step 1 study deck 3

Question 1

where is heme made

Answer 1

in both the cytosol and the mitochondria of RBCs

maturing RBCs lose their ability to synthesize heme when they lose their mitochondria (needed for the first step and the last 3 steps)

heme is synthesized in virtually every organ but the main ones are RBC precursors in the bone marrow and hepatocytes using the CYP450 system

Question 2

how can atrophic gastritis cause anemia (loss of gastric cells, replaced by fibrosis)

Answer 2

causes profound hyper- HCl secretion
inadequate IF production
vit B12 def
elevated methylmalonic acid levels (B12)

causes pernicuous anemia

reticulocyte count increases dramatically once B12 treatment is initiated but hemoglobin and RBC count take up to 8 weeks to normalize

Question 3

what is the most common brain tumor in children

Answer 3

pilocytic astrocytoma

arise in the cerebellum

unlike medulloblastoma (the most common MALIGNANT childhood brain tumor which is solid only and causes hydrocephalus), pilocytic astrocytoma has both cystic and solid components on imaging

Question 4

what are the histology features of:
ependymoma
GBM
medulloblastoma
oligodendroglioma
pilocytic astrocytoma

Answer 4

ependymoma= perivasc psuedorosettes

GBM= pseudopalisading pleomorphic cells with areas of necrosis… GFAP positive

medulloblastoma= homer wright rosettes (cells around a neuropil)

oligodendroglioma= calcified “fried egg” appearance surrounded by a “chicken wire” pattern

pilocytic astrocytoma= GFAP positive hairlike processes with rosenthal fibers (eosinophilic intracytoplasmic inclusions)

Question 5

describe alternative splicing

Answer 5

single gene can code for various proteins by including or excluding exons to make mRNA

this is used by cancer cells to spice out an exon that codes for a transmembrane domain (like Fas- R) converting the protein to a soluble form not expressed on the cell surface and thus allows cells to evade apoptosis

Question 6

describe the blood flow through lung zones 1, 2, and 3

Answer 6

1= doesnt really exist but theoretically there is no blood flow because the high alveolar pressure collapses capillaries… this is the alveolar dead space… but can occur when there is low arterial pressure like in hemorrhage or high alveolar pressure like in positive pressure ventilation

2= pulsatile because venous pressure rises above alveolar pressure during systole which allows to blood to move through

3=continuous blood flow (when a patient is lying supine then technically the whole lung is type 3!)

both V and Q increase from apex to base but perfusion (Q) does so to a greater degree and thus the V/Q ration decreases from apex to base

Question 7

what is impaired that causes megaloblastic anemia

Answer 7

the underlying biochemical feature of megaloblastic anemia is defective DNA synthesis
(“diminished THYMIDINE synthesis”)

in this patient he has anemia (MCV>100), epigastric pain, fatigue, and pancreatic calcifications (we are assuming this is chronic pancreatitis caused by alcohol abuse even though alcohol was not mentioned which causes folic acid def [months] and B12 def [years])

folic acid is needed as a single carbon donor to make purines and pyrimidines and put them in DNA… pancreatic insuff can also lead to B12 def because the pancreatic enzymes are needed to cleave R factor from B12 so it can bind IF and be absorbed

Question 8

where do you see impaired pyruvate decarboxylation

Answer 8

pyruvate dehydrogenase (oxidatively) decarboxylates pyruvate into acetyl coA which then goes into the citric acid cycle

the pyruvate dehydrogenase complex requires thiamine pyrophosphate (TTP) to work
(thiamine=B1)

alcoholics suffer from B1 def and thus impaired pyruvate decarboxylation

Question 9

where do you see intracellular transamination reactions

Answer 9

the first step of AA breakdown is transaminases or aminotransferases

they both require the coenzyme form of vit B6 (pyridoxine) because it is the carrier of the amino group

B6 def causes a hypochromic, microcytic, and sideroblastic anemia

result= you will see low rate of intracellular transamination reactions

Question 10

what is the difference between a localized carcinoid tumor and a metastatic carcinoid tumor

Answer 10

local= would not cause the symptoms seen in carcinoid syndrome because the localized tumor would be behind the liver and the liver has MAO which breaks down the serotonin released by the tumor before getting into systemic circulation (aka its metabolized by first pass metabolism)… the lungs also have MAO and thats why carcinoid problems dont affect the left heart

metastatic= extra-intestinal metastasis are required to produce symptoms

symptoms: flushing, diarrhea, bronchospasm
dx: elevated urine 5HIAA
tx: octreotide for symptomatic patients and surgery for liver mets

carcinoid tumors come from enterochromaffin (endocrine) cells in the small intestine, they produce SEROTONIN, bradykinin, and prostaglandins,…

Question 11

an enveloped RNA virus from animals can now infect humans, which virally encoded protein mutated?

Answer 11

surface glycoprotein

who a virus can infect is based on viral surface proteins and if they can mind host plasma receptors

a mutation in the viral encoded envelope glycoprotein can dramatically affect the range of host cells the virus can attach to or infect

ex= hemagluttanin mut in influenza A that confers a new binding affinity for the neuraminic acid containing glycoprotein on the surface of human nose epithelial cells and can now infect humans

Question 12

give a couple examples of DNA methylation and diseases

Answer 12

DNA methylation changes gene expression without altering genetic code

methylation of:

cytosine guanine dinucleotide repeats (CpGs) in the promotor regions = silencing of those genes by not transcribing them

Fragile X= X linked dominant disorder of increased CGG trinucleotide repeats on the fragile X mental retardation 1 gene (FMR1) leading to hypermethylation of cytosine residues and FMR1 inactivation
(CGG= Congenital Giant Gonads… also large jaw and large ears)

Cytosine methylation is also used in genetic imprinting
(PWS and Angelmans)

methylation= silencing

Question 13

what is epistasis and pleiotropy

Answer 13

epistasis= the allele of one gene affects the phenotypic expression of alleles in another gene

pleiotropy= single gene influences multiple phenotypic traits

Question 14

what are the pulm function test results for COPD

Answer 14

TLC increased
(vvv)FEV1/(v)FVC is decreased
FVC decreased
RV is increased

in COPD you would also expect to see increased erythropoietin production (EPO) due to hypoxia that stimulates the cortical cells of the kidney

Question 15

what does this patient have?
1 yo African American boy
severe swelling and tenderness to hands and feet (very painful)
older brother died of pneumococcal sepsis at age 6yo

Answer 15

he has sickle cell disease (SCD)
AR

you know this because:
1. hemolysis (intravasc and extravasc)- you will detect increased indirect unconj bilirubin, lactate, and decreased haptoglobin (binds free hgb)

2. vasoocclusion (patient’s dactylitis- hand foot syndrome- which results from small infarctions in the bones of the extremities) this is common in SCD patients in the first few years of life since the affected bones still contain hematopoietic bone marrlow
   pain crises/acute chest/leg

ulceration/priaprism(painful erections)/autosplenectomy/and stroke occurs in older kids and adults

3. infections (infections with encapsulated organisms, aka strep pneumo, which killed his brother because of his brother’s functional asplenia)

Question 16

what causes hereditary angioedema

Answer 16

rare AD disorder
causes painless swelling to the lips, face, larynx, and extremities

caused by a C1 inhibitor def

Question 17

what causes a left or right shift in the oxygen hemoglobin dissociation curve

Answer 17

left= (increased affinity to oxygen and thus less oxygen being unloaded to tissues)
decreased H+ (aka increased pH)
decreased 2,3 BPG
decreased temp (hypothermia)

right=
increased H+ (aka decreased pH)
increased 2,3 BPG
increased temp

Question 18

what is familial erythrocytosis

Answer 18

high RBC mass
due to mutation in the beta globin
causes reduced binding of 2,3 BPG (similar to how fetal hemoglobin doesnt bind 2,3BPG well because of its serine residue instead of histadine)

2,3 BPG normally forms ionic bonds with the beta subunits of deoxygenated Hgb A facilitating oxygen release to tissues
mutations that lose this binding pocket’s positive charge causes Hgb A to look like HgF which binds oxygen with a higher affinity because it cant interact with 2,3 BPG

Question 19

what are beta globin tetramers and gamma globin tetramers called

Answer 19

beta tetramer= Hgb H

gamma tetramers= Barts

these are alpha thalassemia findings and have extremely high oxygen affinity (resembling myoglobin) and are ineffective at delivering oxygen to tissues

Question 20

what is the differences between prokaryotic and eukaryotic DNA replication

Answer 20

prok=
3 major DNA pol (1,2,3)
circular DNA
single origin of replication

euk=
5 major DNA pol (alpha, beta, gamma, delta, epsilon)
larger more complex genome
introns and extrons
linear DNA
multiple origins of replication (allows for quick replication)

Question 21

why do you give vit A to kids with measles

Answer 21

measles= fever, cough, congestion, conjunctivitis, and maculopapular rash "koplik spots" (face/hairline --> neck/trunk-->extremities)
highly contagious paramyxovirus spread via resp droplets or contact
vaccine preventable (*child in question was unvaccinated)

supplement with vit A (esp if def) because measles depletes the vit A stores [and can cause keratitis (corneal inflamm) and corneal ulceration] and vit A supplement can help prevent these complications

vit A also decreases risk of other comorbidities (like pnu, encephalitis), recovery time, and length of hospital stay

Question 22

what are caused by def in:

vit B6 (pyridoxine)
vit B12 (cobalamin)
vit D
vit E
vit K

Answer 22

vit B6 def= oral findings (stomatitis-oral ulcers, cheilosis-cracks at the corners of the mouth)… B6 can be given theraputically to decrease ADRs of isoniazid and to decrease homocysteine levels)

B12 def= macrocytic anemia, hypersegmented neutrophils, neurologic signs (paresthesias)… found only in animal products, vegans are at risk

D def= bone problems (rickets-bone softening, osteomalacia-bone softening)

E def= hemolytic anemia and neurologic abnormalities (ataxia)

K def= easy bleeding

Question 23

what do these surface markers correlate to?
CD4
CD7
CD8
CD14
CD20

Answer 23

CD4= T helper cells

CD7= (multi chain complex) T cell marker

CD8= cytotoxic T cells

CD14= monocyte macrophage cell

CD20= B cell marker…. monoclonal ab’s against CD-20 (aka rituximag) have been successful in treating lymphomas

Question 24

Describe SCID

Answer 24

defective T cells (development ) and B cells (dysfunction)
x linked or AR

infections with viruses, fungi, and opportunistic infections (PJ pnu) = T cell loss

sinopulmonary and bacterial infections like pnu and otitis media = B cell dysf due to no Th cells

SCID babies get infections, chronic diarrhea, and failure to thrive
its on the newborn screen
labs= low lymphocytes, low immunoglobulins
tx= stem cell transplant

differential dx= HIV infection

Question 25

what cells are directly involved in a delayed type hypersensitivity reaction (type 4)

Answer 25

CD4+ T helper cells macrophages CD8+ cytotoxic cells B cells are only needed in type 2 reactions [ex= drug induced hemolytic anemia] and type 3 reactions [ex= serum sickness] anergy (failure of normal immune response) to candida Ag is typical of SCID patients

Question 26

what does the pulomary function test results look like for normal aging

Answer 26

TLC unchanged FVC decreased RV increased Patients >35 yo have steady decrease in chest wall compliance due to rib calcification (causing stiffening) and increased thoracic curvature (due to osteoporosis and osteoarthritis) lung compliance increases due to loss of elastic recoil in alveolar ducts (homogenous dilation of the ducts, not due to destruction) decrease in chest wall compliance, increase in lung compliance (increases RV... which because of the unchanged lung capacity, the FVC will decrease) TLC unchanged because the decreased chest wall compliance counterbalances the increased lung compliance in aging you also have decreased FEV1 and diffusing capacity

Question 27

``` this patient has what? 23 yo African American female fatigue nodular rash to the legs cxr with lung nodules and hilar fullness biopsy shows large epithelioid cells, occasional giant cells, and no focal necrosis ```

Answer 27

Sarcoidosis! young black woman with non specific complaints and weight loss inflamm disease, unknown etiology causes non caseating granulomas (made of epithelioid cells= activated macrophages) and multinucleated giant cells with chronic granulomatous inflammation mostly involves the lungs> skin (painful erythema nodosum) cxr= diagnosis stage 1= bilateral hilar LAD stage 2= + pulm infiltrates in the upper lobes stage 3= lung infiltrates only (disease progression leads to dissapearance of the hilar LAD) stage 4= lung fibrosis

Question 28

what is the brief description of how these present: Granulomatosis with polyangiitis (Wegner's) Dermatomyositis SLE Low grade NHL

Answer 28

Wegners= systemic vasculitis of small and medium arteries causes symptoms to URT, lungs(hemoptysis), and kidneys +cANCA Dermatomyositis= autoimmune disorder causes proximal muscle weakness and skin problems (purple eyelids -"helitrope rash", purple scaley knuckles- "gottron's sign") high CPK levels SLE= young woman with butterfly malar rash, sensitivity to light, malaise, anorexia, joint pain NHL= middle aged and elderly constitutional symptoms plus lymph node enlargement biopsy of lymph nodes= atypical lymphocyte proliferation

Question 29

people with chronic granulomatous disease get what type of infections

Answer 29

due to inactivating mutation of NADPH oxidase that fucks up intracellular killing (the normal oxidants theyre missing also activate granule proteases like elastase and cathepsin G that destroy engulfed pathogens) they get **catalase + bacteria and fungal infections** (ex= berkholderia cepacia) causes granuloma formation diffusely dx= measure neutrophil superoxide production (flow cytometry>NBT testing) phagocytes have a backup to NADPH oxidase, and that is most bugs allow for their own hydrogen peroxide waste to accumulate which the phagocyte uses to make hyperchlorite to kill the bug. BUT catalase positive bugs destroy their own hydrogen peroxide and so phagocytes have no other method to attack them ``` catalase + organisms that destroy their hydrogen peroxide: CGD has No BASS in their cat band No= Nocardia B= Burkholderia cepacia A= Aspergillus S=Staph aureus S= Serratia marcescens ```

Question 30

what does this patient likely have? new onset back pain without trauma straining to urinate osteoblastic lesions to the lumbar spine

Answer 30

prostate cancer with metastasis to the bone (PCa disseminates in the blood and affects regional lymph nodes>liver>lung>skeleton) cancers of the pelvis (including the prostate) spread to the lumbosacral spine via the vertebral venous plexus (VVP) [this runs up the entire spinal column and allows for bidirectional flow/regulation of ICP]... hence mets to the brain --> VVP communicates with a number of veous networks including the **prostatic venous plexus** (venous blood from the prostate, penis, and bladder) the skeletal system is a common site for mets due to hematogenous seeding

Question 31

how do exposures to these present: asbestos beryllium coal dust organic dust silica

Answer 31

asbestos= interstitial lung pattern in lower lungs pleural plaques ferruginous bodies fusiform rods with translucent asbestos center and iron containing coating beryllium= ill defined nodular or irregular opacities non caseating epitheloid granulomas with NO obvious associated particles coal dust= nodular interstitial opacities exertional SOB accumulations of coal dust laden macrophages (coal macules) organic dust= hypersensitivity pneumonitis exertional SOB diffuse nodular interstitial infiltrates non caseating granulomas silica= asymptomatic or exertional SOB productive cough calcification of the rim of hilar nodes (eggshell calcification biregringent silica surrounded by fibrous tissue symptoms 10-20 years s/p exposure

Question 32

what is the difference between infectious mononucleosis (IM) caused by EBV vs CMV

Answer 32

EBV= + serum heterophile antibodies (agglutinate with RBCs of other species- ie horse RBCs in the monospot test and sheep RBCs in the Paul Bunnell test) monospot may be negative earlier on but will be positive later classically has sore throat and LAD too CMV= - heterophile ab "mono like syndrome" can be acquired during transfusion of WBC laden blood products (because CMV infects neutrophils and macrophages)... reduce this with irradiation negative for monospot test or paul bunnel test other options of IM like syndrome causes= HHV6, HIV, and toxoplasmosis

Question 33

what do these viruses typically cause? coxsackie A Acute hep C JC virus parvo B19

Answer 33

coxsackie A= viral meningitis and mouth blisters (grey mouth ulcers) in children acute hep c= rarely causes symptoms... transfusion acquired hep c virus causes chronic hepatitis but we have great blood donor screening now JC virus= progressive multifocal leukoencaphalopathy (PML) in immunosuppr (hemiparesis, vision deficits-hemianopsia, cognitive impairment) Parvo B19= erythema infectiosum red flushed "slapped cheeks" aplastic crisis in patients with SCD hydrops fetalis in fetus

Question 34

what problem most commonly follows a post strep GAS impetigo infection

Answer 34

``` PSGN 1-2 weeks later presents with: facial swelling dark cola colored urine HTN bloody urine nephritic symptoms red blood cell cases in urine (damage= immune complexes and complement) ``` not preventable with abx ARF follows GAS pharyngitis not impetigo PSGN can occur after GAS pharyngitis OR impetigo

Question 35

what immune response do you get from the influenza vaccine

Answer 35

inactivated (killed) vaccine via injection live attenuated vaccine by nasal spray each season it has Ag (or attenuated virions) from 3-4 influenza A and B strains the inactivated version induces neutralizing antibodies against the hemagglutinin Ag when exposed to the virus through natural infection, these Ab's inhibit the hemagglutinin from binding the host cell membrane receptors (which is how they enter the cells in endocytosis) thus the influenza vaccine prevents viral entry into host cells side note= inactivated killed vaccines generate humoral response, not cell mediated live attenuated vaccines cause cell mediated response as well as humoral immunity also: neuraminidase on influenza cleaves sialic acid residues on glycoconjugate receptors to allow release and spread of virus oseltamivir = sialic acid analog that competitively inhibits influenza neuraminidase and prevents release of virus

Question 36

what is mucormycosis

Answer 36

an opportunistic infection caused by: rhizopus mucor absidia causes: paranasal sinus problems (face pain, eye pain, headache, nose dx) in a DM or immunosuppr patient the fungi form broad non septate hyphae that branch at right angles (on blood vessel walls) ``` tx= surgical debridement of necrotic tissue amphotericin B (antifungal) ``` side note= if this branched at 45 degree angles ("V" shaped branching) and was septate hyphae it would be invasive aspergillosis

Question 37

what is the differential diagnosis of vaginitis

Answer 37

1. bacterial garnerella = thin, off white discharge *fishy odor* no inflammation pH >4.5 clue cells (*epithelial cells covered in gram variable rods*) positive whiff test (amine odor with KOH) tx= metronidazole or clindamycin you dont have to treat male partner because theyre asymptomatic and treatment wont affect their recovery, treat this patient only if she is symptomatic ``` 2. trichomoniasis = thin yellow green dx smelly frothy dx vaginal inflammation pH >4.5 motile trichomonads ("pear shaped organisms") tx= metronidazole treat her sexual partner ``` ``` 3. candida = thick "cottage cheese" dx vaginal inflammation normal pH (3.8-4.5) pseudohyphae ex= fluconazole ``` side note= normal vaginal dx is epithelial cells with rare WBCs (leukorrhea)

Question 38

what is the pathologic process of ARDS

Answer 38

fluid accumulation in the alveolar spaces in this case her ARDS was caused by sepsis likely from pyelonephritis/urosepsis (can also be caused by pulmonary infections, trauma) ARDS: (first 24 hours of risk factor) fever hemodynamic instability rapid RR in sepsis, cytokines (TNF, IL1, IL6, IL8)activate the pulm epithelium which calls in neutrophils and causes capillary damage and leakage of fluid and protein into alveolar spaces worry that ARDS may turn into aspiration or DIC

Question 39

describe hepatitis E

Answer 39

*un-enveloped ssRNA virus* fecal oral spread causes a high mortality rate in pregnant women disease is usually self limited and is not associated with a chronic or carrier state dx= HEV Ag or HEV RNA detected in stool or liver later on can detect serum transaminases (liver markers) and IgM anti HEV titers side note: hep A/E= fecal oral transmission Hep B/C/D= parenterally transmitted ( D is Dependent on hep B to infect).... hep B/C associated with hepatocellular carcinoma

Question 40

``` what does this kid have? 4yo M high fever nasal discharge cough recent travel to mexico conjunctival injection bilaterally several white spots with a red base inside the mouth no vaccines ```

Answer 40

measles virus (rubeola) enveloped nonsegmented negative sense RNA virus of parayxoviridae family highly contagious airborne or person to person transmission those are koplic spots inside the mouth* soon to follow will be *maculopapular rash* (face out to extremities) he didnt get the MMR vaccine (live attenuated) side note= hep A= jaundice mumps=parotid swelling, orchitis, meningitis pertussis=whooping cough, gram neg bordetella epiglottitis= h flu, gram neg, encapsulated diffuse vesicular rash of different stages=chickepox (VZV) dsDNA enveloped rotavirus= ds RNA watery diarrhea, dehydration, death

Question 41

what two diseases are transmitted by the Ixodes tick

Answer 41

1. babesiosis (babesia microti) =fever, low platelets, hemolytic anemia (high indirect unconjugated bilirubin, high lactate, low haptoglobin), abnormal liver tests, intra-RBC influclusions (ring shaped and "maltese cross" forms) increased risk for severe infection when they dont have a spleen (can manifest as ARDS!) 2. lyme disease (*borrelia burgdorferi) coinfection is common, they occur in similar geographic regions (consider coinfection when they present with babesiosis in regions endemic for lyme disease and they dont get better with treatment) Ixodes is the vector for human granulocytic anaplasmosis

Question 42

how do dengue fever and malaria present

Answer 42

acute febrile illness tropical regions malaria= intravasc hemolysis anemia abnormal LFTs blood smear with ring shaped (not cross shaped) erythrocyte inclusions

Question 43

what vaccines are given to asplenic patients

Answer 43

ones to protect from encapsulated organisms strep pneumo h flu neisseria meningitidis

Question 44

what infection is found in the Ohio and Mississippi River and is associated with bird or bat droppings

Answer 44

histoplasmosis (fungal infection)

Question 45

what bug causes meningitis resistant to cefotaxime | 3rd gen cephalosporin

Answer 45

``` Listeria monocytogenes (gram + rod, intravellular organism, killed by T cell immunity [immature in infants]) Though listeria IS susceptible to ampicillin, thus ampicillin is added to the empiric treatment of meningitis in young infants or immunosuppr ``` cephalosporin resistant organisms: Listeria, MRSA, Enterococci = bc theyre resistant to PBPs atypicals (mycoplasma, chlamydia)= bc they have no cell wall side note= dont forget that all the strep species are susceptible to penicillins and cephalosporins

Question 46

how does a urethral injury present in a male

Answer 46

inability to void full bladder sensation high riding boggy prostate (hematoma below the gland) blood at urethral meatus posterior urethra injury= pelvic fracture (posterior is above the bulb of the penis) posterior= prostatic and membranous [right below prostate] *membranous urethra is relatively unsupported by the adjacent tissues and is the weakest portion of the posterior urethra* pelvic trauma will disrupt the posterior urethra at the bulbomembranous junction prostatic urtehra is supported by the surrounding prostate anterior urethra injury= straddle injuries [where the perineum is struck forcefully such as falling on a crossbar of a bicycle or the top of a fence] (anterior is within the bulb and the remainder of the corpus spongiosum) anterior= bulbous and penile penile urethra is the most commonly injured due to penetrating trauma or instrumentation if urethral injury is suspected, foley catheter placement is contraindicated, it can worsen injury retrograde urethrogram should be done to asses urethral integrity

Question 47

if babies acquire HPV from their mom, where does it infect

Answer 47

HPV in mom (verrucous skin colored genital warts, mild itching, no pain)= "condylomata acuminatum", HPV 6 and 11 it will infect the baby's *true vocal cords* HPV is a small DNA virus that infects stratified squamous epithelium (stratified squamous is found where there is frequent friction [because deeper cells can replace surface cells that are damage] such as: true vocal cords-only place in resp tract with this cell type vagina cervix anus) infants get HPV from mom through the birth canal they can get resp papillomatosis (warty growths on the true vocal cords cause weak cry, hoarseness, and stridor)

Question 48

``` what does this patient have? 25 yo F join pain in hands and proximal fingers bilaterally for months low platelets proteinuria RBC casts in urine ```

Answer 48

SLE she will also probably have: (African American female of childbearing age) constitutional symptoms joint pain butterfly rash and photosensitivity serositis (pleurisy, pericarditis, peritonitis) thrombus events (due to vasculitis and antiphospholipid ab's)- type 2 hypersensitivity response seizures ``` pancytopenia: hemolytic anemia (warm IgG ab's against RBCs- spherocytes, positive direct coombs test, extravasc hemolysis) low platelets (due to ab's... same as idiopathic thrombocytopenic purpura) low WBCs (ab mediated destruction) ``` low complement ANA ab's (sensitive) Anti-dsDNA and anti-Smith (specific) kidney involvement (type 3 hypersensitivity response... most commonly causes diffuse proliferative glomerulonephritis- RBC casts)

Question 49

how does ankylosing spondylitis present

Answer 49

chronic inflammatory arthritis of the spinal and sacroiliac joints presents with low back pain associated with inflamm where tendon inserts onto bone, painful sausage fingers, eye pain/blurriness

Question 50

how does fetal circulation differ from adult circulation

Answer 50

oxygenated blood goes to the fetus via the umbilical vein (highest oxygen content) the ligamentum teres is the remnant of the umbilical vein in the adult the umbilical vein blood first goes to the liver where it bypasses the hepatic circulation via the ductus venosis and enters the IVC (remnant of the ductus venosis is the ligamentum venosum) from the IVC, the blood is sent to the heart where it is either pumped into the pulmonary circulation or it crosses directly from the right heart to the left heart via the foramen ovale some of the blood sent to the pulmonary circulation may bypass the lungs via the ductus arteriosis and pass directly into the descending aorta (remnant of the ductus arteriosus is the ligamentum arteriosum) from the aorta the blood cirulates to all of the fetus deoxygenated blood returns to the placenta via the umbilical arteries which comes off the internal iliac arteries (remnant is the medial umbilical ligaments) side note= the superior vena cava doesnt participate in circulaiton, it only returns deoxy blood from the fetal head and upper extremities

Question 51

describe the development of different hemoglobins of a baby in utero

Answer 51

Hgb formation begins within a few weeks of conception 1st hgb= embyronic hemoglobin (Gower) which is 2 zeta 2 epsilon and is made by the embryonic yolk sac within a few weeks= fetal hemoglobin (hgb F) which is two alpha and two gamma (this will last into the first few weeks of post natal life and gets gradually replaced with Hgb A starting in the 9th month of gestation) thalassemias are hereditary hemolytic anemias due to defective globin chain synthesis beta thal minor= one gene mutation (lack significant anemia) beta thal major= both genes mutated (severe anemia, lack of beta chains causes alpha tetromers and premature lysis of RBCs... beta thal doesnt become symptomatic when you have alpha tetromers, aka when you run out of gamma chains from HgbF) beta thalassemia = greek immigrant parents, healthy at birth, but by 6 months old develops transfusion dependent anemia because RBCs contain insoluble aggregates of hgb subunits

Question 52

which bug is lactose fermenting, indole positive GNR

Answer 52

E coli most common cause of UTI in elderly women indole positive= ability to convert tryptophan to indole (this distinguishes e coli from enterobacter) lactose fermenting= will show up as pink colonies on MacConkey agar

Question 53

how do you differentiate between reactive hyperplasia and malignancy in a lymph node

Answer 53

reactive hyperplasia= benign reversible enlargement due to antigen stimulus follicular hyperplasia- follicles increase in size and number sinus hyperplasia- when sinuses enlarge and fill with histiocytes (stationary phagocytic cell) diffuse hyperplasia- nodal architecture is diffusely effaced by sheets of lymphocytes, immunoblasts, and macrophages described as: - polyclonal, prolif of many different cell types - pleomorphism, increased mitosis, nuclear changes malignancy= aka lymphoma distorted or effaced architecture via the proliferation of malignant cells (greater extent than seen in reactive hyperplasia) this may be follicular or diffuse described as: - **monoclonal transformation from unchecked proliferation (the clonality of a T cell population is assessed via PCR to examine the T cell Receptor rearrangement of genes)** if a single allele for the V region for the TCR predominates in a lymphocytic population= malignancy if there is a monoclonal rearrangment of genes for immunoglobulin variable regions that suggests a B cell lymphoma *key point here is that cancer= monoclonal origin side note= genetic analysis of reed sternberg cells of HL most often reveals monoclonal characteristics

Question 54

what viruses can do genetic shift

Answer 54

genetic shift= reassortment of the genome (combining animal and human strains to infect both species, commonly seen in influenza) these cause pandemics/epidemics esp if they dramatically alter the viral surface glycoproteins (like hemagglutanin) influenza can do this because they have segmented genomes rotavirus also has a segmented genome and can do this ``` segmented genomes: *orthomyxoviruses [influenza] *reoviruses [rotavirus] bunyaviruses [hantavirus] arenaviruses [choriomeningitis virus] ```

Question 55

what abx do you use to treat aspiration pneumonia in an alcoholic

Answer 55

clindamycin ``` aspiration pnu= infection with oral flora most common anaerobic oral flora: -bacteroides -prevotella -fusobacterium -peptostreptococcus (mixed with aerobic bacteria) ``` this can result in necrotizing infections and abscesses best option= clindamycin (inhibits the 50S subunit and fucks up protein synthesis) this one is the most coverage against anaerones and gram positive strep pneumo (just incase there is a component of CAP becaust strep pneumo is the most common cause) ``` bacteriostatic covers MRSA great for aspiration pnu treats gangrene and acne treats endometritis add an aminoglycoside for broad coverage (gentamycin) treats garnerella vaginitis causes c diff diarrhea ``` side note= vanco doesnt cover anaerobes cipro and cefazolin suck at covering anaerobes metronidazole is a great drug for anaerobes but doesnt cover aerobes (and you would need to cover your butt by treating for strep pneumo also when treating an aspiration pnu lung abscess just incase)

Question 56

what are the PaO2, SaO2, and oxygen content patterns for the following? CO poisoning cyanide poisoning anemia (decreased hgb) polycythemia (increased hgb) high altitude

Answer 56

CO poisoning= normal PaO2, decreased SaO2, decreased oxygen content cyanide poisoning= normal PaO2, normal SaO2, normal oxygen content (cyanide inhibits cellular oxidative phosphorylation by inhibiting the iron (Fe3+) in cytochrome c oxidase which lowers the peripheral oxygen consumption)... venous oxygen content will rise... cyanide will also bind the ferrous Fe2+ iron in hemoglobin and form cyanohemoglobin (but not in large enough amounts to change arterial oxygen content) anemia= normal PaO2, normal SaO2, decreased oxygen content (because lower hgb conc)... commonly due to menstration blood loss in premenopausal women polycythemia= normal PaO2, normal SaO2, increased oxygen content high altitude= decreased PaO2, decreased SaO2, decreased oxygen content (Bohr-Haldane effect- the high altitude reduces alveoloar tension and discupts gas exchange at the alveolar capillary interface... this is a right shift which reduces the affinity of oxygen for hgb and can lower SaO2) side note= obesity alveolar hypoventilation is due to reduced chest wall compliance (they have increased lower lobe perfusion causing a V/Q mismatch)... these people have low PaO2 (hypoxemia), low SaO2, and high CO2

Question 57

which bug is causing this? nosocomial pnu visualized with silver stain slow growth on buffered charcoal yeast (supplemented with L-cysteine and iron)

Answer 57

legionella pnu intracellular motile rod faintly stains with gram stain (neutrophils with few or no organisms) silver stain used to visualize cultured on buffered charcoal yeast extract (BCYE) agar supplemented with L-cysteine and iron diagnosis also via urine antigen test legionella commonly contaminates water (think of recent travel or nosocomial) and can get aerosolized *(nosocomial colonization of the hospital water system) increases susceptibility in smokers and lung disease patients causes fever, bradycardia, headache, watery diarrhea causes hyponatremia side note= colonization of hospital staff noses = MRSA poor isolation of patients= c diff, MRSA, VRE widespread abx= resistance widespread IV devices= bacteremia and sepsis

Question 58

what is the surface receptor blocked by a monoclonal ab which targets a specific cell surface receptor found on T cells this surface receptor is used to facilitate destruction of cancer cells by T cells capable of recognizing tumor Ag's

Answer 58

PD-1 cancer immunotherapy: anti- PD1 and anti- CTLA-4 ab's PD-1 = programmed death receptor 1 is expressed on the surface of activate T cells the tumor's ligand (PD-L1) binds and downregulates the cytotoxic T cell response against tumor cells (aka evading destruction by T cells) by giving anti-PD1 and anti-CDLA4 abs, those receptors get blocked and cannot be hijacked by the tumor and thus the T cells stay activated and destroy the tumor cell many cancers use this method to evade the immune system anti-PD1 therapy is useful in treating: advanced melanoma certain lung cancers side note= chemokine coreceptor 5 (CCR5) is used by HIV to bind CD4+ ... CCR5 blockers have been developed to manage HIV patients... CCR5 also promotes the CD4+ T cell anti tumor responses so an ab blocking CCR5 may down regulate the immune mediated tumor desctruction (which is bad!)... CD19 is on B cells CD28 T cell surface protein that interacts with B7 on APCs which provides the costimulatory signal necessary for T cell activation (ab's blocking CD28 without inhibit T cell activation... CTLA-4 can bind B7 and inhibit T cells)

Question 59

which toxin acts similar to diphtheria toxin

Answer 59

resp diphtheria (severe pharyngitis with exudate, neck swelling=cervical LAD, unknown vaccination status bc theyre immigrants) diptheria toxin causes severe myocarditis and heart failure (happened to one of the patients in the vignette) diptheria toxin acts like virulence factor exotoxin A (pseudomonas)... exotoxin A is associated with the high mortality of pseudomonas septicemia ``` psuedomonas makes extracellular products including: exotoxin A collagenase elastase fibrinolysin phospholipase C DNAse ``` these help pseudomonas invade and disseminate diptheria and exotoxin A both ribosylate and inactivate elongation factor 1 (EF2), halting the human cell protein synthesis and causing cell death

Question 60

what bug do each of these toxins belong to and what do they do: diptheria toxin exotoxin A enterotoxin TSS toxin cytotoxin B botulinum toxin pertussis toxin cholera toxin

Answer 60

diptheria toxin= Corynebacterium diphtheriae >inactivates EF2 via ribosylation >thus inhibits host protein synthesis exotoxin A= pseudomonas aeruginosa >inactivates EF2 via ribosylation >thus inhibits host protein synthesis enterotoxin = staph aureus >superantigen >acts locally in GI tract to cause vomiting TSS toxin = staph aureus > superantigen > stimulates T cells leading to widespread cytokine release and shock cytotoxin B= clostridium difficile >causes actin depolymerization >leads to mucosal cell death/necrosis in colon >forms pseudomembranes botulinum toxin = clostridium botulinum >blocks presynaptic release of Ach at NMJ >flaccid paralysis (descending, starting from cranial nerves) >cleaves SNARE ``` pertussis toxin= bordatella pertusis > ribosylates Gi ADP > disinhibits adenylate cyclase > increases cAMP >increased histamine sensitivity and phagocyte disfunction ``` ``` cholera toxin= vibrio cholerae >ribosylates Gs ADP > activates adenylate cyclase >increases cAMP >causes secretory diarrhea, dehydration, electrolyte imbalance ```

Question 61

where to T cells live in lymph nodes

Answer 61

in the paracortex region (thats where T cells and dendritic cells live) the paracortex is internal to the cortex, between follicles and medulla in DiGeorge syndrome, this region is poorly developed because they lack mature T cells (maldevelopment of the 3rd and 4th pharyngeal pouch derivatives leads to absent thymus and no mature T cells) >predisposed to recurrent infections by viruses, fungus, protozoan, and intracellular bacteria a normal paracortex region becomes enlarged when T cells proliferate when theyre fighting a viral infection for example side note: follicles= B cells life here and proliferate here primary follicles = dense and dormant secondary follicles = pale germinal center with proliferating B cells and dendrite cells (in agammaglobulinemia, there are no B cells and thus you dont form the germinal centers or primary follicles) medulla= medullary cords and sinuses (cords= B cells, plasma cells, macrophages..... sinuses= reticular cells [supportive cell/fibroblast that makes collagen] and macrophages) subcapsular sinuses = between the capsule and the cortex... its in direct communication with lymph vessels and cortical sinuses.

Question 62

``` which bug and which virulence factor? UTI culture growing colonies of motile GNR green metalic sheen on eosin methylene blue (EMB) agar hemolysis on blood agar ```

Answer 62

e coli fibrial antigen aka fimbriae/pili/type 1 fibriae/P fimbriae/S fimbriae (used for adhesion to uroepithelium in UTIs) Ecoli= motile GNR, facultative anaerobe, lactose and glucose fermenter, grows well on blood/MacConkey/and EMB agar EMB is used to isolate enteric pathogens... if they ferment lactose they bind the agar and produce a green metallic sheen E coli causes 80% UTIs, meningitis, and gastroenteritis

Question 63

name the agars and bugs

Answer 63

EMB agar-----Ecoli metallic green hoekten agar-----enterics like shigella and salmonella tellurite agar-----corynebacterium regan lowe medium------bordetella eaton agar------mycoplasma dieterle stain-----syphilis silver stain-----(fungi) legionella, pneumocystis naeglar reaction-----clostridium chocolate blood agar (nonselective)----neisseria (selective =thayer martin/mueller hinton agar) giemsa----chlamydia... also Borrelia, Plasmodium, trypanosomes quellung reaction----klebsiella (all encapsulated bacteria) auramine rhodamine stain----mycobacterium TCBS agar----vibrio warthin starry stain---H.pylori indian ink-----cryptococcus neoformans Tzank smear = herpes or VZV Ziehl-Neelsen = acid-fast organisms Carbolfuscin = acid-fast stain Periodic acid-Schiff stain (PAS)= diagnose Whipple's disease (Tropheryma whippelii) darkfield microscopy = Treponema acid fast stain = mycobacterium

Question 64

what are the virulence factors of ecoli and what do they do

Answer 64

LPS= activate macrophages (which release IL1/IL6/TNF alpha)... cause bacteriemia and septic shock K1 capsular polysaccharide = prevents phagocytosis and complement mediated lysis... causes neonatal meningitis verotoxin (shiga like toxin) = inactives the 60S ribosome, stops protein synthesis, cell death.... causes bloody diarrhea heat stabile/heat labile(unstabile) enterotoxins = promote fluid and electrolyte secretion from intestinal epithelium.... causes watery diarrhea P fimbriae= adhesion to uroepithelium... causes UTIs side note: O antigen = outer membrane of gram neg, extracellular portion of LPS lipid A = part of LPS similar for all enterbacteria (causes septic shock)

Question 65

what does lead poisoning look like on histology

Answer 65

kid eating lead paint chips miners industrial workers battery factory workers symptoms: weakness abdominal pain constipation neuro symptoms if severe (headache, cognitive, peripheral neuropathy) blue "lead lines" at the junction of teeth and gingivae Blood smear: **coarse basophilic stippling on a background of hypochromic microcytic anemia (lead inhibits nucleotidase which results in abnormally degraded ribosomal RNA which causes the basophilic stippling [blue dots throughout the RBC, moreso on edges]) (lead also inhibits delta aminolevulinate dehydratase [ALA dehydratase] which reduces iron incorporation into heme and makes RBCs hypochromic) net defect of iron is decreased hgb synthesis side note: - acute intermittent porphyria is due to autonomic neuropathy and has a normal blood smear because RBC production is unaffected - myeloblasts with auer rods = AML - myelophthisic anemia (immature granulocytes and teardrop RBCs) = NHL that invaded bone marrow

Question 66

``` what bug caused this? 1 month old M winter cough SOB rhinorrhea congestion low grade fever wheezes and rales throughout ```

Answer 66

RSV broncholitis viral bronchiolitis = LRT infection before age 2, most commonly due to RSV can also see hypoxemia, tachypnea, retractions (premie babies can get severe infection leading to apnea and or resp failure) illness peaks at day 3-5, cough lasts for weeks side note: - pertussis= URI with whooping, LCTA - CMV= asymp, fever, pulm, liver, mono like syndrome - mycoplasma pnu= URI, atypical - parainfluenza= croup (laryngotracheobronchitis), "barky" seal like cough and inspiratory stridor - strep pnu=lobar pnu in kids, focal rales

Question 67

what is paroxysmal nocturnal hemoglobinuria (PNH)

Answer 67

complement mediated hemolysis due to a gene mutation in PIGA gene (phosphatidylinositol glycan class A) which helps synthesize the GPI (glycosylphosphatidylinositol) anchor protein. this protein helps attach surface proteins that inactive complement (surface proteins such as CD55 decay accelerating factor and CD59 MAC inhibitory protein) a patient with PNH will have abscence of CD55 and CD59 classic triad: 1. hemolytic anemia (hemoglobinuria) 2. pancytopenia (stem cell injury) 3. thrombosis at atypical sites (*here it was the mesenteric vein, but it can also be hepatic vein, portal vein, or cerebral veins) due to the pro-thrombotic factors released during hemolysis chronic hemolysis can cause iron deposition in the kidney **("hemosiderosis")** this can mess up the proximal tubule, cause scarring, and cortical infarcts... iron deposition and microvasc clots can cause chronic kidney disease side note: - cast nephropathy = multiple myeloma (monoclonal free chain deposition in the kidney) - interstitial nephritis = drugs, infection, systemic problems - membranous glomerulonephritis = SLE, drugs, hepatitis, cancer - minimal change disease= drugs, cancer, allergens

Question 68

what/where drains into the superficial inguinal nodes vs the deep inguinal nodes

Answer 68

superficial inguinal= drains cutaneous lymph from the umbilicus down includes the anus below the dentate line (exception are the glans penis and calf) these nodes are in the femoral triangle area deep inguinal = glans penis and posterior calf skin (popliteal lymph nodes) side note: - bladder and prostate go to iliac nodes - testicles go to abd para aortic (retroperitoneal) nodes - upper rectum go to inferior mesenteric nodes

Question 69

where are heterophile ab's found

Answer 69

its a test used to diagnose an in vivo viral infection EBV infects B cells (causing transformation/immortalization) via oncogenes diagnose EBV via heterophile IgM ab's that react with antigens on horse RBCs (monospot) or sheep RBCs (paul bunnell) its a sensitive and highly specific for EBV (like 100%) side note: - measureing cryoglobulins (cold precipitable proteins containing Ig) = hep C - measuring hemadsorption (hemagglutinins or glycoproteins that have a high affinity for RBCs) = influenza or parainfluenza - papanicolaou test (screens cervical cytology for dysplasia) = HPV - Tzank smear = herpes or VZV (prepared with a wright giemsa stain looking for multinucleated giant cells and intranuclear inclusions)

Question 70

what triggers the neoplastic change from hepatitis B into hepatocellular carcinoma

Answer 70

**viral DNA integration into the host genome hepatocellular carcinoma is highly associated with hep B infection integration of viral DNA into the host genome triggers the neoplastic changes ``` other risk factors for hepatocellular carcinoma (liver mass with high AFP-alpha feto protein): hep C alcoholic cirrhosis aflatoxins hemochromatosis ``` side note: - acute infection = HBsAg (surface glycoprotein)... will disappear when ab is formed - infected hepatocytes with hep B get destroyed by cytotoxic T cells - highly infective= HBeAg - recent or acute infection = HBcAg (core)

Question 71

how do you prevent a PE in a post op patient

Answer 71

low dose heparin (binds anti-thrombin 3) smaller emboli PE causes a wedge shaped hemorrhagic infarct (because of the lung's dual blood supply from pulmonary artery and bronchial arteries) lower lobes> upper lobes side note: - aspirin isnt enough to prevent DVT/PE - aggressive rehydration prevents contrast-induced nephropathy and dehydration - FFP stops hemorrhage in warfarin overdose - breathing exercises help prevent atalectasis

Question 72

where do you see a valine (hydrophobic) substitution for glutamic acid (hydrophilic)

Answer 72

sickle cell disease | its a point mutation in the 6th position of the beta globin chain of hgb

Question 73

what does this patient have? trauma s/p car accident requiring packed RBC transfusion once stable he has tingling sensation in fingers and toes serum calcium is low

Answer 73

this patient has paresthesias due to hypocalcemia **due to calcium chelation by a substance in the transfused blood** prior to storage, whole blood (for transfusion) is mixed with solutions containing citrate anticoagulant (packed RBCs come from this whole blood and also contain citrate) citrate can chelate serum calcium [and magnesium] causing hypocalcemia this is most likely to occur following massive transfusions involving more that 5 or 6 liters of blood (which is the equivalent to total body volume) over 24 hours stored RBCs also gradually lose intracellular postassium to the surrounding solution (potentially causes hyperkalemia)

Question 74

what is the difference between primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC)?

Answer 74

``` Primary Biliary Cirrhosis= middle aged white woman Anti-Mitochondrial ab Bile Ductules destroyed Xanthelesma (yellow plaques on eyelids) ``` ``` 　 Primary Sclerosing Cholangitis= p-ANCA ab Bile duct inflammation Beading Onion Skinning Associated with UC ```

Question 75

during a thoracentesis, inserting a needle along the upper border of the 10th rib at the right mid axillary line puts what structure at risk of injury

Answer 75

right hepatic lobe pleural exudates accumulate in the costodiaphragmatic recess when standing up (the potential space that spans from roughly the 6th-8th rib in the front, the 8th-10th rib on the side, and the 10th-12 rib in the back) thoracentesis should be done: between the 6-8th ribs along the midclavicular line between the 8-10th rib along the midaxillary line between the 10-12th rib along the paravertebral line if the needle is inserted higher than described above it risks lung injury insertion at these correct levels **still risks penetrating abdominal structures (liver injury!) inserting a needle in the inferior margin of a rib poses a risk to the subcostal neurovascular bundle side note: the lower border of the lungs are two intercostal spaces above the pleural border (lung is unlikely to be injured)

Question 76

what is injured with a stab wound (right sided) just above the clavicle between the midclavicular line and the lateral sternal line

Answer 76

lung pleura (apex extends through the superior thoracic aperture into the neck) aka the space between the top ribs on both sides can cause: pneumothorax tension pneumothorax (lungs and mediate to the opposite side of the chest.... the increased pressure in the chest cavity causes decreased venous return to the heart and decreases CO... this causes hypovolemic shock symptoms, absence of breath sounds, and hyperresonance on the affected side) hemothorax treatment= thoracostomy or chest tube

Question 77

what do these serum markers identify? CD 15 CD 16 CD 19

Answer 77

CD15= granulocytes and Reed Sternberg cells (HL) CD16= NK cells, neutrophils, macrophages (its a low affinity Fc receptor) CD 19= pre-B cell (CD 19/CD 20= pre B cell).... (CD19/20/21 = mature B cell) lacking B cells (seen in X linked agammaglobulinemia) also puts you at risk for infection with encapsulated bacteria, viruses, and parasites like giardia because you lack neutralizing ab's

Question 78

what is the time course of TB after getting coughed on

Answer 78

1 week into it the bacteria are proliferating intracellularly it takes 2-4 weeks for macrophages or dendritic cells to present antigen to helper T cells to mount a Th-mediated response after the 2-4 weeks T cells activate macrophages to kill using interferon

Question 79

what do each of these do? IL 1 IL 3 IL 4 IL 5 INF gamma IGF beta

Answer 79

IL 1= macrophages secrete IL 1 to stimulate Th cells to proliferate and secrete lymphokines IL 3= active Th cells secrete IL 3 to tell the bone marrow stem cells to grow and differentiate IL 4= Th2 cells secrete IL 4 and IL 13 to cause B cell class switching into IgE IL 5= Th2 cells also secrete IL 5 to activate eosinophils and make IgA INF gamma= Th1 cells secrete INF gamma to activate macrophages and CD*+ cytotoxic T cells IGF beta = tissue regeneration and repair (made my a ton of different cell types) summary: Th 1 cells = interferon gamma, IL 2, etc = activate macrophages and CD8+ T cells (aka Th1 cells = cell mediated immunity to attack intracellular pathogens and type 4 delayed hypersens reactions) Th2 cells = IL 4, IL 13, IL 5, etc = stimulate B cell ab production (aka Th2 cells = humoral immunity) hypothesis: allergic asthma is Th2>>Th1

Question 80

what is the only fungus that lives intracellularly and causes systemic disease?

Answer 80

histoplasma capsulatum lives in macrophages serious infection that may be fatal only in immunosuppressed patients causes hepatospenomegaly and ulcerations of the tongue when disseminated cxr= pulm infiltrates and hilar LAD (chronic findings may mimic TB) lung biopsy/BM aspirate= oval or round yeasts within macrophages grow hyphae on sabouraud agar (because its a dimorphic fungus) dx= Ag in blood or urine measure anti-histoplasma Ab's

Question 81

what do these fungus look like? aspergillus candida cryptococcus blastomyces coccidioides

Answer 81

aspergillus= monomorphic, mold form only septate hyphae acute angle V shaped branching candida= most freq opportunistic infection extracellular ovoid yeast cells with pseudohyphae cryptococcus= encapsulated yeast causes meningoencephalitis and pulm disease extracellular large polysacch capsule inhibits macrophage phagocytosis blastomyces= round yeasts single broad based buds thich double refractive walls coccidioides= disseminated disease large thick walled spherules containing endospores

Question 82

what are consequences of OSA

Answer 82

*pulmonary hypertension right heart failure systemic HTN arrhythmias, CAD, sudden death transient hypercapnia and hypoxemia causes pulm vasoconstriction, endothelial dysfunction, abnormal venous return and CO, and SNS activation

Question 83

a healthy 23 yo runs 5 miles, what do you expect at the peak of his exertion

Answer 83

increase in CO2 content *in the mixed venous blood* increased CO2 being sent to lungs increased O2 being extracted from muscles homeostatic mechanisms maintain arterial blood and pH near resting values

Question 84

in a COPD patient with new oxygen supplementation his resp rate decreases shortly after starting it its caused by a sudden decrease in stimulation to which sensory receptor?

Answer 84

the carotid bodies in healthy people oxygen has little effect on resp drive, its all CO2 driven in patients with COPD, they have a decreased sensitivity to CO2 and usually have profound hypoxemia so oxygen does become a significant contributor to resp drive the rapid increase in oxygen with supplementation reduces peripheral chemoreceptor stimulation and decreases resp rate (these are found in the carotid and aortic bodies and they sense oxygen) side notes: central chemoreceptors in the medulla control depth and rate of resp in response to pH of CSF (influenced by high CO2 indirectly because it forms H+ in CSF) pulm stretch receptors = myelinated and unmyelinated C fibers (regulate duration of inspiration depending on degree of lung distension) "hering-breuer" reflex

Question 85

how do you differentiate between chronic bronchitis and emphysema on lung function tests

Answer 85

``` chronic bronchitis = TLC normal FRC increased pulm compliance normal bronchodilators cause a partial response DLCO is normal ``` ``` emphysema= TLC increased FRC increased more pulm compliance increased bronchodilators cause a non reversible response DLCO is decreased (wall destruction) ``` side notes: cxr of COPD = hyperinflated lungs and flattened diaphragm DLCO (diffusing capacity of the lung for CO) depends on thickness, surface area of the capillary, hematocrit, and volume of pulm capillary blood

Question 86

what is the virulence factor of H flu

Answer 86

the capsule (its one of the encapsulated bacteria that asplenic patients are at risk for) H flu is a gram neg coccobacillus requires factor X (hematin) and V (NAD+) to grow both of these are found in RBCs so H flu grows on chocolate agar (or regular blood agar when you add these two factors with an impregnated disk) causes septic arthritis otitis media meningitis infects non vaccinated or undervaccinated patients type b (Hib) has the polyribosylribitol phosphate polysacch capsule that prevents phagocytosis side note: H flu has fibriae for attachment but these are not the major virulence factor cytotoxic exotoxins = clostridium and corynebacterium alpha hemolysin= staph aureus hyaluronidase = spread (staph aureus, GAS, clostridium)

Question 87

which bug caused this? 23 yo M with cough and pulm infiltrates blood clumps in ice water rapidly uncoagulates when warmed up in observer's hand

Answer 87

mycoplasma pneumoniae this is the effect of cold agglutinins which are ab's made in response to mycoplasma pneumoniae infection, directed against the cell membrane these ab's also happen to similar to antigens on the surface of human RBCs (cause the clumping) these cold agglutinins cause transient anemia in infected patients cold agglutinins are also associated with EBV infection and blood cancers

Question 88

``` what does she have? 35 yo African American female joint pain deep tender nodules on legs hepatomegaly hilar LAD on cxr elevated ACE on blood work negative PPD ```

Answer 88

sarcoidosis (joint pain, skin changes, liver damage, hilar LAD, high ACE levels) her liver biopsy would show *scattered granulomas* (affect the portal triads mostly) non caseating sarcoidosis does not typically cause liver cirrhosis though death from sarcoidosis = pulm fibrosis and cor pulmonale side notes: most common cause of hepatic steatosis (fatty liver) = alcohol periportal liver fibrosis= chronic viral hepatitis

Question 89

describe how to approach an acid base problem

Answer 89

1. look at pH (here the patient has acidosis) 2. differentiate resp [CO2 will be high because it gets retained] vs metabolic [HCO3- gets depleted and will be low] (here the patient has resp acidosis) 3. acute or chronic resp acidosis? **high CO2 causes an increase in H+ in the body** kidneys try to pee out H+ to help excessive H+ being peed out causes increased resorption of bicarb (renal compensation via this mechanism takes 3-5 days to have max effect... thus is a chronic response) acute resp acidosis (<8 hours) = low pH, high CO2, and normal bicarb (ish) chronic resp acidosis (>24 hrs)= low pH, high CO2, and high bicarb ex= COPD exac simply put: bicarb <30 is acute bicarb >30 is chronic acute causes of resp acidosis are ones that cause hypoventilation (retaining CO2) ex= heroin overdose ``` side note (other patterns) -metabolic acidosis = low pH, low CO2, low bicarb (resp system immediately responds with hyperventilation) ex= DKA with kussmaul breathing ``` -resp acidosis = low pH, high CO2, high or normal bicarb (kidneys have delayed response of holding onto bicarb) ex= acute heroin overdose -metabolic alkalosis = high pH, high CO2, high bicarb (resp system immediately responsds with hypoventilation) ex= contraction alkalosis caused by overuse of diuretics [volume loss>increased aldo>aldo retains sodium and loses K+ and H+> loss of H+ causes alkalosis] -resp alkalosis = high pH, low CO2, low or normal bicarb (kidneys have delayed response of losing bicarb) ex= panic attack [hyperventilation>decreases CO2>decreases H+>alkalosis] remember that in metabolic, all arrows go the same direction in resp they go opposite directions between pH and CO2

Question 90

``` what is the cause? 52 yo M non productive cough exertional SOB no hx FVC is 40% of predicted value FEV1/FVC 87% Biopsy shows dense fibrosis, fibroblast proliferation, and cyst formation at the subpleural regions ```

Answer 90

idiopathic pulmonary fibrosis (exertional SOB, dry cough, restrictive profile on PFT, interstitial fibrosis with cystic air space enlargement) IPF is most common also known as UIP (usual interstitial pneumonia) dx= patchy involvement, dense fibrosis, fibroblastic foci alveolar walls collapse and form cystic spaces ("honeycombing") lined by type 2 pneumocytes or bronchial epithelium predominant in subpleural spaces or para septal spaces ``` restrictive lung disease: FEV1/FVC normal (roughly 80%) decreased lung volumes (TLC and FVC) examples: due to muscle weakness (polio and myasthenia gravis), chest wall limitation (kyphosis, scoliosis, and morbid obesity), ↓ pleural compliance (mesothelioma) interstitial lung diseases ``` side notes: - A1AT def= COPD in young person - cryptogenic organizing pneumonia (COP) = interstital pneumonia but has fever/weight loss and histo shows intraluminal plugs of granulation tissue and inflamm debris in distal airways - CF= occurs under 20 yo and histo shows bronchioles with distended thick mucus, hyperplastic, and hypertrophied mucus secreting cells, and bronchiectasis - eosinophilic granulomatosis with polyangiitis (churg strauss) = severe asthma and obstructive pattern, histo shows necrotizing vasculitis with granulomatous inflamm and eosinophil infiltration - pulmonary alveolar proteinosis= gradual worsening SOB and cough, histo shows bilat patchy opacification due to intraalveolar accumulation of amorphous protein and phospholipid material (aka surfactant)

Question 91

what is the defense mechanism for clearing particles from the resp tract in a patient with coal worker's pneumoconiosis (inorganic dust)

Answer 91

phagocytosis larger particles inhaled get trapped in upper airways and get coughed/sneezed out medium particles lodge in the bronchi and proximal bronchioles and get cleared by mucociliary particles small fine particles (<2micro) get all the way down into the resp bronchioles and alveoli and are phagocytosed by alveolar macrophages when macrophages eat inorganic dust they release cytokines and growth factors which cause pulm inflamm and collagen fibrosis immune system memory does not contribute to removal of inorganic dust particles

Question 92

are the typical TB symptoms from primary or secondary TB

Answer 92

secondary (reactivation) upper lobes hemoptysis dissemination of reactivated TB can cause military TB(extrapulmonary) ex= potts disease (spine) or TB meningitis primary TB = mid to lower lungs (Ghon focus) spreads to hilar lymph nodes (Ghon complex= a focus lesion plus lymph node involvement) can lead to a benign calcified Ranke complex (healed Ghon complex) which is not associated with reactivation Ranke complexes can become secondarily infected with aspergillus though and form a fungus ball

Question 93

what causes sputum to have thick walled spherules packed with endospores (know what this looks like on histology)

Answer 93

coccidioides immitis (seen with 10% potassium hydroxide or silver stain) some spherules may be rupturing some may be empty spherules are larger than RBCs surrounding it dimorphic fungus endemic to desert areas like US and Mexico causes lung disease in normal people causes disseminated disease in immunosuppr in environment its mold (hyphae) cultured on sabouraud agar side notes: cryptococcus = yeast with thick capsule... clear halo formed when india ink is used... causes meningitis in immunosuppr cytomegalovirus= pnu in transplant patients... intranuclear inclusions surrounded by a clear halo rhizopus= fungus that affects nose/eyes/brain/lung in immunosuppr... mold form only... broad ribbon like hyphae with rare septations sporothrix schenckii= sporotrichosis lesions (pustules and ulcers) to a wound or associated lymph... fungus from being scraped by a rose bush... condida on hyphae

Question 94

why dont PE's cause tissue necrosis

Answer 94

collateral circulation

Question 95

what is cheyne-stokes breathing (CSB)

Answer 95

commonly seen in patients with advanced CHF its a cyclic breathing pattern in which you have a gradually increasing then decreasing tidal volumes with periods of apnea in between CHF patients have chronic hyperventilation with hypocapnia which induces apnea during sleep when CO2 levels fall below the "apneic threshold" (below the threshold you get apnea in order to build up more CO2 because you did not have enough) the problem is that the apnea causes a build up of CO2 that overshoots where it should be and causes an increase in respirations that causes CO2 to again fall below the threshold the apnea hyperventilation cycle is worsened by prolonged circulation time between the lungs and the brain which results in a discrepancy between CO2 levels sensed by central chemoreceptors and CO2 concentrations in the alveoli you can also see cheyne stokes breathing in neurologic disease (stroke, tumors, TBI) and its a poor prognostic sign side notes: hypothyroidism can cause hypoventilation from resp muscle weakness (you get low tidal volumes) and hypothyroidism patients may develop large tongues putting them at risk for OSA OSA= reductions or cessations in airflow during sleep due to obstruction (but the ventilation cycles remain nearly constant during the apneic periods with minimal cyclic variation in tidal volume)

Question 96

what is TB's virulence factor

Answer 96

sulfatide allows for intracellular bacterial proliferation side note: droplets of infectious size carry roughly 5 organisms in military TB, organisms spread widely throughout the body in small scattered seed like foci of infection

Question 97

``` what bug does this patient have? 56 yo F smoker 2 days of fever, headache, confusion, dry cough abdominal pain watery diarrhea BP 104/63 recent cruise to hawaii lung crackles cxr bilateral lower lobe infiltrates ```

Answer 97

``` legionella pneumonia (pnu= lung infiltrates) ``` ``` exposure to contaminated water fever bradycardia headache confusion watery diarrhea ``` labs: hyponatremia neutrophils and no organisms on gram stain dx= culture it on BCYE (buffered charcoal yeast extract) urine Ag test ``` people at risk: smokers alcoholics immunosuppr COPD ``` side note: remember that cold agglutinin = mycoplasma pneumoniae

Question 98

what bug do you get from bird droppings and bat caves

Answer 98

histoplasma capsulatum **ovoid cells within macrophages** dimorphic fungus that is found as mold in soil found in bird droppings and bat droppings lives in the River basins (Mississippi and Ohio Rivers) the fungal spores are inhaled chronic histoplasmosis in people with lung disease looks like TB side notes: coccidioides= spherules packed with endospores (southwest US) cryptococcus= budding yeast with thick capsule (also in bird droppings) candida= yeasts with pseudohyphae aspergillus= septate hyphae with "V" branching

Question 99

what is the most potent chemotactic derivative of arachodonic acid

Answer 99

leukotriene B4 | the other leukotrienes (C4,D4,E4) cause bronchospasm and mucous secretion think asthma

Question 100

what are the derivatives of the arachodonic acids and what do they do

Answer 100

lipoxygenase pathway: 5-HETE (leukotriene precursor) = chemotactic vs lipoxin A4/B4 = anti inflamm (decreases WBC recruitment) vs **leukotrienes = pro inflamm (B4= chemotaxis of neutrophils moreso than the precursor) (C4/D4/E4= bronchospasm, vasoconstriction, increased permeability) cox pathway: ``` thromboxane A2= pro-thrombotic (vasoconstriction, platelet aggregation) vs prostacyclin = anti- thrombotic (vasodilation, decreases platelet aggregation) vs prostaglandin E2/D2= increases edema (vasodilation, increased permeability) ``` side notes: -bradykinin= vasodilation, permeability, smooth muscle contraction, pain -complement C3a-C5a = histamine release from mast cells, vasodilation, permeability (C5a= activates granulocytes and monocytes, chemotactic) -INF gamma activates macrophages -TH2 cells make IL4 to activate B cells ``` chemotactics: leukotriene B4 5-HETE C5a IL 8 ```

Question 101

what is an adverse effect of oxygen therapy to a newborn with resp distress

Answer 101

retinal damage (abnormal retinal vascularization that extends into the vitreous.... "neovascularizaiton") can also possibly cause retinal detachment with resulting blindness its called retinopathy of prematurity or retrolental fibroplasia this temporary high oxygen levels in the retina causes up regulation of pro-angiogenic factors like VEGF upon return to room air ventilation this is a major cause of blindness in developed nations

Question 102

what is SVC syndrome

Answer 102

facial edema venous distension behind obstruction mediastinal mass obstructing the SVC ``` they can also have: SOB cough headache dizziness confusion cerebral edema high ICP dilated collateral veins in the upper torso that are visible ``` the SVC drains the head, neck, upper trunk, upper extremities its where the right and left brachiocephalic veins come together behind the right 1st costal cartilage it has thin walls and is easily compressed by a mediastinal mass most common causes: lung cancer #1 NHL #2 side notes: - small cell lung cancer= cushing syndrome (ACTH secretion) or SIADH (ADH secretion) - squamous cell carcinoma= hypercalcemia of malignancy (PTHrP secretion) - superior sulcus tumors (aka pancoast tumors) in the lung apex= should pain due to compression of the brachial plexus ----> horners syndrome when cervical SNS ganglia is involved (ptosis, myosis, anhydrosis)

Question 103

what bugs live in Mississippi

Answer 103

histoplasma fungus blastomyces fungus ``` blastomyces dermatitidis: dimorphic fungus pulm infection in normal people is a mold in the environment resp transmission is a yeast in the human (thermal dimorphism) ``` it can mimic CAP or chronic pnu characterized by granuloma formation immunosuppr people also get infections to the skin, bone, and GU histo= round yeast thick walls broad based budding tx= itraconazole side notes: - candida= vulvovaginitis (cottage cheese) and opportunistic infections (esp in neutropenic) - mucor species= sinus infection in immunosuppr (esp DKA) - penicillium=opportunistic (esp AIDS in Asia)

Question 104

what is the most common benign lung tumor

Answer 104

hamartoma aka pulmonary chondroma well defined coin lesions with popcorn calcifications asymptomatic patients 50-60 yo hamartoma= excessive growth of tissue native to the organ involve in the lung this would mean you'd see hyaline **cartilage tissue**, fat, and smooth muscle lined by resp epithelium hamartoma= disorganized cartilage, fibrous tissue, adipose tissue side note: alveloar growth pattern without invasion = bronchioloalveolar carcinoma (peripheral mass or pnu like consolidation) neuroendocrine markers= small cell carcinoma of the lung or carcinoid tumor

Question 105

what clears small particles inhaled that get lodged in terminal bronchioles

Answer 105

ciliated cells mucociliary clearance= within bronchial tree ciliated mucosal epithelium likes the trachea down to the resp bronchioles side notes: (goblet) bronchi--->proximal bronchioles--->(club/clara)terminal bronchioles--->(macrophages)respiratory bronchioles--->alveoli - goblet cells go down to the large bronchioles - club cells (aka clara cells) from the terminal bronchioles down - type 2 pneumocytes = surfactant and stem cell

Question 106

how does chronic lung transplant rejection present

Answer 106

dry cough SOB obstructive pattern of PFTs (airflow limitation) fibrotic destruction of small airways occurs in about half of patients within 5 years chronic rejection affects the small bronchioli producing an obstructive lung disease called "bronchiolitis obliterans" histo= lymphocyte inflamm destruction of small airway epithelium fibrinopurulent exudate granulation tissue in lumen of bronchioli ultimately leads to fibrosis, scarring, and progressive obliteration of small airways remember: chronic transplant rejection is an obstructive pattern lung disease due to fibrosis (its the one that sounds like it has problems from both) side notes: -acute rejection occurs in the first 6 months often asymptomatic found on surveillance biopsies shows perivasc and interstitial mononuclear infiltrates - ischemic reperfusion injury is only seen in the first few days s/p transplant - infection is the leading cause of death in lung transplant patients (CMV.... intranuclear inclusions surrounded by a clear halo [owl's eye inclusion')

Question 107

what drugs treat mycoplasma

Answer 107

anti-ribosomal agents aka macrolides tetracyclines ``` side note: these all have peptidoglycan cell walls and are susceptible to cell wall synthesis inhibitors (like penicillins, cephalosporins, carbapenems, vanco): actinomyces fungus pasteurella (cat bites) borrelia (lyme disease spirochetes) h pylori ```

Question 108

what is the diagnosis? 64 yo M progressive SOB nonproductive cough fatigue past smoker hx joint disease and PUD dullness to the right lung base with decreased breath sounds CT shows right pleural effusion and diffuse nodular thickening of the pleura biopsy shows epitheloid type cells joined by desmosomes, containing abundant tonofilaments, and studded with very ong microvilli

Answer 108

mesothelioma rare malignant mesothelial cells line body cavities (pleural, peritoneal, pericardial) primary risk factor is asbestos exposure (asbestos mining and industrial jobs) pleural effusions are typically bloody main finding on cxr is pleural thickening (smooth or nodular) normal lung parenchyma tumor cells= long slender microvilli and abundant tonofilaments dx= immunohistochemical markers like pancytokeratin side notes: - adenocarcinoma=short plump microvilli (+ glandular elements) - carcinoid tumors=salt and pepper pattern (chromatin with fine and coarse clumps) - small cell lung cancer= chromogranin and synaptophysin positive - squamous cell carcinoma= keratinization and intercellular bridges

Question 109

what pattern of emphysema is seen in A1AT def patients

Answer 109

panacinar basically its COPD in a young person side note: in asthma, DLCO is high because of increased pulm capillary blood volumes

Question 110

how does a combined restrictive and obstructive lung disease present

Answer 110

decreased FEV1/FVC (like obstructive) decrease lung volume (like restrictive) decreased DLCO (like obstructive) due to: multiple diseases present simultaneously pneumoconiosis -(silicosis, asbestosis) sarcoidosis side note: for restrictive lung disease, intrinsic causes have a decreased DLCO where as extrinsic causes have a normal DLCO

Question 111

what is the result of seeing lungs with several large cuboidal alveolar cells with decreased number of granules containing parallel stacks of membrane lamellae

Answer 111

*increased alveolar tendency to collapse* granules containing parallel stacks of membrane lamellae = lamellar bodes (INSIDE TYPE 2 PNEUMOCYTES) (this is where surfactant is stored and transported to the cell surface via exocytosis)... surfactant gets recycled back into the same pneumocyte by endocytosis for reprocessing type 2 pneumocytes produce surfactant without surfactant the alveoli collapse due to increased surface tension (atelectasis)

Question 112

what are the characteristic findings of primary spontaneous pneumothorax

Answer 112

rupture of apical blebs

Question 113

what cell types contribute to the pathology of sarcoidosis

Answer 113

Th1 cells IL 2 and INF gamma sarcoidosis: noncaseating granulomas dysregulated cell mediated immune response due to an unknown Ag cell mediated immunity= Th1 cells Th1 cells secrete IL2 and INF gamma IL 2= stimulates more Th1 cells INF gamma= activates macrophages to make granulomas

Question 114

what cell type and cytokines drive humoral immune response

Answer 114

Th2 cells IL 4 and IL 5 IL 4= tells B cells to become IgE IL 5= activates eosinophils and tells B cells to become IgA

Question 115

what predisposing factors are responsible for a patient's pulmonary lesion that grows several bacterial species including peptostreptococcus and fusobacterium

Answer 115

*seizure disorder* peptostreptococcus and fusobacterium are part of the normal mouth flora (so are prevotella and bacteroides) finding these in her lungs suggests a lung abscess due to aspiration (abscess= identifiable air fluid level on imaging) aspiration is the most common cause of lung abscesses ``` risk factors for aspiration: LOC difficulty swallowing alcoholism drug overdose seizures prolonged anesthesia severe neurologic diseases ``` ``` symptoms= fever night sweats weight loss cough foul smelling sputum (anaerobes) ``` lung abscesses also due to complication of bacterial pneumonia (typically nosocomial pneumonias from bugs like staph aureus, ecoli, klebsiella, or pseudomonas) lung abscesses also due to hematogenous spread of infection to the lung from septicemia or IE (these ones are often multiple abscesses and caused by one bacteria)... most common causes are staph and strep

Question 116

what muscle is dissected when placing a tube to drain a pleural effusion if you go in through the 5th intercostal space in the midaxillary line

Answer 116

*serratus anterior* this lives along the 1st-8th ribs theres three parts, the superior, intermediate, and inferior [arm elevation] parts depending on the insertion site onto the scapula all 3 help with respiration by lifting the ribs when the shoulder girdle is fixed (note that the latissimus dorsa is more posterior than the midaxillary line! whoops) empyema= pus in the pleural cavity tube transversus: serratus anterior muscle>intercostal muscles (external>internal>innermost) >parietal pleura> pleural cavity

Question 117

``` which lung cancer does this patient have? 72 yo M headache lethargy weakness chronic cough decreased appetite smoking hx prolonged expiration and end expiratory wheezes cxr with overinflated lungs and a 2.5cm left hilar mass labs: low Hgb low sodium low plasma osmolarity ```

Answer 117

*small cell lung cancer* small cell lung cancer typically presents as a hilar mass in patients with a smoking history ``` small cell lung cancer causes (paraneoplastic syndromes): SIADH (ectopic ADH) cushing syndrome (ectopic ACTH) lambert eaton myasthenic syndrome cerebellar ataxia ``` we are assuming the patient's hyponatremia is due to SIADH SIADH presentation is vague (ex- lethargy) but untreated it causes seizures or coma physical exam- normal volume status labs with decreased serum osm (due to true hypotonic hyponatremia... this basically means your urine is concentrated when your plasma isnt which is bad and not normal) an essential characteristic of SIADH is urine osm >100 (meaning kidneys cannot produce dilute urine to remove free water you assume is there because hyponatremia supposedly means too much water) SIADH causes: central nervous system disorder medication adverse reaction ectopic secretion by a neuroendocrine tumor side note: - squamous cell lung cancer = hypercalcemia of malignancy (PTHrP) - adenocarcinoma = hypertrophic osteoarthritis, dermatomyositis or polymyositis, migratory thrombophlebitis (trousseau syndrome) - lymphoma= hypercalcemia (due to overproduction of 1,25-dihydroxyvit D) and cerebellar degeneration

Question 118

what disease has impaired activity of NADPH oxidase

Answer 118

Chronic Granulomatous Disease impaired intracellular killing of organisms engulfed by phagocytes infections with catalase positive bacteria and fungi granuloma formation dx= measuring neutrophil superoxide production (flow cytometry>NBT testing) dihydrorhodamine (DHR) flow cytometry= fluorescent green detects superoxide radicals by measuring conversion of DHR to rhodamine CGD patients have decreased fluorescence ``` nitroblue tetrazolium (NBT) testing = NBT + patient's neutrophils normal result makes ROS and will turn the yellow NBT dark blue ``` side note: these two tests would be normal in a myeloperoxidase def because NADPH oxidase is intact still (myeloperoxidase produces bleach inside cells to help intraceullar killing) - adenosine deaminase def= SCID (second most common cause)... AR - cytochrome C oxidase def= muscle and brain findings... AR mut - pyruvate kinase def= chronic hemolytic anemia

Question 119

what accounts for the difference between minute ventilation and alveolar ventilation

Answer 119

dead space volume physiologic dead space= tidal volume x ([CO2 alv- CO2expired]/alveolarCO2)

Question 120

what is the difference between chloride and sodium concentration in a CF patients' sweat versus their resp epithelium

Answer 120

sweat= high in chloride and high in sodium ``` resp epithelium (and thus their mucus)= high in chloride low in sodium (increased absorption of sodium in the epithelium but not in the sweat glands... this means their nasal transepithelial potential difference will be more negative because they have a higher relative amount of negatively charged chloride ions on the surface) ```

Question 121

what is pancoast syndrome and what causes it

Answer 121

pancoast syndrome is caused by a lung cancer at the apex (specifically the *superior sulcus* which is the groove in the first rib formed by the subclavian vessels) pancoast syndrome symptoms are caused by invasion of the cancer into surrounding structures causing: 1. shoulder pain (here it was scapula pain) 2. horners (ptosis, miosis, anhydrosis ipsalaterally) 3. upper extremity edema 4. spinal cord compression (finger numbness) coughing blood= lung cancer here side note: - central lung cancers= squamous and small cell - anterior mediastinal masses (the terrible T's = Thymoma, Teratoma, Thyroid cancer, Terrible lymphoma) - lung cancer assoc with autoimmune Lambert-Eaton myasthenic syndrome

Question 122

what is fat embolism syndrome

Answer 122

bone fracture acute neurologic abnormalitis hypoxemia (SOB, low oxygen sat) petechial rash due to occlusion of *pulmonary microvessels and arteries with fat globules* most occur within 1-3 days after injury fat globules get stained with osmium tetroxide to make them look black on histology

Question 123

``` what bug? 65 y M with fever chills chest pain cough drinker and smoker mild resp distress crackles and decreased breath sounds in right upper obe cxr= large right upper lobe infiltrate gram neg bacilli grows pink on macconkey agar ```

Answer 123

klebsiella pnu cause most of the nosocomial pnu high mortality mostly infects immunosuppr thick capsule seen as a clear zone on gram stain characteristic mucoid growth in culture commonly affects alcoholics (due to microaspiration) upper lobes affected if aspiration occurs while laying down (aka sleeping) klebsiella= currant jelly sputum lung necrosis early abscess formation

Question 124

what does the ABG look like for a PE

Answer 124

pH 7.57 O2 65 CO2 26 HCO3- 23 hyperventilation leads to low CO2 and resp alkalosis kidney excretes bicarb to compensate but not until like 2 days in

Question 125

``` 47 yo with SOB wheezing poor air movement high AST and ALT liver biopsey with diastase treatment and acid schiff staining (reddish pink granules) shown on histology dx? ```

Answer 125

A1AT def AD affects lungs AND LIVER the AAT protein is made in the liver and its fucked up so it cant get out of the liver and builds up and causes damage smokers get emphysema in 30s non smokers in 50s *interalveolar septa destruction* liver disease shows up sooner intracehaptocyte accumulation of AAT molecules leading to cirrhosis granules= unsecreted polymerized AAT protein in periportal hepatocytes (second most common cause of death in these people) also leads to hepatocellular carcinoma side notes: - bronchial hyperreactivity= chronic asthma - interstitial infiltration= interstitial pneumonitis - intraalveolar substance accumulation= alveolar proteinosis - pulm congestion= CHF - pulm vasc obstruction= PE or vasculopathy

Question 126

what is Laplace's law of sphere radius and surface tension

Answer 126

basically the small sphere will collapse before the larger one aka why alveoli needs surfactant to decrease surface tension they show you a model with two elastic spheres with identical surface tension and neither with surfactant. when the clamp is open the little sphere collapses (they DO NOT become equal in size)

Question 127

what fungus infects patients with asthma on steroids and causes proximal bronchiectasis

Answer 127

aspergillus it also infects CF patients imaging shows recurrent fleeting infiltrates and bronchiectasis on CT dx= eosinophilia positive skin test positive IgG test elevated IgE "allergic bronchopulmonary aspergillosis (ABPA)"

Question 128

why does a kid have otitis media caused by H flu if he is vaccinated?

Answer 128

*the strain responsible for the patient's disease does not produce a capsule you are only vaccinated against type b which has a polysacch capsule non capsule h flu causes otitis media sinusitis bronchitis the Hib vaccine contains polysacch capsular elements to induce ab's (humoral immunity) because the ab response in kids is weak, the vaccine is conjugated with a toxoid protein to stimulate Th cells and activate B cell ab formation Hib virulence factor = capsule (made of polyribosylribitol phosphate- aka PRP) PRP capsule protects from phagocytosis and complemented mediated lysis by binding factor H (a circulating regulator protein that normally prevents complement deposition on host cells) conjugate Hib vaccine= PRP conjugated to a protein toxoid

Question 129

OSA vs narcolepsy

Answer 129

OSA= relaxed pharyngeal muscles close off airway (until CO2 rises, chemoreceptors in the carotid bodes go off, and wakes them up, pharyngeal tone comes back) loud snoring with apnea daytime sleepiness frequent awakenings at night morning headaches cognitive symptoms consequences= systemic HTN, pulm HTN, right HF narcolepsy= poor REM sleep daytime sleepiness cataplexy (laughter= loss of muscle tone) sleep attacks hypnagogic (falling asleep)/hypnopompic (waking up) hallucinations sleep paralysis central sleep apnea has significant underlying chronic illness (CHF, cerebrovasc disease, renal insuff)

Question 130

what makes bacterial sputum/pus green

Answer 130

myeloperoxidase its a blue green heme based enzyme released from netrophil azurophilic granules and is used to form hypochlorous acid (bleach)

Question 131

what do you get vaccinated to in a pneumococcal vaccine

Answer 131

the outer polysacch covering of strep pneumo 1. unconj polysacch vaccine (T cell independent response) 2. conjugate vaccine containing polysacch material attached to protein Ag (more robust T cell response) (neisseria meningitidis and H flu are also capsular polysacch vaccines) side notes: - oral cholera vaccine= killed bacteria (not as great) - tuberculosis (BCG) and oral typhoid vaccines= live attenuated bacterial (can cause disease in immunosuppr) - hep B vaccine= recombinant surface protein (same drawbacks of killed vaccine, made by putting DNA into the host yeast to make Ag in large quantities) - diptheria and tetanus vaccine= inactivated toxin (toxoid)

Question 132

what does a collapsed lung look like on cxr

Answer 132

no black area (air) on one side looks like the whole thing is fluid filled kinda "completely opacified hemithorax" make sure to look at the trachea trachea deviates towards the completely white side side note: tension pneumothorax or large pleural effusion causes tracheal deviation away from the affected lung because the excess air or fluid pushes the mediastinal structures cause of complete lung collapse= *obstructive lesion in the mainstem bronchus* preventing ventilation to the entire lung

Question 133

what is damaged in chronic lung rejection

Answer 133

the small airways hyperacute rejection within minutes due to ABO or HLA mismatch "white graft" rejection because of blood vessel spasms, coagulation, and ischemia rare and irreversible acute rejection 1-2 weeks out reaction to HLA cell mediated response (CD*+ specifically) attacks vessels bronchial circulation is not revascularized tx= immunosuppressants chronic rejection months to years major cause of mortality in lung transplants causes bronchiolitis obliterans (small airway destruction) inflamm and fibrosis narrows and obstructs [in kidney rejection you get vasc obliteration]

Question 134

``` what does she have? 62 yo F cough SOB copious tan colored sputum pulm infiltrates histo= columnar mucin secreting cells that line the alveolar spaces without invading the stroma or vessels ```

Answer 134

*malignant neoplasm* this is adenocarcinoma in situ ("bronchioloalveolar carcinoma") peripheral lung cancer grows along intact alveolar septa well differentiated dysplastic columnar cells side notes: -hamartomas= "coin lesions"

Question 135

what does lactic acid buildup represent

Answer 135

decreased oxidative phosphorylation lactic acid increases with exercise and seizures with reduced oxygen delivery diminished lactate clearance via the liver (liver failure or hypoperfusion) cyanide poisoning (decreased oxygen utilization) enzyme defects (glycogen storage diseases like von Gierke or mitochondrial myopathies)

Question 136

``` what does she have? 19 yo F s/p MVC celiacs disease pneumonia (x3) low BP high pulse spleen lac blood transfusion with O- blood then develops facial swelling, hives, SOB ```

Answer 136

*selective IgA def usually asymptomatic recurrent sinopulmonary infections and GI infections (giardia) autoimmune disease ANAPHYLAXIS during TRANSFUSIONS low or absent IgA levels normal IgG or IgM this is the most common primary immunodeficiency Patients with severe IgA def form IgE ab's against IgA (anti IgA ab's) when transfused with blood products that contain a small amount of IgA (RBCs, platelets, FFP) they get potentially fatal anaphylaxis these patients need to wear medical bracelets to say they need blood products that are washed of residual plasma or get blood from an IgA def donor side notes: - acute ABO incompatibility causes hemolysis and circulatory collapse due to IgM and IgG reaction with Ag's - C1 inhibitor def= hereditary angioedema triggered by transfusions - leukocyte adhesion def= recurrent skin and mucosal infections

Question 137

which phase of disease is this? 65 yo M with overwhelming pulmonary infection autopsy shows right lower lobe is pale, firm, and airless histo= alveoli filled with exudate containing neutrophils, fibril, and some fragmented RBCs

Answer 137

Gray hepatization These are the stages of lobar pnu: 1. congestion (first two days) lobe is red, heavy, boggy vasc dilation, alveolar exudate with mostly bacteria 2. red hepatization (day 2-3) red, firm lobe, liver like consistency alveolar exudate now with RBCs, neutrophils, and fibrin 3. gray hepatization (day 4-6) gray brown firm lobe (aka pale!) RBCs disintegrate (fragmented RBCs) alveoli still contain neutrophils and fibrin 4. resolution restoration of normal architexture enzymatic digestion of the exudate

Question 138

what are the dimorphic fungi species

Answer 138

dimorphic fungi grow mold at 25-30 C and yeast at body temperature 5-37 C 1. sporothrix pricked by a rose thorn while gardening cigar shaped 2. coccidioides thick walled spherules filled with endospores 3. histoplasma ohio and mississippi rivers bird and bat droppings live in macrophages 4. blastomyces ohio and mississippi rivers doubly refractile wall single broad based bud 5. paracoccidiodes

Question 139

what does IL 12 do and why do you care if its deficient

Answer 139

macrophages make IL 12 telling naiive cells to become Th1 Th1 cells then make INF gamma that activate the macrophages without IL12 you worry that you cannot activate macrophages macrophages are needed for type 4 delayed hypersensitivity reactions and cytotoxicity against organisms like mycobacteria thus people who are deficient get severe mycobacterial infections treatment is to bypass IL 12 and just give INF gamma to directly stimulate macrophages to do their job side note: - CD3 and CD4 are markers of naiive Th0 cells - Th1 cells make IL 2, INF gamma, and lymphotoxin beta (T cell immunity!) - Th2 cells make IL 4, IL5, IL10, and IL 13 (B cell immunity!)

Question 140

what are the typical bugs that cause CAP and what causes atypical pnu

Answer 140

``` CAP: strep pneumo (encapsulated) h flu (encapsulated) moraxella klebsiella staph aureus ``` atypical: mycoplasma chlamydia legionella

Question 141

what are the virulence factors of strep pneumo and what do they do

Answer 141

**capsule = prevents phagocytosis (needs this to cause disease) IgA protease = inactivate IgA adhesions= adhesion to epithelial cells pneumolysin= punches holes in cell membrane and causes lysis side notes: - gram neg bacteria's LPS causes DIC - GAS M protein is anti phagocytic (interferes with opsonization by the alternative complement pathway) and also binds fibrinogen

Question 142

why does interstitial lung disease cause supernormal expiratory flow rates

Answer 142

increased radial traction on airway walls from the fibrotic tissue in the interstitium aka increased elastic recoil

Question 143

what kind of protein is the CFTR protein that is mutated in CF

Answer 143

its a transmembrane **ATP gated** chloride channel AR delta F508 mutation CFTR= CF transmembrane conductance regulator protein 2 ATP bind the channel and then the pore opens (normally) movement of Cl- encourages Na+ to cross whic hydrates mucus (normally)

Question 144

why does venous blood have higher chloride content than arterial blood

Answer 144

due to **carbonic anhydrase** in the chloride shift within RBCs, carbonic anhydrase turns CO2 and water into bicarb bicarb diffuses out of the RBC and into the plasma to maintain electrical neutrality, Cl- diffuses in to take the place of HCO3-

Question 145

what are the risks of second hand smoke exposure

Answer 145

``` premature babies low birth weight SIDS (definition extends to 1 yo) otitis media asthma resp tract infections ``` up to half of SIDS is due to second hand smoke exposure even smoking outdoors doesnt help because chemicals are absorbed and retained in clothing, skin, and hair

Question 146

what does this person have and what mediates it? 24 yo M paroxysmal breathlessness and wheezing no recognized triggers normal exam and hx sputum shows granule containing cells and crystalloid masses

Answer 146

extrinsic allergic asthma mediated by ***IL 5*** (because IL5 activates eosinophils and tells B cells to make ab's) paroxysmal breathlessness and wheezing in young patient unrelated to aspirin, infection, irritants, stress, or exercise but remember its IL4 that makes IgE sputum: granule containing cells = eosinophils crystalloid masses= charcot leyden crystals (that contain eosinophil membrane protein) Th2 cells make IL 5

Question 147

what kind of lung damage is caused by tricuspid valve endocarditis

Answer 147

young patient with IVDA presenting in septic shock most likely developed septic pulmonary emboli from tricuspid valve endocarditis these cause multiple wedge shaped hemorrhagic lesions in the periphery of the lung (See a gross picture) hemorrhagic infarction of the lung is due to dual blood supply this is all due to staph aureus side notes: -mycotic aneurysms can be a complication of endocarditis and very rarely are actually associated with fungal infections despite the name

Question 148

what contributes to the formation of a lung abscess

Answer 148

**lysosomal content release by macrophages** and neutrophils "air fluid level"= abscess side notes: - eosinophils kill parasites with major basic protein - INF gamma forms the phagolysosome, NO synthase, granulomas, and caseous necrosis (NOT abscesses) - IL12 stimulates NK cells and causes secretion of INF gamma

Question 149

what virus to lung transplant patients get

Answer 149

CMV! most centers give prophylaxis for these patients with valganciclovir CMV = **enveloped dsDNA virus** in the herpesviridae family attacks esophagus, colon, and eyes histo= enlarged cells with intranuclear and intracytoplasmic inclusions (viral particles) "owl eyes" (the surrounding halo)

Question 150

what is this describing? | "cell surface bound Ab bridging by Ag"

Answer 150

anaphylaxis type 1 hypersensitivity reaction when the allergen, aka the Ag interacts with cell bound specific IgE, the IgE ab's cross link and cause degranulation of mast cells and release of chemical mediators (histamine prostaglandin leukotrienes) result is vasodilation permeability bronchoconstriction hemodynamic instability

Question 151

what kind of drug is ipratropium

Answer 151

anticholinergic agent derived from atropine blocks Ach at muscarinic receptors blocking BB SLUDGE (locally) this is less effective than beta 2 agonists takes like 60-90 minutes to start working side notes: - albuterol is a beta 2 agonist - flunisolide = inhaled steroid - methylxanthines (thophylline and aminophylline)= block phosphodiesterase to increase cAMP and thus cause bronchial dilation - zeleuton= inhibits the lipoxygenase pathway of arachidonic acids to prevent formation of leukotrienes - magnesium sulfate= blocks calcium into airway smooth muscle

Question 152

what do cromolyn and nedocromil do

Answer 152

they are cromoglycates= mast cell stabilizing agents that inhibit mast cell degranulation independent of the triggering stimuli they are second line treatment first line is steroids these *prevent the preformed vesicles from exocytosing the mast cell* side notes: - omalizumab= anti IgE ab - glucocorticoids= inhibit gene transcription - zileuton = inhibits formation of leukotrienes - montelukast and zafirlukast= inhibit the leukotriene receptor CysLT1 - antihistamines= block histamine receptor - also, asthma can have completely normal PFTs

Question 153

what is the interaction with theophylline and ciprofloxacin

Answer 153

theophylline is an adenosine receptor blocker and phosphodiesterase blocker (low doses it acts like caffiene) used for asthma and COPD it prevents breakdown of cAMP and thus causes broncho dilation its metabolized by the liver CYP enzymes ``` these drugs inhibit the CYP enzymes: ciprofloxacin cimetidine macrolides verapamil (also infection with fever can do it) ``` these prevent breakdown of theophylline and cause toxicity due to the drug's narrow theraputic window ``` toxicity= CNS symptoms (tremor, seizures) GI problems CV problems (arrhythmias) ``` DEATH from theophylline toxicity= seizures and tachyarrhythmias (does NOT prolong the QT) tx= give activated charcoal to reduce absorption beta blockers to protect from arrhythmias benzos and barbs for the seizures side note: -haloperidol (D2 blocker) can cause neuroleptic malignant syndrome [fever, AMS, rigidity, autonomic instability]

Question 154

how do you confirm the diagnosis of asthma if they have no symptoms and completely normal testing

Answer 154

you use bronchoprovacation techniques such as giving *methacholine* or histamine administration/exercise/cold air inhalation to elicit symptoms and confirm the diagnosis methacholine is a muscarinic agonist (BB SLUDGE) if methacholine causes a decrease in FEV1 they have bronchial asthma negative methacholine test rules out asthma

Question 155

important facts about small cell lung carcinoma, go!

Answer 155

also called undifferentiated or oat cell carcinoma its only 10-20% of all malignant lung cancers associated with SMOKING CENTRALLY located arise from the primitive cells of the basal layer of the bronchial epithelium microscopy=round or oval cells scant cytoplasm large hyperchromatic nuclei tumors form sheets or clusters there is abundant mitosis it causes NEUROENDOCRINE differentiation neuroendocrine marker= CHROMOGRANIN (also enolase and synaptophysin) **neuroendocrine marker also= neural cell adhesion molecule (NCAM aka CD56) some small cell carcinomas also express neurofilaments SCC is the most aggressive type of lung cancer rapid invasion and distant spread they often make hormones too (like ADH) sensitive to chemo and radiation yet still terrible 5 year survival "salt and pepper" nuclear chromatin side notes: - papillary thyroid cancer= psammoma bodies (calcium) - squamous= keratin pearls - non small cell carcinomas express mucin and mutation of epidermal growth factor receptor (EGFR) and KRAS genes - glial fibrillary acidic protein (GFAP) = astrocytomas - vimentin= found in mesenchymal cells= diagnoses sarcomas

Question 156

in a patient with COPD, how does oxygen therapy cause CO2 retention

Answer 156

3 pathways **major one**1. baseline pulm vasoconstriction --> O2 causes vasodilation that diverts blood away from well ventilated regions---> net effect is an increase in physiologic dead space (V/Q mismatch)... aka much more places with adequate ventilation but not perfusion---> CO2 retention from less surface area for gas exchange 2. baseline- high hb affinity for CO2--> O2 causes a decreased affinity of hb for O2 (haldane effect)--> this increases blood CO2 levels 3. baseline peripheral chemoreceptor stimulation---> O2 causes a decrease in peripheral chemoreceptor stimulation---> decreases minute ventilation---> CO2 is retained

Question 157

what is oxygen toxicity

Answer 157

when hyperoxia produces ROS injurs airways and lung parenchyma ``` symptoms: substernal heaviness pleuritic chest pain cough SOB within 1 day of breathing pure oxygen ```

Question 158

what does hyperventilation cause

Answer 158

low CO2 no affect on O2 resp alkalosis not associated with increased lactate hypocapnia causes cerebral vasoconstriction and decreased cerebral blood flow

Question 159

what is TB's virulence factor

Answer 159

*cord factor* described as mycobacteria growing in parallel chains in a "serpentine cord" pattern cord factor= mycoside made of two mycolic acid molecules bound to a disaccharide trehalose without cord factor it cannot cause disease it also shuts down neutrophils, damages mitochondria, and releases TNF side notes: - acid fast= mycolic acid (mycobacterium and nocardia) - sulfatides in TB stop the fusion of lysosomes to phagosomes allowing them to live in macrophages

Question 160

what are the buzz words for resp tract infections in kids

Answer 160

common cold = rhinovirus, influenza, coronavirus croup= barking cough and stridor = parainfluenza (paramyxovirus family) diptheria = pseudomembrane = corynebacterium diptheriae epiglottitis = dysphagia and drooling = H flu bronchiolitis = wheezing= RSV side notes: - rubella (german measles) = togaviruses - parvoviruses (parvo19)= aplastic crisis in SCD, fifth disease (erythema infectiosum), and hydrops fetalis

Question 161

what are triggers of asthma

Answer 161

``` animal dander dust mites cockroaches pollens molds cigarette smoke air pollution exhaust fumes perfumes viral URIs rhinosinusitis aspirin NSAIDS non selective beta blockers exercise cold air dry air GERD emotions- stress, depression ``` food related asthma most commonly caused by added preservatives such as sulfites

Question 162

hilar LAD pulm disease constitutional symptoms non caseating granulomas +/- african american +/- female

Answer 162

sarcoidosis side notes: - adenocarcinoma= non smokers - mycobacterium avium complex (MAC)= immunosuppr... causes granulomas - HL= constitutional symptoms and LAD (reed sternberg cells) be able to identify a non caseating granuloma on histology

Question 163

what are heart failure cells

Answer 163

hemosiderin laden macrophages aka siderophages suggestive of prior pulm congestion and edema due to chronic heart failure

Question 164

what are ferruginous bodies

Answer 164

asbestos fibers coated in iron they stain brown with hematoxylin and eosin stain or dark blue with a prussian blue stain

Question 165

what is a good treatment for severe uncontrolled asthma despite inhaled steroids, LABAs, SABAs, and oral steroids...

Answer 165

anti-IgE ab's aka omalizumab subcutaneous injection this allows patients to stop the oral steroid and decrease the inhaled steroid side notes: -H1 receptor antagonists are not useful in treating asthma (only for hives and allergic symptoms)

Question 166

where is elastase in the lungs made?

Answer 166

from infiltrating neutrophils AND MACROPHAGES

Question 167

what is the Reid index

Answer 167

ratio of thickness o f mucous gland layer in bronchial wall submucosa to the thickness of the bronchial wall between the resp epithelium and bronchial cartilage used to measure mucous gland enlargement it measures the area of the mucous gland over the entire bronchial wall (not including cartilage) normal = 0.4 this increases in chronic bronchitis can be used to measure duration and severity of the chronic bronchitis

Question 168

will the PCWP be normal in ARDS?

Answer 168

yes pancreatitis is a major risk factor for ARDS diffuse injury to the pulm micro vasc endothelium and alveolar epithelium causes permeability and leaky capillaries leading to pulm edema if PCWP was high it would make you think of cardiogenic pulm edema (decompensating LV failure) ARDS causes hyaline membrane formation

Question 169

Pulmonary vascular resistance is lowest at what lung volume

Answer 169

vasc resistance lowest at the *functional residual capacity aka residual volume plus expiratory reserve volume (everything left over after a normal tidal volume exhale) increased lung volumes increase pulm vasc resistance due to capillary stretching decreased lung volumes increase pulm vasc resistance due to radial traction on large vessels

Question 170

what does asbestos put you at risk for

Answer 170

bronchogenic carcinoma>mesothelioma ``` also asbestosis (pulm fibrosis with asbestos bodies--> golden brown beaded rods with translucent centers) pleural disease (pleural plaques on the lower lungs and diaphragm) cancer ``` found in shipbuilding workers construction workers textile industry workers side notes: - alkylating agens and benzene cause acute leukemia - h pylori, smoked meats and fish, and smoking causes gastric cancer - beta naphthylamine in aniline dyes and the rubber industry cause bladder cancer

Question 171

what is gilbert syndrome

Answer 171

mutation in genes coding for glucuronyl transferase needed to conjugate bilirubin causes jaundice (unconj bili) during times of stress

Question 172

what is acute intermittent porphyria (AIP)

Answer 172

defects in porphobilinogen deaminase acute attacks of abdominal pain neuropsych symptoms red/brown cola colored urine

Question 173

what is the result of pyruvate kinase def

Answer 173

hemolytic anemia AR presents: pale yellow eyes large spleen

Question 174

what is porphyria cutanea tarda (PCT)

Answer 174

defects in uroporphyrinogen decarboxylase most common form of porphyria chronic photosensitivity blistering in the sun high uroporphyrinogen in the urine

Question 175

what does the ABG look like for an aspirin intoxicity

Answer 175

they present with fever tinnitus rapid respirations they get a primary resp alkalosis (hypervent) followed by metabolic acidosis (gives them a metabolic acidosis with anion gap) mixed acidosis and alkalosis picture is when the CO2 and the bicarb are not normal ``` pH 7.38 CO2 20 (due to resp alk- salicylates stimulate the medullary resp center) HCO3 12 (low because accumulation of ketoacids/lactate/pyruvate bind the bicarb) ``` salicylates increase fat breakdown uncouple oxidative phosphorylation inhibit the citric acid cycle

Question 176

what causes a primary spontaneous pneumothorax

Answer 176

**apical subpleural blebs rupture** (due to a large change in alveolar or intrapleural pressure) causes air trapping between the pleural spaces tall thin males in their 20's no preexisting lung disease risk factors= smoking, tallness (because of more negative intrapleural pressures in the apicies)

Question 177

what is a newborn with intestinal obstruction due to a green inspissated fecal mass indicative of

Answer 177

CF a green inspissated mass in the distal ileum= dehydrated meconium (dx= meconium ileus) very specific finding for CF CF patients die of treatment resistant persistant infections like pneumonia, bronchiectasis, and cor pulmonale

Question 178

what is the difference between hirschsprung disease and meconium ileus

Answer 178

``` hirschprung= down syndrome obstruction at the rectosigmoid colon normal meconium consistency positive squirt sign (death due to enterocolitis) ``` meconium ileus= CF ileum obstruction meconium is inspissated (thick) negative squirt sign

Question 179

how do you treat cyanide poisoning

Answer 179

1. create methemoglobinemia [with sodium nitrite] so cyanide binds that and then treat with methylene blue to get rid of the methemoglobinemia 2. give [sodium thiosulfate, a **sulfur donor**] to promote liver rhodanese mediated conversion of cyanide to thiocyanate to get peed out 3. hydroxocobalamin is given, which is a cobalt moiety used to bind intracellular cyanide ions and form cyanocobalamin which is excreted in the urine summary: use nitrite, sulfur, or cobalt! cyanide poisoning from too much nitroprusside nitroprusside is an IV vasodilator which gets metabolized to NO and cyanide cyanide is a potent mitochondrial toxin it binds Fe3+ in cytochrome C inhibits the ETC and halts aerobic respiration ``` presents with AMS seizures cardiovasc collapse lactic acidosis bright red venous blood ``` beware if the patient has kidney failure

Question 180

why does iron poisoning lead to bloody vomit and bloody stool

Answer 180

iron is directly toxic to gastric mucosa cells

Question 181

what is the treatment for beta blocker toxicity

Answer 181

beta blocker toxicity= slow heart rate low BP low blood sugar tx= glucagon it increases CAMP increases cardiac contractility

Question 182

what is the treatment for acetaminophen toxicity

Answer 182

N-acetylcysteine its a glutathione donor acetaminophen causes liver damage following a latent period

Question 183

what is the treatment for rat poison ingestion

Answer 183

rat poison is where they discovered warfarin! basically rat poison is superwarfarin (brodifacoum- a long acting 4- hydroxycoumarin derivative_ treatment acutely is #1 FFP (repleat factors 2,7,9,10) also give vit K you can give vit K alone if they have prolonged PT or PTT but no active bleeding) side notes: - cryoprecipitate = F8, F13, vWF, fibrinogen - desmopressin= increases vWF and F8 - heparine overdose treatment= protamine sulfate

Question 184

give the key facts about the lung cancers

Answer 184

1. adenocarcinoma by far the most common peripheral causes clubbing and hypertrophic osteoarthropathy (clubbing of the joints) ``` 2. SqCC next most common central causes necrosis and cavitation also causes hypercalcemia smoking ``` ``` 3. SCC aggressive central causes cushings SIADH lambert eaton myasthenia syndrome autoimmune treatment= chemo and radiation smoking ``` 4. large cell carcinoma peripheral causes gynecomastia and galactorrhea tx for all non small cell carcinomas= surgery

Question 185

what happens to the lungs of patients with systemic sclerosis

Answer 185

*intimal thickening of pulmonary arteries* due to collagen aka pulm HTN as a result of the damage to the pulm arterioles presents as accentuated pulm component of the second heart sound signs of right heart failure due to cor pulmonale systemic sclerosis= sclerodactyly and raynauds phenomenon (CREST syndrome=local variant of systemic sclerosis) side notes: -RA causes pulm fibrosis... methotrexate treats RA and can also cause pulm fibrosis

Question 186

how do you screen for celiacs disease

Answer 186

checking for tissue transglutaminase

Question 187

what is varenicline

Answer 187

smoking cessation drug its a partial agonist at the nicotine Ach receptors (it competes with the full agonist-nicotine to prevent nicotine from binding) it reduces withdrawal cravings and lowers the reward effects of nicotine

Question 188

what cells secrete a substance that controls iron storage and release by other cells?

Answer 188

liver parenchymal cells release hepcidin hepcidin is the central regulator of iron homeostasis [it can increase absorption from duodenum or stimulate release from macrophages] when iron levels are high or when there is inflammation around, hepciden gets made by the liver to store iron away hypoxia and increased RBC production lower hepcidin cause iron needs to be used ferroportin (pore that transfers intracellular iron to circulation) binds hepcidin, is internalized, and then degraded this decreases iron absorption and inhibits the release of iron by macrophages once in cells, iron can bind to ferritin for storage or enter circulation via ferroportin (basolateral side of enterocyte) where its transported via transferrin then once again gets internalized by some other cell with a transferrin receptor

Question 189

``` what does she have? 42 yo F fever sore throat no cough tonsillar exudate large cervical lymph node- non tender symptoms resolved with abx but lymph node only slightly decreased with size) over the next year the lymph node fluctuates in size but does not disappear patient asymptomatic ```

Answer 189

follicular lymphoma = persistent fluctuating LAD who had an unrelated pharyngitis at initial presentation its the most common super slow growing NHL comes from B cells course is waxing and waning middle aged patients histo= cleaved and non cleaved follicle center cells in a nodular pattern most have t (14;18) translocation overexpression of bcl-2 oncogene that blocks programmed cell death side notes: - ALL= children, LAD, HSM, bleeding, bone pain - Burkitt lymphoma= aggressive, chemo responsive, B cell NHL, EBV virus, down regulated c-myc proto oncogene, tumor in face/jaw/abd, rapid growth, tumor lysis syndrome - Diffuse large B cell lymphoma= most common NHL, rapidly growing neck/mass, waldeyer's ring (oropharyngeal lymph tissue) and GI involved, "B" symptoms - hairy cell leukemia= splenomegaly, pancytopenia, old men, hair like projections from cytoplasm, tartrate resistant acid phostphatase (TRAP +) - mycosis fungiodes= cutaneous T cell lymphoma, in dermis and epidermis, form pautrier microabscesses, causes plaques that are confused with eczema or psoriasis

Question 190

``` what does he have? somnolence lethargy oliguria diarrhea that became bloody high BUN and Cr fragmented RBCs on smear ```

Answer 190

HUS from EHEC (O157H7)'s shiga like toxin HUS= small blood vessel hemolytic anemia, low platelets, renal insuff HUS usually in kids under 10 yo EHEC from undercooked beef side notes: - fried rice gastroenteritis= bacillus cereus - raw oysters= vibrio - raw eggs/chicken= salmonella - canned beans= clostridium

Question 191

what things are assoc with downs syndrome

Answer 191

``` ALL! AML dementia mental retardation epicathal folds flat face cleft palate nuchal fold thickening palmar crease endocardial cushion defects duodenal and jejunal atresia hypotonia gap between 1st and 2nd toes ``` due to meiotic nondisjunction in the ovum increases with increasing maternal age side notes: - fragile X (missing long arm)= large testes - SCD= chr 11 - rickets= mutations that affect calcium and phosphate metabolism and bone mineralization

Question 192

``` what does she have? 15 yo F fever sore throat anterior and posterior cervical LAD splenomegaly **(plus a picture of atypical CD8+ cytotoxic T cells which look like the edges of a lymphocyte are sticking to the RBCs around it- look one up) ```

Answer 192

Infectious mononucleosis due to EBV EBV infects B cells by binding the CD21 receptor then cytotoxic CD8+ T cells proliferate in order to destroy the virus side note: -CD14 - macrophages/monocytes

Question 193

what causes warfarin induced skin necrosis

Answer 193

deficiency of protein C (super short half life)or protein S leads to transient hypercoagulability, occlusion of microvasc and skin necrosis warfarin inhibits epoxide reductase (needed to regenerate vit K) decrease in F 2,7,9,10,C,S treatment= stop warfarin and give FFP or protein C

Question 194

what lab findings would you expect for: (PT, PTT, platelet count, BT) hemophilia A and B vWF def DIC uremic platelet dysfunction heparin warfarin immune thyrobocytopenia

Answer 194

``` hemophilia A (8) and B (9) PT normal PTT increased platelets normal BT normal ``` ``` vWF def PT normal PTT normal or increased platelet normal BT increased [remember that vWF used for platelet adhesion to damaged vessels and also protects F8 from degredation] ``` ``` DIC PT increased PTT increased platelets decreased BT increased ``` ``` uremic platelet dysfunction PT normal PTT normal platelets normal bleeding time increased [uremic toxins accumulate in patients with renal dysfunction which causes excessive bleeding due to impaired platelet aggregation/adhesion... "qualitative platelet disorder]... tx= dialysis ``` ``` heparin PT normal PTT increased platelet normal (except in heparin induced thrombocytopenia) BT normal ``` ``` warfarin PT increased PTT increased a little platelets normal BT normal ``` ``` immune thyrobocytopenia PT normal PTT normal platelets decreased BT increased ```

Question 195

if you have cyanide poisoning why do you inhale amyl nitrate (red skin, SOB, dizz, palp, flush skin, chemical fume exposure, tachycardia)

Answer 195

to convert hemoglobin into methemoglobin Fe3+ (**increased affinity for cyanide**) otherwise cyanide will inhibit cytochrome c oxidase in the mitochondria and mess up oxidative phosphorylation (lactic acid with increase and the venous arterial O2 gradient will narrow) other cyanide poisoning antidotes= hydrocobalamin (B12 precursor and thiosulfate these both allow cyanide to be peed out nitrates trigger methemoglobinemia

Question 196

what is the most prominent hemoglobin type in a 2 day old baby with beta thalassemia trait

Answer 196

trick question, its a baby so fetal hemoglobin (alpha2 gamma2) starts 8-14 weeks old as a fetus (when liver and spleen start making RBCs) up until its replaced by Hb A around 6 months old baby zeta and epsilon chains are only present in the first few weeks of embryogenesis

Question 197

what labs do you expect to see in a kid with HUS from EHEC

Answer 197

*high serum indirect (unconj) bilirubin oliguria/anuria, increased creatinine = AKI increased bleeding time because low platelets side notes: -streptozyme testing= looks for GAS ab's used to retrospectively diagnose strep

Question 198

how does beta thalassemia affect DM in a patient

Answer 198

HbA1c are affected by alterations in RBC survival conditions that increase RBC turnover like beta thalassemia hemolytic anemia can cause falsely low HbA1c levels Hb A2 [alpha2 gamma2] is elevated in beta thal to compensate for underproduction of beta chain

Question 199

some patients with non small cell lung cancer have a chromosome rearrangement that causes a fusion between EML4 and ALK which results in a constitutively active tyrosine kinase that causes cancer what other disorder is this similar to?

Answer 199

CML t(9;22) BCR-ABL fusion protein oncogene makes a constitutively active tyrosine kinase tx= protein kinase inhibitor= imatinib side notes: - burkitt=8/14/c-myc - follicular lymphoma=14/18/BCL2 - Li-Fraumeni=AD/p53 suppression - mantle cell lymphoma=11/14/cyclin D1

Question 200

woman with microcytic hypochromatic anemia

Answer 200

iron def anemia from blood loss though, not poor diet (even though she denies symptoms expected in bleeds) this chick wasn't alcoholic enough men and women (not menstrating/pregnant/lactating) have enough iron for the most part

Question 201

North South West blot go

Answer 201

North RNA South DNA West protein side notes: -alternative splicing post translation creates different mRNA and thus different proteins (thats why theres different mRNA found in different body dissues) -transcriptional factors only turn things on or off they dont change structure

Question 202

what is the classic triad of congenital toxoplasmosis

Answer 202

1. hydrocephalus (macrocephaly in an infant because their skull hasnt fused) 2. intracranial calcifications 3. chorioretinitis (its due to an in utero infection in the first 6 months of pregnancy) side notes: - you get herpes during delivery (intrapartum) - ophthalmia neonatorum causes conjunctivitis due to chlamydia and neisseria, these cause blindness, infection during birth - GBS acquired during birth

Question 203

what protein does retrograde vs anterograde transport across nerves

Answer 203

retrograde towards nucleus= dynein (establishes latent infection) anterograde towards skin/away from nucleus= kinesin (reinfection) side notes: - lamins= help make up nuclear envelope and organize genes - selectins= help WBCs exit vessels at site of inflammation - spectrin= cytoskeleton protein, RBC shape, defect causes spherocytes - vimentin= holds organelles in place inside cells

Question 204

what is the scary complication of taking lamotrigine (anti seizure med) ps- this drug blocks voltage gated sodium channels

Answer 204

skin rash (preceeded by flu like symptoms) specifically SJS/TEN (toxic epidermal necrolysis) SJS >10% of the body surface area TEN >30% these lesions have epidermal necrosis and subepidermal bullae... stop med immediately with any rash also beware of: carbamazepine phenobarbital phenytoin

Question 205

what is this patient deficient in ``` SOB fatigue unstable gait impaired vibration sense in the lower extremities pale conjunctiva/nail beds/palms ```

Answer 205

vit B12 (test= check a serum methylmalonic acid level*) vit B12 is needed to go from: methylmalonic acid ---- (B12/methylmalonyl coA mutase)----> succinyl coA and homocysteine ---(B12/methionine synthase/THF methyl donor)----> methionine without enough B12, methylmalonic acid builds up and impairs myelin synthesis homocysteine builds up and impairs DNA synthesis the fatigue, pallor, and SOB= megaloblastic anemia characteristic findings= subacute combined degenerating dorsal column (sensory) and lateral corticospinal tract (motor) also assoc with spasticity side notes: -vit B2 def (riboflavin)= normocytic anemia and inflammation of the lips/mouth/tongue (test for RBC glutathione reductase activity) -def in pyruvate kinase means you cannot make pyruvate and you get hemolytic anemia because of impaired ATP production -vit B1 (thiamine) def= wernicke korsakoff and beriberi (measure RBC transketolase acitivity, will be decreased because it uses B1 as a cofactor) beriberi= weakness and LOR in the lower limbs without endoneural inflamm

Question 206

guillain barre is caused by what bug

Answer 206

campy light microscopy shows segmental demyelination and endoneurial inflammatory infiltrate with lymphocytes and macrophages side notes: -botulism toxin is not actively secreted, its released into food upon autolysis it causes diplopia, diff swallowing, diff speaking within 12-36 hours (descending from the cranial nerves) -guillain barre is ascending from the lower extremities (symmetric, ab molecular mimicry, assoc with GI infection or URI because its due to campy) ``` -MG does not get better with repetitive nerve stimulation (ab to post synaptic nicotinic receptors) LEMS does (ab against pre synaptic voltage gated calcium channels) LEMS is assoc with paraneoplasic SCC of the lung (both= weakness starts in proximal extremities) ``` -puffer fish=tetrodotoxin= blocks sodium influx into nerves patient becomes consciously paralyzed -TCA are anticholinergics and overdose causes muscarinic blockade (BBSLUDGE)

Question 207

what is werdnig hoffman syndrome

Answer 207

spinal muscle atrophy type 1 degeneration of anterior horn cells due to mutation in SMN1 gene causes symmetric progressive weakness proximal>distal in childhood

Question 208

what are the overdose symptoms of a first line depression drug

Answer 208

SSRIs overdose: symptoms due to problems derived from *tryptophan she has serotonin syndrome ``` neuromuscular excitation: hyperreflexia clonus rigidity tremor ``` ``` autonomic stimulation: hyperthermia tachycardia diaphoresis vom/diarrhea ``` AMS: agitation confusion serotonin syndrome often presents when SSRIs given with MAO inhibitors or triptans tryptophan is a precursor of serotonin metabolism via tryptophan hydroxylase and amino acid decarboxylase tx= supportive serotonin receptor blockers =*cyproheptadine (a first gen antihistamine with nonspecific 5HT1 and 5HT2 receptor coverage) supportive treatment with short acting antihypertensives (esmolol, nitroprusside)... avoid longer acting ones like propranolol benzos can be used to treat the agitation and reduce HR and BP side notes: - glutamic acid is the precursor of GABA - histidine is the precursor for histamine (allergic reactions) - methionine is the precursor for cysteine, carnitine, taurine, and lecithin - tyrosine is a precursor for thyroxine, dopamine, epi, norepi, melanin - flumazenil is the antidote for benzo overdose