Quiz 4 Flashcards
Nascent chylomicron
- where is it formed?
- what does it consist of?
- how does it undergo maturation?
- Formed in the intestinal epithelium
- Consists of
- TGs
- cholesterol esters
- phospholipids
- Apo B48 (truncated ApoB100) -> does NOT bind to LDLr - Maturation
- released into lymph -> blood stream
- picks up ApoE, ApoCII, and ApoCIII from HDL
- apoCIII blocks ApoE binding site
How do TGs get into adipocytes and muscle cells? Describe the mech
Binding of ApoCII with LPL found on endothelial cells
LPL secreted by tissues in response to insulin
TGs -> broken down into 3 FAs + glycerol -> FAs taken up by tissue and glycerol taken up by liver
What is the fx of hepatic lipase?
Digestion of chylomicron remnant
Nascent VLDL
- where is it made?
- what does it consist of?
- what happens to it?
Made in the liver
Consists of
- endogenous TG + TG from chylomicron remnant
- endogenous cholesterol + cholesterol esters
- phospholipids
- apoB100
Picks up ApoE, ApoCII and ApoCIII from HDL -> bind to LPL -> releases FFAs -> becomes IDL
What are the 2 fates of IDL particles?
- Endocytosed by liver (ApoE mediated) -> recycled to VLDL
2. Further digested by LPL -> becomes LDL -> delivers cholesterol esters to cells through endocytosis
HDL related enzymes/proteins
- ABC-1
- LCAT
- CETP (include disadvantage)
What is a major role of HDL?
ABC-1 - transporting cholesterol from cell to HDL
-helps get cholesterol across plasma membrane
LCAT - Forms cholesterol ester
-activated by ApoA-I
CETP - exchanges cholesterol for TGs from
-can promote atheresclerotic disease -> cholesterol uptake by tunica intima of arteries -> oxidation
HDL -> carry cholesterol back to the liver
-SRB-1r on liver binds to HDL -> internalization -> recycling of cholesterol
What mediates LDL endocytosis by cells?
Presence of ApoB100 -> binds to LDLr
Describe the sxs of LPL deficiency w/ regards to
- chylomicrons
- LDL
- VLDL
What other deficiency shows the same sxs
- chylomicrons -> elevated
- LDL -> low
- VLDL -> normal
ApoCII deficiency = same sxs
Hepatic lipase def leads to?
Hypertriglyceridemia
-inc duration of LDL and HDL in circulation
How does the chylomicron remnant get into hepatocytes
ApoE -> binds to LDLr and LRP
ApoB48 -> bind to LRP
ABSORPTIVE ENDOCYTOSIS
If there is an excess of cholesterol, which enzyme promotes storage?
aCAT -> Stimulate production of reesterification to form cholesterol esters (storage form)
What allows LDL to fall of the LDLr in the endosome?
-dec in pH which is sensed by the EGF region -> dissociates the receptor from the particle
How can we inc HDL levels?
- exercise
2. Alcohol
SR-B1
- where is it found?
- what role does it play?
Found on hepatocytes
Allows for uptake of HDL-2
Role of scavenger receptors in atherosclerosis
UNREGULATED uptake of oxidized LDL by macrophages
-receptors are NOT downregulated
Product and substrate for HMG-CoA reductase
Substrate - HMG-CoA
Production - Mavalonate
Describe the hypothesis for muscle pain associated with statins
Reduction in CoQ10 (ubiquinone) due to decrease in Farnasyl PP
Protein prenylation requires which 2 intermediates of the cholesterol synthesis pathway
GPP and FPP
HMG-CoA reductase activity regulation
- what increase
- what decreases
What controls rate of synthesis?
- Insulin -> inc activity by blocking adenyl cyclase
- Glucagon and AMP dependent phosphorylation -> decreased activity
- the phosphorylated form of HMG-CoA reductase in INACTIVE
Rate of synthesis -> SREBP (Sterol levels)
Tangier disease
- defect
- inheritance
- pathognomonic signs
- presentation
- defect in ABCA1
- autosomal recessive
- orange tonsils
Presentation
- inc level of immature HDL (reduced HDL)
- inc cellular level of cholesterol esters
- inc atherosclerosis risk
LCAT deficiency
- observed effects
- risk of atherosclerosis?
Observed
- reduced HDL and LDL
- inc phospholipids
No inc in atherosclerosis
Abetalipoproteinemia
- defect
- effects
Defect -> MTP
-needed for chylomicron (ApoB48) and VLDL (apoB100) synthesis
Effect
- low chylomicron and VLDL levels
- reduced absorption of dietary fats and fat soluble vitamins
Defect in LDL bind to LDLr effects
Defective LDLr -> familial hypercholesterolemia
- achilles tendon xanthoma
- corneal arcus
-increase serum cholesterol due to inc in serum LDL levels
Hepatic lipase deficiency effects
Triglyceride rich HDL and LDL
Dysbetalipoproteinemia
- defect
- effects
-apo E2 isoform -> doesn’t bind to LDLr properly
Effects
- elevation of chylomicron and VLDL remnants
- elevated blood levels of TGs and cholesterol
Fx of PCSK9? implications in controlling cholesterol
Binds to LDL + LDLr complex and PREVENTS recycling of the receptor back to the membrane
mAb against PCSK9 dramatically lowers LDL levels
What is the tetrad for metabolic syndrome?
- Impaired glucose regulation/insulin resistance
- fasting glucose > 100 - Abdominal obesity
- High BP
> 130/85 - Hyperlipidemia (
- High TGs > 150
- Low HDL < 40 in men and < 50 in women
BMI
- obese
- pre-obese
OBESE > 30
Pre-OBESE = 25-30
kg/m^2
Summarize relationship between obesity and atherosclerosis
Hint: discuss the effects on increasing BMI
Inc BMI -> inc TNF-alpha
Inc TNF-alpha -> inc serum FFAs
- inc activity of HSL
- dec activity of LPL
Inc TNF-alpha -> inc IL-6
- dec in LPL
- in the liver:
- > inc TG synthesis -> inc VLDL
VLDL is atherosclerotic
Summary - obesity related hypertriglyceridemia due to:
- inc synthesis of TG and secretion of VLDL (IL-6)
- dec in LPL activity (TNF-alpha + IL-6)
- inc in HSL activity (TNF-alpha)
THIS IS EFFECT IS MOSTLY DUE TO ABDOMINAL (OMENTAL) FAT -> acts more like an endocrine system
Summarize the relationship b/w obesity and insulin resistance (diabetes)
hint: 2 mechanisms stemming from same primary problem
Insulin resistance due to INCREASED serum FFAs in basal state leading HIGH levels of insulin (poorly regulated) -> downregulation of insulin receptors
- Dec uptake of glucose by muscle -> inc gluconeogenesis using the FFAs
- inc levels of circulating glucose -> inc insulin secretion
- dec uptake of insulin by the liver - Inc FFA -> take up by pancreas -> buildup of acetyl-CoA -> conversion of pyruvate to OAA -> INC levels of NADPH -> inc insulin release
- pancreas becomes insensitive to glucose
- downregulation of insulin receptors (downstream effects)
- exhaustion of beta cells in the pancreas
3 categories of afib etiology
- Conditions that stretch the atria
- conditions that irritate the atria
- metabolic abnormalities
- thyrotoxicosis
- Alcohol
- Sympathomimetics, theophylline
- hypoxia
In general, where do the drugs used to control ventricular rate in afib act? Give some examples
AV node
- digoxin
- diltizem
- beta blocker
- amiodarone
Drug used to cardiovert in afib
Ibutilide
- given IV
- can cause vfib
Features which favor return of NSR
- Reversible precipitating cause
- Short duration of atrial fibrillation
- Limited left atrial enlargement (LA <5 cm by echo)
Best drug to maintain NSR in afib
Amiodarone
T/F - VF NOT associated w/ acute MI or reversible metabolic/drug cause has a high risk of recurrence
TRUE!!!
-30% w/ in 1 year
tx of choice for patients resuscitated from VT/VF?
Implantable cardioverter/defib
What’s the cutoff at which an aortic aneurysm has risk of leaking and should be txed?
5 cm
Most common site for atherosclerosis
2nd MC?
Lower aorta and iliac arteries
2nd - proximal coronary arteries
Chronic cocaine use hits which arteries in the heart?
Intramural coronary arteries
Hypovolemic shock due to what type of infarct
Subendocardial infarct
-subendocardial myocardium gets most of O2 from LV lumen -> cells high in glycogen content (huh?)
When can a myocardial infarct be seen grossly?
Peak of neutrophilic infiltrate?
highest risk of myocardial rupture?
12-24 hours -> light or dark mottling
Days 1-4
Days 4-7
Troponin
- complex specific for myocardium
- time to become abnormal post MI
- time to max elevation
- duration of elevation
Troponin I -> myocardium
- time to become abnormal post MI = 4-6 hours
- time to max elevation = 14 - 18 hours
- duration of elevation = 7 - 14 days
CK-MB
- why is it used
- time it takes to return to normal
Used to dx REINFARCTION
Back to normal in 48 hours
What is the metabolic regulator involved with matching flow to myocardial oxygen demand
ADENOSINE
Most common anginal equivalent? more common in males or females?
DYSPNEA
-anginal equivalents more common in females
NY heart association classification of angina
Class I - Ordinary physical activity does not cause angina
Class II - Slight limitation of activity
Class III - Marked limitation of activity
-angina with 1-2 blocks of walking and climbing one flight of stairs
Class IV - Inability to carry on any physical activity without discomfort
-anginal symptoms may be present at rest.
Microvascular angina
-patient population
- Peri-menopausal women
* Disease of micro vessel’s inability to vasodilate -> can’t recruit coronary vascular reserve
Most sensitive ECG finding for ischemia?
ST depression (horizontal)
Exercise stress test
- positive
- negative
- non-diagnostic
- . POSITIVE: ECG: Ischemic ST segment depression - ≥1mm horizontal or downsloping ST depression
- NEGATIVE: Patient reaches 85% maximum predicted heart rate (MPHR)* without ST depression
- NONDIAGNOSTIC: No ischemia but patient fails to reach 85% of their maximum predicted HR.
Tx of chronic stable angina - most drugs designed to:
A) increase supply
B) decrease demand
B
3 subtypes of acute coronary syndrome
- Unstable angina
- Non-STEMI (NQMI)
- STEMI
Hallmarks of unstable angina
- Key feature - abrupt new onset of anginal sxs or sudden change in severity of previously stable angina
* hx is very important- New onset of angina = acute coronary syndrome/unstable angina until proven otherwise
- last month or 2 onset
- particular focus on accelerated pattern of sxs - this is a clear hallmark of unstable angina
- High risk of coronary thrombosis if not taken care of
- Clinical evaluation is EXTREMELY important
- New onset of angina = acute coronary syndrome/unstable angina until proven otherwise
Non-STEMI presents with?
But does not have?
Difference from unstable angina?
Non-STEMI angina WITH positive biomarkers….but WITHOUT total coronary occlusion (no ST elevation, no development of Q waves.)
“interrupted MI”
unstable angina does NOT have pos biomarkers (no necrosis)
List 5 things than should be done for initial medical management of unstable angina/Non-STEMI
 Inhibit platelet aggregation (ASA)
Prevent thrombus formation (heparin)
Maximize supply:
– Nitrates, O2
Minimize excessive demand
– Pain control (morphine), Beta blocker
Stabilize plaque -> STATINS
- 80 mg atorvastatin
- better blood flow to ischemic beds
Fill the blanks:
Women < 55 have (blank) prevalence of CAD but (blank) mortality compared to men
LOWER; HIGHER
Door to ballon time =
60 min
Higher risk of arrhythmia (VT/VF) following MI is in patients with?
reduced EF (<30%)
Complete the sentence:
In civil cases, to show medical malpractice, the standard that the plaintiff has to prove is
Preponderance of the evidence
What are the 4 criteria to prove medical malpractice
- Breach
- Damages/harm
- Causation
- Duty
Is pneumonia an immediate life threatening cause of chest pain?
What are others?
NO!
- acute coronary syndrome
- pulmonary embolus,
- aortic dissection,
- tension pneumothorax,
- pericarditis with pericardial tamponade,
- esophageal rupture.
Characteristics associated with increased inadvertent discharge of a patient with missed cardiac ischemia (8)
Younger patient age Atypical symptoms Women Nonwhite race Physician inexperience Lower-volume EDs Failure to detect ischemia on initial ECG Failure to obtain an ECG
Is cocaine a classic risk factor CAD?
List the rest (7)
NO!!!
Advanced age Male sex Hypertension Diabetes mellitus Hypercholesterolemia Premature CAD in a first-degree relative Cigarette smoking
4 risk factors for CV events that can’t be controlled
Father/brother w/ heart disease or stroke before 55
Mother/sister w/ heart disease or stroke before 65
Being male
Early menopause
Age
MCC of myocarditis
Describe the postinflammatory possibilites
VIRAL
Possibilities
- return to normal
- cardiac dilation -> systolic dysfx
- can also get myocardial fibrosis
How can influenza pneumonia cause myocarditis?
CYTOKINE RELEASE by macrophages in the lung
MCC of myocarditis in infants?
Coxsackie virus A and B
Which vaccine can cause hypersensitivity myocarditis?
Smallpox
Most common worldwide cause of restrictive cardiomyopathy?
Amyloidosis
Differentiate systolic vs diastolic HF w/ regards to EF and contractility
Both are normal in diastolic dysfx (compliance prob)
Both are decreased in systolic dysfx (contractility problem)
Defective contractile protein associated w/ HCM?
beta-myosin heavy chain
Most common underdxed condition that affects the heart and leads to HF is
systemic htn
4 receptors that mediate myocardial hypertrophy
AGII, endothelin, insulin-like GF, carditropic cytokines
matrix metalloproteinases (MMPs) are involved in which pathology?
myocardial remodeling
Rheumatic fever
- causative organism
- pathogenesis
- dxic features
- which valves are hit?
ORGANISM
-Group A beta hemolytic streptococci
PATH
- type II hypersensitivity
- Abs to M protein x-react w/ self Ags
VALVES
- mitral - almost always
- mitral + aortic -> less common
DIAGNOSIS - JONES criteria
-elevated ASO or anti-DNase B titers
FEVERSS
Fever
Erythema marginatum
Valvular damage (vegetation and fibrosis)
ESR
Red-hot joints (migratory polyarthritis) Subcutaneous nodules
St. Vitus’ dance (Sydenham chorea)
ANOTHER MNEMONIC
- J - joint problems
- migratory polyarthritis
- Wrists, knees and ankles
- migratory polyarthritis
- O - heart probs
- Pancarditis
- All 3 layers of the heart
- THIS IS THE KEY PROB
- Pancarditis
- N - nodules
- Subcutaneous
- E - erythema marginatum
- Appears more red at margins of rash
- Annular
- S - sydenham’s chorea
Histology for rheumatic fever myocarditis
- Granulomatous w/ macrophages
* Chronic inflammation
* Giant cells w/ fibrinoid material- Lymphocytes
- Called Aschoff nodules - pathognomonic for RF
- REMEMBER THIS
- Caterpillar nucleus cells are found here
- Anitschkow cells - enlarged macrophages
w/ ovoid, wave , rod like nucleus
- Anitschkow cells - enlarged macrophages
List 3 complications of aortic stenosis
LVH
CHF
Impairment of coronary outflow
-syncope w/ exertion
Mitral valve prolapse heart sound
More common in men or women
pathology?
- Midsystolic click and late systolic crescendo murmur (click-murmur)
- > click due to sudden tensing of chordae tendineae (think of parachute opening)
Dec preload -> sound closer to S1
Inc preload -> sound closer to S2
WOMEN > MEN
Myxomatous degeneration of mitral valve
Fill in the sentence:
Strains w/ a selective advantage in adhering to (what 3 things) produce disease w/ a lower bacterial inoculum
Platelets, fibronectin or fibrin
What does the following adhere to?
S. aureus
Oral streptococci
Strep viridans
Candida albicans
S. aureus -> fibronectin binding properties
Oral streptococci -> dextran
-also plays role in cavity formation
Strep viridans -> fim A
Candida albicans -> adhesins
Blood culture criteria for infectious endocarditis
Major blood culture criteria for IE include the following:
• Two separate blood cultures positive for organisms typically found in patients with IE (including viridans streptococci, Streptococcus bovis, Staphylococcus aureus or HACEK* group)
- Blood cultures persistently posiOve for one of these organisms, from cultures drawn more than 12 hours apart
- Three or more separate blood cultures drawn at least 1 hour apart
DRAW BLOOD BEFORE GIVING ANTIBIOTICS
MC pathogen associated w?
- native valve IE
- IE of prosthetic valves
- IE of IV drug users
Next most common?
- native valve IE -> staph aureus and viridans streptococci
- IE of prosthetic valves -> Staph epidermidis (coag neg)
- IE of IV drug users -> staph aureus
- > less commonly fungi + gm neg bacilli
Next most
Streptococci and enterococci
Staph aureus
- characteristics
- pathogenesis mechs
Gm pos, catalase pos, coag pos
- Microcapsule
- prevents phagocytosis
- adherence
- Adhesins
- allow for binding to host cell proteins (damaged tissue)
- Protein A
- Messes up the Ab by binding to Fc site
Staph aureus
- colonizers of?
- primary reservoir?
- transmission?
- mucosa and skin
- anterior nares
- autoinoculation
Streptococci - groups
- Endocarditis
- RF
- Endocarditis
- Group D
- viridans strep (no group) -> alpha hemolysis (INCOMPLETE) - RF
- Group A
- beta hemolytic -> COMPLETE HEMOLYSIS
- M protein = antigenic
Enterococci
- hemolytic?
- grow in presence of?
- 2 types of infections they can cause
- pathogenesis
- non hemolytic (most)
- grow in presence of salt and bile
- nosocomial (hospital acquired)
- endocarditis
BIOFILM production
-resistant to many antimicrobial agents
-found in normal gut flora
Strep viridans
- hemolytic?
- normal flora?
- sensitive to which antibiotic
alpha hemolytic
-viridans = green
YES - normal flora
PENICILLIN
40-60% of native valve endocarditis in community practice due to?
Viridans strep and strep bovis
List 2 gm neg aerobic bacilli that cause IE
Pseudomonas aeruginosa
Enterobacteriaceae
-health care contact
Definition of critical aortic stenosis
FIXED CO -> no inc on demand
Valve area <0.6cm^2
Cardinal sxs of severe/critical aortic stenosis
Implications?
- dyspnea
- angina
- syncope
High risk for sudden cardiac death
List 3 reasons for syncope w/ critical AS
- Syncope - 3 reasons
* Extreme LVH -> inc in risk of VT/VF* Aortic ring abuts IV septum * Calcification get into upper part of IV septum -> heart block * Critical AS -> fixed CO * Exertion can’t be accommodated by an inc CO * Can’t meet the demand
Most sensitive for differentiating mild/moderate from critical AS
Single S2
-absent aortic component of S2
tighter stenosis -> longer murmur + later peak + softer A2
How can you differentiate HOCM from AS?
-HOCM
Valsalva -> dec venous return -> dec preload -> inc obstruction of LVOT outlet tract -> INCREASE in intensity of murmur
-AS
Valsalva -> DECREASED intensity of murmur
How to conduct a systematic review
- 5 A’s
- PICOTT
! Ask • Define the question • PICOTT o Population o Intervention o Comparison o Outcome o Type of question (therapy, diagnosis, prognosis, harm) o Type of study (i.e. RCC in therapy questions)
! Acquire
• Conduct the literature search
! Appraise
• Apply your own inclusion/exclusion conclusion
! Apply
• Summary effect statement
! Assess? Assess? Anyone? No? Ok.
Tests for heterogeneity
I^2 statistics should what percentage?
Z-score
Forest plots
I^2 stats
< 40%
-means that studies are low enough to compare
Z-scores
<0.05
