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
