Missed Questions Uworld - Week 2 Flashcards
1
Q
What would signify a twisted, serpentine pattern/parallel chains of growth of a mycobacterial organisms?
A
Consistent with the presence of cord factor
Cord factor = mycoside = composed of 2 mycolic acid molecules bound to the disaccharide trehalose; correlates with virulence [responsible for inactivating neutrophils, damaging mitochondria and inducing release of TNF; inhibits macrophage activation]
In a mycobacteria, NO cord factor = NO disease
2
Q
What is the difference between T-test and analysis of variance test (ANOVA)?
A
T-test is used to cmpare teh difference between the means of 2 groups; when more than 2 groups are to be compared, ANOVA is used
3
Q
When does the epithelium of the airway change?
When you stop having goblet cells?
A
By the TERMINAL BRONCHIOLES, the airway epithelium changes from pseudostratified cilated columnar to cilated simple columnar
CIlia is present through the respiratory bronchioles but not present in the alvolear ducts or in the alveoli.
Mucin producing cells/goblet cells end in the smallest bronchi, just before the bronchioles begin
4
Q
What happens to the following in repsones to high altititude:
PO2, PCO2, pH
A
DEC PiO2 –> hypoxemia –> reduction in arterial oxygen tension –> triggers chemoR in the carotid bodies to stimualte ventilation –> HYPERVENT –> decrease in arterial CO2 –> respiratory alkalosis, pH rises acutely!, renal compensates by increasein the loss of bicar (24-48 hour delay)
2+ days –> complete or partial compensated respiratory alkalosis
Hypoxemia and the associated ventilatory response persists for hte duration of the ascent, but magnitude reduces with acclimatization
LONG TERM:
INC in 2,3 DPG, Hb, pulmonary diffusing capacity, vascular endothelial growth factor induced angiogenesis, INC cellular mito, hemoconcentration
5
Q
What are examples of delayed-type hypersensitivity reactions
How do the work?
A
CONTACT dermatitis, granulomatous inflammation, tuberculin skin test, candida extrac skin test
Type IV
delayed meaning they take about 1-2 days after antigen exposure [think of waiting 48-72 hours for TBtest]
Antigen is taken up by dendritic cells and presented to CD4+ T cells on MHC II molecules [usually TH1] release interferon-gamma –> stimulate and recruit macrophages leading to a moncytic infiltration of the area where the antigen is indtorudced
also “walling off” of infection
6
Q
Tx for oral thrush?
A
Candida fungi
Tx: Nystatin
swish and swallow
polyeye antifungal w/mxn similar to amphotericin B/ergosterol molecules in teh funal cell membrane - causing pores adn leakage of funacl cell contents
7
Q
Nocardia
A
gram positive rod - beaded/branched
partiall acid-fast, aerobic
affects immunocompromised
could seen as pulmonary infection (similar to TB), brain aabsecess, and skin
TX: sulfonamides, and drainage of abscesses
8
Q
APC and
+ IL 12 and interferon gamma –>
+ IL4
A
+IL12/interferon gamma –> TH1 –> inteferon gamma, IL2- lymphotoxin B
CELL MEDIATED [intracellular, mycobacterial infections]
activation of macrophages and CD8+ T cells
mediation of delayed type hypersen reactions
HUMORAL:
+IL4 –> TH2, b cell, plasma cells –> antibodies
initation of antibody response, regulation of immunoglobulin class switching
[extracellular viruses or bacteria]
9
Q
what bacteria are spore forming and found in soil?
A
Bacillus anthracis and membrers of hte genus clostridium
10
Q
Verenicline
Use?
A
Reduction of nicotine craving
reduction of pleasureable effects of cigarettes and other tabacco products
Partial stimulaiton of nicotinic acetylcholine R-
competes with nicotine (full agonist)
reduces nicotine withdrawal
prevents nicotine from binding and inducing rewarding response
11
Q
what is the deficiency seen in hyper IgM syndrome?
A
genetic deficiency in the enzymes responsible for isotype switching (such a d DNA recombinase) or in the CD40 T lymphocyte ligand that is essential in inducing B cell to switch classes
elevated/NL IgM
unable to synthesize all other immunoglobulin heavy chain constant regions
clinical effects = recurrent sinus and airway infections (due to IgA deficiency)
Tx: IvIg
12
Q
Decrease breath sounds could be an indicaiton of what? (5)
A
DEC breath sounds: pleural effusion, atelectasis/bronchial obstruciton, pneumothorax, or tension pneumothorax
13
Q
What is the characteristic breathing pattern seen in pt with advanced CHF?
A
Cheyne-stokes breathing
cyclic breathing pattern in which apnea is followed by gradully increasing then decreasing tidal volumes until the next apneic period
chronic hyperventilation with hypocapnia – induces apnea during sleep when the pp of CO2 falls below a certain level (apneic threshold)
[this type of breathing pattern is also seen in other neurologic disease states - stroke, brain tumors, traumatic brain injury - poor prognostic sign]
14
Q
When is kussmaul breathing seen?
A
Kussmaul breahting is deep and labored breathing pattern often associated with severe metabolic acidosis, particularly diabetic ketoacidosis
15
Q
What are common features seen in the sputum of asthmatics?
A
Curchmann spirals (shed epithelium formed whorled mucus plug)
Charcot-Leyden crystals (eosinophilic, hexagonal, double pointed, neddle-like crystals formed from breakdown of eosinophils in sputum)
16
Q
What are the different types of infections caused by candida in HIV pt with..
CD <500
and CD<100
A
@ CD <500: oral thursh
@ CD <100: esophagitis
17
Q
What is the classic presentation of Legionella?
A
High fever with relative bradycardia, headache confusion, pneum with watery diarrhea
Lab findings: hyponatremia, sputum gran stain showing many neutrophils but few to no organisms (often affecting smokers)
dx: urine antigen test
* acquring diagnositc sputum sample is difficult and unreliable, often sowing few or no bacteria since unique LPS chains on the outer membrane inhibit gram staining*
tx: respiratory fluoroguinolones or newere macrolides
18
Q
What is thought to cause sarcoidosis?
A
Dysregulation of cell-mediated immune response to an unidentified antigen that results in the formation of non-caseating granulomas
Cell-mediated is driven by Th1 type CD4+ T helper cells, secrete IL2 and interferon gamma
IL2- stimulates teh autcrine proliferation of TH1
Interferon gamma activates macrophages, promoting granuloma formation
Lung granuloma in sarcoid are result of intra-alveolar and interstitial accumulations of CD4+ T cells due to oligoclonal expansion and increased levels of IL2 and IFN-gamma
19
Q
Chronic granulomatous disease:
Pathogensis
clinical manifestations…what infections are highly seen?
Diagnosis:
A
Pathogen: inactivating mutation affecting NADPH oxidase [nl fxn: ROS formation, needed for microbicidal activity, activate granule proteases]
Clinical manifestations: recurrent infections with CATALASE POSITIVE bacteria and fungi
lungs, skin, lym, and liver most commonly involved, diffuse granuloma formation
Dx: measurement of neutrophil superoxide production
DHR flow cytometry (preferred)
NBT testing
20
Q
What are some catalase positive infections?
A
Staph Aureus
Burkholderia cepacia
Serratia marcesens
Nocardia
Aspergillus
21
Q
Why is pancreatitis a major risk factor for ARDS?
A
Pancreatitis results in the release of a large amount of inflammatory cytokines and pancreatic enzymes into the circulation, leads to infiltration of neutrophils into the pulmonary interstium and alveolar spaces
diffuse injury to the alveolar epithelium and pulmonary micorvascular endothelium results in a leaky alveolar capillary membrane and signficiant pulmonary edema
ARDS is typically characterized by progressive hypoxemia refractory to oxygen therapy and diffuse interstitial edema in the absence of cardiogenic causes
first 1-6 days, alveoli become lined with waxy hyline memrbanes
22
Q
What are the classic presentation of dermatomyositis?
What are 2 clinical signs associated with dermatomyositis?
A
Autoimmune
proximal muscle weakness and skin involvement including a violaceous discoloration of the upper eye lids (heliotrope rash) and raised violaceous scaling eruptions of the knuckes (Gottron’s sign)
CPK levels are typically elevated
23
Q
Clinical pres of pertussis
What are the stages (3)
A
aka whopping cough aka 100 years cough!
Three phases
- catarrhal stage - URI type of infection
- Paroxysmal stage - severe coughing spells, with the classic whoop or post-tussive emesis (puke!)
- convalescent stage - cough improves
cxr could be unrevealing
no vaccination or adult with no recent booster
24
Q
What mediates the cough reflex?
A
The internal laryngeal nerve (branch of superior laryngeal nerve CN X) mediates the afferent limb of the cough reflex above the vocal cords
this nerve contains only sensory info (in contrast to the external laryngeal and recurrent laryngeal) carries sensation from the mucosa superior to the vocal cords
**foreign bodies can become lodged in the piriform recess and may cause damage to the nerve, impairing the cough reflex
25
What nerves are involved in the gag reflex?
**Afferent** limb of the gag reflex is mediated predominately by **glosopharyngeal nerve CN IX**, while the **efferent limb is carried by the vagus CN X**
26
What fungus could produce allergic sensistivity to patients with asthma or CF?
What could be a consequence of recurrent sensitivites/reactions?
Aspergillus fumigatus -
asthmatics or pts with CF could develop an allergic hypersensitivty reaction to the fungus --\> allergic bronchopulmonary aspergillosis **ABPA**, which occurs in *_5-10% of corticosteroid-depedent asthmatics_*
Pts have high levesl of **serum IgE**, **eosinophilia**
and IgE + IgG serum antibodies to Aspergillus
intense airway inflammation and mucus plugging with exacerbations and remissions
repeated exacerbations may produce transient **pulmonary infiltrates and proximal** **_bronchiectasis_**
27
Two immunodeficiences could present with absent thymic shadow on CXR and recurrent infections?
What are the two and how can you distinguish between them?
Severe combiend immunodeficiency (SCID) and Thymic aplasia/DiGeorge sydrome
*_SCID_* - a T cell deficiencey --\> B cell deficiency too
you get **recurrent infections** of all - viral, bacterial, fungal, protozoa
**Failure to thrive**
**_DIARREHA_**, THRUSH (yeast!)
*_DiGeorge*_ - _*tetany_* due to **LOW CALCIUM (absent thymus and parathroid**) **LOW PTH**, LOW T cells
Reccurent infections - viral and fungal mostly
T cell deficiency
**CONOTRUNCAL ABNORMALITIES** (tetralogy of fallot, truncus arteriosus), **craniofacial abnormalities**
28
Sharp pain worse with inspiration could be due to what?
where cause this pain be refered to?
What nerves are involved?
phrenic nerve C3-C5, delivers motor innervation to the diphragm and carries pain fibers from the diphgramatic and mediastinal pleura
irritaiton of the *_**PARIETAL** pleura_* in either area will cause a sharp pain worsened by inspiration that will be referred to the **C3-C5 distribution at the base of the neck and over the shoulder**
**[visceral pleura has no pain fibers]**
29
What effect does a panic attack have on the arterial partial pressures?
Panic attack --\> hyperventilation --\> decreased arterial CO2
_hyperventilation DOES NOT decrease the pO2 or the arterial oxygen content_
Will produce **respiratory alkalosis**, increase pH and decreased pCO2
**\*Hypocapnia --\> cerebral VASOCONSTRICTION!\***
--\> decreased cerebral blood flow = *dizziness, weakness, blurred vision symptoms*
30
What congential abnormality is highly associated with CF pt?
What are the symptoms?
What is a differential diagnosis?
Meconium ileus
meconium obstruction at level of ileum, inspissated with _negative squirt sign_
distended abdomen, refuse to eat, palpable interstinial loops, _dark green emesis_, air fluid levels and small bowel dilation in plain film
enema doesn't relieve obstruction
**Hirschsprung disease** (lack of neuronal innervation - more associated with ***down's syndrome***, obstruction occuring at rectosgmoid post dilated colon/megacolon; normal meconium consistency and + squirt sign
31
What clinical triad is suggestive of a fat embolism syndrome?
ACUTE ONSET of **neurologica abnormalities**, **hypoxemia**, **petechial rash** in a pt with a severe _long bone and or pelvic bone fractures_
most commonly in the first 24-72 hours but can occur up to 2 weeks later
fat from bone marrow --\> vascular sinusoids -\> *pulmonary microvessels*
**occlusion of microvessles impairs pulmonary gas exchagne and induces hypoxemia**
free FA cause local **toxic injury to the endotheium** with the potential to cause **ARDS**
others escape via **precapillary AV shunts** that open due to increase *_pulmonary artery pressure_* --\> CN, dermal capilaries, and sometimes thrombocytopenia due to platelet adhesion
32
Sudden upward jerking of the arm could cause injury to what nerves?
What clinical presentation could this have?
injury to the **lower trunk of the brachial plexus** - carries nerve fibers from **C8 to T1**, that contribute to the *_median and ulnar nerves_*
--\> **innervate all the intrinsic muslcs of the hand**
Injury to the lower trunk of the brachial pelxus --\> paralysis of all the intrinsic hand muscles = **Klumpke's palsy**
relative _sparing of the extrinsic flexors_ and _extensors_ of the hand contributes to the total claw hand deformity
[lumbricals normally flex MCP joints and extend DIP and PIP]
33
What type of test could be used to rule out asthma?
why is this useful?
Methacholine challenge test
a cholinergic muscarinic agonist
assesses bronchial hyperactivity, a central pathophysiological feature of asthma. BHR can be quantified as teh concentration of an inhaled aerosolized bronchoconstrictive substance req to produce a **20% decline in FEVi**
because this test has _high sensitivity_, used to **exclude a diagnosis**
**SNout = sensistivty rules OUT**
**SPIN = specificit rules IN**
34
What is a cross-over study?
Subejcts are randomly allocated to a sequence of 2 or more treatments given conesecutively - simplest model is a AB/BA type of study in which subjects allocated to teh AB study receive treatmetn A followed by treatment B, and viseversa in the BA arm
Crossover trials allow the patietns to serve as their own controls
DRAWBACK - teh effects of one treatment may "carry over" and alter the response to subsequent treatments/confounding effects; to limit this disadvantage, a washout (no treatment) period is often added between consecutive treatments. The washout period is designed to be long enough to allow the effects of prior treamtents to wear off
35
Clinical features of Turners syndrome
XO:
Short stature, broad chest
cystic hydromas (congenital lymphatic malformation) --\> web neck
lymhadema in hands and feet
ovarian dysgenesis (abnl growth during embryonic growth and develeopment and ***_premature ovarian failure/amenorrhea/premature menopause_***), **streak gonads** --\> *_dec estrogen --\> inc LH/FSH (due to lack of negative feedback)_*
*Inc risk to develop dysgerminomas*
**BICUSPID aortic valves**
**PREductal coartation** (intracardiac anomaly during development, leads to decrease blood flow through the left side of the heart --\> hypoplastic development of the aorta)
Horseshoe kidneys
NL ovarian development during fetal life BUT lack of parental X during development, causes loss of ovarian follices by age 2 -- 45X.
36
What is renal blood flow?
RBF = volume of blood that flows through the kidney per unit time
RBF - dependent on the pressure difference between teh renal artery and renal vein, as well as the resistance in the renal vasculature
*tightly regulated, to keep RBF constant over a wide range of systemic blood pressures*
RBF = [renal artery pressure - renal vein pressure] / renal vasulature pressure
**RBF = PAH clearance / (1-hematocrit =plasma)**
**PAH clearance = (urine [PAH]Xurine flow rate) / plasma [PAH]**
37
Tx for gonorrhea?
Third generation cephalosporin (**ceftriaxone**) + macrolide (**azithromycin** or doxyclicine - possible chlamydia co-infection)
38
Where does heme metabolism occur and what is the pathway?
Heme metabolism starts in in macrophages
via heme oxygenease --\> biliverdin (giving a green color if in a bruise) --\> + biliverdin reductase to bilirubin
Unconjugated bilirubin binds to albumin in the blood and is further removed by the liver, where it is conjugated by UDP-glucuronosyl-transferase/bilirubin glycuronyl transferase/UGT to conjugated bilirubi by glucoruonic acid and further moved in bile
39
What vitamin a overdoes could lead to intracranial hypertension, skin changes and hepatosplenomegal?
Vitamin A
Three stages: acute, chronic and teratogenic!
Acute - can occur after a single ingestion of a single high dose of vitam in A --\> n/v, vomiting, vertigo and blurred vision
Chronic - alopecia, dry skin, hyperlipidemia, hepattoxici, hepatospleno, visual difficulties; papilledema when present, is suggestive of cerebral edema in the setting of benign intracranial hypertension(psedutumor cerebri)
Teratogenic effects --- excessive vitamin A ingestion, include mcirocephaly, cardiac anomalies, fetal death (esp first trimeseter)
40
CN III exits where in the brain stem?
What arteries could affect this nereve? where would a deficit be localized to?
What eye is affected?
CN III / oculomotor carries general somatic efferent fiber and general visceral efferent paraysmpathteric fiber, exits the midbrain and courses between the posterior cerebral and superior cerebellar arteries
aneuryms arising from either artery can lead to a non-pupil sparing third nerve palsy, which presents with unilateral H/A, eye pain, diplopia, dilated nonreactive pupil and ptosis with teh **IPSILATERAL** eye in teh down and out psoition
41
The medication polyethylene glycool is used for what and is similar to what dz?
Constipation
similar to lactase deficiency
osmotic laxatives = non absorable/poorly absorable substances that attract water into the itnestinal lume, thus distending the intestinal wall and increasing peristalsis
rapid laxative effect
[magnesium hydroxide and other magnesium containing compounds such as magnesium citrate are other osmotic laxatives]
42
difference between osmotic and secretory diarrhea?
Osmotic is uusally due to an offending agent, and usually goes away when the agent is removed (ie - lactose); it is watery, and loose
Secretory, does not stop with feeding/does not stop with fasting, watery and loose and high in electroylte content (ie high in chloride and potassium!) high volume
43
what are example of dzs are associated with the following deficiencies?
T-cell dysfunction?
Deficient intraceullar killing?
Inability to form the MAC?
T-cell dysfunction? DiGeorges; thymic hypoplasia, recurrent viral and fungal infections
Deficient intraceullar killing? chronic granulomatous disease (increased infection with catalase POSITIVE, staph etc- inability of phagocytes to syntheseize NADPH oxidase, an enzyme essential to the lysosomal oxidative burst)
Inability to form the MAC? recurrent infections by **Neisseria** species
44
Coronary artery blood flow -
when does it occur?
what regulates it?
occurs during dyastole
During the zone of autoregulation, increases in coronary blood flow are primarily mediates by the relative myocardia hypoxia that occurs during times of increased work
increased myocardia oxygen requirements during exercise can only be achieved hrough corresponding increases in coronary blood flow since extraction of oxygen is already at a max
**Nitric oxide** and **adenosine** are the most important factors involved in coronary blood flow autoregulation
45
What is the most significant risk factor for UTI in a catherized patient?
the DURATION
preventative measures include: avoiding unncecessary catheterization, using sterile technique when inserting the cather and removing the catehrer promtply when no longer needed
46
Inferior MIs are associated with what type of HR change?
what medication is give and what is a some side effects?
Bradycardia, since usually inferior MIs are due to blockage of RCA, and thus the artery respoinsible for the SA and AV node perfusion
Atropine blocks vagal influence on the nodes, effective in increasing HR in patients
Atropine side effects are due to the **muscarinic receptor blockade in other organs**
in the eyes- mydriasis, results in narrowing of the anterior chamber angle and diminished outflow of aqueous humoer - precipiates angle-closure glaucoma in pt with shallow anteiror chambers or higher tha normal intraocular pressure; presents iwth unilateral severe eye pain and visual distubrances
47
what could prevent herpes reactivation?
recurrence of genital herpes can be reduces through **daily treatment** with oral valacyclovi, acyclovir or famciclovir.
48
C. tetani,
what is its mxn of pathogen?
what can protect us from it?
**Tetanospasmin**, is a protein **extoxin** produced by C. tetani that can travel by a **RETROGRADE** axonal transport into the CNS -- *_heavy chain binds ganglioside receptors on neuronal membranes and the light chain inhibits release of glycine and GABA from inhibitory interneurons_*
--\> absence of interneurons inhibitor NT = sustain muscle contration/tetanus
Prominent sx: masseter muscle spasms/lockjaw, **opisthotonos**, dyphagi and facial muscl spasm/**risus sardonicus**
tantanus is preventd by tetanus toxoid/formaldehyde-inactivates tetaus toxin vaccination-- elicits **HUMORAL immunity specific for TETANUS TOXIN and for prophylaxis** after an injury if the wound is grossly contamintated = ***_antitoxoin antibodies_*** / active immunity
49
What could cause QT prolongation in a young individual, otherwise healthy?
Usually congenital
Jervell, lange-Nelsen Syndrome (cardio + sensorineural deafness)
Romano-ward syndrome (cardiac only)
QT inverval begins at QRS and ends at end of T wave, prolongcation reflects prolonged action potentional, determined in part by potassium currents though channel porteins, contributing to the delayed rectifier current Ik of the cardiac action potential
may predispose to torsades de pointes / ventricular tachyarrhythmia
50
What requirements must be bet for an RNA molecule purified from a virus **to be infectious**?
= on its own, must act as a mRNA capable of using the host's intraceullar machinery for translation
**= single-stranded POSITIVE sense virus**
**RNA SS negative strands require an RNA-depedent RNA polymerase**
**dsRNA - requires a specific viral RNA polymerase, present intact virion to gain entry into the host cell**
51
what area of the eye is associated with the left temporal hemiretina?
how is this visual field processed? (what is the pathway?)
The left temporal hemiretina receives visual info from teh nasal visual field
Visual info then remains ipsilateral to that eye...transmitted via the left optic nerve to the lateral aspeic of the opti chiams, then joins the visual signals from the right nsal hemiretina, and travesl via the left optic tract to the left geniculate body in the thalamus, then travels via the ipsilateral optic radiations to the ipseilateral primary visual cortex for visual processing
52
What are symptoms associated with hydrocephalus?
What are potential complications?
macocepahly, poor feeding, muscle hypertonicity, hyperrefelxia (due to **upper motor neuro injury** cauesd by **stretching of the periventricular pyramidal tracts**!)
TX: surgical placement of a shunt to bypass teh obstruction most often iva teh ventriculoperitoneal route
53
Presentation of tertiary syphillis
cardiovascular involvement with gummas
gummas = necrotizing granulomas occuring on the skin, mucosa, subcutaneous tissue and bones or within other organs
[chancre is seen in primary syphillis; condylomata lata occuring during secondary syphillis]
neurosyphilis can occur at ANY STAGE (VDRL positive of CSF)
54
drug of choice for beta blocker overdose?
Beta blocker overdose --\> diffuse non-selective blocakde of peripheral beta adrenergic receptors, causing depression of myocardial contractility, bradycardia and varying degress of AV block = low cardiac output stage
**_Glucagon_**, drug of choice for beta blocker overdose
*_acts of G protein coupled receptors_*, increasing intraceullar cAMP and thus increasing the release of intraceullar calcium druing muscle contraction
increasing heart rate and cardiac contractility
55
What type of injury does CCl4 produce?
CCL4 is **oxidized by the P450 oxidase** system in the liver
--\> **formation of the free radical** CCl3 which reacts with structural lipids of cell membreanes --\> lipid degradation and hydrogen peroxide formation = **lipid peroxidation --\> form new radicals,**
cell injry due to CCl4 develops rapidly and leads to swelling of the ER, destruction of mitochondria and increased permeability of cell membranes = culminate in hepatocyte necrosis
56
Theophylline:
indication
overdose sx
overdose indication
Used to treat asthma and other lung dz
acute intoxication - n/v, abdominal pain, diarrhea, cardiac arrhythmias, seizures
*_**Seizures** are the major_* cause of morbidity and mortality in theophylline intox
**tachyarrhythmias** are the other major concern but usually donot cause QT prolongation
57
What type of reaction is associated with membraneous nephropathy?
Idiopathic membranous nephropathy is associated with circulating **IgG4 antibodies** to the **phospholipase A2 receptor** which might play a role in the development of the disease
58
What AA is only essential during times of growth?
**Arginine**
Time period of positive nitrogen balance
[recall arginine is also essential for NO production]
59
What are period of positive nitrogen balance?
= amt of nitrogen incorporated exceed the amount excreted and its associated with:
Growth
Pregnancy
recovery phase of injury or surgery
recovery from condition associated with negative nitrogen balance
60
what conditions are associated with negative nitrogen balance?
Neg nitrogen balance = nitrogen loss exceeds incorporation
Protein malnutrition (Kwashiorkor)
Dietary deficiency of even 1 essential amino acid
starvation
uncontrolled diabetes (increase protien breakdown needed for gluconeogenesis)
infection (break down of tissue and etc)
61
how do you calculate initial drug concentration?
How is a drug eliminated in zero-order kinetics?
How is a drug eliminated in 1st order kinetics?
Initial drug con = inital dose / vd
Vd = volume distribution; theoretical volume of drug required if it was all in the plasma; higher Vd = drug binds more to tissue, etc
Zero- order kinetics refers to a constant amount of drug being eliminated no matter how much concentration is left.
* capacity limited elimination*
* PEA = phenytoin, ethanol, aspirin (a pea looks like a 0)*
1st order kinetics follows half life; every half life, 50% of the drug is eliminated; rate of elimination is directly proportional to drug concentration
*flow limited elimnation*
62
What characterizes nephrotic syndrome?
which is hte most common nephrotic syndrome in adults?
generalized edema, marked proteinuira \>3.5 g/day
membranous glomerulopathy
spike and dome appearance; diffuse thickening with NO increase in cellularity (vs membranoproliferative glomeruloneprhitis - hypercellular glomeruli)
85% are idiopathic
others are secondary to:
1. Systemic diseases: DM, solid tumors (lung/colon), immunologic disorders (SLE)
2. Certain drugs - gold, penicillamine, NSAIDS
3. Infections - hep B, hep C, malaria, syphillis
63
How would you calculate incidence?
how would you calculate RATE of incidence?
Prevalence?
Mortality rate?
of NEW cases / total population AT RISK (ie - population without the dz)
of new cases minutes number of deaths/cures / TOTAL population
Prevalence = # of ppl with dz/total population at a specific point of time
of deaths per year / TOTAL population
64
What would be the pancreatic makeup of an individual with DM I?
With DM II?
**_DM I_**: strong linkage with HLA class II makeup, pacreatic iselt infiltration with leukocytes (insulitis) and antibody against iselts antigents; genetics HLA-DQ and DR are most important determinants of type 1 DM; DR4 and DR4 haplotypes are seen in more than 90% of subjects
_**DM II**, due to increased insulin resistance or defective insulin secretion:_ pancreatic iselt **amyloid (amylin polypeptide)** deposition, NO INFLAMMATION! Genetics plays a role but unknown
-amylin is stored in insulin secretory granulesa nd is co-secreted with insulin from pancreatic beta cells...deposits of amylin are universally seen in the pancreatic iselts of pt with DM II
65
What are the gene mutations associated with alzheimers?
Az has a strong genetic predisposition; 30% of pt have a family hx of dz
**Early-onset (familial Az Dz is associated with three gene mutations: Amyloid precursor protein (APP on chrome 21), presenilin 1 (chrom 14) and presenilin 3 (chrom 1)**
--\> thought to promote the production of A B-amyloid
**Late-onset** familial Az Dz is associates with _apolipoprotein E4 genotype_ (thought that ApoE4 could be involved in the formation of senile plaques)
66
Where is enterococcus normally colonized within our bodies?
After when could we see endocarditis?
Enterococcus is a component of the normal colonic and urogenital fora and is capable of growing in hypertonic saline and bile
It is a gammy-hemolytic, catalase-negative and pyrrolidonyl arylamidase-positive
Enterococcal endocarditis represents **about 30% of nosocomial endocarditis** cases (usualy elderly men who have recently undergone manipulaiton of areas colonized by the organism)
**GU instrumentation or catherization** has been associated with enterococcal endocarditis
[dental extraction is associated with endocarditis caused by viridans group strep - causes SBE in already abnormal heart valves; S bovis could cause bacteremia/IE associated with colonic cancer]
67
What is the mechanism of action of omalizumab?
recombinat huminized IgG1 monoclonal antibody that bidns withIgE to inhibit the action of IgE with its receptor on mast cells, basophils and other cell types, and decreases allergic response.
68
Panic attack?
Immediate and long-term treatment
Immediate- bezodiazepines
long-term- SSRI/SNRI and/or cognitive behavior therapy
69
What drug should we worry that might mask hypoglyemic symptoms in patients with diabetes mellitus?
**insulin-secreting pancreatic B cells** have both **alpha2** and **beta2 receptors** - simulation of alpha2 receptors inhibits insulin secretion, stimulation of **beta2 receptors INCreases insulin secretion**
**Non-selective beta blockers** exacerbate hypoglycemia and MASK its adrenergic symptoms mediates by noreepinethrine and epinephrine
For this reason, they should be used with caution in patients with diabetes mellitus
If B-blocker is necessary, **selective B1 antagonist** should be used instead.
70
Why can't mature erythrocytes syntehsize heme?
Describe heme synthesis:
They use their ability to sytnehseize heme when they lose their mitochondria.
Mitochondrai is ncessary for the first and final 3 steps of heme synthesis.
Heme synthesis- occurs partyly in the mitochondria and partly in the cytoplasm. It is synthesized in virtually every organ but the principal sites of synthesis are erythrocyte precursor cells (located in the bone marrow) and hepatocytes (use heme in microsomal cytochrome P450 system)
71
# Define the following:
Adenomyosis:
Leiomyoma:
Endometriosis:
Posterir vaginal wall prolapse:
**Adenomyosis:** when endometrial tissue exits within and grows within the muscular layer of the uterine wall; usually presents with dysmenorrhea, abnormal uterine bleeding and/or chronic pelvi pain in parous women; bulk related symptoms are atypical; usually presents as uniform, globular uterine enlargement
**Leiomyoma**: aka fibroids. monoclonal tumors, each derived from a distinct progenitor cell; can be located on the serosal surface of the uterus (subserosal), within ithe uterine wall (intramural) or below the endometrium (submucosal). Irregular uterine enlargement could put pressure on other organs causing bulk-related symptoms/pelvic pressure. Fibroids in teh posterior uterus can put pressure on the colon and can lead to constipation; while others can cause urgency, incomplete emptying...
Endometriosis: **endometrial tissue found outside of the endometrium ;** 2 out of the following 3 - endometrial glands, endometrial stroma hemosidern pigment
Posterir vaginal wall prolapse: rectocele, can also cause constipation but not uterine enlargement
72
Lesch-Nyhan Syndrome
Etiology
Pathogenesis
SX: Gout/hyperuricemia, intellectual disability, self-mutilating behavior in a boy, dystonia, chreoathetosis
X-linked recessive
**Deficiency: HGPRT** = hypoxanthine-guanine phosphoribosyltransferase enzyme, that normally functions in the **purine salvage** pathway to *_convert hypoxanthine back to inosine monophsphate and guanine back to guanosine monophsopate_*
ABSENT HGPRT --\> INC degradation of guanine and hypoxanthine bases in uric acid --\> **INC the demand for de novov _purine_ synthesis**
73
What is the typical clinical presentation for someone with atropine poisoning?
What antidote could be given?
"blind as a bat, mad as a hatter, red as a beet (although it vasoconstricts), hot as a hare (hyperthermia), dry as a bone, the bowe and bladder lose their tone and the heart runs alone"
**Atropine** = reversible _cholinergic antagonist_ that selective acts on muscarinic recetpors
Effects can be reversed by cholinesterase inhibitors (**physostigmine**)
Think of this when: Jimson weed/datura stramonium posoning aka Gardener's mydriasis - jimson weed produce toxins (belladonna alkaloids) that posses strong *_anticholinergic properties_*
74
How is menopause diagnosed?
occurs on average about ~ 51 y/o, diagnosable retrospectively after 12 months of amenorrhea, an elevated FSH level confirms diagnosis
Ovarian failure before teh age of 35 is considered premature
During the menopause transition, **FSH levels increase** due to ***_resistant ovarian follicles and lack of feedback from inhibin; estradiol and progesterone levels gradually decrease during the menopaus transition due to decreased ovarian function_***
sx: related with hypoestrogenic symptoms (hot flashes, vaginal dryness)
75
Bulimia nervosa is..
an eating disorder characterized by alternating binging and compensatory wt reduction (vs binge eaters). Pt can develop bilateral parotid gland enlargement, erosion of tooth enamel, irregular menses adn abnormal electrolytes
Also seen, INC salivary amylase, calluses on the dorsum of their hands (Russell sign)
76
What would an ectopic pregnancy reveal?
Ectopic pre is characterized by implantation outside of the uterus; it would reveal decidualized endometrium only, consistent with dilated, coiled endometrial glands and vascularized edematous stroma - these changes occur in the luteal phase of the menstrual cycle, under the influence of progesterone as the endometrium prepares for implantation.
Embryonic and trophoblastic tissue will be absent from the from the uterus. (no villi)
[if glands are found, it would be indicative of endometrial adenocarcinoma]
77
Myasthenia Gravis could be classified as what type of hypersensitivity?
Type II hypersen, characterized by IgM and/or IgG autoantibodies that bind to cell surface antigens and/or extracellular matrix compoennts
Another example: Godpasture syndrome - production of autoantibodies directed agaisnte the glomerular basement membrane collagen in the renal glomeruli and lung alveoli
78
How is Neisseria meningitidis transmitted?
how does it become mengitis?
Neisseria meningitidis transmits person to person via respiratory droplets usually from asymptomatic carriers with nasopharyngeal clonization -- invading mucosa epithelium and gaining access to the bloodstream... It then enters the blood stream and subsequently colonizes the choroid plexus through the BBB and enters the meninges causing meningitis.
79
Which veins are used for bypass grafting?
Usually, the **left internal mammary (thoracic) artery** is the preferred vessels for bypass grafting due to superiorpatency rates -
When multiple are coronary arteries or vessels other than LAD require revascularization, **great saphenous** vein grafts are commonly used
Located SUPERFICIALLY in the leg, and is hte longest vein in the body
Coarses superiorly from the medial foot, anteror to the medial malleolus, and up the medial aspect of the leg and thigh.
Surgenous access the great saphenous vein in the medial leg or less commonly near its point of termination in the femoral triangle of hte upper thigh
80
What are the costellation of symptoms involved in temporomandibular disorder and what nerve is most likely involved?
include - uniliateral facial pain that worsens iwth jaw movement and ear discomfort
sx originate from temporomandibular joint TMJ derangement, pathologic contraction of the muscles of mastication and hypersensitivity of the nerves that supply the jaw
the Mandibular nerve is the largest branch of the trigeminal nerve and contians both motor and sensory componets, It supplies sensation to the TMJ and mandibular teeth, etc...
motor fibers innervate teh muscles of mastication (medial and lateral pterygoid, masseter, temporalis), muscles of the floor of the mouth, tensor veli palatini and the tensory tympani in the middle ear.
As a result --\> pt with TMD involving the mandibular nerve can have both jaw pain and otologic symptoms
81
What is the sequence of BASE excision repari?
(not to be confused with NT excision repari or mismatch repair)
**glycosylase --\> endonuclease --\> lyase --\> polymerase --\> ligase**
beings with recognition of abnormalbases by sepecific glycosylates --\> cleave the altered DNA bases from the parent DNA molecule, leaving an empty surgar phosphate site called an apurinic/apyrimidinic site --\> endonuclease then cleaves the 5' end of the AP site before a lyase (phosphodiesterase) enzyme subsequently completes extraction of the AP site form teh DNA molecule by removing the remaining sugar pshonate
DNA polymerase then fills the gap with the corrected surgar phosphate base --\> sealed by ligase
82
Patients with prolong and profound neutropenia are esp high risk for viral and fungal infections
What are the most common fungal spp?
**Aspergillus** -- pulomonary; think immunocompromised pt; combo of fever, chest pain, cough, dyspnea and hemoptysis
**Candida**
83
**What are the common effects:**
Loop direutics [furosemide, bumetanide, torsemide]
hypokalemia, hypomagnesemia, hypocalcemia and ototoxicity
84
What are the common effects:
Thiazide diuretics [chlorthalidone, hydrochlorothiazide]
hypokalemia, hyponatremia, **hyperuricemia** and **hypercalcemia**
**@distal convoluted tubule, cause enhaced Na+, Cl- and water excretion**
Thiazides work by blocking Na+/Cl- symporters in the distal convoluted tubules, causing enhaced Na, Cl and water excretion.
Since only a small amt of filtered Na+ reaches the distal tubules, thiazes are not as efficacious as loop diuretics; unlike loop diuretics, thiazides can cause hypercalcemia
85
What are the common effects:
Potassium sparing diuretics [triamteren, spironolactone]
ALL - hyperkalemia
additionally, spironolactone causes gynecomastia, anti-andrgen effects
86
What are the common effects:
Carbonic anhydrase inhibitors [acetazolamide]
Metabolic acidosis
87
What are the common effects:
Osmotic diuretics
mannitol
**hypernatremia**, **pulmonary edema**
88
What is the histology of folicular lymphoma?
Follicular lymphoma is a type of non-hodgkin's lymphoma
B-cell tumor composed of predom centrocytes with fewer nuber of centroblast
Lymphopoliferative disorder
It is characterized by aggregates of packed follicles that obsucre the normal lymp node architecutre
90% of pt with follicular lymphoma have a **t(14,18)** translocation, which causes overexpression of the
**anti-apoptotic BCL-2 protein**
89
Where could we see N-Myc?
overexpression of N-Myc proto-oncogene protein is common in neuroblastoma and small cell carcinoma of the lung
90
What cultures can be used to grow C. diptheriae?
cysteine-tellurite agar as dark black, slightly iridescent colonies
Loffler's medium wehre it will develop cytoplasmic metachromatic granules
91
What is MacConkey agar used to gro?
Can grow many enteric bacteria
is a bile-salt containing agar that restricts teh growth of most gram positive organism
92
What is bordet-Gengou medium used for?
used to culture the very sensitive bordetella pertussis, causitive agent in whooping cough
93
What medications should be AVOIDED in a patietn with hypertrophic cardiomyopathy?
Pt with HOCM have a **dynamic left ventricular outfow tract** (LVOT obstruction) that **worsens with dec left ventricular volume** - caused by pt ecreased preload and/or reduced systemic vascular resistance
_AVOID_
**Vasodilators** (dihydropyridine calcium channel blockers, nitroglycerin and ACE inhibitors), decrease systemic cascular resistance, leading to decreased afterload and lower Lv volumes
**Diuretics** - decrease LV venous filling/preload and greater outflow obstruction
94
Excess accumulation of transudative fluid in the interstitial tissues occurs under what conditions:
(4)
1. Elevated capillary hydrostatic pressure
2. Dec plasma oncotic pressure
3. Sodium and water retention
4. Lymphatic obstruction
Moderate increase in capillary fluid TRANSUDATE can be offsent by a compensatory INC in tissue lymphatic drainage that ocurs due to INC interstitial fluid.
Clinically apparent edema appears only when net plasma filtration has risen sufficiently to overwhelm the resportpive capacity of the tissue lymphatics.
95
BCl-2 normal action?
Inhibits apoptosis via **prevents cytochrome C** from escaping the mitochondira --
[cytochrome C would leak out and activate captases,etc --\>apoptosis]
Overexpression of BCl2, occurs in follicular lymphoma, secondary to translocation of the bcl-2 oncogene from chromsome 18 to the Ig heavy chain locs on chromosome 14 [t(14,18)]
96
Follicular lymphomas express what tumors?
Express pan B-cell antigens (CD19, CD20 and CD 79a), CD21 adn CD10
The characteristic cytogenetic abnormality associated with follicular lymphoma is translocatio of the bcl-2 oncogene from teh 18 to the Ig heavy chain locus on chromosome 14
Juxtaposition of the bcl-2 gene with teh Ig heavy chain region results in overexpression of the Bcl2 portien product--\> protein inhibits apoptosis of tumor cells = facilitating neoplastic growth
97
What is conductive hearing loss?
What is sensorineural hearing loss?
How can the Rinne and Webster test be used to determine either?
Conductive = imparied transmission of air vibrations to inner ear
Sensorineural = cochlea or auditory nerve involvement
**Rinne**: compairs air vs bone conduction via the mastoid bone
Air is heard louder and longer than bone..therefore there is a positive/normal test if the sounds ins heard best at the external auditory meatus (air conduction) and negative (abnormal) if the pt hears the vibration better at the mastoid
**If bone conduction is greater than air conduction suggests conductive hearing loss**
**Weber:** performed by placing a vibrating tuning fork on the middle of the forehead equidistant from both ears. Vibration carried by the bone conduction isnormally heard equally in both ears...vibration heard louder in one ear is abnormal.
Conductive hearing loss --\> laterization ot the affected ear (as conduction deficit masks the ambient noise in the room, allowing the vibration to be heard better)
Sesorineural hearing loss --\> laterizaiton to the unaffected ear as the unimpiared inner ear can better sense the vibration
98
What does the arteriovenous concetration gradient of a drug reflect?
What does this tell us abou tits onset of action?
AV concentration gradient is the difference between the concentration of a gas anesthetic in arterial and venous blood - the solubility of the anesthetic in the peripheral tissue is a major factor determining the size of AV gradient
AV concetration gradiet reflects the overall tissue solubility of an anesthetic
Anesthetics with high tissue solubility are characterized by **large AV** concetration gradients and **SLOWER onsets of action.**
99
In DKA patients, what must be measured along with administration of insulin?
Potassium, to avoid hypokalemia
Insulin stimulates the shift of potasisum from the ECM compartment to the intracellular compartemnt --\> decreasing serum potassium levels
Hyperkalemia occurs in untreated DKA because low pH will cause hydrogen ions to go into cells whichoccurs in exchagne for positive charged ions that moves out of the cells, leading to hyperkalemia.
Initial management of DKA requires aggressive fluid resuscitation and correction of hyperglycemia with insulin
100
finasteride:
mxn?
what is it used for?
WHat is a common side effect of
5-alpha reductase inhibitor; decreases conversion of testosterone to DHT
used for BPH and male pattern baldness
common side effect is: increase hair growth
101
What symptoms would point us to DiGeorge Syndrome?
What is it due to?
What are the three major organs that includes?
Recurrent infections, thymic hypoplasia/aplasia, cleft palate, VSD
DUe to 22q11 microdelection --\> variable presentation
CATCH-22
Cleft Palate
Abnormal Facies
Thymic aplasia --\> T-cell deficiency
Cardiac defects (VSD, tetralgy of Fallot, truncus arteriosus)
Hypocalcemia
22q11 deletion
Specifically includes: thymic, parathyroid and cardiac defects
102
What compound is the primary reducing equivalent (ie - electron carrier) used in tissues that synthesize steroids?
NADPH is the electron carrier used for steroid synthesis. It serves as a carrier for reducing equivalents
NAPDH is a product of the HMP shunt
Derived from Vitamin B3 / niacin
NADPH is used in:
Anabolic processes (steroid and fatty acid synthesis), respiratory burst, cytochrome p450 system, gluthiaone reductase
103
What are the side effects of prednisone?
What vitamin supplement could modulate some of the adaverse effects?
side effects include: cushing-like symptoms, increased risk for infection, cataracts, acne, hypertension, hyperglycemia, peptic ulcers and psychosis, osteoporisis
exercise, calcium, VITAMIN D, bisphosphonates and in postmeno women estrogen therapy all help reduce incidence of osteo in the setting of predniseon although dont appear to prevent bone mineral loos from teh femoral beck or distal radius
104
What is the drainage of the RIGHT adrenal gland?
What other orgran mirrors this flow?
right adrenal vein --\> IVC
VS left side..
drianed into the left adrenal vein --\> left renal vein --\>IVC
105
What is Conn syndrome?
= *_primary_* **_HYPERALDOsteronism_** from an adrenal adenoma
primary hyperaldo can also come from bilateral adrenal hyperplasia but Conn syndrome is associated with failure to suppress aldosterone with salt loading
Conn would be seen as a single well-circumscribed adenoma with lipid-laden clear cells
106
what dz are associated with HLA DR5?
Hashimotos Thyroiditis
Pernicious anemia
107
What is one way to tell he difference between ectopic ACTH and adrenal adenoma?
ectopic - ACTH will not be low
adrenal adenoma --\> lots of cortisol thus neg feedback on anterior pit --\> dec ACTH
108
what are elevated levels of urine metanephrine indicative of?
increased catecholamines and metanephrines in the urine and plasma are indicative of **pehochromocytoma**
[most tumors secrete epinephrine, NE, DA --\> episodic hypertension; sx occur in "spells", relapse and remit]
sx: 5Ps - **Pressure (INC bp), pain (h/a), Perspiration, Palpitations, Pallor**
treatment would be irreversible alpha antagonist (ie-phenoxybenzamine) followed by beta-blockers prior to tumor resection.
alpha blockade must be achieved before giving beta-blockers to avoid hypertensive crisis
109
what is the genetics behind achondroplasia?
autosomal dominant form of dwarfism, FGFR3 gene --\> abnormal cartilage formation
short staturew with short limbs but usually have a nearly normal sized head and trunk,
associated with advanced PATERNAL AGE
110
how could we tell 17alpha hydroxylase deficiency from 21 hydroxylase deficiency?
BOTH have virilization in XX from excess testosterone
21 --\> HYPOtension (could present with syncope)
17 --\> HYPERtension, due to to 11-deoxycorticosterone
BOTH low adolsterone
111
Supracondylar humoral fractures are common pediatric elblow fractures often occur after hyperflexion or hperextesion injuries (falling onto an outstretched arm)
What nerve or artery is most likely to be affected in an anterolateral displace of the proximal fracture frament?
In a medialateroal displacement?
common sx.
Anterolateral displacement --\> radial nerve [radial n. runs in the anterior lateral aspect] --\> wrist drop due to denervation of hand/finger extensor muscles + sensory loss over the posterior forearm/dorsolateral hand
Mediolateral --\> median nerve and brachial artery injury
--\> w/medial neuropathy have sensory loss over the first 3 digits and weakness on flexion of the first 3 digist and wrist.
--\> brachial artery may result in a pulesless hand due to vascular insufficiency
112
What is one important characteristic of costosternal syndrome that separates it from other chest pains?
reproduced with palpation, worsen with movements or changes in position (ie - horizontal arm flexion), no palaple warmth, swelling or erythema
113
Percarditis...how do the follwing changes alter the pain?
Laying flat?
Leaning foward?
Inflammation of pleura or periocardium --\> sharp pain worsen with inspiraiton
- usually folllows URI
Laying flat --\> WORSE
Leaning forward --\> RELIEF
114
If a test has a 95% chance of being negative, what is the probably that at least 1 will be positive?
Probably that at least 1 is positive = 1 - (probablity that they are all negative)
= 1 - (.95)^n (n=number of samples)
question: 1284 on Uworld
115
progressive dyspnea, fine crackles, clubbing and diffuse reticular opacities is consistent with what lung disease?
what chagnge does this have on the airways?
Interstitial lung disease --\> progressive fibrosis with thickening and stiffening of the pulmonary interstituim
**INC _lung_ elastic recoil** and airway widening due to increased outward pulling/**radial traction** by teh surroudning fibrotic tissue --\> decrease in airflow resistance leads to supranormal expiratory flow rates
overall DEC lung volumes (dec FVC, dec FEV1, DEC TLC)
BUT INC FEV1/FVC ratio since FEV1 decreases less than FVC due to airway widening relative to the low lung volumes
116
What is the most effective therapy for treating hypertriglyceridemia?
Fibrates -fenofibrate or gemfibrozil
[work by activating peroxisome proliferator-activated receptor alpha PPAR-alpha--\> INC lipoprotein lipase activity]
[note: a calorie restricted diet with increase exercise and reduced alcohol intake can provide a rapid and significant drop in TG levels]
Severe hypertriglyceridemia could cause acute pancreatitis
[pancreatitis lipase metabolize TG to FFA, which have a toxic and inflammatory effect on the pancreas -- risk for pancreatitis increases triglyceride levesl and occurs mostly when TG are \>1000]
117
What is the indication for bile-acid binding resins?
For Ezetimibe?
IE- cholestyramine
bindg bile acids in the GI tract interferw ith enterohepatic bile acid circulation
Ezetimibe- selectively inhibts intestinal cholestrol absorption; indicated in the tx of hypercholesterolemia
118
What structure does not form in a lymph node in a patietn with X-linked agammaglobulinemia --Bruton's?
Findings: Intact T lymphocyte function (noted by skin antigen testing, such as Candida is reactive!!)
BUT recurrent infections and very low immunoglobulin levels are suggestive of Bruton's
Due to a mutation in the **bruton tyrosine kinase** gene that causes **failure of bone marrow pre-B cells** to **develop into mature B-lymphocytes**
**--\> very low/absent B cells in the peripheral blood and lymphoid tissue**
B lymphocytes normally aggregate in the cortex of lymph node to form lymphoid follicles --
Primary follices are dense and dormant
SEcodnary have a pale germinal center containing proliferating B cells in response to an antigenic stimulus...
THERFORE: germinal centers and primary lymphid follices DO NOT FORM due to an absence of B cells
119
What fungal infection is related with subcutaneous mycosis found in palnts?
--\> **sporotrichosis**
caused by Sporothrix schenckii
dimorphic fungus found in teh nature environment in the form of mold/hypahe; resides in plants and plant debris in the soild. ENterns through skin breaks/thorn prick and spreads ALONG THE LYMPHATICS (see reddish noducles up along the lymphocyte line)
Initial lesion: reddish nodule --\> later ulcerates
Bipsy: **GRANULOMA** consisiting of histiocytes, multinucleated gian cells and neutrophils, surrounded by plasma cells
dx: culturing affected area and isolated S. schenckii
Antifungal meds is needed (itraconazole)
120
What are the most common risk factor for acute respiratory distress syndrome?
Sepsis and pulmonary infections (other: aspiration)
**Sepsis**: cytokines (TNF, IL1, IL6 and IL8) circulate in response to infection --\> **activation of pulmonary epithelum** --\> increased recruitment and extravastion of **neutrophils** into the lung tissues, provoing an **inflammatory response that leads to _capillary damage_** and **leakage of proteins and fluid into the alveolar space**; as more alvolar space becomes fluid-filled, pateints develop worsening hypoxia and respiratory failure
121
What is carotid sinus hypersensitivity?
What are the afferent/efferent nerves responsible for the carotid sinus?
What is the mxn of carotid sinus massage?
pressure on the carotid sinues --\> symptoms such as decreasing BP, dec pulse, syncope
Carotid sinus, is a dilation of the internal carotid artery just above the bifurcation of the common carotid artery--the baroreceptors here are **impt for BP control** and use arterial wall stretch as an indicator of systemic BP
Afferent: Hering nerve a branch of the glossopharyngeal nerve IX --\> medullary centers --\> parasympathetic impulses via the Vagus nerve X
Thus a carotid sinus massage--\> stimulates the baroreceptors and increasing parasympathetic output --\> dec blood pressure via peripheral vasodilation, dec CA via dec contractilty/strovke volume and HR.
122
aortic arch brachoreceptors afferent and efferent nerves?
afferent: Vagus
123
What happens during a vasectomy and what could we expect?
Transection of vas deferences - functions to not only transport from epididymis to the ejaculatory duct but also to store and protect sperm following spermatogeneisis --\> pt can still have viable sperm up to 3 moths and at least 20 ejaculations followng vasectomy
It has no effect on sperm distal to the ligation, little/minimal effect on the volume of ejaculation and no effect on libido/mainatence of an erection.
124
what type of inheritance pattern in spina bifida?
multifactoral
different genes play a role; environmental, folate deficiency...
closer a relative is to the affected person, more likley the relative is to develop trait, but not much else is known.
125
What determines external and internal male/female genitilia?
SRY gene on the Y chromosome codes for teh testes-determining factor = TDF --\> responsible for differentiation into the testes contianing both the sertoli and leydig cells.
The sertoli cells produce mullerian-inhibitory factor (MIF) that PREVENTS the development of the female genitalia...and the leydig cells secrete testosterone necessary for the development of the male internal genitalia.
Therefore-
No Sertoil --\> female genitalia (degeneration of paramesonephrotic/mullerian duct)
No Testosterone --\> no male internal genitalia, no external genitalia (with 5 alpha reductase coverstion to DHT)
126
Septic Arthritis-
Sx
common bugs
mgmt
migratory arthritis with an asymmetric pattern; affected joints are swollen, red and painful (no trauma)
STD: synovitis (knee), tenosynovitis (hand), dermatitis (pustules)
Bugs: S. Aureus, Strep, N. gonorrhae
Acute synovitis best eval - diagnostic arthrocentesis and synovial fluid analysis --\> crystal analysis, cell count, gram stain and culture + blood cultures if septic arthritis is supsected
127
Tx for specific phobias?
Exposure-based behavioral therapy, in which patients are systematically confronted with their feared objects or situations are the _most effective tx_ or specific phobias
acutely - short acting bezodiazepines if therapist is not available or insufficient timeme but have limited role
128
What is vertebral subluxation?
Vertebral malaligment
Long standing chronic rhematoid arthritis can involve the cervical spine and cause joint destruction with subluxation
atlantoaxial joint is often involved and more prone to sublaxation as the C1/atlast has a high degree of mobility relative to the axis C2/odontoid and body with limited intrisnic body stability
--\> destruction of transverse ligmanets /progressive erosion or fracture --\> spinal cord compression due to posterior displacement of the odontoid
sx of atlantoaxial instability with subluxation include neck pain, stiffness or neurological findings (reticular pain); ENDOTRACHEAL intubation with extension of the neck can worsen teh subluxation with possible acute compression of the spinal cord and/or vertebral arteris
pt can develop paralysis with decreased or absent reflexes below the level of compression (spinal shock) hypotension due to loss of sympathetic tone and/or sudden death
129
What does PAS stain for? (acid-schiff positive)
Stains for polysac such as glycogen and mucosubstances such as glycoproteins, glycolipids mucin in tissue
130
Glycogen storage disease II
SX
enzyme deficiency
infant, with severe cardiomegaly/MYOPATY, poor feeding, weakness (can't hold his head up), exercise intolerance; hypotonia, macroglossia
KEY: **lysosome will show accumulaiton of glycogen in lysosomes (enlarged + PAS positive), nl blood glucose**
**lysosomal acid α-1,4-glucosidase deficiency/**
**acid maltase**
responsible for breaking down glycogen iwthin teh acidic environment of lysosomes; most glycogen is degraded in cytoplasm but a small amt is engulged in lysosomes esp in hepatocytes and myocytes; pathological accumulation of glycogen wihtin liver and muscle lysosomes (hepatosplenmegaly and myopathy); ballooning of lysosomes interfere with contractile function
131
What sx are presented with deficiency in pyruvate kinase?
Pyruvate kinase is the enzyme that converts PEP --\> pyruvate in glycolysis
Deficiency of the enzyme cauess chronic hemolytic anemai, splenomegaly, and iron overload due to the impaired erythorcyte surivival
132
What is polycystic kindey disease associated with?
Berry aneurysms --\> SAH! when rupture --\> Sudden onset of SEVERE H/A (worst of their life; none like this before - nuchal rigiditiy could presnt due or will in 24 hrs to meningeal irritaiton; papilledema and pupillary dilation could be noted but no focal neurological findings; mgmt: CT scan of the brain WITHOUT CONTRAST is the most commonly used imaging study for diagnosis of SAH and should be done withitn first 24 hours of onest; positive in 90% of pt; if suspicion is high but neg CT could do a lumbar puncture to see the presence of blood in the CSF = **xanthochromia**)
mitral valve prolapse
benign hepatic cysts
Autosomal dominat; numerous cyst --\> enlarged kidnesy destroying kidney parenchyma
133
bacterial vaginosis
common sx
common bug
dx
tx
most commonly caused by overgrowth of the **anaerobic gram-variable rod (G. vaginalis)**
**grayish-white discharge with fishy order** that becomes more prominent with addition of potassium hydroxide (whiff test),
we mount micro dichrage and cytologi show CLUE CELLS (vaginal, squamous epithelial cells covered with multiple small adhere G vaginalis organisms
No vaginal inflammation
Tx: metronidazole or clindamycin
134
What muscles --\> complete abduction of the arm above the horizontal?
Trapezius (spinal accessory CN IX) --\> arm abduction above the horizontal
Deltoid (axilliary n. C5-C6) --\> abduction of the arm at angles below the horizontal
135
What is open angled glaucoma?
Tx?
Progressive loss of peripheral vision from elevated intraocular pressure
[glaucoma is otpic neuropathy characterized by atropy of the optic nerve head; usually associated with ICP; increased cup to disc ratio due to loss of ganglion cell axon]
**Timolol and other nonselective beta-blockers** work bu diminished the secretions of aq humor by the ciliary epithelium
**Acetazolamide** - CA inhibitor also decrease aq humor secretion by the ciliary epithelium
**Prostaglandin F2alpha,** (latanoprost, travoprost), and **cholinomimetics** (pilocarpine, carbachol) decreaes intraocular pressure by increasing the outflow of aq humor @ cilliary muscle
136
what are gap junctions made of?
Tight?
Adherens?
Desmosomes?
hemidesmosomes
Gap - Connexins --\> intracellular communication
Tight - claudins, occludin --\> paracellular barrier
Adherens - cadherins --\> cellular anchor
Desmosomes - cadherins/desmogleins.desmoplakin --\> cellular anchor
Hemidesmosomes - integrins --\> cellular anchor
137
Systemic mastocytosis
Sx and associations
cloncal mast cell proliferation occurs in the bone marrow, skin and other organs
associated with mutations in the **KIT** **receptor tyrosine kinase**
**INC histamine release from degranulaiton of mast cell**s --\> syncope, flushing, hypotension, pruritius, urticaria
AND --\> INC gastric acid secrtion --\> gastric ulcers
excess acid also inactivates pancreatic and intestinal enzymes causing diarrhea
138
Which nuclei in the hypothalamus mediates satiety and hunger?
Ventromedial - mediates satiey (if you zap it, you'll grow ventromedially!!)
**L**ateral - mediates hunger (if you zap it, you will shrink laterally) - inhibited by lep**tin!**
139
What are specific features UNIQUE to Graves?
pretibial myedema (lymphocytic infiltrative dermopathy) and exopthalmous (periorbital edema and eye movement limitations)
\*NOT caused by the thyroid hormone but rather AI responce directed agasint the TSH receptor - receptor found throughout the body, particularly on adipocytes and fibrolast --\> cytokines released by activated T cells increase fibroblast proliferation and secretion of glycosaminoglycans, resulting in mucinous edema and tissue expansion
caused by an AI response directed against the TSH receptor that results in the accumulation of glycosaminoglycoans within the affected tissue
140
Osteitis fibrosa cystica
most characteristic skeletal manifestations of p**rimary hyperparathyroidism**
bone pain, subperiosteal erosins affectin gthe phalanges of the hand, salt and peper skull and bronw tumor bone cysts
Osteolytic cysts
141
major side effects of clozapine?
neuropenia, agranulocytosis, seizures
tx req guidelines re enrollment in a centralized program that regularly monitors the patients absolute neutrophil count
Must watch clozapine clozely! (req WBC monitoring)
142
ACE inhibitor common side effect:
decrease GFR, hyperkalemia, cough; angioedema is a rare but life-threatening side effect
143
Acut inermitten porphyria are due to accumulation of what to precursors?
What are 2 possible etiologies?
Tx?
Due to the accumulation of aminolevulinate (ALA) and porphobilinogen (PBG) resulting from inherited PBG deaminase defcicienyc combined with ALA synthase induction (typically due to certain medications, alcohol use or low-caorie diet)...
Mgmt: glucose or hemin inhibits ALA synthease activity (rate-limiting enzyme)
sx: abd pain, neurlogical manifestaionts, no photosen, portwine colored urin, PBG and ALA in urine
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What are the side effects of Niacin?
What are tehy mediated by?
what is a way to alleviate?
used in tx for hyperlipidemia
effective in raising HDL cholesterol levels and lowering TG and LDL
Main side effects: cutaneous flushing, warmth, itching, primarily mediated by release of prostaglandings (PGD1 and PGE2) --\> give aspiring, which inhibits prostaglandin syntehsis, can reduce these sx if given 30-60 mins before niacin administration
also reduced with slow-release preps or if taken with food; also tend to fade over time due to tachyphylaxis
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what is the purpose of clavulanic acid, sulbactam and tazobactam to antibiotic treatment?
beta-lactamase inhibitors
concurrent administration with a penicilin expans the spectrum of activity to include strains of b-lactamase syntehsizing bacteria that are resistant to for example amoxicililin alone
beta-lactamase produced by certain bacteria, hydrolyze the beta-lactam ring of penicililin family antibiotics rendering them ineffective; additiong the beta-lactamase inhibiting compounds allow susceptible antibiotics to retain efficacy against bacteria
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characteristic of autism spectrum:
lack of social engagement
speech delay
repetitive play
insistence on sameness
boys\>girls
sx typically recognized by 2; can occur with varying degrees of language and intellectural impairment
Other features: impaired joint attention (lack of pointing, brining objects ot others), motor steretypies (hand flapping, spinning), hyper/hypo reactivity to sensory imput
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what is....and what are they indicative of
Asboe-Hansen sign:
Nikolsky sign:
Asboe-Hansen sign - bullae spread laterally when pressure in applied on top
Nikolsky sign: new blisters may form with gental traction or rubbing
Indicative of pemphigus vulgaris- autoimmune bullous dz characterized by painful flaccid bullae and erosins on the skin and mucosal lesions; autoantibodies against desmosomes (desmogleins 1 and 3), disrupting cohesion of keratinocytes
show **intraepithelial cleavage, acantholysis/detached keratinocytes, ratained keratinocytes along BM, and an eosinophilic inflammatory infilatate**
**epidermal intercellular IgG and C3 depoits**
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IgG agasint tissue transglutaminase results in..
dermatitis herpetiforms and celiac sprue
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Alcohol withdrawl
sx and tx
sx start within 8-13 hours after the last drink and include: insomnia, tremulousness, anxiety adn autonomic hyperactivity (variable bp, diaphoresis, tachy)
Seizures occur 12-48 hours
Delirium tremes (disorientation, severe agitaiton fevere) 48-96 hours
First like - benzodiazepines (for sx and to prevent progression)
Long acting preferred: diazepam, chlordiazepoxide
pt with liver dz, use: lorazepam, oxazepam, temazepam (**LOT**) - do not undergo oxidative metabolism in the liver and have no active metabolites!
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What gene is responsible for short stature in turners syndrome?
most commonly caused by _paternal_ meiotic nondisjunction during gametogeneiss
loss of paternal X chrome --\> missing X in most or all cells --\> 45XO
[note: other pt are missing the X is some of their cells = mosaicims -- mosaic turner syndrome 45 x/46XX]
Loss of X chrome --\> missing **SHOX gene**, which is *_responsible for long bone growth_* --\> short stature
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What is the sequence of events that causes amenorrhea in a person with low weight?
Reduced adipose tissues --\> reduced leptin --\> reduced leptin inhibits pulsatile gonadotropin-releasing hormone (GnRH) from hypo --\> decrease in LH and FSH and low estrogen --\> amenorrhea
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Influenza vaccine:
Live vs killed what is the immune response of our body after exposure to virus?
**Inactivated/killed/component** viral vaccines predominately generate a _humoral immune response_
**Live-attenuated viral vaccines** can generate a strong _cell-mediated immune_ response i_n addition to providing humoral immunity_
all individuals **age \>6 months** should be immunized, esp HCW, immunocomp, chronic ill, elderly
inactivated versions of the influenza vaccine function mainly by **inducing neutralizing antibodies against the hemagglutinin antigen (HA)** in selected viral strains -- antibodies formed **inhibit the _binding of HA to sialylated receptors_ on the host cell membrane**, *preventing the live virus from entering cells via _endocytosis_*
