Timed-Random Flashcards
1
Q
What enzyme is responsible for the conversion of NE to Epi? What upregulates this enzyme?
A
Phenylethanolamine-N-methyltransferase (PNMT)
It is upregulated by cortisol
2
Q
PPO vs HMO vs POS (Point of Service)
- Compare the monthly premiums
- Compare copayments and deductibles
- Is a PCP referral required for specialist visits?
- Size of network
- May go outside network?
A
3
Q
Inheritance of CF
A
Autosomal recessive
4
Q
What receptors on the juxtaglomerular cells are responsible for stimulating renin release? What drugs take advantage of this fact, to decrease BP?
A
B-1 receptors (which is why B-blockers can help dec. blood pressure)
5
Q
Describe the specific effect of the superantigens assc. with TSS
A
THey interact with MHC II on APCs (macrophages) and w/ T-cell receptor to widely activate T cells.
(this leads to IL2 release from T cells, and TNF / IL1 release from macrophages, ultimately causing shock symptoms)
6
Q
What are the (3) main sx of vitamin A overuse?
A
- Intracranial HTN
- skin changes
- Hepatosplenomegaly
7
Q
What do RAS genes code for?
A
A family of small G-proteins involved in signal transduction in the Ras-MAPK pathway
8
Q
Describe the activation of Ras proteins (2 steps)
A
- Growth factor ligand binds to a receptor tyrosine kinase on the cell membrane, causing autophosphorylation
- Proteins interact with Ras, promoting GDP removal and GTP binding!
9
Q
Describe the work that activated Ras does.
A
It begins a phosphorylation cascare that results in the activation of mitogen-activated protein kinase, which enters the nucleus to influence gene transcription.
10
Q
Under normal cricumstances, how does Ras protein become inactivated?
A
It has intrinsic GTPase activity , that allows it to hydrolyze the attached GTP
11
Q
The KRAS gene is a member of what gene subfamily?
A
Ras
12
Q
Name the (4) nerves/ vessels which enter the orbit via the superior orbital fissure
A
OSATO
- Oculomotor nerve
- Superior Ophthalamic vein
- Abducens nerve
- Trochlear nerve
- Opthalmic nerve (CN V1) branches
13
Q
What is the most common cause of death in patients who have been struck by lightning?
A
Cardiac arrhythmias/ arrest
14
Q
What hormone is often increased in liver cirrhosis? What can this lead to?
A
Estrogen (leading to gynecomastia + spider angiomas + hair loss + testiclar atrophy)
15
Q
Which cells found in the lungs, contain elastase? How do they keep it controlled?
A
Macrophages (control w/ Tissue Inhibitos of Metalloproteinases- TIMPs)
and
Neutrophils (control w/ serum a1 antitrypsin)
16
Q
The proximal ureter receives its blood supply from what artery? The distal ureter?
A
Proximal: renal artery
Distal: superior vesical artery
17
Q
Acute bacterial parotitis
- Occurs most commonly in who?
- Bacteria most commonly involved?
- Dx
A
- Common in elderly, postoperative patients who are intubated or dehydrated
- S. Aureus
- Elevated serum amylase (in the presence of normal serum lipase/ no evidence of pancreatitis)
18
Q
How does eithanol block gluconeogenesis?
A
Ethanol metabolism reduces NAD+ to NADH and increases the NADH/NAD+ ratio.
This inhibits all other pathways requiring NAD+, including reactions required for gluconeogenesis.
19
Q
Describe the essential differences in excitation-contraction coupling in cardiac vs skeletal muscle
A
Cardiac Muscle: surface membrane depolarization → opening of voltage-sensing DHPR channel → Ca2+ dependent activatin of RyR2 channel (calcium induced calcium release)
Skeletal Muscle: surface membrane depolarization → conformational change in voltage-sensing DHPR channel → allosteric activaton of RyR channel (mechanical coupling)
20
Q
Attributable Risk Percent (definition + calculation)
A
The excess risk in the exposed population that can be attributed to the risk factor.
ARPexposed = 100 x [(RR-1)/RR], where RR = relative risk
21
Q
What are the (2) major effects of Clostridium perfingens?
A
- Late-onset food poisoning (consisting of transient watery diarrhea)
- Clostridial myonecrosis (gas gangrene)
22
Q
What is the best ausculatory indicator of the severity of a patient’s mitral regurgitation?
A
Presence of an audible S3 (indicating a large volume of regurgitant flow re-entering the ventricle during mid-diastole)
23
Q
What is the indication for drugs which act on H1 receptors vs H2 receptors
A
H1 = allergies
H2 = acid (GERD, ZE, etc.)
Both are histamine receptors
24
Q
Isoproterenol
(MOA)
A
Nonselective B-adrenergicc agonist (leads to inc. vasodilation, inc. cardiac rate, and inc. contractility)
25
Lesions on the medial foot cause, what type of lymphadenopathy?
On the lateral foot?
_Medial_: **Inguinal** lympadenopathy
_Lateral_: **popliteal** and **inguinal** lymphadenopathy
26
What type of injury does Carbon tetrachloride (CCL4) cause, and how?
It causes free radical injury, after being oxidized by the P450 system. The result is CCl3 which causes lipid degradation and formation of H2O2
27
_Isotretinoin_
Indication and Contraindication
_Indication_: Used to tx severe acne w/ significant scarring
_Contraindication_: Pregnancy, due to high risk of teratogenicity
28
What is Annular Pancreas? What might it cause?
The _ventral pancreatic bud_ abnormally encircles the 2nd part of the duodenum, forming ring of pancreatic tissue. May cause **duodenal narrowing.**
29
What molecule does insulin promote activation of, in order to increase glycogen synthesis?
**Protein phosphatase**, via the PI3K pathway
30
What type of cells are seen in the pulmonary vasculature in cases of an Amniotic fluid embolism?
**Fetal squamous cells**
31
Name the muscles/areas that the _musculocutaneous nerve_ innervates/provides sensory innervation to (3)
1. Movement to Major forearm flexors
2. Movement Corcobrachialis
3. Sensory to lateral forearm
32
What drug group is responsible for most of the overdoses in the country?
Opioids
33
What organelle serves as the primary site of ribosome synthesis and assembl?
The _nucleolus_ (All ribosomal RNA except 5S RNA is transcribed here)
34
What are the two ways in which Beta-blokers ameliorate the sx of thyrotoxicosis?
1. Decreasing the effect of adrenergic impulses on target organs
2. Decreasing the rate of peripheral T4 to T3 conversion
35
What types of procedures are associated with enterococcus endocarditis?
Genitourinary instrumentation or catheterization
36
_Aschoff bodies_
What are they and with what dz process are they found?
What is another name for the cellular component?
They are interstitial myocardial granulomas, found in myocarditis due to acute rheumatic fever
The macrophages are aka as caterpillar cells
37
Describe the echocardiogram assc. with Transposition of the Great Arteries (TGA)
Aorta lying anterior to the pulmonary artery
38
In an MI, when does loss of cardiomyocyte contractility occur?
Within the first _60 secs (1 minute)_ after the onset of total ischemia.
39
What effect do Ach and adenosine have on cardiac pacemaker cells?
They reduce the rate of spontaneous depolarization of cardiac pacemaker cells by prolonging phase 4
40
What is the effect of excercise on LV EDP?
On systemic vascular resistance?
_LV EDP_ is increased due to the increased return
_Systemic vascular resistance_ decreases due to large levels of vasodilation in muscles
41
Patient presents due to lightheadedness/ passing out while buttoning a tight shirt collar.
1. Most likely dz process
2. What nerve is most assc. with this dz process?
1. Carotid sinus hypersensitivity (triggered by pressure from the shirt)
2. The afferent limb of the carotid sinus reflex is a branch of the **glossopharyngeal nerve**
42
Trousseau syndrome
Migratory superficial thrombophlebitis assc. with visceral CA
43
What are the main causes of pulsus paradoxus. Name one option for tx
**Pericardial dz**, asthma and COPD
Beta-adrenergic agonisists are useful for the asthma/COPD etiologies
44
When is an aortic stenosis murmur at its loudest?
The intensity is proportional to the magnitude of the LV to aorta pressure gradient during systole, (i.e. whenever aortic pressure is at its strongest)
45
Which ventricle forms the apex of the heart?
The left ventricle
(All other chambers lie medial to the midclavicular line)
46
Other than trauma, what is one major cause for cardiac tamponade?
Viral pericarditis w/ signficant pericardial fluid accumulation
(following a respiratory infection)
47
Describe the histo of myxomas
Scattered cells within a mucopolysaccharide stroma, with abnormal blood vessels and hemorrhaging
48
Most common site of injury during a traumatic aortic rupture
Aortic isthmus
50
What is the pathognomnic presentation for a large patent ductus arteriosus complicated by Eisenmenger syndrome?
Differential clubbing and cyanosis w/o blood pressure or pulse discrepancy
51
What is the most common CV manifestation associated with SLE?
Pericarditis
52
Almost 100% of cases of Hypertrophic Cardiomyopathy result from mutations in genes encoding what?
Beta-myosin heavy chain
| (A cardiac sarcomere protein)
53
Most severe AE of the anthracyclines (rubicins)
Cumulative dose-related dilated cardiomyopathy, due to formation of free radicals in the myocardium
54
Beta Blocker MOA
They dec. AV nodal conduction, leading to an increased AV nodal refractory period
55
What are the (2) _main_ effects of **nitrates**?
1. **Venodilation** (as well as general vasodilation)
2. **Decreased preload** (i.e. decreased LV EDV and EDP)
All told, this results in decreased left ventricular systolic wall stress and myocardial oxygen demand
56
Path of _mitochondrial myopathy_
What does muscle biopsy show?
Myopathy + Lactic Acidosis due to failure of oxidative phosphorylation. Muscle biopsy often show **"ragged red fibers"**
57
For neonates infected with Hep B, what is their...
1. level of HBV replication?
2. level of liver enzymes?
3. risk of chronic infection?
1. High HBV replication
2. mildly elevated liver enzymes
3. very high (90%) risk of chronic infection
58
PaO2
A measurement of the partial pressure of oxygen dissolved in the **_plasma only_**! (not in the RBCs)
59
When is _anovulation_ most common?
In the first several years after menarche (immature H-P-Ovarian axis), and in menopause.
60
Explain the rapid onset and short duration of action for drugs similar to propofol
They are **_lipophilic_** and thus readily diffuse across membranes.
First accumulate in tissues with _high blood flow_ (like brain, hence rapid onset), then dubsequently redistributed to organs receiving less blood flow, like fat or muscles (hence short duration)
61
MOA of SSRIs
Blockade of the serotonin transporter
62
Blood flow is directly proportional to the vessel radius raised to what power?
The **_4th_** power
63
Effect of ACE-I on GFR
Decreases GFR (because AT-II can no longer constrict the efferent arteriole)
64
Role of muscarinic agonists, in glaucoma tx
Increase trabecular outflow of aqueous humor
65
Role of prostaglandin agonists in glaucoma
Increase uveoscleral outflow of aqueous humor
66
Role of B-blockers and a2 agonists in tx of glaucoma
Decrease **secretion** of aqueous humor via the _ciliary epithelium_
67
_Naltrexone_
1. MOA
2. Indication
1. Mu-opiod receptor
2. First line tx for moderate to severe alcohol use disorder (blocks the rewarding and reinforcing effects)
68
Elastase from what cells, are inhibited by alpha-1 antitripsin?
Neutrophils
69
Why might patients with signficant renal dysfunction demonstrate prolonged bleeding time?
Accumulation of uremic toxins impair platelet aggregation and adhesion (no effect on platelet count, PT or aPTT)
70
What rxns does _Thyroid peroxidase_ catalyze? (3)
1. Oxidation of iodide
2. Iodination of thyroglobuin
3. Coupling rxn between 2 iodized-tyrosine residues
71
How can malignant, nonseminomatous **germ cell** testicular tumors cause hyperthyroidism?
They secrete very high levels of hCG, which can bind the **TSH receptor** (leading to _paraneoplastic hyperthyroidism_)
72
What is the best determinate of oral bioavailability of a drug?
AUC (Oral)/ AUC (IV)
This assumes they've been administered at equal doses
73
Why is _N-myc_ capable of being detected by DNA probes?
It is a transcription factor and thus is capable of _binding DNA_.
74
What prompt eosinophils to release their cytoplasmic granules to kill a parasite?
When parasites enter the body they are coated by IgG and IgE which bind to the Fc receptor on the eosinophil, prompting it to degranulate.
(**Antibody-dependent cell-mediated cytotoxicity**)
Eos also contribute to _late stage_ hypersensitivity
75
76
What is moa of mineralocorticoid receptor antagonists? What diseases are they good for and who should they not be used for?
Give (2) examples
(Spironolactone and Eplerenone)
They prevent aldosterone from binding to its receptor in the distal renal tubules, leading to increased sodium excretion.
Indications: CHF and reduced left ventricular EF
Contraindications: Hyperkalemia and renal failure
77
What is NE extravasation and what is the treatment?
Blanching of vein into which NE is being infused due to NE leakage causing major a1 receptor activation and subsequent constriction.
Use _phentolamine_ (alpha-receptor blocker)
78
Tetralogy of Fallot Pathophysiology and clinical presentation
**VOIR**:
1. VSD
2. Overiding aorta
3. Infundibular pulmonary stenosis
4. RVH
_Presentation_: Cyanosis; Improvement w/ squatting (increases SVR)
79
Define accuracy vs reliability
_Accuracy_: the degree to which the aerage measurment value matches that of the gold standard
_Reliability_: reproducibility of a result
80
What cranial nerves and what aortic arch derivatives are associated with each pharyngeal/aortic arch (1-6)
1. CN V; Maxillary artery
2. CN VII; Stapedial artery (regresses)
3. CN IX; Common carotid and prox. internal carotid
4. CN X (superior laryngeal); True aortic arch and Subcalvian arteries
5. Obliterated
6. CN X (recurrent branch); Pulmonary arteries and Ductus arteriosus
81
What are the normal adult pressures in the cardiac chambers, the pulmonary artery and the aorta (minimum and maximum)
**RA**: 0 and 8 mmHg
**RV**: 4 and 25 mmHg
**PA**: 9 and 25 mmHg
**LA**: 2 and 12 mmHg
**LV**: 9 and 130 mmHg
**Aorta**: systolic BP
82
How does _A-fib_ look on an EKG? In this condition, what ultimately regulates the number of atrial pulses which reach the ventricle?
* On _EKG_, it is characterized by: **absent P waves, irregularly irregular R-R intervals,** and **narrow QRS**
* Ventricular response is based on transmission of the abnormal impulses through the AV node. _The AV node refractory period regulates the number of impulses._
83
Dystrophic vs Metastatic calcification
What conditions do they each occur in?
_Dystrophic_: Occurs normally, w/ age, in **damaged** or **necrotic** tissues in the setting of **normal calcium levels**.
_Metastatic_: Occurs in normal tissue in the setting of **hypercalcemia**
84
_Retinal Artery Occlusion_
Presentation?
Pathogenesis?
What is the path most likely taken to occlude the artery?
_Presentation_: Acute, painless, monocular vision loss
_Pathogenesis_: Thromboembolic complications of athersclerosis in the **internal carotid**.
_Path_: Internal carotid --\> Ophthalmic artery --\> retinal artery
85
What is the MOA for _ANP and BNP_? How is this similar to sildenafil?
ANP and BNP are similar to NO. They activate _guanyl cyclase_ which increases the levels of _cGMP_. cGMP leads to relaxation of vascular smooth muscle and vasodilation, via myosin light-chain dephosphorylation
_Sildenafil_ is a phosphodiesterase inhibitor and therefore decreases degradation of cGMP, ultimately causing the same result.
86
_Aortic Regurgitation_
1. Presentation
2. Describe how the pulses may feel
3. Describe the murmur and the best way to hear it
4. What is the state of the pulse pressure?
1. _Presentation_: progressive fatigue + dypsnea
2. _Pulses_: "water-hammer" pulses (bounding femoral and carotids) and head-bobbing with each heartbeat (de Musset sign)
3. _Murmur_:
* Decrescendo murmur after A2
* High-pitched, blowing quality
* Best heard at left sternal border, at 3rd/4th intercostal space, with the patient _sitting up and leaning forward_
4. The pulse pressure is widened
87
What are "Lichtenberg figures" and what are they associated with?
Erythematous cutaneous marks in a fern-leaf pattern.
They are pathognomonic of **_lightning strikes_**
88
MOA of _Sotalol_
It has both beta-adrenergic blocking properties and class 3 antiarrhtmic (K+ channel blocking) properties. It prolongs the PR interval and the QT interval.
89
What is the indication for an ace-inhibitor? For a thiazide?
**ACE-inhibitors**: inhibit chronic angiotensin II-mediated remodeling that occurs in association w/ MI and CHF
**Thiazides**: useful as an initial treatment for essential HTN w/o CHF or diabetes
90
1. Name the non-selective beta-blockers
2. Name the selective beta-blockers
3. Why would you choose selective over non-selective?
1. _Non-Selective_- Propanolol, timolol, and nadolol
2. _Selective_- metoprolol, atenolol, acebutolol and esmolol
3. Selective only target B1, so if you have patients w/ COPD/asthma, you want to only use these.
91
1. Name the anthracycline chemotherapeutic agents.
2. What is their most severe side effect
3. How does it present?
4. How is this SE prevented?
1. Doxorubicin, daunorubicin, epirubicin and idarubicin
2. Their most severe side effect is a cumalitive dose-related _dilated cardiomyopathy_ due to free-radical formation
3. Presents w/ right and left ventricular CHF
4. Prevented via **dexrazoxane**- iron-chelating drug which reduces free radical formation
92
Digoxin MOA
Digoxin directly blocks the Na/K+ pump in myocardial cells, leading to increased intracellular Na. This slows functioning of Na+/Ca+ exchanger, thereby keeping Ca+ trapped in the the myocardial cell as well, increasing contractility.
93
What is Trousseau sign? What does it indicate?
It is when superficial venous thromboses may appear in one site, resolve, and occur in another site. This often indicates _visceral cancer._
94
Piercing of femoral artery above the inguinal ligament can signficantly increase the risk of what hemorrhage in what location?
Retroperitoneal
95
Buerger's disease (thromboangiitis oblierans)
1. Main population demographics
2. Pathophysiology
3. Presentation
4. Tx
1. Heavy smokers, males
2. **Path**- Segmental thromboding vasculitis
3. **Presentation**- Intermittent claudication which can lead to gangrene, autoamputation, and superficial nodular phlebitis. Also associated w/ Raynauds
4. **Tx**: smoking cessation
96
Tricuspid Valve Endocarditis
1. Most common bug associated?
2. Usual patient population?
3. Potential complications?
1. Staph aureus is #1. Pseudomonas is #2
2. IV drug users
3. These patients can develop multiple septic emboli in lungs. Resulting pulmonary infarcts will be hemorrhagic due to dual blood supply.
97
**Varicocele**
1. Pathophysiology?
2. Presentation?
1. Increased pressure in the left gonadal vein resulting in valve leaflet failure and varices of the testicular pampiniform plexus
2. Presents with flank/abdominal pain and gross or microscopic hematuria
98
_Niacin (nicotinic acid)_
1. Indication
2. Adverse Effects
3. What is the mechanism for the adverse effects and how can they be prevented?
1. Used in the tx of hyperlipidemia. Effective in raising HDL cholesterol levels, and lowering LDLs and TGs
2. SEs include cutaneous flushing, warmth and itching
3. SEs are mediated by release of prostaglandins and can therefore be prevented by aspirin.
99
Blockage of what vein causes symptoms similar to those in SVC syndrome, except only on one side of the body? What are those symptoms?
Blocking of the Brachiocephalic vein
Shows one sided face-swelling, arm swelling and engorgement of subcutaneous veins .
100
In the _pathogenesis of atherotic plaques_, What is responsible for promoting migration of smooth muscle cells from the media into the intima, and subsequent proliferation?
The release of _Platelet-derived growth factor (PDGF)_ by locally adherrent platelets, endothelial cells, and macrophages.
101
What is the most common condition predisposing a patient to infective endocarditis in...
1. Adults in wealthier nations?
2. Poorer nations/ children?
1. Mitral valve prolapse/ mechanical valves
2. Rheumatic fever
102
What is the "Number Needed to Treat", and how is it calculated?
It's the number of patients that need to be treated with a medicatin to avoid a negative outcome. It is 1 divided by the percent difference in outcome between the control and the experiment
103
What are the effects of nitrate? (3 general categories of effects)
Side Effects?
* Primarily **venodilators** (but also vaso) that increase **peripheralvenous capacitance**
* Reduce cardiac preload and afterload and LVEDP and volume, reducing work of heart
* Modest effect on arteriolar dilation
_Side Effects_: HA, cutaneous flushing, hypotension
104
Thiazide diuretics
1. MOA
2. Effects
3. AEs
1. Inhibit Na+/Cl- co-transporter in the DCT, thereby decreasing reabsorption of NaCl
2. Lower BP by decreasing intravascular volume, reduce CO, and lower systemic vascular resistance
3. Dec. insulin secretion and glucose uptake, and increase LDL cholesterol and TG levels
105
**Patent Ductus Arteriosus (PDA)**
1. Pathology
2. Why is it patent
3. Clinical manifestations
4. Typical age at presentation
5. Tx.
1. Vascular connection between the main pulmonary artery and the aorta still remains after birth
2. Patent due to prostaglandin E2 production by the placenta
3. Clinical features vary by size: _Small_: continuous machine-like murmur w/ no other symptoms. _Large_: progressive pulmonary HTN, reversal of shunt (now right-to-left), ultimately leading to **HF** and **cyanosis** (Eisenmenger syndrome), particularly in lower extemities.
4. Childhood
5. Tx: **Indomethacin** (prostaglandin E@ inhibitors)
106
_Hypertrophic Cardiomyopathy_
1. Key potential clinical consequences (2)?
2. Histo
3. Pathology
4. Dx of this consequence?
5. What actions make those sx better or worse?
1. Left ventricular outflow obstruction; sudden death in stressful situation
2. Extreme myofiber disarray w/ interstitial fibrosis
3. Mutations in genes encoding cardiac sarcomere proteins
4. Harsh crescendo-decrescendo systolic ejection-type murmur best heard along left sternal border and apex
5. * Mechanisms dec. preload or afterload _increase obstruction_ -- such as sudden standing or nitro.
* Mechanisms inc. preload or afterload _decrease obstruction_ -- such as squatting, sustained hand grip, or passive leg raise
107
_Aortic Dissection_
1. Most important risk factor
2. What specific layer tears?
3. What genetic issue predisposes for aortic dissection?
1. HTN is most important risk factor
2. Tunica intima is the layer which tears away
3. Marfan's which leads to _cystic medial degeneration_
108
_Liver Angiosarcoma_
1. Pathology?
2. Describe the cellular change
3. Main carcinogens associated?
1. Rare malignant vascular endothelial cell neoplasm associated w/ carcinogen exposure
2. Neoplasm composed of CD-31 PECAM1 (platelet endothelial cell adhesion molecule). Indicates that a tumor has risen from vascular endothelial cells.
3. Implicated chemicals include arsenic (pesticides), thorotrast (contrast), and polyvinyl chloirde (industry plastic)
109
MOA of B-Blockers
B-Blockers decrease AV nodal conduction, leading to an increased AV nodal refractory period
110
_Pulsus Paradoxus_
1. What is it?
2. How is it detected?
3. Why does it happen?
4. What disease processes is it associated with? (4)
1. An exaggerated drop (\>10mmHg) in systolic BP during inspiration
2. Detected when taking the BP, by listening to the difference between when korotkoff sounds are first heard during expiration and the pressure at which they are heard throughout all phases of respiration
3. Inspiration inc. venous return and normally this expands RV into pericardium but if this expansion can't happen, the interventricular septum pushes into the LV, dropping LV EDV and subsquently the stroke volume
4. Pericardial disease, acute cardiac tamponade, asthma, COPD
111
_Aspirin_
MOA
Aspirin impairs prostaglandin synthesis by irreversibly inhibiting COX. Inhibition of COX-1 in platelets prevents synthesis of thromboxane A2, a potent stimulator of platelet aggregation and vasoconstriction.
112
_Clopidogrel_
1. MOA
2. Indication
_MOA_: Irreversibly blocks the P2Y component of ADP receptors on the platelet surface and prevents platelet aggregation
_Indication_: Just as effective as aspirin for prevention of CV events and should be used if patient has aspirin allergy.
113
What is the most common location on the aorta for a traumatic aortic rupture (blunt aortic injury)?
The **aortic _isthmus_** (located just past the aortic arch)
114
_Statins_
1. Indication
2. MOA
3. Side effects
4. What sort of things can help lead to adverse effects from Statins
1. _Indications_: Tx of hypercholesterolemia
2. Inhibit **HMG-CoA reductase**, thus blocking hepatic cholesterol synthesis. This forces the liver to _increase surface expression of LDL receptors_, thus pulling LDL from circulation
3. _SE_: Myopathy, rhabdomyolysis, and hepatoxicity
4. Drugs that interfere w/ statin metabolization, particuarly via cytochrome p450 enzymes (ex. fibrates)
115
*Streptococcus gallolyticus* (formely S. Bovis) can cause **endocarditis** and **bactermia**. When this bug is cultured in the blood, workup for _what_, is absolutely essential?
**_Colonic malignancy_** with colonoscopy
116
Describe the Sx of Digoxin Toxicity
| (what ion is often elevated?)
* Typically presents w/ cardiac arrhythmias and nonspecific GI, neuro and visual (color change) sx
* Elevated K+ is another sign of digoxin toxicity (due to inhibition of Na-K-ATPase)
117
_AV Shunts_
1. What affect do they have on preload/afterload?
2. What might the physical exam reveal?
1. AV shunt _increases_ the **preload** and _decreases_ the **afterload** by routing blood directly from the arterial system to the venous system
2. Physical exam may reveal pulsatile mass w/ thrill on palpation. Ausculation reveals a constant bruit over the site.
118
What is the **most common** _congenital heart lesion_?
1. Dx/ Presentation?
2. Effect on blood oxygenation
3. Prognosis?
_Ventricular Septal Defects_
1. Small VSDs have a loud, "blowing", holosystolic **murmur** at the mid/lower left sternal border (louder with handgrip). Murmur is usually inaudible _until_ 4-10 days when pulmonary vascular resistance declines enabling left-to-right shunt.
2. Right ventriclular blood has increased O2 content
3. Most are clinically insignficant and close spontaneously
119
_Prinzmetal's (variant) Angina_
1. Pathology?
2. When does it occur?
3. Dx?
4. Tx?
5. What drug can make it worse?
1. Episodic, transient attacks of **coronary vasospasm**
2. Usually occurs at rest and during late night/early morning
3. Temporary transumral MI w/ ST elevation on EKG
4. Tx with vasodilators and CCBs
5. **_Ergonovine_** can provoke vasospasm and can *aid in diagnosis*
120
How is tolerance to nitrates avoided?
You must provide a nitrate-free interval every day in patients w/ long acting nitrates.
121
How is nitric oxide synthesized?
It is synthesized from arginine by NO synthase
122
What are the _only_ cells within atherosclerotic plaque which are capable of synthesizing collagen isoforms and ECM?
Vascular Smooth Muscle Cells (VSMCs)
123
When given with a Statin, what drug is most likely to lead to myopathy or even rhabdomyolosis? Why?
Fibrates (like Gemfibrozil). They impair the hepatic clearance of Statins leading to excessive blood levels.
124
_Aortic stenosis_
1. Common murmur
2. Sx
3. Main causes
1. Crescendo-decrescendo murmur **right sternal border**
2. Typically asymptomatic. If advanced can present w/ exertion and inlcude syncope, dizzyness, angina or even HF
3. **Main causes**: abnormal valve w/ calcification (e.g. bicuspid aortic); calcified normal valve; or rhemuatic heart disease
125
_Carcinoid Syndrome_
1. What is it?
2. What can it progress to?
3. How does a blood/urine test tell us about severity?
1. Fibrous thickening with endocardial plaques limited to the right heart
2. May progress to pulmonic stenosis and/or restrictive cardiomyopathy
3. Severity correlates with plasma levels of _serotonin_ and urinary excretion of the serotonin metabolite, **5-hydroxyindoleacetic acid**
126
Main Side Effect difference between ACE-I's and ARBs
ACE-I's raise the level of Bradykinin causing non-productive cough.
ARBs do not.
The two drugs are very similar otherwise
127
How does the effect of Rheumatic Heart Disease on the mitral valve vary as the patient's age changes?
_First few decades of life_: MR
_Middle-aged_: MS (most common cause of MS)
_Elders_: Mixed mitral disease (S and R)
128
MOA of class 3 antiarrhytmic agents
They block K+ efflux from cardiac myocytes and prolong phase 3 of the myocyte AP
129
SE profile for _ACE-Inhibitors_ (2)
1. Bradykinin induced cough and angioedema if there is accumulation
2. First dose hypotension due to volume depletion
130
_Phenoxybenzamine_
1. MOA
2. Indication
3. Effect
1. _Irreversible a1 and a2 antagonist_ that effectively reduces the arterial vasoconstriction induced by NE.
2. **Pheochromocytoma**
3. Because it is irreversible, even very high concentrations of NE (like those seen in pheochromocytoma) cannot overcome its effects
131
_Isoproterenol_
1. MOA
2. Effect
1. Non-selective Beta-_agonist_
2. Increases myocardial contractility and decreases systemic vascular resistance
132
_Dopamine:_ What is the effect of...
1. Low doses?
2. Medium doses?
3. Very high doses?
1. _Low dose_: stimulate D1 receptors in the renal and mesenteric vasculature
2. _Medium dose_: stimulate B-1 receptors, increasing cardiac contractility
3. _High dose_: stimulate a-1 receptors, producing generalized vasoconstriction
133
_Antiarrhythmic drugs_
Drugs + Predominant actions
**Class IA, IB, IC**
1. _IA_: **Dispyramide, Procainamide, Quinidine**- *slows AP conduction velocity; prolongs APD*
2. _1B_: **Lidocaine, Mexiletine, Phenytoin**- *Shortens APD* (no effect on AP conduction velocity)
3. _1C_: **Flecainide, Propafenone**- *Slows AP conduction velocity; minimal effect on APD*
"Double Quarter Pounder; Light Mayo and Pickles; Fries Please"
134
What are the type II Anti-arrhythmics?
Beta-blockers
135
_Antiarrhythmic drugs_
Drugs + Predominant actions
**Class III**
**Amiodarone, Dronedarone, Dofetilide, Sotalol** (also class II)
*Prolongs APD by blocking K+ channels* (no effect on AP conduction velocity)
136
_Antiarrhythmic drugs_
1. Drugs + Predominant actions
2. Potential SEs
**Class IV**
**Verapamil; Dilitiazem**
1. *Slows sinus node discharge rate; slows AV nodal conduction and prolongs refractoriness*
2. Can lead to severe bradycardia and hypotension (especially in combo with a beta-blocker)
137
Relationship between blood flow and radius
Blood flow is directly proportional to vessel radius raised to the fourth power.
138
_Jervell and Lange-Nielsen Syndrome_
1. Pathology
2. Clinical presentation
3. Mode of inheritance
4. What other disease is this similar to?
1. Congenital **long-QT syndrome**; thought to result from mutations in a K+ channel protein
2. Syncopal episodes; sudden cardiac death (*torsades de pointes*);
3. _Autosomal recessive condition_
4. Similar to Romano-Ward syndrome
139
What sometimes occurs between days 2-4 following a transmural MI? Why?
**Early-onset pericarditis** develops in 10-20% of patients. It represents an inflammatory reaction to adjacent cardiac muscle necrosis.
140
_Cystic Medial Degeneration_
1. Characteristics
2. What does it predispose you for?
3. Who is it common in?
1. _Myxomatous_ (weakening of connective tissue) changes with pooling of proteoglycans in the _media layer of large arteries_
2. **Aortic dissections/ Aneurysms**
3. Younger patients with _Marfan Syndrome_
141
_Adult type Aortic Coarctation_
1. Key triad
2. View on imaging
1. (1) upper body hypertension; (2) diminished lower extremity pulses; (3) enlarged intercostal artery _collaterals_
2. **Notching of ribs** as a result of the enlarged, tortuous intercostal arteries
142
Permissiveness
**When one hormone allows another to exert its maximal effect** (ex. cortisol allows NE to work even better although cortisol has no direct vascular effect itself)
143
_Cutaneous, strawberry-type capillary hemangiomas_
1. Pathology
2. Prognosis
1. Benign congenital tumor of unencapsulated aggregates of closely packed, thin-walled capillaries
2. Initial growth followed by regression (excellent prognosis)
144
Why does listening to heart sounds at end expiration make them more audible?
Decreased lung volume, bringing the heart closer to the chest wall.
145
What are the (2) mechanisms by which beta-blockers lower blood pressure?
1. Reducing myocardial contractility and HR
2. Decreasing renin release by the kidney
146
What phase of the AP corresponds with the QRS of the EKG?
QT?
QRS = Phase 0
QT = Phase 3
147
What receptors is epinephrine capable of affecting?
a1, B1, and B2
148
Following focal ischemia in an MI, how long until there is a **loss of cardiomyocyte contractility?**
Loss of focal contractility occurs within _60secs_!
149
_Fenoldopam_
1. MOA
2. Indication
3. Effects (3)
1. _MOA_: selective peripheral D1 receptor agonist
2. _Indication_: given IV ti lower BP in HTN crisis, especially in patients with **renal insufficiency**
3. _Effects_: (1)Arteriolar dilation, (2) increased renal perfusion, and (3) promotion of diuresis/ natriuresis
150
_Fibrates_
1. MOA
2. Effect
3. Compare this to fish oil
1. _Activates_ peroxisome proliferator-activated receptor alpha **(PPAR-a)**.
2. This leads to _decreased hepatic VLDL_ production and increased _Lipoprotein lipase_ activity, thus **lowering triglyceride levels**
3. Fish oil supplements w/ O3FA dec. VLDL and ApoB production
151
_Dihydropyridine CCBs (Anti-hypertensives)_
1. Main examples
2. Indications
3. SEs
1. *Amlodipine and Nifedipine*
2. Effective for monotherapy or in combination with other agents for Tx of HTN
3. **_Peripheral Edema_** and _Dizziness/ Lightheadedness_
152
What sort of procedure is associated with _enterococcal endocarditis_
Genitourinary instrumentation or catherization (enterococcus is a component of normal colonic and GU flora)
153
Main phase "0" difference between regular cardiac cell and a pacemaker cell
Regular cardiac cell: 0 = Na+ rush
Pacemaker: 0 = Ca2+ rush
154
_ASD_
1. What is the usual pathology?
2. What other cardiac condition is often also present?
3. Dx
4. Potential consequence
5. What genetic disease is also associated?
1. Failure of the _endocardial cushions_ of the atrioventricular canal to fuse completely during embryonic development can lead to a lower interatrial septum defect
2. **Malformation of mitral valve** leading to mitral regurg is often present
3. Wide, fixed splitting of the second heart sound (S2)
4. Pulmonary HTN
5. _Down syndrome_
155
In patients with mitral regurg, what is the most reliable ausculatory finding to assess severity
The presence of a left-sided **_S3 gallop_**. This indicates high regurgitant volume and left ventricular volume overload
156
Why is it that calcium channel blockers affect smooth and cardiac muscle, but not skeletal?
**Cardiac and smooth muscle** cells depend on extracellular _calcium influx_ into cells via L-type calcium channels. **Skeletal muscle** cells do not, because they have a _direct mechanical coupling_ of the L-type channel and the RyR.
157
Ortner syndrome
When mitral stenosis causes left atrial dilatation sufficient to impinge on the left laryngeal nerve
158
Myocardial hibernation
A state of _chronic myocardial ischemia_ in which myocardial metabolism and function is **reversibly** reduced in order to match a reduction in coronary blood flow, thus _preventing myocardial necrosis_
159
_Drug-induced Lupus Erythematosus_
1. Presentation
2. Dx
3. What is almost never seen?
4. Drugs normally implicated
1. New onset of lupus symptoms
2. Anti-nuclear antibodies (ANA) and anti-histone antibodies
3. Anti-dsDNA **_ALMOST NEVER SEEN_**
4. _HIP_: **_H_**ydralazine, **_I_**soniazid, **_P_**rocainamide
160
What is usually the most key component of the pathogenesis of AAAs?
Transmural aortic wall inflammation
161
Lipofuscin
Yellow-brown, granular product of lipid peroxidation and considered to be a sign of "wear and tear"/aging.
162
_Prostacyclin vs Thromboxane A2_
Compare their effects
**_Prostacyclin_**: vasodilates, *inhibiting platelet aggregation* and increasing vascular permeability
**_Thromboxane A2_**: prostaglandin which enhances platelet aggregation and causes vasoconstriction
163
_Kawasaki Disease_
1. What type of disease is this?
2. Presentation
3. Potential consequence
4. Tx
1. Medium-vessel vasculitis
2. **CRASH** and **burn**
* **_C_**onjuctival injection, **_R_**ash, **_A_**denopathy, **_S_**trawberry tongue, **_H_**and/foot changes (edema and erythema) and _fever_
3. Risk of **coronary artery aneurysm**
4. Tx w/ *IV and aspirin*
164
_Diphteria_
1. Epidemiology
2. Micro/pathology
3. Clinical Sx (4)
4. Complications (3)
1. Endemic in developing countries
2. ***Corynebacterium diphtheriae*** colonize repiratory tract and secrete _diphtheria toxin_ (inhibits protein synthesis via **ribosylation** of EF-2)
3. (1) Pseudomembrane; (2) cervical adenopathy (3)sore throat (4) fever
4. (1) Suffocation due to edema/pseudomembrane aspiration; (2) Heart failure/ (3) neuro toxicity from the toxin
165
_Vascular and Immunologic Manifestations of Infective Endocarditis_
(3) Vascular
(2) Immunological
_Vascular_:
1. Systemic emboli
2. Mycotic aneurysm
3. Janewy lesions (**nontender**- palms/soles)
_Immunologic_:
1. Osler nodes (**Painful**- toes/fingertips)
2. Roth spots
166
_Coronary Sinus_
1. What does it serve as?
2. Under what condition might it be dilated?
1. Serves as the endpoint of venous drainage from the coronary blood supply, _draining directly into the right atrium_
2. Will be dilated by any factor that dilates the right atrium (most commonly **pulmonary HTN**)
167
_Paroxysmal Supraventricular Tachycardia_
1. Presentation
2. Tx
3. Potential SEs of tx (4)
1. Sudden onset palpitations
2. Tx w/ adenosine
3. _SE_: (1) Flushing, (2) chest burning (from bronchospasm), (3) hypotension, (4) AV block
168
_Giant Cell Arteritis_
1. Also known as?
2. Main Sxs (4)
3. What does the artery look like on biopsy?
1. aka _Temporal_ arteritis
2. **Jaw Claudication**, HA, facial pain, and vision loss
3. Temporal artery biopsy demonstrates granulomatous inflammation of the media
169
_Torsades de Pointes_
1. Pathology
2. What are the most common precipitants? (3 categories + examples)
1. Polymorphic v.tach that occurs in the setting of a congenital or acquired _prolonged QT interval_
2. **Medications** such as certain (1) _antiarrhythmics_ (sotalol, quinidine); (2) _antipsychotics_ (haloperidol); (3) _antibiotics_ (macrolides, fluoroquinolones)
170
_Paradoxical Embolism_
1. Pathology
2. Dx
1. When a thrombus from the venous system crosses into arterial circulation (as oppose to the pulmonary) via an abnormal connection between the right and left cardiac chambers
2. May see **fixed splitting of S2** if a shunt is present
171
Of all major vascular beds, which (2) are most susceptible to athersclerosis?
1. Lower abdominal aorta
2. Coronary arteries
172
_Mitral Stenosis_
1. What is the best/most reliable asuculatory indicator of the severity?
1. The interval between A2 and the opening snap (OS). **Shorter interval = more severe stenosis**
173
_Right Ventricular MI_
1. Presentation
2. Pathology
3. What does the hemodynamic assessment reveal? (CVP? Wedge pressure? CO?)
1. Presents with hypotension, elevated JV pressure, _clear lungs_
2. Most often occurs in the setting of **acute inferior wall MI**
3. CVP= inc.; Wedge pressure = dec.; CO = dec.
174
How is carotid sinus massage useful for termination of paroxysmal SVT?
It leads to increased parasympathetic tone causing temporary inhibition of the SA node and the prolongation of AV node refractory period
175
_Osler-Weber-Rendu Syndrome_
1. What is the other name?
2. Genetics
3. Clinical Presentation
4. Possible consequences
1. Hereditary hemorrhagic **_telangiectasia_**
2. Autosomal dominat
3. Presence of telangiectasias in the skin and mucous membraes of the lips, oropharynx, respiratory tract, GI tract and urinary tract
4. Rupture of these vessels may cause epistaxis (**_nosebleeds_**), GI bleed, or hematuria
176
_Lidocaine_
1. What class drug?
2. MOA?
3. Effect?
1. IB antiarrhythmic
2. Binds (mostly) to **inactivated sodium channels** and rapidly dissociates
3. Effective in suppressing v.tach induced by rapidly depolarizing and ischemic myocardium.
177
Fick Principle
An alternative means for calculating cardiac output.
CO = O2 consumption/ AV O2 difference
178
Which cell types have B1 receptors?
Cardiac tissue and renal juxtaglomerular cells
179
a-1 blockers are useful for the treatment of ... (2 conditions)
What natural secretion has these same effects?
HTN and benign prostatic hyperplasia (relaxes the bladder)
**ANP/BNP** has the same effects
180
Which blood vessel carries blood with the _lowest content of oxygen_ in the body
Coronary sinus
181
Describe the process of _Infective Endocarditis_ (4)
1. Disruption of normal endocardial surface (usually in areas of maximum turbulence)
2. Focal adherence of **fibrin and platelets**, forming _sterile fibrin-platelet nidus_
3. Colonization by microorganisms (*strep* to damaged areas; *staph* to damaged or normal areas)
4. Formation of macroscopic vegetations made of debris
182
_Polyarteritis nodosa_
1. Pathology
2. What organ is normally spared?
3. Presentation
4. Potential consequences
1. Segmental, transmural, necrotizing nflammation of medium to small sized arteries in _any_ organ
2. **Lungs are spared**
3. Can be cutaneous manifestations, including livedo reticularis and palpable purpura
4. Inflammation can result in ischemia, infarcation, or hemorrhage and _bead-like aneurysm formation_
183
Coordinate each artery with the leads associated with them
1. LAD
2. LCX
3. RCA
1. Anterior and Septal
2. Left lateral
3. Inferior and Right
184
What are the afferent and efferent limbs leading to/away the carotid bodies?
_Afferent_: **G****lossopharyngeal nerve**
_Efferent_: **Vagus nerve**
185
What is the main side effect which limits the long-term efficacy of arteriolar vasodilators. Give (2) main examples of these drugs
Ex: Hydralazine and minoxidil
There can be reflex sympathetic stimulation (leading to **inc. HR**, contractility, and CO) and also stimulation of the RAA system leading to **sodium and fluid retention/edema**
186
Name the precursor protein/peptide responsible for localized amyloidosis for each of the following organs:
1. Cardiac atria
2. Thyroid gland
3. Pancreatic islets
4. Cerebrum/cerebral blood vessels
5. Pituitary gland
6. _Multi-organ_ amyloid deposition?
1. Cardiac atria: **atrial natriuretic peptide**
2. Thyroid gland: **calcitonin**
3. Pancreatic islets: **islet amyloid protein**
4. Cerebrum/cerebral blood vessels: **B-amyloid protein**
5. Pituitary gland: **prolactin**
6. Multi-organ amyloid deposition? **Immune globulin light chains**
187
What bones meet at the pterion? What vessel lies underneath it?
Frontal, parietal, temporal, and sphenoid bones
**Middle meningeal artery** (branch of the maxillary artery)
188
Which bug is associated with right-sided endocarditis in IV drug users?
Staph aureus
189
What (2) drugs are selective vasodilators of coronary vessels? How can they affect the heart _negatively_ during ischemic events?
**Adenosine and dipyridamole**
They can lead to _coronary steal_ because they vasodilate everything in the heart. The vessels going to ischemic areas are already maximumly dilated so they only lose out on blood.
190
Compare cardiac tissue conduction velocity between the:
AV node, purkinje system, ventricular muscle, and atrial system
**_P**_ark _**At**_ _**Vent**_ure _**Av_**enue
*Fastest*- Purkinje system, Atrial system, Ventricular system, AV node- *slowest*
191
_Nitroprusside_
1. MOA
2. Effect
3. Indication
1. Short-acting balanced venous and arterial vasodilator
2. Decreases both preload and afterload, thus maintaining stroke volume
3. Indicated for hypertensive HF
192
_Dobutamine_
1. MOA
2. Indication
3. Effect (3)
1. B-agonist (predominant activity on B1 receptors)
2. Management of refractory HF w/ severe LV systolic dysfunction/ cardiogenic shock
3. (1) Positive **inotropic** effect (2) weakly positive **chronotropic** effect (3) mild **vasodilation**
4. Some increased O2 consumption due to increased chronotropy
193
What percentage of vessel must be blocked to qualify as stable angina?
\> or equal to 75%
194
Formula for half life
Vd x .7/CL
195
Formula for Maintenance dose
Cpss (steady-state plasma concentration) x CL/[bioavailability fraction]
196
Formula for Loading dose
Vd x Cpss (steady state plasma concentration)/ [bioavailability fraction]
197
**Kussmaul sign**
Paradoxical rise in JVP during inspiration, because volume-restricted right ventricle is unable to accomadte the inspiratory increase in venous return.
Associated with **constrictive pericarditis**
198
Order the class one subcategories based on sodium-channel-binding strength (as measured by use dependence)
1C \> 1A \> 1B (least use dependent)
199
Structural cardiac changes due to aging are generally not prominent before the age of...
65y/o
200
_Familial chylomicronemia syndrome_
1. Which protein is defected? (2)
2. Which lipoprotein is elevated?
3. Major manifestations?
1. _Defected_: Lipoprotein lipase; ApoC-II
2. _Elevated_: Chylomicrons
3. _Manifestations_: **Acute pancreatitis**; lipemia retinalis (milky lipids in retinal vasculature); eruptive skin xanthomas; hepatosplenomegaly
201
_Verrucous endocarditis_
1. Who does it occur in?
2. What is it?
3. Potential consequence?
1. Occurs in up to 25% of patients with SLE
2. Can cause small cardiac valvular vegetations on either side of a valve, resulting in fibrotic valve thickening and deformity
3. May cause acute coronary syndrom in young patients with **normal coronary arteries**
202
What is an appendage, in the context of the heart?
It is a small saclike structure that is particularly susceptible to thrombus formation
203
What is the most common genetic cause for:
Hypertrophic cardiomyopathy?
Dilated cardiomyopathy?
1. _Hypertrophic_: Autosomal dominant mutations in cardiac sarcomere proteins (usually **beta-myosin heavy chain**)
2. _Dilated_: Autosomal dominant mutations of myocyte cytoskeleton (**dystrophin**) or **mitochondrial enzymes**
204
How is the pathogenesis of Non-bacterial thrombotic endocarditis (_NBTE_) related to that of _Trousseau's_?
They can both be induced by disseminated cancers, usually due to some hypercoagulable state.
205
What does _Prussian blue stain_ detect?
Intracellular iron
206
What is responsible for swelling in myocardial cells during ischemia?
Ion pump failure due to ATP loss, leading to increased intracellular Na+ and Ca2+
207
Describe the hemodynamic profile of aortic regurg (3 key differences from normal)
1. Higher pressure peaks (more blood in LV)
2. Loss of dichrotic notch
3. Steeper fall in aortic pressure
208
Path and Presentation of patients with 21-hydroxylase deficiency
Deficient cortisol and aldosterone synthesis + adrenal androgen overproduction
_Males_: normal genitalia + vomiting, hypoTN, hyponatremia, hyperkalemia
_Females_: ambiguous genitalia (+ sx above)
209
_Antiphospholipid Antibody Syndrome_
1. Type/ cause of antibodies
2. Sx (2)
1. Antiphospholipid antibodies (either primary or due to **_SLE_**)
2. Venous or arterial thromboembolism (in the presence of **paradoxical inc. PTT)** + recurrent pregnancy loss
210
Why do patients with _Antiphospholipid antibody syndrome_ often get false positive syphillus exams?
Presence of anticardiolipin antibody (which is tested for in Treponema pallidum, but is also present in this dz)
