever
this is a MIXED acid-base (normal pH) vs a compensatory response (does not correct pH completely)
-metabolic acidosis + respiratory alkalosis
Effect of corticosteroids on neutrophil count?
What organ become catabolic? anabolic?
Increased demargination; neutophilia
catabolic - bone (decreased calcium absorption, inhibition of osteoblast activity), adipose, muscle, lymphocytes, adrenal cortex, skin
anabolic - liver - increases glycogen synthesis and gluconeogenesis
Herpesvirus is enveloped; where do they get the phospholipid from?
nuclear membrane
Intestinal atresia distal to the duodenum
- Vascular accidents in utero
- apple peel atresia occurs when the superior mesenteric artery is obstructed; the result is a blind-ending proximal jejunum, a length of absent bowel and mesentery and finally a terminal ileum surrounding a distal ileocolic vessel
Fulminant hepatitis
can be due to halothane which is highly hepatotoxic; cannot be distinguished histologically from viral hepatitis (centrilobular necrosis and inflammation of the portal tract); associated with high ALTs, leukocytosis, eosinophilia, increased PT
estrogen and its relation to bone mass
low estrogen leads to increased production of inflammatory cytokines and (IL-1 and TNF-alpha)
Manometry findings in esophageal disorders
achalsia - reduced number of inhibitory ganglions cells; decreased amplitude in the mid-esophagus; increased tone and incomplete relaxation at the lower spinchter
esophageal stricture - progressive difficulty with solid food; long history of GERD, decreased LES
schleroderma - decreased LES tone, GERD, impaired motility
esophageal spasm - multiple contractions in mid to low esophagus
NSAID-associated chronic renal injury
chronic interstitial nephritis and papillary necrosis; nsaids collect in the medulla and are thought to cause glutathione depletion with subsequent lipid peroxidation
also decrease PGE synthesis causing constriction of medullary vasa recta leading to ischemic papillary necrosis
calcifications may be present
cell layers of the stomach
mucosa - most superficial
upper glandular - oxyntic parietal cells that make acid and intrinsic factor
lower glandular - basophilic chief cells that secrete pepsinogen
muscularis mucosa
submucosa
ethercept
inhibits TNF alpha activity by competitively binding to to it and preventing its interaction with the cell surface receptor
Intracellular organisms
chlamydia legionella listeria mycobacterium neisseria meningitis nocardia rickettsia salmonella typhi
cryptococcus neoformans
histoplasma
pneumocystis
plasmodium
toxoplasma
diarrhea that can be acquired from domestic animals
Campylobacter
hormone-sensitive lipase
found in adipose tissue; responsible for the synthesis of free fatty acids and glycerol; provides substrate for gluconeogenesis and ketone body formation
contra-indicated in Prinzmetal’s angina (elevated ST segments)?
triptans and dihydroergotamine
How to treat cyanide toxicity from nitroprusside overdosage
- sodium nitrate to form methemoglobin
- hydroxycobalamin to bind to cyanide
- sodium thiosulfate as a detoxifying sulfur donor
Hospice care
Less than 6 months to live
etoposide/podophyllin mech of action
irinotecan
inhibits sealing activity of DNA topoisomerase II; usually the enzyme causes causes double-stranded nicks
inhibits topoisomerase I which causes single-stranded nicks
what can cause elevated creatine kinase?
muscle weakness without increase in CK?
statin therapy, myositis, HYPOTHYROIDISM, muscular dystrophies
cushings, polymyalgia rheumatica
hibernating myocardium
ischemic preconditioning
LV systolic dysfunction due to reduced coronary blood flow at rest that is partially or completely reversible by coronary revascularization
repetitive episodes of angina prior to MI can delay cell death after complete coronary occlusion
Cryptococcus
round, oval budding yeast
Dengue virus
the first infection can cause a self-limited disease in adults; secondary infection is from a different serotype with a more serious presentation (4 serotypes)
Commonly used clinical disinfectants
DO NOT KILL SPORES
alcohol - disrupts cell membrane, protein denaturing
chlorhexidine - disrupts cell membrane, cytoplasm coagulation
KILLS SPORES
H2O2 - free radicals that oxidize cell components
iodine - halogenates things
septic abortion caused by which organisms?
infection of products of pregnancy - Staph aureus and gram negative rods
BUMETANIDE behaves like what?
furosemide
medicines associated with osteoporotic fractures?
anticonvulsants that induce Cp450 (increase vitamin D catabolism) - phenytoin, phenobarbital, carbamazepine
aromatase inhibitors, medroxyprogesterone, GnRHs analogs (decrease estrogen)
PPIs (decrease calcium absorption)
corticosteroids, heparin (decrease bone formation)
side effects of methotrexate?
inhibition of rapidly growing tissues - oral and GI mucosa (ulcers), bone marrow (pancytopenia), hepatotoxicity
DILI caused by?
slow ACETYLATORS
EPTI-FIBA-TIDE and TIRO-FIBAN
block IIb/IIIa receptors on platelets
cyclophosphamide with what?
mesna; hemorrhagic cystitis is caused by urinary excretion of the toxic metabolite acrolein; mesna binds acrolein in the urine
First-line for ventricular arrythmias (especially in ischemic myocardial tissue)
class 1B
amiodarone is first choice
maintenance dose
(plasma steady state * clearance)/1
calcification on CT around heart
constrictive pericarditis
differential clubbing and cyanosis without blood pressure or pulse discrepancy
PDA with eisenmenger
