step 1 study deck 3 Flashcards
where is heme made
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
how can atrophic gastritis cause anemia (loss of gastric cells, replaced by fibrosis)
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
what is the most common brain tumor in children
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
what are the histology features of: ependymoma GBM medulloblastoma oligodendroglioma pilocytic astrocytoma
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)
describe alternative splicing
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
describe the blood flow through lung zones 1, 2, and 3
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
what is impaired that causes megaloblastic anemia
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
where do you see impaired pyruvate decarboxylation
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
where do you see intracellular transamination reactions
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
what is the difference between a localized carcinoid tumor and a metastatic carcinoid tumor
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,…
an enveloped RNA virus from animals can now infect humans, which virally encoded protein mutated?
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
give a couple examples of DNA methylation and diseases
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
what is epistasis and pleiotropy
epistasis= the allele of one gene affects the phenotypic expression of alleles in another gene
pleiotropy= single gene influences multiple phenotypic traits
what are the pulm function test results for COPD
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
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
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)
- 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
- infections (infections with encapsulated organisms, aka strep pneumo, which killed his brother because of his brother’s functional asplenia)
what causes hereditary angioedema
rare AD disorder
causes painless swelling to the lips, face, larynx, and extremities
caused by a C1 inhibitor def
what causes a left or right shift in the oxygen hemoglobin dissociation curve
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
what is familial erythrocytosis
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
what are beta globin tetramers and gamma globin tetramers called
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
what is the differences between prokaryotic and eukaryotic DNA replication
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)
why do you give vit A to kids with measles
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
what are caused by def in:
vit B6 (pyridoxine) vit B12 (cobalamin) vit D vit E vit K
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
what do these surface markers correlate to? CD4 CD7 CD8 CD14 CD20
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
Describe SCID
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
what cells are directly involved in a delayed type hypersensitivity reaction (type 4)
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
what does the pulomary function test results look like for normal aging
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
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
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
what is the brief description of how these present:
Granulomatosis with polyangiitis (Wegner’s)
Dermatomyositis
SLE
Low grade NHL
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
people with chronic granulomatous disease get what type of infections
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
what does this patient likely have?
new onset back pain without trauma
straining to urinate
osteoblastic lesions to the lumbar spine
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
how do exposures to these present:
asbestos
beryllium
coal dust
organic dust
silica
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
what is the difference between infectious mononucleosis (IM) caused by EBV vs CMV
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
what do these viruses typically cause?
coxsackie A
Acute hep C
JC virus
parvo B19
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
what problem most commonly follows a post strep GAS impetigo infection
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
what immune response do you get from the influenza vaccine
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
what is mucormycosis
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
what is the differential diagnosis of vaginitis
- 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)
what is the pathologic process of ARDS
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
describe hepatitis E
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
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
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
what two diseases are transmitted by the Ixodes tick
- 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!) - 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
how do dengue fever and malaria present
acute febrile illness
tropical regions
malaria= intravasc hemolysis
anemia
abnormal LFTs
blood smear with ring shaped (not cross shaped) erythrocyte inclusions
what vaccines are given to asplenic patients
ones to protect from encapsulated organisms
strep pneumo
h flu
neisseria meningitidis
what infection is found in the Ohio and Mississippi River and is associated with bird or bat droppings
histoplasmosis (fungal infection)
what bug causes meningitis resistant to cefotaxime
3rd gen cephalosporin
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
how does a urethral injury present in a male
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
if babies acquire HPV from their mom, where does it infect
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)
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
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)
how does ankylosing spondylitis present
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
how does fetal circulation differ from adult circulation
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
describe the development of different hemoglobins of a baby in utero
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
which bug is lactose fermenting, indole positive GNR
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
how do you differentiate between reactive hyperplasia and malignancy in a lymph node
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
what viruses can do genetic shift
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]
what abx do you use to treat aspiration pneumonia in an alcoholic
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)
what are the PaO2, SaO2, and oxygen content patterns for the following?
CO poisoning
cyanide poisoning
anemia (decreased hgb)
polycythemia (increased hgb)
high altitude
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
which bug is causing this?
nosocomial pnu
visualized with silver stain
slow growth on buffered charcoal yeast (supplemented with L-cysteine and iron)
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
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
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)
which toxin acts similar to diphtheria toxin
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
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
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
where to T cells live in lymph nodes
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.
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
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
name the agars and bugs
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
what are the virulence factors of ecoli and what do they do
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)
what does lead poisoning look like on histology
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
what bug caused this? 1 month old M winter cough SOB rhinorrhea congestion low grade fever wheezes and rales throughout
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
what is paroxysmal nocturnal hemoglobinuria (PNH)
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:
- hemolytic anemia (hemoglobinuria)
- pancytopenia (stem cell injury)
- 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
what/where drains into the superficial inguinal nodes vs the deep inguinal nodes
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
where are heterophile ab’s found
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)
what triggers the neoplastic change from hepatitis B into hepatocellular carcinoma
**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)
how do you prevent a PE in a post op patient
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
where do you see a valine (hydrophobic) substitution for glutamic acid (hydrophilic)
sickle cell disease
its a point mutation in the 6th position of the beta globin chain of hgb
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
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)
what is the difference between primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC)?
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
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
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)
what is injured with a stab wound (right sided) just above the clavicle between the midclavicular line and the lateral sternal line
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
what do these serum markers identify?
CD 15
CD 16
CD 19
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
what is the time course of TB after getting coughed on
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
what do each of these do?
IL 1
IL 3
IL 4
IL 5
INF gamma
IGF beta
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
what is the only fungus that lives intracellularly and causes systemic disease?
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
what do these fungus look like?
aspergillus
candida
cryptococcus
blastomyces
coccidioides
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
what are consequences of OSA
*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
a healthy 23 yo runs 5 miles, what do you expect at the peak of his exertion
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
