Exam I Flashcards
(405 cards)
1
Q
Hypertension: Systolic blood pressure increases with age due to
a. less elastic tissue within the aorta (non-compliance)
b. decreased aortic dilation during systole
c. decreased diastolic recoil (dec. diastolic blood pressure)
A
All of the above
- elastin replaced by collagen
- widened pulse pressure (SBP - DBP)
2
Q
Preload is determined by
A
EDV
- proportional to Right Atrial Pressure
- Inc. RAP = Inc. preload (more blood pumped into the ventricle)
3
Q
Purkinje fibers are specialized conducting fibers composed of electrically excitable cells larger than cardiomyocytes. What can be found in the cells of purkinje fibers?
A
-few myofibrils
-Mitochondria
(cardiac action potentials)
**quicker and more efficient than any other cells in the heart
- voltage gate Na channels
- stain based on glycogen
- maintain consisten heart rhythm
- synchronized contractions of the ventricles
4
Q
Hypertension: Primary Hypertension (a.k.a. Essential HTN) is HTN with no known secondary cause (idiopathic). It is typically induced by Sodium, a primary determinant of the ECF volume.
When Sodium exceeds the capacity of the kidney to excrete it, blood volume will initially expand, resulting in increased SV and inc. CO. What follows?
A
CO = HR x SV MAP = CO x TPR
- Autoregulation will try to maintain constant blood flow:
- -CO will decrease over time
- -TPR increases (inc. BP) - inc. Na = Inc. vascular tone (vasoconstriction due to inc. intracellular Calcium)
Tx: weight loss, diet, aerobic exercise. limit alcohol
5
Q
The following describes what kind of capillaries?
- complete basal lamina
- pinocytotic vesicles
- no fenestrae
- continuous epithelium
A
Continuous (somatic) capillaries
6
Q
Valvular disorder: The following describes what valvular disease
- decrescendo (dec. pressure during diastole)
- “water hammer pulse” (inc. SBP; dec. DBP)
- high pitched “blowing” in early diastole
- Inc. with squatting
- Decreased with Valsalva
A
Aortic regurgitation
*retrograde flow in LV during diastole
7
Q
Pharmacology: Drugs for hypercholesterolemia include:
a. bile acid binding resins
b. Niacine
c. Ezetemibe
d. Fibrates
A
A-C
**NOT niacin
8
Q
Hypertension: Calculate Mean arterial Pressure (MAP)
*Pressure against the arterial walls
A
CO x TPR (systemic vascular resistance)
1/3 SBP-DBP + DBP
[SBP + 2(DBP)]/3
9
Q
Describe the Pacemaker (SA node) Action potential
A
Pacemaker: No phases 1 and 2
PHase 4: HCN “funny current”
- -T-type Ca2+ channels
- -inc. Na influx
- -Dec. K+
Phase 0 (slope): L-type Ca2+
Phase 3: Voltage gated K+ channels
10
Q
Valvular disorders: What are the effects of pre-load and afterload on heart murmurs?
- Inc. preload
- Dec. preload
- Inc. afterload
- Dec. afterload
A
- Inc. preload (squatting, leg raising)
–more blood to heart
*louder murmur
(except HOCM, MVP) - Dec. preload (valsalva)
–prevents blood to heart
*soft murmur
(except HOCM, MVP) - Inc. afterload (hand grip)
*louder regurgitant
(except HOCM, MVP) - Dec. afterload (amyl nitrite)
* louder HOCM, MVP
*HOCM, Mitral Valve Prolapse
11
Q
Claudication is pain with ambulation that is caused by too little blood flow to your legs or arms.
The following describes what type of claudication?
“Pain similar to that of classic claudication, but does not involve the calves or does not resolve within 10 minutes of rest”
A
Atypical exertional leg pain type II
*obturator stenosis type
12
Q
Cardiomyopathy: A myocardial dysfunction associated with an enlarged heart, dilated ventricles (or just LV) and impaired systolic function (HFrEF).
In this case, the heart is enlarged, heavy and flabby due to dilation of all the chambers.
Common pathophysiology includes:
- Myocyte injury
- LV dilation
- Decreased pumping force (due to hyperextension,)
- dec. contractility
- dec. SV
- Inc. Ventricular filling Pressures
- Decreased forward Cardiac Output
A
Dilated cardiomyopathy
- LV dilatation
- -mitral regurgitation (stretched annula of mitral valve) - Inc. Ventricular Filling Pressure
- Systemic congestion: JVD, hepatomegaly, edema
- Pulmonary congestion: dyspnea, orthopnea, rales - Dec. CO
- fatigue
- weakness
- dec. renal flow
NOTE: Remember, because the ventricles are stretched, there is decreased pumping force, and thus less blood is ejected — resulting in backup of fluid in the heart and lungs.
13
Q
Lympatic capillaries begin as blind ending capillaries. They drain into the interstitial fluid produced when the plasma forced from the microvasculature by hydrostatic pressure doesn’t return the blood via osmotic pressure. There are openings between the endothelial cells. What holds these openings in place?
A
anchoring filaments
(elastin)
–interstiatil fluid enters via openings
- backflow of lymph stopped by endothelial folds
- no tight jxns or fenestrations
14
Q
Platelets are small, granulated bodies that aggregate at sites of vascular injuty. They lack nuclei and function in surveillance (of bv’s), formation of blood clots and in tissue repair.
There are 3 groups of platelets:
- Alpha granules
- Delta granules
- Lysosomal granules
Describe the alpha granules within platelets and how they aid platelet functions?
A
- Alpha (α) granules: hemostatic functions
- most numerous
- Adhesion: fibrinogen, von Willebrand
- Coagulation: plasminogen, α-2 plasmin, thromoxane A2 (aggregation, constriction)
- Endothelial cell repair: platelet-derived growth factor (PDGF)
15
Q
Venules accompany arterioles. What are key features of venules
A
-broad, irregular lumen
- Intima: thin
- Media: thin; no SM
- Adventitia: thickest layer
- receives blood from capillaries
- responds to vasoactive agents (leukotrienes, 5HT, histamine)
16
Q
Anti-hypertensives: In managine HTN, the initial step is normally non-pharmacologic. Which of the following are non-pharmacologic methods for working w/ hypertension?
a. reduce body weight
b. smoking cessation
c. sodium restriction (minimal effect in non-sensitive individuals)
d. alcohol restriction (5+ drinks/week lower bp)
e. Inc. exercise (dec. b.p.)
A
Answer: all of the above
17
Q
Weibel Palade bodies can be found in capillaries and play a role in what?
A
Endothelial blood clotting
18
Q
Vascular disorders: ______ is the he interstitial collection of protein-rich fluid due to disruption of lymphatic flow.
Obstruction of lymphatics secondary to surgery and/or radiation results in impaired lymphatic drainage and thus accumulation of interstitial fluid
A
Lymphedema
19
Q
Single largest cause of death since 1900
A
Ischemic heart disease
20
Q
Anti-hypertensive drugs: _______ lower blood pressure by reducing peripheral vascular resistance and blunting the Na+ handling effects of aldosterone
A
Indirect vasodilators
*prevent production or action of Ang II
21
Q
Congenital defects: What changes in fetal circulation occur at birth?
a. UC clamped (no more nutrients from mother)
b. breathing begins
c. inc. systemic b.p; decrease pulmonary pressure
d. changes in pressure facilitate closure of ductus arteriosus
e. inc. pressure in LA and dec. pressure in RA - facilitates closure of foramen ovale
A
All of the above
- DA constricts – blood leaves RV to lungs
- IVC now carries ONLY deox blood back to heart
- Ductus venosus degenerates = ligamentum venosum
22
Q
Valvular diseases:
- ______ is a narrowed valve. It fails to open completely and tends to impede forward flow.
- ________ (insufficiency) is the failure of a valve to close completely. It tends to allow reversed flow (Backflow)
A
- Stenosis
- -harsh sound - Regurgitation
- -blowing sound
*auscultation and echocardiogram for valvular diseases
23
Q
THe vascular endothelium enables the passage of molecules and gases. It also retains blood cells and large molecules. What are other major roles of the vascular endothelium (endothelial cells)?
A
- Vasoactive substances
- Angiogenesis (new b.v.’s)
- Prostacyclin
- Modulate SM activity
- Blood coagulation
- Regulate migration of inlammatory cells
- Destabilize tight junctions
- Ang I to Ang II
24
Q
Anti-hypertensive drugs: True/False: Centrally acting (a2 agonists) sympatholytic drugs are used for HTN that is difficult to treat, but is not typically a 1st or 2nd choice drug unless the HTN is refractory.
A
True
25
Anti-hypertensive Drugs: List the Dihydropyridine drugs (calcium channel blockers; direct vasodilators)
nifedipine, nicardipine, amlodipine
26
Pharmacology: Drugs for Hypercholesterolemia and Hypertriglyceridemia include:
a. Statins and Niacin
b. Statins and FIbrates
c. Fibrates and Niacin
Answer: A
27
Vascular endothelium also plays a major role in the modulation of SM activity by releasing SM relaxing factors and contracting factors. List examples of each
Relax:
-NO, prostacyclin, prostaglandin A2
Contract:
-endothelin, prosta H2, thromboxane
28
Histology: Tunics of the Heart - The pericardium of the heart is composed of the
1. Fibrous pericardium (tough CT)
2. Serous pericardium
What are the layers of the Serous pericardium?
Double layered serous membrane:
a. parietal pericardium – fused to fibrous pericardium
b. visceral pericardium (a.k.a. epicardium)--covers the heart
--serous fluid fills the pericardial cavity between parietal & visceral layers
29
Valvular disorders: Of the following, which is the most common etiology for mitral regurgitation (failure of valve to close during systole)?
a. Infective endocarditis
b. Mitral valve prolapse
c. Rheumatic fever
d. Hypertrophic cardiomyopathy
e. Calcification of mitral annulus
Answer: Mitral valve prolapse
30
Valvular disorders: Distinguish between acute aortic regurgitation and chronic aoric regurg.
1. Acute:
-rapid valve failure
(dilatation secondary to dissection)
-dyspnea, crackles, CXR = fluid in lungs
2. Chronic
- -gradual
- -asymptomatic (w/ compensation)
- -palpitations, SOB, Chest pain (inc. LV EDP; dec. coronary),
* sudden cardiac death
31
Large waist circumference that's at least ____ inches for men and ____ inches for women is a visible sign of metabolic syndrome
Women: 35"
Men: 40"
32
Valvular disorders: A patient presents with complaints of chest pain (angina), and dyspnea on exertion. He reports syncopal episodes.
You suspect
Aortic stenosis
SAD: HFpEF
- -dec. TPR (dec. CO)
- -dec. coronary flow (Inc. O2 need, dec. O2)
- -LVH = inc. LV EDP
- -LVH = dec. LV compliance
- -inc. LV pressure = inc. LA, pulmonary = edema
33
Pharmacology: Bile acid binding resins are oral drugs that bind to bile acids in the GI tract and prevent their reabsorption. These include:
1. colestipol
2. cholestyramine
3. cholesevelam
By binding bile acids, what does this cause?
1. Increased utilization of cholesterol to form bile acids
2. inc. LDL receptor expression
* inc. clearance of cholesterol out of b.v's
NOTE: cholesterol is used to make bile acids (emulsifiers of fat)
34
Shock: Type of shock that normally occurs from massive blood loss (trauma, rupture vessel, ectopic pregnancy).
Physical exam findings include:
1. decreased skin turgor (young patients)
2. dry skin/axillae
3. dry tongue/oral mucosa
4. obvious trauma
Hypovolemic shock
- Dec. CO
- Inc. TPR (compensation; NE on a1)
- Dec. LVEDP (PCWP)
History:
-vomiting, diarrhea, hematomesis
35
Cardiomyopathy: _______ is a an autosomal recessive disorder most commonly caused by mutation in HFE gene (hepcidin) leading to unregulated Fe absorption in the GI tract.
Patients present with hyperpigmentation, hepatomegaly and diabetes mellitus. Complications include development of restrictive cardiomyopathy with progression to ventricular dilation.
Hereditary hemochromatosis
* excess iron deposition (and liver, pancreas, endocrine, heart).
* restrictive cardiac defect w/ progression to ventricular dilation
Diagnose: Genetic tests and Endomyocardial biopsy (Prussian blue stain)
36
Ejection fraction is a comparison of the volume of blood pumped out of the LV to the volume of blood that remains after contraction. Calculate EF
EDV - ESV/EDV
37
Hypertension: What role does Hypercalcemia play in secondary hypertension?
ex; Primary hyperparathyroidism
*increased contraction of arteriolar SM = TPR
38
Pharmacology: The following drugs may be used to treat what disorder?
1. Dalteparin (LWWH)
2. Enoxaparin (LMWH)
3. Fondaparinux (Synthetic)
4. Heparin
Acute Venous Thromboembolism
39
Cardiac atria have _____ endocardium, while ventricles have ____.
Thick endocardium
Ventricles: thin
40
Sensory nerve endings include:
1. Baroreceptors
2. Chemoreceptors
Where are these found?
1. Baroreceptors: carotid sinus and aortic arch
2. Chemoreceptors: carotid and aortic bodies
* bifurcation point of carotid
41
Hypertension: True/False: Damage to the baroreceptor reflex (e.g. autonomic neuropathy) can lead to extremely labile blood pressure
True
42
One of the major roles of the vascular endothelium is the secretion of vasoactive substances. What is the function of these substances?
Contract/Relax SM of the vascular wall
43
Pericardial disorders: When would we see Kussmaul's sign (rise in JVP on inspiration)?
In anything that restricts cardiac filling (filling of the Rt. atrium)
* leads to backup of blood in the jugular vein
- Constrictive pericarditis, Cardiac tampnade, Restrictive cardiomyopathy
44
Myocardial oxygen consumption is a major determinant of coronary blood flow.
Rate pressure product is a good estimate of myocardial oxygen consumption. How do you calculate RPP?
HR x SP (systolic blood pressure)
*also important in heart failure -- minimize workload of heart by manipulating RPP
45
Lipoprotein Disorders - dislipidemias: A patient presents with premature coronary artery disease, corneal arcus and tendon Xanthoma.
Labs include:
- inc. LDL from birth
- inc. cholesterol
- foam cells
- normal TGs
You suspect which type of lipidemia?
Type IIa (familial hypercholesterolemia)
* AD
* dec. LDL receptors (inc. LDL, dec. clearance)
46
Shock: The prime mediator of inflammatory response in sepsis and septic shock.
It causes decreased myocardial contractivlity, and increased vascular permeability (vasodilation).
TNF
47
ANti-hypertensives: It is important to properly select anti-hypertensive drugs for patients with specific traits or concurrent diseases.
What are the preferred drugs for
a. pregnancy
b. asthma
c. BPH
d. osteoporosis
A. pregnancy
- preferred: methyldopa, labetalol
- NOT: ACEI, ARB, aliskiren, diuretics
B. Asthma
- -CCB, ACEI, ARB
- -NOT: beta blocker
C. BPH
--alpha blocker
D. Osteoporosis
--DIuretic (thiazide type)
48
Anti-Hypertensive Drugs: Sympatholytic drugs are anti-hypertensives that act to relax SM and blunt the effects of NE.
There are 3 subclasses:
1. α-Adrenoceptor antagonists (a1)
2. β-Adrenoceptor antagonists
3. Centrally acting Drugs
B-adrenoceptor drugs may be selective or non-selective. Distinguish b/t the two.
1. Non-selective
- -affect B1 and B2 (heart and lung)
- -dec. b.p
- -bronchoconstriction
ex: propanolol
2. B-1 Selective:
- -heart only
ex: atenolol (not 1st choice)
ex 2: metoprolol
3. β and α selective
ex: carevdilol and labetalol
- -after heart attack
49
What is a foam cell?
Macrophage that ingests oxidized LDL
*tunica intima
50
Anti-hypertensives: ______ lower blood pressure by relaxing vascular SM
direct vasodilators
51
Congenital defects: This is the most common congenital heart disorder in ADULTS because it tends to be asymptomatic until later in life.
It is characterized by Increased SaO2 in the RA, RV and PA (pulmonary artery) due to abnormal shunting of blood from the LA to the RA (L to R shunting).
What are possible outcomes of an ASD?
Atrial Septal Defect
1. Eismenger
- -switch to R to L shunting once pulmonary HTN develops
- -elevated RV pressure (straining; RVH)
2. Paradoxical embolus
- -DVT thrombus in the leg that crosses the ASD into the LA and enters systemic circulation
- -infarcts downstream
52
Pericardial disorders: Constrictive pericarditis is distinguished by the loss of pericardial elasticity. This decreased elasticity impedes filling (similar to restrictice cardiomyopathy).
True/False - In constrictive pericarditis, granulation and fibrous tissue is deposited after healing of pericarditis. scarring obliterates the pericardial cavity, and calcifiction occurs, encasing the heart.
True
Restricted filling = dec. CO
Signs/Symptoms:
* *RHF w/ elevated jugular venous pressure (JVP)
* *Kussmaul's sign (inc. JVP on inhalation)
- Hypotension and Shock
- Hepatomegaly (nutmeg liver) Peripheral edema, Crackles
- PR depression, Scratchy sound (pericardial friction rub), Pericardial knock **
Tx: Colchicine
53
ANti-hypertensive Drugs: What are common adverse side effects of the following vasodilators? Also include contraindications.
1. Calcium channel blockers:
- Dihydropyridine
- Diltiazam
- Verapamil
2. Other vasodilators
- Hydralazine
- Minoxidil
- Nitroprusside
- Fenoldopam
1. Calcium channel blockers
1. Dihydropyridine
- -reflex tachycardia
ContraX: Any anti-hypertensives
2. Diltiazam
- -bradycardia
ContraX: any anti-hypertensives
etc.
3. Other vasodilators
a. Hydralazine:
- -Lupus like syndrome
- -NSAID Contra X
b. Minoxidil
- -hypertrichosis
- -NSAIDS contraX
c. Nitroprusside
- -thicyanate/cyanide toxicity
- -ContraX: Any hypo/hypertensives (nitrates and ED meds)
54
Hypertension: Baroreceptors are responsible for short term blood pressure regulation.
Describe what happens to the baroreceptors in the presence of increased blood pressure
1. Inc. b.p
2. arterial wall distends
3. Stretch of mechanoreceptors (carotid sinus and aortic arch)
4. electrical signal generated = sent to medulary brainstem nuclei
- --via CN 9 and CN 10
5. Dec. sympathetic outflow
6. Dec. blood pressure
*short term
55
Cardiomyopathy: A myocardial dysfunction associated with an enlarged heart, dilated ventricles (or just LV) and impaired systolic function (HFrEF).
Common pathophysiology includes:
1. LV dilation
2. Decreased pumping force (due to hyperextension,)
3. dec. contractility
4. dec. SV
5. Inc. Ventricular filling Pressures
6. Decreased forward Cardiac Output
Dilated cardiomyopathy
1. LV dilatation
- -mitral regurgitation (stretched annula of mitral valve)
5. Inc. Ventricular Filling Pressure
- Systemic congestion: JVD, hepatomegaly, edema
- Pulmonary congestion: dyspnea, orthopnea, rales
6. Dec. CO
- fatigue
- weakness
- dec. renal flow
NOTE: Remember, because the ventricles are stretched, there is decreased pumping force, and thus less blood is ejected --- resulting in backup of fluid in the heart and lungs.
56
Cardiomyopathy: A myocardial disorder in which the heart muscle is structurally and functionally abnormal (in the absence of coronary artery disease, HTN, valvular disease or congenital heart disease).
Cardiomyopathy
1. Systolic dysfunctions
- -dilated cardiomyopathy
2. Diastolic dysfunctions
- -hypertophic cardiomyopathy
- -restrictive cardiomyopathy
57
Differential DIagnosis: VINDICATE
```
V = vascular
I = Infection
N = neoplasm
D = drugs
I = inflammatory/idiopathic
C = _______
A = Autoimmune
T = _____
E = ______
```
```
C = congenital
T = trauma
E = endocrine/metabolic
```
58
Congenital defects: Tetralogy of Fallot is an example of a Right to Left shunt that results from anterosuperior displacement of the infundibular septum (aorta displaced to right side).
It is marked by:
1. Overriding aorta
2. RV outflow tract obstruction (due to overriding aorta)
3. VSD
4. RV hypertrophy
Because poorly oxygenated blood is flowing into systemic circulation, the patient must have a protective shunt to survive. What are these shunts?
1. Atrial septal defect (ASD)
- -inc. SaO2 in RA
- -blood shunted to L heart has higher SaO2
2. Patent ductus arteriosus (PDA)
--shunts poorly ox blood from aorta to pulmonary artery for oxygenation in the lungs
(shunts blood toward lungs)
59
Hypertension: Severe HTN (DPB > 12ommHg) with end organ damage
HTN emergency
*eye: retinal hemorrhage, papilledema
*heart: MI, angina
Brain: cerebral infract; seizures
60
What is an example of a ligand that binds selectin? Where is it found?
Lewis S. antigen (endothelial cells)
61
Histology: Arteries are distinguished by the organization and thickness of the smooth muscle in what muscle layer? What are the 3 types of arteries?
Tunica media
1. Large/Elastic
2. Muscular
3. Arteriole
62
vascular disorders: What are the symptoms of a rupture following an abdominal aortic aneurysm? What is the greatest predictor of rupture?
1. sudden onset of severe flank pain (retroperitoneal bleed)
2. hypotension (blood loss)
Greatest predictor: diameter of aneurysm (?5cm)
Tx: endovascular/open surgery
63
Pharmacology: Which of the following correctly describes the pharmacokinetics of ezetimibe?
a. 1/2 life: 22 hours
b. metabolized via conjugation with glucuronate
c. 80% excreted in feces
d. use alone or combined with "statin"
Answer: All of the above
*Adverse effects: headache, myalgia
EX: Vytorin (ezetembe + simvastatin)
64
Lipoportein DIsorders: Hypertriglyceridemia is characterized by increased VLDL.
Factors that can increase hepatic VLDL include:
a. insulin resistance (type II DM)
b. obesity
c. regular alcohol consumption
d. nephrotic syndrome
e. high carbohydrate diet
f. exogenous estrogens
g. Cushing's syndrome
All of the above
Findings: chylomicrons (less dense) float on surface of blood sample
**creamy layer on surface
65
Platelets are small, granulated bodies that aggregate at sites of vascular injuty. They lack nuclei and function in surveillance (of bv's), formation of blood clots and in tissue repair.
There are 3 groups of platelets:
1. Alpha granules
2. Delta granules
3. Lysosomal granules
Describe delta (dense core) granules
2. Delta (δ) [dense core granules]:
Mediate vascular tone:
Serotonin, Adenosine Diphosphate [ADP], and Calcium
66
Type of shock that normally occurs from cardiac failure of any cause (e.g. MI, valvular dysfunction, tamponade)
Physical exam findings include:
1. diffuse crackles
2. new murmur
3. muffled heart sounds
4. Inc. JVP? ECG abnormalities?
Cardiogenic shock
- impaired LV pump
- Dec. CO
- Inc. LVEDV (blood accumulates in ventricle)
-Inc. TPR (vasoconstrictors)
67
Shock: Confirmation of shock can be accomplished with measuring ______
Serum lactate
*build up of lactic acid due to anaerobic metabolism
68
Vascular disorders: Which of the following is a potential complication of atherosclerosis?
a. ischemia
b. plaque rupture
c. aneurysm
*image slide 8
All of the above
a. ischemia
- -plaque in lumen = dec. flow
b. plaque rupture = overlying thrombosis; obstruct flow
c. aneurysm
- -dilated region of vessel due to weakened wall
- -secondary ischemic injury to the tunica media due to inc. diffusion distance from the lumen
69
Pericardial disorders: Pericardial effusion refers to accumulation of excess fluid around the heart. Under normal conditions, the space b/t the visceral and parietal pericardium can accommodate a very small amount of fluid.
______ occurs when the amount of pericardial fluid is increased to the point it impairs cardiac filling. This varies w/ the rate of fluid accumulation in the pericardial sac.
Cardiac tamponade
- rapid accumulating effusion (e.g. hemopericardium) - 100- 200mL
- slow effusion: gradual (1L or more before tamponade develops)
70
Lipoprotein Disorders: True/False: When intracellular cholesterol levels are low, sterol regulatory element binding protein (SREBP) is released -- increase transcription of HMG-CoA reductase -- increase cholesterol synthesis.
True
71
True/False: About 85% of people who have type 2 diabetes also have metabolic syndrome
True
72
Cardiomyopathy: Cocaine use is associated with dilated cardiomyopathy.
Although the mechanism is not well understood, it is believed to have a direct toxic effect and induce a hyperadrenergic state in the heart (inc. catecholamine effect; vasoconstriction).
What are examples in which this "catecholamine effect" can lead to cardiomyopathy?
1. pheochromocytoma (excess catechols)
- -myocardial necrosis leading to DCM
2. Takotsubo cardiomyopathy
- severe psychologic stress and LV contractile dysfunction
73
Valvular disorders: Progression of aortic valve stenosis is accelerated (<50y/o) in those with abnormal A-V valves. This makes the leaflets more susceptible to trauma (fibrosis and calcification).
True
* congenital bicuspid AV
* chronic rheumatic heart disease
* radiation injury
74
Thromboembolic Disorders: The coagulation cascade involves two pathways, the intrinsic and the extrinsic both of which involve several special proteins known as coagulation factors that are activated one after the other in a "cascade" effect. The end result is a blood clot that creates a barrier over the injury site, protecting it until it heals.
Fibrinogen (zymogen) is activated to form fibrin via what factor? Clot formation occurs via what other factor?
Thrombin; Factor 13A
75
Shock: Which of the following is a complication of shock?
a. ischemic enteritis/colitis
b. global cerebral ischemia (encephalopathy)
c. waterhous-friedrichsen syndrome
All of the above
*cerebral:
--anoxic "red neurons"
(dead reds)
* Waterhouse-friedrichsen
- -hemorhagic adrenal
- -neisseria meningitis
76
Lipoprotein Disorders - Secondary Hypercholesterolemia:
Secondary Hypercholesterlemia and formation of atherosclerotic plaques may be caused by several different factors including lifestyle and disease.
Renal disease, specifically nephrotic syndrome, is a common cause of hypocholesterolemia. Nephrotic syndrome results from
- loss of proteins in the urine (dec. oncotic pressure)
1. Compensate by inc. synthesis and decreasing clearance of lipoproteins (hyperlipoproteinemia)
**Inc. total and LDL cholesterol
77
Vascular disorders: Which of the following are clinical findings of aortic dissection?
a. CHest pain
b. New distolic murmur
c. Loss of pulses
d. Mediastinal widening
e. Death
ALL
a. chest pain
- -most common
* ant. or post. chest
* tearing
b. murmur
- -aortic regurg.
c. loss of pulse
- -false lumen compresses branches
e. death
- -rupture in pericardium, pleural cavity, massive hemorrhage
78
The dichrotic notch on a curve represents
Aortic valve closing
79
Pharmacology Thromboembolic Disorders: The following Fibrinolytic drugs are Tissue plasminogen activators (t-PA)
1. streptokinase
2. anistreplase (Activator complex: streptokinase + plasminogen)
What is their mech of action?
Non-specific plasminogen binding; Increased bleeding risk
80
Valvular disorders: Describe what happens to the aortic and pulmonic vs. the Tricuspid and Mitral Valves during
1. Systole
2. Diastole
1. Systole
- Aortic and Pulmonic: Stenosis
- Tricuspid and Mitral: Regurg.
2. Diastole
- Aortic and Pulmonic: Regurg.
- Tricuspid and Mitral: Stenosis
81
Lipoprotein Disorders - dislipidemias: A patient presents with eruptive xanthomas, pancreatitis and lipidemia retinalis. You suspect ________ lipidemia.
It is a result of decreased _______ activity.
Type V (familial mixed hypertriglyceridemia) is a combination of Type I and Type IV.
--Decreased capillary
lipoprotein lipase activity
--high chylomicrons and VLDL
*slide 17
82
Lipoprotein disorders: There are 5 major classes of lipoproteins:
1. Chylomicrons
2. Very Low Density Lipoproteins (VLDL)
3. Intermediate Density Lipoproteins (IDL)
4. Low density Lipoprotein (LDL)
5. High Density Lipoprotein (HDL)
These are the smallest lipoproteins with the highest density. They are involved in reverse cholesterol transport (tissues to the liver)
HDL's
83
Pericardial disorders: A patient presents with complaints of sharp, retrosternal chest pain that worsens with inspiration and when supine. He reports the pain improves when sitting and leaning forward.
On auscultation, you note a high-pitched, scratchy sound that is heard when the patient leans forward and doesn't breathe (friction rub)
EKG reveals diffuse "ST" elevation
You suspect
Acute pericarditis
1. Chest Pain:
- sharp, retrosternal chest pain
- worse w/ inspiration and supine
- better when sitting and leaning forward
- -pain may be referred to scapula (phrenic nerve)
2. Pericardial friction rub
- high pitched, scratchy sound (leaning forward and not breathing)
* differ from pleural rub = can't hear when not breathing
84
Congenital defects: With R to L shunts, deoxygenated blood from the Right side of the heart is shunted to the Left side of the heart. Low oxygen levels of the blood cause cyanosis of the lips, fingers and toes (cyanotic congenital heart disease).
What are the 4 main causes of cyanotic congenital heart disease?
1. Tetralogy of Fallot
2. Transposition of the Great vessels
3. Truncus arteriosus
4. Total anomalous pulmonary venous return
NOTE: systemic complications - secondary polycthemia and infectious endocarditis
85
Cardiomyopathy: What are the signs of heart failure associated with dilated cardiomyopathy?
a. displacement of the apical impulse
b. bibasilar crackles (pulmonary edema)
c. S3, S4 heart sound
d. fxnal mitral (or tricuspid) regurgitation due to dilated ventricle
e. mural thrombi
All of the above
NOTE: functional regurgitation: pansystolic murmur at the apex w/ radiation to the axilla
86
Valvular disorders: True/False: murmurs are due to abnormal flow across a valve
True
*auscultation = first clue
87
Pharmacology: What drugs may be used to Tx Pulmonary embolism?
```
Heparin
Fibrinolytic drug (alteplase)
```
*catalyze formation of plasmin -- lyses fibrin clot
88
Lipoprotein Disorders - Secondary Hypercholesterolemia:
True/False:
Secondary Hypercholesterlemia and formation of atherosclerotic plaques may be caused by several different factors including
True
89
Lipoprotein disorders: There are 5 major classes of lipoproteins:
1. Chylomicrons
2. Very Low Density Lipoproteins (VLDL)
3. Intermediate Density Lipoproteins (IDL)
4. Low density Lipoprotein (LDL)
5. High Density Lipoprotein (HDL)
THese are the largest and least dense lipoproteins. They carry diet-derived TG's to the periphery and are also formed within enterocytes of the SI
Chylomicrons
*mainly composed of TG's
90
Hypertension: Secondary HTN due to adrenal disorders including
1. Primary aldosteronism (Hyperaldosteronism)
2. Cushing syndrome
3. Pheochromocytoma
Hyperaldosteronism is due to either an aldosterone-secreting adrenal adenoma or bilateral adrenal hyperplasia. What are the effects?
1. excess aldosterone
- -inc. Na/H2O retention
- -inc. blood volume
- -inc. K+ and H+ excretion
NET: HTN, hypOkalemia, metabolic ALKalosis
91
Valvular disorders: Incompetence of a valve due to an abnormality in one of its support structures.
* displacement of papillary muscles
* stretching of annulus
Functional regurgitation
*prevent proper closure of normal mitral/tricuspid valves
92
Cardiomyopathy: Patients with dilated cardiomyopathy often present with heart failure (systolic dysfunctions; excessive stretching of sarcomeres).
Typical signs and symptoms of dilated cardiomyopathy include:
a. dyspnea on exertion progressing to dyspnea at rest w/ orhopnea
b. paroxysmal nocturnal dyspnea
c. Increased tissue perfusion
Answer: A and B
Dec. Tissue perfusion (Dec. CO = Dec. exercise tolerance)
*abdominal pain after meals due to mesenteric ischemia
93
Hypertension: What drugs can pose risk for secondary hypertension?
1. oral contraceptives
- -inc. synthesis of angiotensinogen
* *most common HTN in young women
2. Cocaine (sympathomimetic)
- -sympathetic activity
3. ALcohol (dose related)
4. Vasopressors
--Ang II
Catecholamines
94
Histology: A defect in the tranport of lymph due to abnormal vessel development or damaged lymph vessels.
Fluid and proteins accumulate in the interstitial spaces, and induces inflammation.
Lymphedema
*fibrosis, impaired immune response, degeneration of CT
95
Muscular arteries function as distributing vessels. Describe their functions
**handout page 8
96
Vascular disorders: A complication of DVT that involves a clot (or portion) that breaks off and travels through the bloodstream (from the deep vein of leg) to the lung, where it becomes lodged and blocks flow
Pulmonary embolism
97
Vascular disorders: Abnormally dilated, tortuous veins produced by prolonged increased intraluminal pressure leading to vessel dilation and incompetence of venous valves.
This usually arises in superfcial veins of leg (e.g. saphenous) because the venous pressures are elevated by prolonged standing.
Varicose veins
Risk factors:
-obesity, pregnancy, prolonged standing
* may develop superficial vein thrombosis
* Slide 29
98
Lipoprotein disorders: There are 5 major classes of lipoproteins:
1. Chylomicrons
2. Very Low Density Lipoproteins (VLDL)
3. Intermediate Density Lipoproteins (IDL)
4. Low density Lipoprotein (LDL)
5. High Density Lipoprotein (HDL)
These lipoproteins are of intermediate size and density and are formed by the degradation of VLDL by lipoprotein lipase
Intermediate density Lipoprotein (IDL)
99
Pharmacology: Statin drugs are metabolized by CYP 3A enzymes, with the exception of pravastatin (which has fewer drug interactions.)
Common contraindications of statins are CYP3A4 inhibitors. Which of the following is an example?
a. erythromycin
b. azole antifungal drugs (ketoconazole)
c. anti-depressants
d. HIV protease inhibitors
e. aspirin
Answer: A-D
*Inhibition of CYP 3A can cause toxic build up of statin drug
100
Vascular disorders: Symptoms of Peripheral Vascular disease, a complication of atherosclerosis, include:
a. intermittent claudication (narrowed femoral artery)
b. sores/ulcers that heal slowly
c. cool skin, temperature
d. strong pulse
Answer: A-C
*diminished pulse; bruits
NOTE: intermittent claudication = pain with walking; relief with rest
(demand ischemia)
101
Congenital disorders: Narrowing of the aorta distal to the origin of the left subclavian artery.
This results in increased b.p. and flow proximally (high pressure in upper extremities) and decreased blood pressure distally (dec. b.p. in lower extremities).
Clinical manifestations depend on the degree of narrowing.
Coarctation of the aorta
* unknown pathogenesis
* dilation of aorta immediately distal to coarctation
* Inc. afterload (LV) and subsequent LV hypertrophy
* dec. renal blood flow -- inc. RAAS -- inc. HTN
102
Valvular disorders: _____mitral regurgitation features:
- increased LA size and compliance
- lower pulmonary venous pressures
- dec. cardiac ouput
Chronic mitral regurgitation
103
Pharmacology: A disorder involving elevated LDL (cholesterol)
Hypercholesterolemia
Normal LDL < 100
104
Hypertension: Secondary HTN due to adrenal disorders including
1. Primary aldosteronism (Hyperaldosteronism)
2. Cushing syndrome
3. Pheochromocytoma
Cushing syndrome has mile _____ activity, while Pheochromocytoma is due to a _______-secreting tumor within the adrenal medulla.
1. Cushing: mineralcorticoid
2. Pheochromocytoma: Catecholamine-secreting tumor (inappropriate release of NE/E)
* pain,
* inc. pressure (a1; vasoconstriction and B1 ; HR and contractility)
* palpitation, perspiration
105
Vascular disorders: A patient presents with pain, tenderness, induration, and erythema along the course of a superficial vein. It is due to inflammation and/or thrombosis, and less commonly infection of the vein.
Although generally benign, it can be complicated by DVT or Pulmonary embolism.
Superficial phlebitis
* pathogensis: inflammation/vein thrombosis
* associated w/: IV lines, underlying DVT, S. aureus, or pancreatic carcinoma (procoagulants; superficial migratory thrombophlebitis - Trousseau's syndrome)
106
What is the thickest layer of the aorta?
tunica media
107
Cardiac Tumors: Cancer may involve the heart either by direct extension of the primary tumor or by metastatic disease (2ndary - more common). Direct extension occurs mainly from cancers of the lung, breast, esophagus and mediastinum. Extension may occur via IVC as well.
Primary:
1. Myxoma
2. Angiosarcoma
3. Rhambomyosarcoma
4. Metastatic melanoma
A patient presents with a bening tumor within the left atrium. It is pedunculated, with a "ball-valve effect". Complications include embolization of tumor fragments.
Myxoma
**most common primary heart tumor in adults
Diagnosis: echocardiography
Others:
2. Angiosarcoma
- -rare
- -malignant (endothelial cells; may include heart)
3. Rhabdomyoma
- -benign
- -lethal arrhythmia (conduction pathways)
- -most common primary pediatric cardiac tumor
- -associated w/ tuberous sclerosis (hamartoma of cardiac myocytes)
*spontaneous regression
108
Pharmacology Thromboembolic Disorders: Warfarin is metabolize by CYP 450 enzymes, and thus has many drug interactions.
What are the common contraindications that can lead to increased PT time (longer to clot)?
a. cephalosporins
b. heparin
c. aspirin
d. rifampin
A-C
1. Cimetidine (Histamin Rec. antagonist; ulcers)
2. Aspirin (high dose)
3. Cephalosporins (anti-bacterial, pneumonia)
4. Heparin
5. Hepatic Disease
109
Hypertension: Consistently elevated b.p. out of the office, but not elevated based on in-office readings. (b.p. appears normal)
Masked HTN
110
Lipoprotein disorders: There are 5 major classes of lipoproteins:
1. Chylomicrons
2. Very Low Density Lipoproteins (VLDL)
3. Intermediate Density Lipoproteins (IDL)
4. Low density Lipoprotein (LDL)
5. High Density Lipoprotein (HDL)
These lipoproteins are small and aid in transport of cholesterol to tissues. They are taken up by target cells via receptor-mediated endocytosis
Low density lipoproteins
*bad fat
LDL = Total CH - HDL - [TG/5]
111
Valvular disorders: Clinical manifestations of mitral stenosis include:
a. atrial enlargement
b. LVH
c. dyspnea
d. fatigue, decreased exercise tolerance
Answer:
-atrial enlargement, dyspnea, fatigue
NOTE: inc. risk of atrial fibrillation, inc. pulmonary pressure, dec. CO
112
Hypertension: This is due to ruptured saccular "berry" aneurysm.
HTN is a predisposing factor to both the development and rupture of these aneurysms. It is often described as the "worst headache (HA) of my life"
SUbarachnoid hemorrhage
**slide 30
* thunderclap headache
* circle of willis
113
Hypertension: _______ is due to acute injury to the kidneys resulting from severe HTN.
Pathologic findings include:
1. fibrinoid necrosis of small arterioles
2. hyperplastic arteriolosclerosis (onion skinning)
3. increased serum creatinine (renal damage)
4. increased b.p. (renal)
Acute hypertensive nephrosclerosis
* HTN narrows renal vessels resulting in renal ischemia and inc. b.p.
* slide 34 and 35 images
NOTE: HTN is #2 cause of kidney failure after diabetes
114
Anti-hypertensive drugs: Angiotensin Inhibitors decrease b.p. by preventing Na and water reabsorption (dec. CO) and inhibiting Ang. II-induced vasoconstriction.
What are examples of Angiotensin Inhibitors?
1. ACE inhibitors
- -No Ang I to ANg II
ex: captopril (6-12hrs), enalapril (IV form), lisinopril
2. Angiotensin receptor antagonists (ARBs)
- -block Ang. II receptor binding
- -cardioprotective
ex: losartan, valsartan (recall)
3. Direct Renin inhibitor
* *not for combo therapy with ACE inhibitors or ARBs
115
Pharmacology: The following accurately represents Statin pharmacokinetics, with the exception of what statin drugs?
1. short half lives (2-3 hours)
2. administer in the evening (peak effect during cholesterol synthesis)
1. Atorvastatin (Lipitor)
- -long 1/2 life (11-14hr)
- -can be administered anytime
2. Rosuvastatin (19 hours)
116
The tunica intima is composed of
endothelial cells + CT (subendothelial)
117
List the steps in conduction of the heart
1. SA nodal cells (specialized cardiac muscle cells)
2. Internodal tract
3. AV nodal cells
4. AV bundle of HIS
- -purkinje like fibers
5. Right bundle
- -purkinje like
- -extend into moderator band
6. Left bundle
- -subendocardial purkinje like
118
Vascular disorders: Painful red subungal nodule that
arises from smooth muscle cells of the glomus body (an arteriovenous structure involved in thermoregulation)
Glomus tumor
119
Vascular disorders: Malignant tumor of endothelial cells that forms pink-red to purple patches, plaques, and nodules. It is caused by HHV-8 and is a common malignancy in AIDS.
Kaposi's sarcoma
*skin, mouth, GI, legs in older men of Mediterranean descent
120
________ act as the stop-cocks of capillaries. They are the final branch of the arterial system and act to regulate the distribution of blood to different capillary beds via vasoconstriction or vasodilation (localized regions).
Arterioles
* Tone = partial contraction
* resistance vessels
* 1-4 layers of SM
* major determinant of b.p
*Weibel Palade granules in endothelial cells (vWF w/ VIII and selectin)
121
The fibrocollagenous skeleton is composed of dense, regular CT/fibrous rings. It provides support for the heart and also functions in:
a. anchoring valve cusps
b. prevents overdilation of valve openings
c. provides insertions for bundles of cardiac muscle
d. blocks direct spread of impulses
Answer: all of the above
122
Hypertension: Diastolic blood pressure primarily depends on ________
Peripheral vascular resistance (PVR; TPR)
* arteriolar vasoconstriction (a1 receptors)
* resistance = luminal radius ^4
123
Pericardial Disease: The pericardium is a 2-layered sac composed of visceral and parietal components.
The__1___ pericardium adheres firmly to the epicardium, while the outer __2__ layer is fibrous and dense. These layers are separated by a pericardial space containing up to 50mL of fluid (ultrafiltrate of plasma). The pericardium is well innervated, so inflammation can produce severe pain.
1. Visceral pericardium
2. Parietal pericardium
Fxns:
- cardiac efficiency (limit acute dilation)
- distribute hydrostatic forces
- reduce external friction
- barrier against infection/malignancy
124
Valvular disorders: Compensation for aortic stenosis
LVH, inc. LV pressure
125
Cardiomyopathy: A type of restrictive cardiomyopathy caused by hypereosinophilia and release of the product major basic protein. This results in tissue necrosis followed by scarring of the necrotic area
Loeffler endomyocarditis
NOTE: endomyocardial fibrosis seen (w/ large mural thrombi similar to tropical disease)
126
Valvular disorders: The following describes what valvular disorder?
Young female with psychiatric Hx and myxomatous valve disease. Mid-systolic click is heard on auscultation.
Mitral Valve Prolapse
127
Lipoprotein disorders - Exogenous pathway of Lipid processing and fat absorption:
What happens to the nascent chylomicrons when they re-enter the bloodstream from the lymph?
1. HDL transfers apo E and apo CII to the nascent chylomicron = mature chylomicron
2. Apo CII activates lipoprotein lipase
- -in the capillaries (endothelium) of adipose and muscle tissue
- -convert TG's to Fa's and glycerol for uptake
* *insulin induces Lipo lipase
3. Removal of cholesterol-rich chylomicron remnants by the liver
- -mb receptors on hepatocytes recognize apo E
- -receptor-mediated endocytosis of remnant lipoproteins and subsequent digestion
- -release of products into cytosol
128
Shock: True/False - Inadequate tissue perfusion leads to decreased ATP and decreased aerobic metabolism. The cell is forced into anaerobic metabolism, involving metabolism of pyruvate to lactate w/ less ATP production
True
* failure of ion pumps
* accumulation of lactic acid (metabolic acidosis)
NOTE: restore O2 = reverse effects
129
Pharmacology: Cholesterol that is moved from peripheral cells to the liver. "good fat"
HDL
130
Congenital disorders: An 8 year old female presents to the clinic with HTN and a cardiac lesion. You note elevated blood pressure in her upper extremities, with dec. blood pressure in her lower extremities. Femoral pulse is absent (or delayed) compared to her radial pulse.
On auscultation you note a pansystolic murmur beneath her left clavicle.
CXR reveals rib notching.
You suspect
Aortic coarctation
- tortuous retinal vessels
- prominent carotid pulse
- systolic murmur beneath left clavicle
NOTE: commonly associatioed with Turner syndrome and/or Intra-cranial aneurysms
131
Placed percutaneously, passed through the venous circulation into right heart, and finally into small PA. at this point a balloon at the end of the catheter is blown up. Measures “wedge pressure” of pulmonary capillary (PCWP).
PCWP is an approximation of what?
Left atrial pressure and LV End diastolic pressure
*CO measured through thermodilution
132
Cardiomyopathy: In the case of Hypertrophic cardiomyopathy (asymmetric thickening of interventricular septum,) patients are often asymptomatic at rest. However, manifestations may develop due to decreased LV EDV and LV outflow tract obstruction (as the mitral valve comes into contract with the thickened septum).
What are the symptoms? How is it diagnosed?
-most symptomatic during exercise w/ or w/out dehydration (e.g. young athlete unable to be resuscitated)
Symptoms:
- chest pain, dyspnea, syncopre
- sudden death
Diagnosis:
- family screening
- incidental detection of heart murmur or ECG
NOTE: patients diagnosed with HCM should avoid physical exertion
Tx: beta blockers (B1); septal myomectomy
133
Hypertension: The following describes what disorder?
1. Angiopathy of unknown etiology
2. Involves medium size arteries (e.g. renal arteries)
3. Characteristic “string of beads” appearance: alternating areas of thickened and thinned vessel wall with narrowing of the vessel lumen.
Fibromuscular dysplasia
* 2nd most common cause of renovascular HTN
* usually female 8:1, white and younger (~50yrs)
134
Vascular disorders: Normally, valves in the veins of the leg prevent blood from flowing backwards. However, blood clot and associated inflammation can cause damage to these these valves. The damaged valves may become leaky and allow fluid to pool.
The leg becomes painful, red, and swollen.
What is this disorder?
Post-thrombotic syndrome
135
Lipoprotein Disorders: True/False: HDL can either directly transport cholesterol and cholesterol esters to the liver or it can transfer cholesterol esters to other lipoproteins via the cholesterol ester transfer protein (CETP).
True
136
Vascular disorders: Arteriolosclerosis is commonly associated with Hypertension.
There are two general patterns:
1. Hyaline
2. Hyperplastic
______ is characterized by luminal obliteration and appears as "onion skinning"
Hyperplastic arteriolosclerosis
*Slide 7
137
Congenital defects: In utero, the ductus arteriosus acts to shunt deoxygenated blood from pulmonary artery (via the RV) to the aorta, bypassing the lungs.
Closure of the ductus arteriosus normally occurs 1-2 days after birth. However, in pre-term babies, it may remain patent (open).
What are signs/symptoms of patent ductus arteriosus?
1. Increased SaO2 in the pulmonary artery
- -L to R shunting
- -pulmonary HTN
- -LVH and dilatation
2. Machinery-like murmur
3.Differential "cyanosis"
--pink upper body
--cyanotic lower body
[Eismenger (shunt reverses): deox blood into aorta below subclavian)
138
Valvular disorders: The following describes what valvular disorder?
- Family History of sudden cardiac death
- Similar to other murmurs (maenuvers give it away)
1. Louder w/ dec. preload
2. Louder w/ decreased afterload
3. Softer w/ inc. pre-load
4. softer w/ inc. afterload
HOCM
*hypertrophic obstructive cardiomyopathy
139
Vascular Disorders: Hardening of the Arteries (arterial wall thickening and loss of elasticity).
Occurs in 3 general patterns:
1. Arteriosclerosis
2. Monckeberg medial sclerosis
3. Atherosclerosis
*Image: slide 6
Arteriosclerosis
1. Arterio...
- small arteries arterioles
- narrowed lumen - downstream ischemia
- hyaline vs. hyperplastic
2. Monckeberg
- -calcified muscular arteries
- -aging (no impaired flow)
3. Atherosclerosis
- -most frequent
* clinically important
140
Which phase of the SA node action potential sets the heart rate?
PHase 4
141
Cardiomyopathy: Dilated cardiomyopathy can either be familial (50%; AD) or it can be acquired.
Familial form is often due to a mutation in the Titin gene (TTN).
Which of the following is an acquired cause?
a. infectious myocarditis (viral)
b. medications
c. alcohol
d. cocaine
e. nutritional deficiency
f. pregnancy (peripartum cardiomyopathy)
All of the above
2. Medications
- -Anthracyclin (doxorubicin; anti-neoplastic) -- dose-related toxicity
- -Trastuzumab (recombinant monoclonal Ab to HER2)
3. Alcohol
- ->10% of heart failure
- -OH and acetaldehyde (metabolite) = cardiotoxins
- -reversible
- -issues: vacuolization of myocytes, Mt abnormalities, myocardial fibrosis
142
Pharmacology Thromboembolic Disorders:
This is an oral anti-coagulant that blocks Vitamin K reductase, preventing the carboxylation of clotting factor prothrombin
Warfarin
**antagonist
NOTE: Max effect is 3-5 days AFTER starting therapy. Effect is NOT immediate
143
Cardiomyopathy: Infectious myocarditis is an acquired cause of Dilated cardiomyopathy.
It is usually viral and is characterized by "lymphocytic inflammation with myocyte necrosis". However, it may be due to protozoan infection.
List examples of each
Viral: Coxackievirus, HIV, Flu
Protozoa: Trypanosoma cruzi (S. and Central America)
144
Pharmacology: Niacin may be used in which of the following disorders?
a. hyperchlesterolemia
b. hypertriglyceridemia
c. low HDL
d. A and B only
What are adverse effects of Niacin?
Answer: A - C
* can Tx A and B together
* inc. HDL
Adverse:
- cutaneous flushing
- gastric irritation
- myopathy
- glucose intolerance (careful w/ diabetes px)
145
Vascular disorders: Which of the following is a risk factor for atherosclerosis?
a. elevated LDL cholesterol
b. cigarettes
c. HTN (BP > 130/80)
d. low HDL cholesterol
e. diabetes
Answer: all of the above
Also:
--family history of premature CHD (age 55; 65)
--Age (men > 45; women > 55)
--lifestyle
146
Cardiomyopathy: A restrictive cardiomyopathy that is characterized by fibroelastic thickening involving the left ventricular endocardium.
It is most common in the first 2 years of life, but is a relatively uncommon disease.
Endocardial fibroelastosis
NOTE: diffuse involvement may lead to rapid and progressive cardiac decompensation and death
147
Valvular disorders: A patient presents with a mid-systolic click then murmur (heart sounds) of mitral regurgitation.
What is it?
Mitral valve prolapse
*click = snapping of chordae tendinae (systole)
148
When activated, platelets undergo a shape change that is induced by what structural elements?
MT's, MF's and myosin
149
Lipoprotein Disorders - dislipidemias: Frederickson classification dyslipidemias are associated with severe hypertriglyceridemia and are predisposed to acute pancreatitis.
There are 5 main types of dyslipidemias: Types I - V.
This lipidemia is known as familial chylomicronemia and often presents in infancy. It is caused by autosomal recessive trait of Lipoprotein lipase (LPL) deficiency or altered apo C-II.
Type I dyslipidemia
NOTE: may see attacks of acute pancreatitis and eruptive xanthomas in early chi ldhood. Lipidemia retinalis (milky arteries and veins) also.
Labs:
- elevated chylomicrons
- normal to high cholesterol
- high TG's
150
Pharmacology: Low HDL-cholesterol can lead to an increased risk of developing what?
Inc. risk of Heart DIsease
Normal values: 40-60
151
Congenital disorders: A developental defect where the aorta and pulmonary artery fail to separate into two vessels, and thus share a common trunk. This leads to intermixing of blood.
It is treated by surgical repair. If not treated, 85% mortality by 1 y/o.
Truncus arteriosus
152
Pharmacology: Bile acid binding resins are typically used in patients that do not tolerate other drugs or to provide an additive effect with other drugs.
When should these drugs be administered? What are contraindications?
Administer: before meals, at bedtime
Absorption: not from gut
Contraindications: inhibit absorption of digoxin and thyroid hormone
Adverse effects: few; constipation
153
Pharmacology Thromboembolic Disorders: The following are drugs used to Tx thromboembolic disorders:
1. anti-coagulant drugs
2. anti-platelet drugs
3. fibrinolytic drugs (clot busting)
_______ drugs act on coagulation factors in the blood and include Warfarin, Heparin (and its synthetic versions), Bivalirudin and Rivaraxaban.
Anti-Coagulant Drugs
1. Warfarin
- -inhibits synthesis of coagulation factors
2. Heparin (enoxaparin, Dalteparin, Fondaprinux)
- -indirectly inactivate coagulation factors
3. Bivalirudin, Rivaroxaban
- -directly inactivate coagulation factors
154
Anti-hypertensives: Pharmacological management of HTN depends on the severity of the HTN.
True/False: In patients with mild HTN, b.p. may be normalized with a single drug. Thiazide diuretics are often the first choice, but an ACE inhibitor, ARB, CCB may be used. Beta blockers are NOT the first choice for monotherapy, especially in African AMericans.
True
*calcium channel blockers = good for African Americans
NOTE: presence of concomitant disease should influence selection
155
Afterload is determined by what the ventricle is working against when ejecting blood. For the left ventricle, afterload is determined by
Aortic pressure
inc. pressure = inc. afterload
156
Pharmacology Thromboembolic Disorders: Heparin binds and activates _______ which inactivates clotting factors Thrombin, Xa, and others.
Antithrombin III (AT-III)
* anti-coagulant
* endogenous protease anti-coagulant
157
Hypertension: Flow of blood through a tear in the aortic intima with separation of the intima and media. Normally creates a false lumen (channel).
It usually forms within 10cm of the aortic valve and may propagate proximally or distally. HTN is the major risk factor.
Aortic dissection
Manifestations:
- sudden severe sharp "tearing/ripping" chest pain radiating to back
- syncope
- loss of pulses (L. subclavian)
- bowel ischemia
- aortic regurgitation
158
Shock: Shock is a condition of impaired tissue perfusion due to a failur eof the cardiovascular system. It normally results in organ dysfunction.
There are 3 types:
1. Hypovolemic
2. Cardiogenic
3. Distributive
Describe these
1. Hypovolemic
- -decrease in volume
- -dec. CO (dec. SV)
*trauma, vomiting, diarrhea
2. Cardiogenic
- -dec. cardiac function
- -dec. CO and hypotension
*myocardial infarction, acute valve dysfunction
3. Distributive
- -loss of TPR (widespread vasodilation)
*sepsis (most common); PAMPS), anaphylaxis (Type I) neurogenic (loss of sympathetic tone)
159
Lipoprotein Disorders: LDL provides cholesterol for synthesis of hormones, cell membranes and bile salts.
LDL receptors are downregulated by:
a. diet high in saturated fat
b. familial hypercholesterolemia (heterozygotes > homo)
c. hypothyroidism (TH needed for LDL receptor synth.)
d. Estrogen
Answer: A-C
Upregulated by:
- estrogen
- low sat. fat
- statins
- meds to dec. bile acid uptake
Calculation:
LDL = TC - HDL - [TG/5]
160
Pharmacology - Acute Coronary Syndromes (ACS):
Treatment of coronary angioplasty and stent placement may involve which of the following drugs?
a. LMWH
b. Bivalirudin (I.V.)
Epitifibitde/Tirofiban
c. Aspirin
d. Clopidogre/Prasugrel
All of the above
161
Pharmacology: What is the mechanism of action of statin drugs?
HMG-CoA reductase inhibitors
1. prevent cholesterol formation (Liver)
2. increase LDL receptor expression (inc. uptake/clearance of free LDL cholesterol)
3. dec. serum total and LDL cholesterol
162
Lipoprotein Disorders - Fredrickson Classification:
True/False: For Type II (familial hypercholesterolemia), Homozygotes are more adversely affected than heterozygotes.
True
Values:
1. Heterozygotes
- -one mutant LDL receptor
- -LDL b/t 200-400mg/dL
2. Homozygotes
- -rare
- -both mutant LDL receptors
- -CHD in early childhood
- -florid xanthamatosis
163
Vascular disorders: This is formed when macrophages attempt to ingest LDL, but are not completely able to degrade it and end up forming "foam cells"
Fatty streak
* first gross manifestation of atherosclerosis
* slide 12, 13
164
HDL cholesterol level of less than _____ for women and _____ for men is a risk factor for metabolic syndrome
Women: less than 50mg/dl
Men: less than 40mg/dl
*fasting blood sugar level of 100mg/dl or higher is a metabolic risk factor
165
Blood pressure of _____ or higher is a risk factor for metabolic syndrome.
Triglyceride level of ___ is a risk factor for metabolic syndrome.
Blood pressure: 130/85
Triglyceride level: 150mg/dl
166
The basic constituents of the walls of blood vessels are
endothelial cells and smooth muscle cells
-E.C. matrix (elastin, collagen, GAG)
3 layers: tunica, media and adventitia
*most prominent in arteries
167
True/False: One of the major roles of the vascular endothelium (endothelial cells) is Angiogenesis (formation of new blood vessels).
True
* wound healing
* tumor vascularization
168
Small and Medium sized veins are identified by the small or medium-sied muscular arteries they follow
True
*valves: tunica intima + elastic tissue
169
Vascular disorders: Benign vascular tumor comprised of large dilated blood-filled vascular spaces; may rupture if large.
Most commonly a benign tumor of liver and spleen
Cavernous hemangioma
170
Shock: A patient presents to the ER with signs of swelling of the lips and tongue, difficulty swallowing and flushing of the skin with hives. He demonstrates shortness of breath and complains of abdominal pain.
He states he consumed lobster for dinner an hour ago.
What is his diagnosis?
Anaphylactic shock
* allergen -- IgE
- -mast cells and basophils (histamine)
NET results: massive vasodilation and inc. vascular permeability (dec. perfusion)
171
Pharmacology: ________ are used to reduce elevated triglycerides. They bind PPAR-alpha RE and induce transcription of Lipoprotein Lipase (which removes TG from VLDL) and HDL apoprotein.
Fibrates (oral)
ex: gemfibrozil; fenofibrate
1. inc. FA catabolism
2. dec. VLDL secretion
3. inc. VLDL clearance
172
Congenital disorders: A developmental defect in which the pulmonary veins do NOT connect to the Left atrium.
There are various forms, but all involve the blood being brought back to the right side of the heart. Treatment involves surgical repair (or mortality in 1st year).
Total anomalous pulmonary venous return
NOTE: must have ASD to get ox blood to system
173
Pharmacology Thromboembolic Disorders: Heparin acts to indirectly inhibit thrombin formation.
How is heparin (and its synthetic derivatives) administered?
Heparin: IV infusion
(unfractionated)
Low molecular weight Heparins (Enox, Dalte, Fonda): Subcu injection (max effect at 3-5 hrs)
174
Shock: Manifestations of shock are those of decreased tissue perfusion. These include:
a. dec. cerebral function
b. ischemic enteritis/colitis
c. cool, clammy skin and peripheral cyanosis
d. dry mucous membranes, inc. skin turgor
e. metabolic acidosis (accum. of lactic acid)
Answer: All of the above
175
Platelets are small, granulated bodies that aggregate at sites of vascular injuty. They lack nuclei and function in surveillance (of bv's), formation of blood clots and in tissue repair.
There are 3 groups of platelets:
1. Alpha granules
2. Delta granules
3. Lysosomal granules
Lysosomal granules contain ______ that aid in thrombi dissolution.
Lysosomal (λ) granules
-hydrolytic enzymes (thrombi dissolution)
176
Valvular disorders: What are the consequences/complications of valve disorders?
1. pressure overload
- -stenosis
2. volume overload
- -regurgitation
3. high speed "jets" of blood that injure endocardium
- -hemolysis of RBC's
- -due to stenosis
4. Heart failure
177
Vascular disorders: Atherosclerosis can cause acute and chronic clinical manifestations.
Which of the following is a chronic manifestation?
a. acute MI (sudden cardiac death)
b. stroke
c. angina pectoris
d. intermittent claudication
e. Renovascular HTN (stenosis)
Answer: C-E
others = acute
Slide: 17
178
Vascular disorders: Acute occlusion of peripheral artery can occur with peripheral vascular disease. In this case, atherosclerotic plaque ruptures with embolism, and occludes peripheral vessels.
What are the 5 P's that indicate acute occlusion?
1. Pulselessness
2. Paralysis
3. Parasthesia
4. Pain
5. Pallor
NOTE: DIagnosis of PVD:
Angiography; Ankle-brachial index <0.9
179
Type of shock associated with severely decreased TPR (i.e., widespread vascular dilatation).
Common etiologies include;
1. sepsis
2. anaphylaxis
3. neurogenic
Distributive shock
*CO normally increased (compensatory)
2. Anaphylaxis
- -Type I (IgE - mast cells)
3. Neurogenic
- -widespread loss of sympathetic tone involving resistance vessels
180
Vascular disorders: Arteriolosclerosis is commonly associated with Hypertension.
There are two general patterns:
1. Hyaline
2. Hyperplastic
______ occurs when the arteriolar wall is thickened with increased protein deposition (hyalinized). Narrowing of the lumen occurs.
Haline arteriolosclerosis
Image: Slide 7
181
Pharmacology: Cholesterol remnant of VLDL (after TG's removed). It moves from the blood to peripheral cells and to the liver
LDL
*bad fat
182
What factor is secreted by vascular endothelium (endothelial cells) to aid in blood coagulation?
- von WIllebrand factor
| - tissue factor
183
What tunic (epicardium, pericardium, endocardium) contains fat?
Epicardium
184
Hypertension: Chronic systemic HTN is the major cause of LV hypertrophy.
True/False: Increased thickness of the left ventricle can lead to decreased compliance and increased need for O2 (ischemia).
It can also lead to the diplacement of the Point of Maximal Impulse (PMI) inferolaterally. The PMI may also become more pronounced.
True
NOTE: apical impulse ID"d during palpation of precordium at PMI
NOTE 2: PMI normally (quarter sized) and at midline of 5th intercostal space
185
Cardiomyopathy: In Restrictive cardiomyopathy, deposits of _____ may be found within the atria, ventricles, coronary vessels, conduction system, and valves.
This can be diagnosed via Congo Red staining (proteins appears apple green in polarized light)
Amyloid
(Amyloidosis - insoluble B-pleated sheets)
NOTE: most common cause of cardia amyloid is deposition of Ig Light Chains (AL) seen in plasma cell disorders (multiple myeloma)
186
Valvular disorders: The most common mitral valve lesion. It involves systolic billowing of the mitral valve into the left atrium. It affects more females than males and is usually sporadic.
It is is commonly associated with "myxomatous degeneration" of the valve leaflets
Mitral valve prolapse
* regurgitation across mitral valve
* often asymptomatic
187
What cranial nerve is mainly responsible for carrying the sensory fibers from the carotid sinus & the carotid body?
CN 9
*carotids feedback to brain (afferent)
NOTE: aortic = vagus
188
Hypertension: How do diseases of the renal system potentially promote secondary hypertension?
Renovascular disease:
--activation of RAAS
Primary renal disease
189
Pericardial disorders: True/False - Most neoplasms of the pericardium are secondary (either direct extension from an adjacent process or due to metastatic disease from elsewhere).
Common primary tumors include:
- lung and breast carcinoma
- melanoma
- lymphoma
- rarely, mesothelioma may arise within the pericardium
True
190
What organ is the primary source of ACE?
lung endothelial cells
191
Lipoprotein Disorders - Endogenous Pathway:
The endogenous pathway provides a reliable supply of TGs for energy needs when dietary fat isn’t available.
What are the steps in the endogenous pathway?
1. Liver packages cholesterol and TG's into VLDL
- -accompanied by apo B 100
2. VLDL catabolized by Lipoprotein Lipase
- -release FA's to muscle and adipose
3. VLDL interacts w/ HDL
- -exchange TF for cholesterol ester
- -mediated by cholesterol ester transfer protein
* *important for reverse cholesterol transport
4. 50% of IDL cleared by liver via apo E
5. Remaining IDL catabolized into LDL
192
Macrophages are found within what type of capillaries?
Sinusoidal
193
Congenital defects: You are performing a routine follow up on a 2 year old patient when she suddenly starts ccrying. You note cyanosis that resolves when the patient squats.
CXR reveals a boot shaped heart (RV hypertrophy)
Tetralogy of Fallot
- R. to L shunt
- Displaced infundibular septum (aorta displaced to the right)
- Overriding aorta: narrows RV outflow tract (inc. RH; RV hypertrophy and VSD)
2. Decreased SaO2 in LV and aorta (due to R to L shunting)
- --VSD
3. Tet spell
- -hypoxic spell (crying or feeding; spasm of IV septum)
- -relieved by squatting (compress vessels; inc. SVR and LV pressure -- dec. R to L shunt)
194
Explain how endothelial cells modulate smooth muscle activity
1. SM relaxing factors
- NO
- prostacyclin
- prostaglandin I2
- bradykinin
- ADP
2. SM contraction factors
- endothelin
- prostaglandin H2
- thromboxane A2
3. Angiotensin conversion to Ang. II
- renin-angiotensin system
- ACE (from lung endothelium/sometimes kidney)
- blood pressure
* *vasoconstriction
195
Congenital defects: This is the most common congenital heart disorder in CHILDREN/KIDS. It is characterized by mixing of blood b/t the LV and the RV causing increased SaO2 in the RV and pulmonary artery. This increase in blood volume and O2 eventually leads to pulmonary hypertension and RV hypertrophy.
**Initially Left to RIght Shunting; Changes to R to L
Ventricular Septal Defect
1. high pressure in LV causes shunting from L to R
2. Inc. amount of blood to R side and to lungs
3. Compensate: pulmonary HTN (ireversible)
4. Right ventricular Hypertrophy
5. Reversal of Shunt (Eisenmenger) from Right to Left
(due to Pulmonary hypertension and RV hypertophy)
196
Lipoprotein Disorders - Secondary Hypercholesterolemia: Hypothyroidism may induce secondary hypercholesterolemia due because synthesis of LDL receptors requires thyroid hormone. Decreased thyroid horomone results in decreased LDL receptors and less cholesterol taken up by the liver.
True
LDL remains floating around in circulation to be deposited within tissues (e.g., vasculature)
197
Pharmacology: What drugs may be used to treat long term prophylaxis?
Warfarin and Rivaroxaban
198
In what layer of the heart are purkinje fibers found?
Endocardium (subendocardial layer)
199
Shock: Which of the following is a complication of shock?
a. diffuse alveolar damage (ARDS)
b. circumferential subendocardial infarct
c. centrilobular hepatic necrosis
d. acute tubular necrosis
ALL of the Above
a. ARDS
- dec. gas exchange
b. Global hypoperfusion
- -circumferential subendocardial infarct
c. necrotic tissue around central vein
d. damaged epithelail cells of kidney tubule
200
Lipoprotein Disorders: True/False: There are two major lipids in the body: Cholesterol and Triglyceride. They are both insoluble in the blood and are transported within lipoproteins.
Lipoproteins possess surface proteins that are cofactors and ligands for various lipid-processing enzymes. Lipoproteins are classified by size and density (defined as the ratio of lipid to protein) and are important because high LDL and low HDL are major risk factors for atherosclerotic heart disease.
True
Outer surface: Hydrophilic (apolipoproteins, cholesterol and phospholipids)
Hydrophobic core: TG's and cholesterol esters
201
Vascular disorders: Extrinsic compression or thrombosis of the SVC.
Etiologies include: primary lung carcinoma, mediastinal lymphoma, thrombosis (IV devices).
Superior venal caval syndrome
* puffiness; blue and purple discoloration of face, arms and shoulders
complications: renal hemorrhages, stroke
202
Pericardial disorders: Pericarditis that occurs several weeks (2-6wks) after an injury to the heart (e.g. MI, surgery, trauma) is known as Post-cardiac injury syndrome or Dressler Syndrome.
Post-cardiac injury syndrome is thought to arise secondary from an immune reaction to Ags that originate from injured myocardial tissue. The Abs deposit on the pericardium, resulting in inflammation.
How is it diagnosed? Treated?
NOTE: "Px presents with acute chest pain several weeks after MI or Heart Surgery"
Dx:
- clinical manifestations of pericarditis 2-6 wks post-cardiac injury (e.g. pleuritic CP, friction rub, ECG changes, fever)
- Gross: fibrinous pericarditis and effusion
Tx:
-NSAIDS
203
What are potential sites for pharmacological manipulation of arterial pressure?
1. vadodilators
2. B-adrenergic receptor antagonists
3. a-blockers
4. angiotensin receptor antagonists
5. centrally acting sympatholytics
6. ACE inhibitors
7. diuretics
204
Anti-hypertensive drugs: True/False: The β-blocker esmolol is for HTN emergencies and is given orally.
Don't drop b.p. <25-30% so as to avoid compromised perfusion.
False
**Given by I.V.
205
Lymphatic disorders: Inflammation of the lymphatics as a result of an infection distally (e.g. strep pyogenes -- hyaluronidase enables invasion of lymph channels)
Lympangitis
206
Pharmacology: The following drugs may be used to treat what disorder?
1. Dalteparin (LWWH)
2. Enoxaparin (LMWH)
3. Fondaparinux (synth)
4. Rivoraxaban (Xa inh.)
Surgical prophylaxis
207
Lipoprotein Disorders - dislipidemias: Type III hyperprolipoproteinemia ( familial dysbetalipoproteinemia) is autosomal recessive and due to a deficiency in _____.
Describe Type III
--deficiency of apo E
**dec. liver uptake of LDL and chylomicron remnants
**Findings: eruptive xanthomas, premature coronary heart disease, and PVD
208
Pharmacology Thromboembolic Disorders: Warfarin is metabolize by CYP 450 enzymes, and thus has many drug interactions.
What are the common contraindications that can lead to decreased PT time (clot quicker)?
1. Barbiturates (CNS depressants)
2. Rifampin (antibitioc, TB, meningitis)
3. Diuretics
4. Vit. K
5. Hereditary resistance
**NOTE warfarin can cause hemorrhage
209
The main site of blood pressure control
Arteriole
210
Claudication is pain caused by too little blood flow to your legs or arms.
The following describes what type of claudication?
"exertional lower extremity pain that does not begin at rest and causes the patient to stop walking. It resolves within 10 minutes of rest
Classic claudication
211
Pharmacology - Acute Coronary Syndromes (ACS):
To treat bleeds, which may be used?
a. Protamine sulfate
b. Vitamin K
c. Fresh frozen plasma
d. Aminocaproic acid
e. Vitamin B
Answer: A-D
a. Protamine sulfate [+ charge binds heparin]
b. Vitamin K (warfarin)
c. Fresh plasma (severe bleeds)
d. Aminocaproic acid (blocks plasminogen activation; inhibits fibrinolysis)
212
Vascular disorders: The following describes what type of aneurysm?
1. Aneurysm secondary to an infection
- -Infection weakens the vessel wall
- -Variety of etiologic agents (bacterial and fungal)
2. Risk of thrombosis +/- infarction, rupture
Mycotic aneurysm
213
Histology: Selectin can be produced by secretion of ____ or _____ by macrophages
TNF, IL-1
214
Lipoprotein Disorders - dislipidemias: Frederickson classification I (high chylomicrons), IV (high VLDL), and V (high chylomicrons and VLDL) dyslipidemias are associated with severe hypertriglyceridemia and are predisposed to acute pancreatitis.
There are 5 main types of dyslipidemias: Types I - V. This is the most common type of lipidemia and is known as familial hypertriglyceridemia. It is autosomal dominant and presents in adulthood.
Type IV
* increased VLDL production
* acquired EtOH (MCC), DM, OCP, renal failure, drugs
215
Lipoprotein disorders - Exogenous pathway of Lipid processing and fat absorption:
Following ingestion, lipids (TG's) are digested into free fatty acids and 2-monoacylglycerol and are absorbed in the enterocyte. Following their absorption, the lipids are reformed/repackaged into chylomicrons via apo _____, forming nascent chylomicrons. These nascent chylomicrons are then released from the intestinal cells back into the bloodstream (via lacteals/lymphatics).
Apo B48
* form nascent chylomicrons
* released back into the bloodstream from enterocytes
216
Pharmacology Thromboembolic Disorders Eptifibitide and Tirofiban are anti-platelet drugs that act by blocking _______ receptors on platelets, thus prevening fibrinogen cross-linking and inhibiting platelet aggregation.
Block Glycoprotein (GP) IIb and IIIa receptors
217
Vascular disorders: Atherosclerosis underlies the pathogenesis of coronary, cerebral and peripheral vascular disease. It causes more morbidity and mortality in the U.S. than any other disorder.
Which of the following is a risk factor for atherosclerosis?
a. hypercholesterolemia
b. smoking
c. hypertension
d. diabetes mellitus
Answer: all of the above
218
Vascular disorders: Plaque formation characteristically occurs at areas of branching/curvature where blood undergoes changes in velocity/direction (turbulence).
Areas of pre-dilection include:
a. proximal LAD
b. proximal renal arteries
c. carotid bifurcation
d. iliac birfurcation
e. abdominal aorta
Answer: all of the above
219
Vascular disorders: A benign non-neoplastic vascular lesion that disappears (blanches) when you compress the body.
Spider angioma
*excess estrogen (OCP, pregnancy, cirrhosis)
220
Pharmacology: Statins are HMG-CoA reductase inhibitors. Of the following statin drugs, which are activated in the GI tract?
a. Lovastatin
b. Simvastatin
c. Pravastatin
d. Atorvastatin
e. Fluvastatin
f. Rosuvastatin
Answer: A and B
NOTE: HMG-CoA reductase (rate limiting enzyme in cholesterol synthesis)
221
The receptors for Ang II. are located on what cells?
Endothelial and SM cells
222
Lipoprotein Disorders: True/False: elevated LDL levels are associated with atherosclerosis.
Etiologies include:
1. familial hypercholesterolemia
2. diet high in sat. fat
3. dec. estrogens (inc. CHD in post-menopause
4. Hypothyroidism (secondary)
*optimal <100mg/dL
True
223
Shock: Decreased tissue perfusion is a consequence of dec. CO, TPR or both. Perfusion can be maintained up to a point with compensatory mechanisms.
Which of the following is an example of this?
a. In response to decreased CO, baroreceptors signal SNS to inc. TPR via vasoconstriction (a1)
b. If TPR is decreased (distributive shock), body attempts to inc. CO (B1) by increasing HR and contractility.
c. If TPR is decreased, the body attempts to inc. CO by increasing PNS activity
ANswer: A and B
NOTE: Shock is likely when systolic b.p. <90.
224
Vasa vasorum is the vessel to the vessels (within tunic adventitia). High density of vasa vasorum in arteries can lead to what?
atheromatous plaque formation
225
Pharmacology: Cholesterol may be acquired via the diet or formed in the liver. Cholesterol is formed from what precursor? What is the rate limiting enzyme involved in cholesterol synthesis?
Acetyl CoA
HMG-CoA reductase
STEPS: acetyl coA -- mevalonic acid (via reductase) -- cholesterol
226
Vascular disorders: The following lists the stages of plaque formation. Describe the characteristics of each stage
1. Fatty streak
2. Plaque progression
3. Plaque disruption
1. Fatty streak
- -endothelial dysfunction
- -lipoprotein entry
- -foam cells
2. Plaque progression
- -SM cell migration into intima
- -fibrous cap over lipid core
3. Hemodynamic stress/degraded ECM
- -disrupted plaque/rupture
- -thrombus formation
*Slide 11
227
Shock: A 68 year old male presents to the ER with hypotension, tachycardia and fever. He demonstrates altered mental status and decreased urine output.
A CBC shows leukocytosis.
What is his most likely condition?
Septic shock
* kidneys: dec. urine
* colon: hematochezia
* brain: altered mental status
* liver: dec. synthetic act.
* heart: dec. fxn
228
Pharmacology - Acute Coronary Syndromes (ACS):
Treatment of STEMI (ST-elevated myocardial infarction) may involve which of the following drugs?
a. Fibrinolytic drug (tenecteplase, alteplase)
b. Aspirin (preventative)
c. LMWH (preventative)
d. Warfarin
Answer: A-C
NOT warfarin
229
Congenital disorders: True/False: Anomalous aortic origin of a coronary artery refers to variations in location of the origins of the coronary arteries.
True
NOTE: origin of Left main coronary artery with a posterior retroaortic course can lead to compression
230
Lipoprotein disorders: Various apolipoproteins serve to direct the lipoproteins to specific tissue receptors.
Which of the following is/are examples of lipoproteins
a. apo E
b. apo A-1
c. apo C-II
d. apo B-48
e. apo B-100
All of the above
1. Apo E
- -chylomicron remnant uptake
2. Apo A-1
- -activates lecithin-cholesterol acetyltransferase (LCAT)
- -reverse cholesterol transport
3. Apo C-II
- -cofactor for lipoprotein lipase
4. Apo B-48
- -chylomicron secretion
5. Apo B-100
- -ligand for binding to LDL receptor
231
Lipoprotein Disorders: The major functions of this lipoprotein include:
1. transport excess cholesterol obtained from peripheral tissues to the liver
2. exchange proteins and lipids with chylomicrons and VLDL
HDL
- exchanges proteins/lipids (apo E and CII to chylomicrons and VLDL - returned to HDL after digestion)
- obtains cholesterol from other lipoproteins/cell membrane and converts it to cholesterol esters (LCAT rxn)
232
Vascular disorders: Which of the following can be a complication of atherosclerosis?
a. vessel weakness (aneurysm)
b. plaque rupture
c. renal artery stenosis
d. peripheral vascular disease
Answer: all of the above
b. plaque rupture:
- -thrombus
- -abrupt occlusion
- Net: infarct
c. Renal stenosis
- -renovasc. HTN
233
Pericardial disease: Acute pericarditis is acute inflammation of the pericardium that may arise from ______ or _______.
Pericardial effusion (excess fluid within the pericardial sac may occur.
Isolated process: Viral infection (most common)
| Association with systemic disease: Autoimmune, renal failure
234
Anti-hypertensive Drugs: Initially, thiazide diuretics _____ blood volume and thus, cardiac output. However, over time, the drugs decrease peripheral vascular resistance that may be secondary to a reduction in the sodium content of SM cells.
decrease blood volume
235
Describe the steps in an EKG
1. P wave: depol atria
2. QRS interval: depol ventr.
3. T-wave: ventricul. repol.
PR-interval: Delay of AV
--ventricles fill
ST segment: ventr. repol. starts
236
What are the 3 tunics of the heart?
1. Inner: endocardium
2. Middle: Myocardium
- -muscle cells - spirally
3. Outer: epicardium
- -serous and adipose
- -visceral layer of serous pericardium
*central region: fibrous skeleton containing valves and cardiac muscle cells
237
Pharmacology: _______ is a drug that localizes in the brush border of the SI and inhibits sterol reabsorption in the intestine.
It acts to decrease LDL cholesterol (20%), decrease TG's, and increase HDL.
What is its mechanism of action?
ezetimibe
*inhibits absorption of cholesterol (50%)
238
Vascular Disorders: _______ describes a tear in the aortic intima that allows blood to flow into the media. As blood flows into the media, it separates the intima from the media creating a “false” lumen and constricting the "true lumen". Most are felt to arise secondary to degenerative changes within the media (called cystic medial necrosis)
Aortic dissection
Risk factors:
1. ****HTN (stress on aortic wall)
2. Marfan syndrome (mutation in FBN1; fibrillin-1 CT protein)
(dilatation of aortic root; ectopia lentis)
3. pre-existing aortic aneurysm
* most common in older men
239
Valvular disorders: WIth aortic regurgitation, the SV by the LV is increased. The volume of regurgitated blood increases LV EDV (preload).
True/False: unless the process develops acutely, the LV can compensate by dilating and undergoing hypertrophy
True
*eventually leads to ischemia and heart failure
240
Lipoprotein disorders: There are 5 major classes of lipoproteins:
1. Chylomicrons
2. Very Low Density Lipoproteins (VLDL)
3. Intermediate Density Lipoproteins (IDL)
4. Low density Lipoprotein (LDL)
5. High Density Lipoprotein (HDL)
These are the second largest class of lipoproteins. They carry endogenously formed TG's to peripheral tissues.
Very Low Density Lipoproteins (VLDL)
*mainly TG's
NOTE: VLDL = TG/5
241
Hypertension: Determinates of Arterial blood pressure are ____ and ______
1. Cardiac Output
(SV and HR)
2. Peripheral Resistance
(Vascular Structure and Function)
242
What is the tunica adventitia composed of?
Type I collagen, elastin and reticular fibers
243
Shock: Loss of ATP can lead to failure of ion pumps in the cell. Most notably are the Na/K+ ATPse and Ca2+ ATPase.
What occurs when these pumps fail?
1. Na/K pump
- Na, H20 influx
- K+ efflux
- cell swells
2. Ca2+ pump
- -Inc. cytosolic calcium
- -enzyme activation (proteases, endonucleases)
- -cell injury/apoptosis
244
Pharmacology: Which of the following are acceptable drug combinations?
a. Ezetemibe (BABR) + Statin
b. Statins + Fibrates or preferably niacin
c. Fibrates and Niacin
Answer: A and B
*Fibrates and Niacin both lower TG's = too excessive
245
Pharmacology: Common adverse side effects of Statins includes LIver toxicity and Muscle issues.
List examples of each
Liver:
-elevated enzymes (ALT)
Muscle:
- myalgia (inc. creatine kinase)
- myositis (inflammation, inc. CK)
- Rhambomyolysis (muscle cells disintegrate, myoglobinuremia)
246
Vascular Disorders: Describe the steps in the development of an atheroma.
1. Hypercholesterolemia (inc. LDL)
- -deposit LDL
2. LDL oxidized = inflammation
- -inc. adhesion molecules
3. Monocytes adhere and migrate into INTIMA
- -macrophages
4. Macrophages digest lipids = foam cells
- -spongy w/ lipids
- fatty streak
5. SM cells migrate from tunica media into Intima toward fatty streak
- -PDGF from endothelial cells
- -deposit ECM = atherosclerotic plaque
6. Plaque calcifies
247
Cardiomyopathy: A type of cardiomyopathy distinguished by Left ventricular hypertophy in the absence of abnormal loading conditions (valve issues, HTN). It is usually familial (AD) and is due to mutation in various sarcomeric contractile protein genes, especially
- cardiac B-myosin heavy chain
- cardiac myosin binding protein C
In this case, the interventricular septum is usually thicker than the rest of the Left ventricle.
Hypertophic cardiomyopathy
Gross: asymmetric hypertophy of inter-ventricular septum (dec. compliance; impaired diastolic filling and elevated b.p.)
Histologic: myocyte hypertrophy, myocyte disarray, interstitial fibrosis
*Slide 7
248
Cardiomyopathy: Peripartum Cardiomyopathy is a form of dilated cardiomyopathy that occurs in either the last month of pregnancy or in the first 5 months after delivery.
It has many causes including pregnancy-induced HTN, nutritional deficiencies and/or volume overload.
True/False: Older mothers tend to have increased risk. In addition, setting of twins, malnutrition and HTN are contributing factors
True
*most improve -- some require cardiac transplantation or die
249
If a patient presents with arteriosclerosis, what happens to PP and systolic pressure?
inc. PP, inc. systolic, inc. MAP
250
Hypertension: Aldosterone is secreted from the Zona glomerulosa of the adrenal cortex and acts on the DCT to inc. reabsorption of Na (and water) in response to decreased blood pressure. Describe the RAAS system
1. dec. renal perfusion = inc. renin
2. Angiotensinogen --renin -- Angiotensin I
3. Angiotensin I --ACE -- Angiotensin II
4. Angiotensin II
* direct vasoconstriction
* aldosterone
* Na reabsorption
* water follows
* inc. plasma volume = inc. CO and b.p.
251
Valvular disorders: A patient presents with dyspnea, crackles and cough with fatigue.
Upon assessment, you find they have a pansystolic murmur. What is their disorder?
Mitral regurgitation
252
Lipoprotein disorders - Endogenous pathway: True/False:
| Cholesterol in sufficient quantity downregulates LDL receptors and decreases LDL uptake
True
NOTE: HMG-CoA reductase = rate limiting step in cholesterol synthesis
253
Valvular disorders: The following describes what valvular disorder?
- holocystolic (throughout systole)
- History of Rheumatic fever
- Radiates to axilla
Mitral regurgitation
254
What do weibel-palade granules contain and where are they found?
Von Willebrand Factor and Selectin
--tunic Intima of Arterioles
255
Anti-Hypertensive drugs: What are common side effects of Sympatholytic Drugs?
1. a-antagonists
2. b-antagonists
3. centrally acting
1. alpha-antagonists
- -1st dose syncope (w/ diuretic)
- -orthostatic hypotension
Contraindications:
--all BP lowering meds
2. B-antagonists
- -bradycardia
- -bronchoconstriction
- -impaired glycogenolysis
*NSAIDS dec. Hypotension
3. Centrally acting drugs (clonidine)
- -dry mouth**
- -fatigue, sedation, rebound HTN
Contraindications:
- Tricyclic anti-depressants dec. hyptensive effect
- CNS depressants = sedative effect
256
Pharmacology: A disorder involving elevated chylomicrons or VLDL (TG's)
Hypertriglyceridemia
257
Valvular disorders: Murmur location (area where it is the loudest) and timing (when does it occur).
Describe timing and the effect of breathing on heart murmurs
Timing:
1. Systole
—stenosis
(Holosystolic, early/mid, late)
2. Diastole
—early, mid, late
Breathing:
1. Inspire: (Rinspiration)
—inc. venous return to R.
—murmurs generated from R. Side inc. in intensity
2. Expiration (Lexpiration)
—inc. blood into lung
—Left heart murmurs
258
Refers to an area of abnormal arterial dilation due to weakening of the wall for whatever reason (e.g., atherosclerotic plaque, HTN).
There is normally increased incidence with age and is greater in males than in females. It is usually asymptomatic (pulsatile abdominal mass).
Abdominal aortic aneurysm
* usually below renal arteries
* secondary to weakened vessel wall (atheroscl... or defective CT)
NOTE: complications:
- -mural thrombus
- -rupture
259
Hypertension: Indicate normal blood pressure vs. Elevated blood pressure vs. Hypertensive blood pressure
Normal:
Systolic < 120mmHg
Diastolic < 80 mm Hg
2. Elevated
Systolic 120-129
Diastolic <80
3. Hypertension
Systolic 130-139 OR
Diastolic 80-89
NOTE: if disparity = higher value determines the stage
260
Pharmacology: Niacin (nicotinic acid) acts to lower LDL and TGs by
a. inhibiting VLDL secretion from the liver
b. increasing HDL
c. inhibiting lipolysis in adipocytes
Answer: all of the above
*inhibits lipolysis -- dec. FA's that can be incorporated into VLDL
261
What platelet granule contains serotonin?
Delta/Dense core granules
262
Large veins are composed of
longitudinal smooth muscle (in thick adventitia)
1. Intima: endothelium/subendo
2. Media: thin w/SM
3. thickest & best developed
* collagen, elastic, reticular
263
Renin arises from
Angiotensin II
* vasoconstrictor
* can cause hypertension
264
Vascular disorders: Venous thrombosis may be caused by stasis of blood flow (prolonged immobilization) or hypercoagulable disorders.
Normally, it occurs in the deep veins of the legs (*calf, popliteal, femoral) and less commonly in the portal vein.
What are acute signs of DVT?
1. Homan's sign
- -calf pain (dorsiflexion of foot)
2. pitting edema distal to thrombosis
3. stasis dermatitis
265
Other functions of vascular endothelial cells include:
1. regulate migration of inflammatory cells
2. destabilize tight junctions
3. Angiotensin I to Angiotensin II
Explain each
1. Migration
- -transendothelial migration (neutrophils)
- Selectins
2. Destabilize
- -via Angiopoeitin II
3. Ang I to Ang II
- -ACE
266
Elastic arteries are conducting vessels.
Describe the features of elastic arteries. What are examples of elastic arteries?
Aorta and its branches
1. Tunica intima:
- thick
- CT: collagen, *elastin, reticular
* mainly SM
2. Tunica media:
* *thickest layer
- SM
- elastic
3. Adventitia:
- thin CT
* prevent expansion during systole
267
Claudication is pain caused by too little blood flow to your legs or arms.
The following describes what type of claudication?
"Pain similar to that of classic claudication, but does not cause the patient to stop walking"
Atypical exertional leg pain type I
268
Diuretics have what effects on the following:
1. peripheral vascular resistance
2. cardiac output
3. Blood volume
4. LV hypertrophy
Decrease all (or no change in LV)
269
Hypertension: Elevated BP in the office, but does not meet the diagnostic criteria for HTN based on out of office readings
White coat hypertension
*Out of office: Normal range
270
Anti-hypertensive drugs: Diuretics are cheap anti-hypertensives that also have low adverse effects.
_______ are the BEST anti-hypertensive diuretics. They are appropriate for patients with mild or moderate hypertension and with normal cardiac function.
Thiazides
*Hydrochlorothiazide and Chlorthalidone
NOTE: act at distal tubule; inc. Ca2+ reabsorption (dec. urine excretion -- prevents renal stones and osteoporosis)
271
Lymphatic disorders: Congenital malformation of the lymphatics (usually in the neck) - causes failure of lymphatic drainage into venous system. Leads to dilated lymphatics. More common in Turner’s syndrome (45XO); resolution results in webbed neck
Cystic hygroma
272
Valvular disorders: Most common cause of mitral stenosis
-due to an immune response against streptocococal Ag (cross reacts with host protein on heart valve)
Chronic rheumatic heart disease
| *thickening, fibrosis, calcification of valve leaflets
fusion of commissures; fusion of chordae tendinae
273
Congenital defects: Patent ductus arteriosus is maintained by _____ and treated with ______
Maintained: PGE2
Treatment: IV indomethacin (NSAID)
--inhibits prostaglandins (via cyclooxygenase)
274
Shock: Septic shock is the most common type of distributive shock. It causes life-threatening organ failure 2o to the host's response to infection. During sepsis, macrophages respond by secreting TNF and IL-1.
What are the effects?
1. Hypothalamus
- -tachycardia
- -fever
2. Capillary endothelium
- -neutrophils
- -clotting activation
3. Vessel wall:
- -NO (vasodilate)
4. Cell hypoxia
- -dec. TPR
- -lactic acidosis
NOTE: response to LPS (gram -) and Lipoteichoic (gram +)
275
Anti-diuretics: True/False: Diuretics during pregnancy are only for cases of heart disease and are NOT typically used to treat essential HTN
**NO ACE or ARBs during pregnancy
True
276
Platelets are formed from __________ via thrombopoeitin
megakaryocytes
277
Resistance is affected by
Viscosity, Length of blood vessel = direct
Radius = indirect
*small radius = high resistance
278
Hypertension: Thickening of retinal arteriolar walls due to HTN.
Complications include:
1. Hemorrhages
- rupture of microaneurysms
2. Papilledema
- -swelling of optic disk
3. Hard exudates
- -leakage of protein
4. Cotton wool spot
- -ischemic damage
5. AV nicking
- -compression of retinal veins creating a depression in the wall of the venule
Hypertensive retinopathy
Images: slide 37, 38
279
Pericardial disorders: True/False - Viral and idiopathic pericarditis is usually self-limited, and treatment is usually supportive (NSAIDS)
True
280
Pharmacology: Triglycerides from the diet that travel to the intestine and then the blood to peripheral cells
Chylomicrons
281
Lipoprotein Disorders: HDL is involved in Reverse cholesterol transport (transporting cholesterol from the tissues back to the liver). The higher HDL, the better (<40mg/dL is low).
Which of the following increases HDL levels?
a. Physical activity
b. ALcohol intake
c. Nicotinic Acid
d. Estrogen
Answer: all of the above
Decrease:
- sedentary
- high carb diet
- inc. body weight
- inc. VLDL (inverse to HDL)
282
Hypertension: True/False: RIsk of stroke increases with increasing age and BP
True
283
The tunica media is composed of what type of muscle?
SM
* elastic + reticular fibers (III)
* internal elastic lamina b/t media and intima
284
Hypertension: What role do thyroid disorders in inducing secondary hypertension?
Hyperthyroidism: inc. contractility (inc. SBP)
Hypothyroidism: peripheral vasoconstriction (inc. DBP)
285
Congenital defects: Match the diseases with the associated heart defect
a. Down syndrome
b. Rubella
c. Turner Syndrome (45X)
d. DiGeorge
a. Septal defect
b. Patent ductus arteriosus
c. Coarctation of the aorta
d. Tetralogy of Fallot
286
Describe depolarization of the Heart
PHase 0: uptstroke: Na2+ influx
PHase 1: K+ efflux
Phase 2: Plateau
- -Ca2+ influx
- -L-type
Phase 3: downslope; rapid depol
- -Ca2+ close
- -K+ channels (out)
Phase 4: Na, Ca2+ close
--K+ open
287
Platelets (thrombocytes) are small, granulated bodies that aggregate at sites of _______. How are they formed?
aggregate at sites of vascular injury
* contain blood element
* formed by megakaryocytes (bone marrow)
* majority in circulation; rest in spleen
- -remove spleen = inc. platelet count (thrombocytosis)
288
Describe the features of Fenestrated capillaries with no diaphragms
-Complete and thick basal lamina
* more leaky
* podocytes: restricted to kidney
289
Lymphatic disorders: damage to thoracic duct (e.g., surgery, tumor); lot of triglycerides present in lymph (chylomicrons) thus the characteristic milky white color
Chylous effusion
slide 39
290
Congenital disorders: True/False - patients with less severe coarctation can live long enough to develop collateral vessesl that partially bypass the obstruction
True
* aorta -- subclavian -- internal thoracin -- intercostals
* ultimately get reversal of blood flow through the intercostal arteries to the aorta
NOTE: rib notching may occur (wearing away bone due to enlarge pulsating intercostal arteries)
291
Lipoprotein disorders: True/False: Elevated triglyceride levels (Hypertriglyceridemia) are independently associated with cardiovascular risk, particularly coronary risk (via atherosclerosis).
True
-may be direct or indirect
Clinical manifestations:
- -Xanthoma striata (discoloration of palmar creases)
- -Eruptive xanthomas (accumulation of Tg's within macrophages)
- -Acute pancreatitis
- -Atherosclerosis
**slide 22
292
Valvular disorders: True/False - Aortic regurgitation usually arises:
2. Secondary to leaflet damage (endocarditis, bicuspid AV)
3. Secondary to aortic root dilation (poorly controlled HTN, aortic aneurysm)
True
293
Pharmacology Thromboembolic Disorders: The coagulation cascade involves two pathways, the intrinsic and the extrinsic both of which involve several special proteins known as coagulation factors that are activated one after the other in a "cascade" effect. The end result is a blood clot that creates a barrier over the injury site, protecting it until it heals.
In this cascade, prothrombin is a zymogen that is activated to its active enzyme form ______ (protease) via factor Xa.
Thrombin
294
Lipoprotein Disorders - Secondary Hypercholesterolemia:
Secondary Hypercholesterlemia and formation of atherosclerotic plaques may be caused by several different factors including lifestyle and disease.
How can lifestyle induce secondary hypercholesterolemia?
- high saturated fat diet
| - sedentary lifestyle
295
Vascular disorders: _____
Refers to an alteration in endothelial phenotype seen in many different conditions that is often both proinflammatory and prothrombogenic.
It is responsible, at least in part, for the initiation of thrombus formation, atherosclerosis, and the vascular lesions of hypertension and other disorders.
Endothelial dysfunction (vascular injury)
Effects:
* SM cell recruitment/prolif
* matrix synthesis
* NET result: thickened tunica intima and impede blood flow
296
Cardiomyopathy: True/False: The cardiomyopathies are partially familial due to mutations in various genes that encode for Sarcomere proteins.
These proteins include Titin (esp. in familial forms of dilated cardiomyopathy) because it connects Z discs to limit the range of stretch.
True
*dystophin, lamin, B-myosin heavy chain, myosin binding protein C, etc.
297
Lipoprotein Disorders - Endogenous Pathway: True/False: LDL carries most of the circulating cholesterol. This cholesterol is taken up by cells via receptor mediated endocytosis (clathrin; plasma membrane).
True
* LDL binds LDL receptor via apo B 100
* LDL receptors recycled back to membrane
298
Cardiomyopathy: A type of Restrictive Cardiomyopathy seen in children and young adults in Africa and the Tropics.
It is characterized by fibrosis of the ventricular endocardium and subendocardium. This fibrosis leads to:
- diminished volume
- diminished compliance of affected chambers
- restrictive
Endomyocardial fibrosis
299
Cardiomyopathy: Nutritional deficiency is an acquired method of dilated cardiomyopathy.
There are different types of deficiencies that can contribute to this kind of cardiomyopathy including:
1. Thiamine deficiency
2. Hypocalcemia
3. Hypophosphatemia
4. Hypomenesemia
Distinguish b/t these
1. Thiamine
- -poor nutrition/alcholism
- "wet beriber"
- vasodilations and high CO followed by low CO
2. Hypocalcemia
- -directly compromises myocardial contractility
3. Hypophosphatemia
- -alcoholism or recovery from malnutrition
- -reduces myocardial contractility
4. Hypomagnesemia
- -impaired absorption or inc. renal excretion
- LV dysfunction
300
Pharmacology Thromboembolic Disorders:
Rivaroxaban (oral) and Bivalirudin (injection) are direct inhibitors of Thrombin formation.
Rivarox... acts by inhibiting ______, while Bivalirud... inhibits ______
1. Rivaroxiban: inhibits Factor Xa
- -alternative to Warfarin
- -less coagulation monitoring
- -CYP 450
2. Bivalirudin: inhibits Thrombin (clot formation from fibrinogen)
- -percutaneous coronary intervention
- -heparin induced thrombocytopenia
301
Pharmacology Thromboembolic Disorders:
Aspirin (administered at a low dose) inhibits _____ in platelets resulting in decreased Thromboxane A2 synthesis. This results in decreased platelet aggregation
COX-1
NOTE: little effect on COX-2 on endothelial cells (prostacyclin; dec. aggregation)
302
True/False: The left ventricle is 3x thicker than the right
True
* more pumping force
* flattens the right ventricle into a crescent
303
Sympathetic fibers often travel with arteries (and veins) to their destination which is
SM or glands
304
Hypertension: Which of the following is considered a complication of HTN?
a. development of atherosclerosis
b. LV hypertrophy
c. aortic dissection
ALl of the above
a. atherosclerosis = major risk factor for coronary heart disease
* inc. w/ age and b.p.
b. concentric LV hypertrophy is due to pressure overload on the LV
305
Most capillaries are supplied by _____ and drain into _______. Describe any differences that occur throughout the body
Supplied by arterioles; drain into venules
Differences:
1. Skin: arteriovenous shunts or anastomoses (coiled)
2. Venous portal system:
- -capillary bed drains into vein and into another capillary bed
- -quick delivery of molecules
* *anterior pituitary gland and liver
306
Vascular Disorders: Regardless of the underlying trigger, endothelial dysfunction initiates process.
Where is damage more prominent? What follows endothelial injury?
Damage prominant: areas of inc. wall stress (bifurcations)
1. adhere/emigration of monocytes into intima
- --macrophages
2. macrophages engulf lipids (foam cells)
3. Cytokine release and SM migration into area
307
Hypertension: The primary mechanism for rapid buffering of blood pressure in response to acute fluctuations (postural changes) is
Baroreceptors
*adapts to chronic hypertension (reset to higher pressure; reflexes are downregulated)
308
Valvular disorders: The following describes what valvular disorder?
- opening snap
- history rheumatic fever
Mitral stenosis
*Operating System is MicroSoft
309
Pharmacology Thromboembolic Disorders: The following are drugs used to Tx thromboembolic disorders:
1. anti-coagulant drugs
2. anti-platelet drugs
3. fibrinolytic drugs (clot busting)
List the anti-platelet drugs and their sites of action
1. Aspirin
- -dec. Thromboxane A2 (TxA2)
2. Clopidogrel, Prasugrel
- -dec. GP receptors
3. Eptifibitide, Tirofiban
- -Fibrinogen; aggregation
310
Anti-hypertensive drugs: Potassium sparing diuretics are weak diuretics that are used to AVOID hypOkalemia. THey are often given with Thiazide to prevent hypokalemia. THese are mild diuretics.
What are examples of K+ sparing diuretics?
Spironolactone
1. Adverse effects:
- hyperkalemia
2. Drug Interactions:
- ACE inhibitors and K+ supplements (inc. hyperkalemia)
311
Cardiac output is the volume of blood pumped by the heart every minute
Calculate CO
SV x HR
Rate of O2 consump/arterial - venous
312
Pharmacology: True/False: Statins also have anti-inflammatory effects in the vasculature
True
*stabilize plaques
313
Formation of atherosclerotic plaque is caused by dysfunctional endothelial cells that increase the expression of cell adhesion molecules and increase the permeability for LDL cholesterol molecules.
What happens following damage to the endothelium?
a. circulating monocytes migrate to the injured endothelium (tunica intima)
b. endothelial cells produce free radicals which oxidize LDL's
c. oxidized LDL's are ingested by macrophages forming foam cells
d. endothelial cells produce PDGF to stimulate SM migration to the tunica intima
All of the above
1. Circulating monocytes find injured endothelium and migrate to tunica intima
* become macrophages.
2. Endothelial cells produce free radicals
- oxidize LDLs
- LDL's eaten by macrophages (foam cells)
* cholesterol deposits form crystals
3. Endothelial cells secrete Platelet-derived growth factor (PDGF)
- stimulate migration of the SM cells from the tunica media to the tunica intima.
- SM cells make ECM inc. tunica intima thickness
314
Cardiomyopathy: What signs can be visualized on an X-ray of Dilated cardiomyopathy?
1. Cardiomegaly
--cardiothoracic ratio >50%
(normal is 1/3)
2. Inc. pulmonary vascular markings w or w/out pleural effusion
- -pulmonary edema
315
Valvular disorders: What makes mitral valve prolapse better?
What makes it worse?
1. Squatting
- -inc. blood volume in LV -- delays prolapse (reduce click/murmur from S1)
2. Standing
- -dec. blood vol.
- -earlier click/murmur (close to S1)
316
Congenital defects: When pressure in the R. heart exceeds that in the L. heart, reversal of the L-R shunt may occur. This is known as
Eisenmenger Syndrome
* *Reversal from L-R to R to L
* *occurs after development of Pulmonary artery (PA) HTN and RV hypertrophy
317
Anti-hypertensive drugs: Which of the following are common adverse effects associated with thiazide and loop diuretics?
a. hypokalemia
b. hyperlipidemia
c. hyperuricemia
d. aggravated diabetes
e. all of the above
Answer: all of the above
NOTE: contraindications: NSAIDS, ACE (hypotension)
318
Stroke volume is the volume of blood pumped out (LV) with every contraction (heartbeat).
What factors affect SV?
Contractility, Preload
* inc. preload = inc. SV
* inc. contractility = inc. SV
* dec. afterload = inc. SV
319
Hypertension: HTN induced vascular injury may lead to the formation of Charcot-Bouchard microaneurysms in the deep portions (basal ganglia) of the brain. THese are prone to rupture.
This is better known as
Intracerebral hemorrhage
*slide 29
320
Anti-hypertensive drugs: Sympatholytic drugs are anti-hypertensives that act to relax SM and blunt the effects of NE.
There are 3 subclasses:
1. α-Adrenoceptor antagonists (a1)
2. β-Adrenoceptor antagonists
3. Centrally acting drugs (a2 agonists)
Give examples of alpha-adrenoceptor antagonists.
Doxasosin, Prazosin, Terasozin
NOTE: Sympatholytics are NOT 1st line drugs for MILD Hypertension
321
Hypertension: Secondary HTN is secondary to an identifiable cause.
When should you consider a secondary cause?
a. severe or resistant HTN
b. acute rise in b.p. over a previously stable value
c. proven age of onset before puberty
d. <30 yrs w/ no family history of HTN and no obesity
e. physical exam or lab abnormalities that correspond to known cause of HTN
ALl of the above
322
Pharmacology Thromboembolic Disorders: Fibrinolytic (thrombolytic) Drugs catalyze the formation of _____, which lyses the clot
plasmin
| *Advantageous to convert ‘clot-bound’ plasminogen
zymogen tp plasmin
323
Calculate SV
EDV - ESV
324
Pharmacology: Fibrates may be used to treat both Hypertriglyceridemia (elevated TG's) and low HDL levels.
Which of the following are adverse effects of these drugs?
a. myopathy; rabdomyolysis
b. bone marrow suppression
c. exfoliative dermatitis
d. celiac-like symptoms
Answer: A-C
*NO celiac
325
Name the 4 types of capillaries and their locations in the body
1. Continuous/Somatic
- -CNS, PNS, muscle & lung (blood-air barrier)
2. Fenestrated/Visceral
- endocrine glands, kidney tubules, intestine
3. Fenestrated w/ no diaphragms
- glomerulus
4. Sinusoidal:
- Liver, bone marrow, spleen
- **Kupffer cells seen here
326
The pericardium of the heart functions to protect/anchor the heart, prevent overfilling of the heart, and provides a friction-free environment. The pericardium of the Heart is composed of 2 layers:
1. Fibrous Pericardium
2. Serous pericardium
Which of these is the most superficial? Which layer lines the surface of the heart?
1. Fibrous pericardium
- superficial
2. Serous pericardium (deep): 2 layers
a. Parietal: lines internal surface of fibrous pericardium
b. Visceral: epicardium lines surface of heart
*pericardial cavity in between layers
327
Vascular DIsorders: In the normal state, Normal BP, laminar flow, and low growth factor levels promote a basal endothelial cell state that maintains a nonthrombotic, nonadhesive surface with appropriate vascular wall smooth muscle tone.
However, in injured state or when exposed to toxicants, what happens to the vascular wall?
- develop procoagulant surface
- inc. adhesion of infalmmatory cells
- express factors that contract SM or cause proliferation
ex: turbulent flow, hypertension, complement, bacterial products, viruses, cigarettes
328
Valvular disorders:
1. _____ mitral regurgitation features:
- normal left atrial size and compliance
- high LA and pulmonary venous pressure
- pulmonary congestion/edema
Acute MR
329
Pericytes are cells located near or around blood vessels. What are prominent features of pericytes?
Multipotential: differentiate into endothelial or SM cells
330
Describe the conduction system of the heart
1. SA (pacemaker)
2. AV (floor of right atrium)
3. Bundles of His (interventricular septum)
4. Purkinje fibers (myocardium of ventricles)
331
Vascular disorders: The following describes what type of aneurysm?
1. MC peripheral artery aneurysm
2. Often bilateral
3. Usually presents with distal limb ischemia secondary to thrombosis or embolism (rupture less common)
4. May be palpable, confirm with U/S
Popliteal artery aneurysm
332
Vascular disorders: Which of the following pose as additional risk factors for the development of atherosclerosis?
a. Inflammation
b. Hyperhomocystinemia
c. Metabolic syndrome
d. Lipoprotein A [Lp(a)]
All of the above
a. Inflammation
- -risk of MI, stroke, PAD
- -C-reactive protein measures risk
b. Hyperhomocystinemia
- -inc. risk of coronary athero; PAD, stroke
c. Metabolic
- -central obesity; insulin resistance; HTN, dyslipidemia (high LDL, low HDL)
d. Lipoprotein A
- -altered LDL
- -inc. coronary and cerebrovascular disease (independent of total cholesterol and LDL)
333
Shock:
Distinguish b/t the following mechanisms of shock:
1. _______: widespread dilation of resistance vessels. Not enough volume to provide tissue perfusion.
2. ______: lack of volume to support perfusion needs.
3. ______: Pump failure; can't move blood around to body.
4. ____: intrinsic or ext. obstruction of circulation (e.g. pulmonary embolism; tamponade)
1. Distributive shock
- -widespread dilation of vessels
2. Hypovolemic
- -not enough volume
3. Cardiogenic
- -pump failure (heart)
4. Obstuctive
- -obstruction of vessel
334
Anti-Hypertensive Drugs:
What are common adverse effects of ACE inhibitors vs. ARBS vs. Aliskrein?
1. ACE
- -cough
- -contraindicated during 2nd and 3rd trimesters
Interactions: hyperkalemic w/ K+ sparing
2. ARBs
- -avoid during pregnancy
Interactions: Hyperkalemic w/ K+ sparing
3. Aliskrein
- -avoid during pregnancy with renal impairment or diabetes
Interactions: --hyperkalemic w/ K+ sparing
--verapamile, cyclosporine, quinidine
335
One of the major roles of the vascular endothelium (endothelial cells) is secretion of Prostacyclin which is formed from arachidonic acid in the presence of prostacyclin synthase.
What is the function of prostacyclin?
- prevents platelet adhesion (blood clotting)
| - vasodilation of vascular SM cells (cAMP)
336
Most blood vessels (esp. SM) are supplied with sympathetic nerve fibers known as _____. What are their functions?
Nervi vacularis/vasorum: Nerve to vessels
* Main function:
- -vasoconstriction
*sympathetic ff -- dilation
337
Anti-hypertensive drugs: True/False - Phentolamine and Phenoxybenzamine are Sympatholytic alpha receptor antagonists that are used to treat HTN associated with pheochromocytoma and HTN emergencies. They are not for run of the mill Hypertension.
True
338
Hypertension: True/False: HTN affects approximately 75 million adults in the U.S. and is the major risk factor for strokes (ischemic and hemorrhagic), MI, vascular disease, and chronic kidney disease
True
339
Cardiomyopathy: A type of Cardiomyopathy distinguished by stiff walls that impairs ventricular filling and leads to increased LV diastolic pressures with reduced diastolic volume.
Systolic function and wall thickness are normal.
Restrictive cardiomyopathy
* familial: mutations in troponin I and B-myosin heavy chain
* gross: dilation of atria and small ventricular cavities
* histology depends on etiology
340
Shock: This type of distributive shock is caused by an interruption of sympathetic vascular tone.
Ultimately, vagal innervation becomes unopposed leading to peripheral vasodilation, hypotension and bradycardia.
Neurogenic shock
* decreased tissue perfusion
* dec. CO
* dec. preload
341
Pericardial disorders: Hemopericardium is a terminal event characterized by blood in the pericardial sac.
Which of the following is a common cause of hemopericardium?
a. trauma
b. myocardial rupture after MI
c. Iatrogenic (epicardial coronary artery rupture from catheter)
d. aortic dissection w/ rupture into pericardial space
e. hemorrhage after valve surgery (anti-coagulants)
f. viral infection
Answer: A - E
342
If a patient presents with aortic stenosis, the aorta cannot easily pump blood to the system. What happens to PP, MAP and systolic pressure?
all decrease
343
Vascular disorders: ____ refers to the confined space b/t the clavicle and the 1st rib. Structures that pass through include brachial plexus, subclavian artery and subclavian vein.
It causes cervical rib and tight anterior scalene muscles.
Thoracic Outlet Syndrome
Manifestations:
1. venous compression (arm edema)
2. arterial compression (cool arm w/ dec. pulse)
3. nerve root: parasthesias
Test: Adson's (loss of radial pulse w/ arm outstretched and head toward arm)
344
Pharmacology: Triglycerides formed by liver hepatocytes that travel to the blood and then to peripheral cels
VLDL
345
Diapedesis occurs where?
Post-capillary venule
346
Pharmacology - Acute COronary Syndromes (ACS):
Treatment for Unstable Angina and non-STE ACS can involve
1. Aspirin
- -COX-1
2. CLopidogrel/Prasugrel
- -block ADP
3. Eptifibitide/Tirofiban
- -block fibrinogen binding at GP receptors
4. LMWH/Fondaparinux
- -antithrombin III
347
Pharmacology: Drugs for treating Hypertriglyceridemia and/or Low HDL include
a. Fibrates
b. Niacin
C. Statin
Answer: A and B
348
Vascular disorders: True/False - Extension of thrombosis into popliteal vein or more proximally, which occurs in up to 25% of patients with untreated calf vein thrombosis, are at an increased risk of PE.
True
349
Valvular disorders: The following describes what valvular disorder?
- holocystolic
- intravenous drug abuse (HIV, Hep, etc.)
Tricuspid Regurgitation
Want to Tri some drugs?
350
Pericardial disorders: During cardiac tamponade, once the amount of fluid within the pericardium inhibits filling of the heart, the patient will exhibit what signs/symptoms?
a. Increased jugular venous pressure (JVD)
b. Hypotension (dec. CO)
c. Muffled heart sounds
d. pulsus paradoxus
e. all of the above
Answer: ALL
NOTE: pulsus paradoxus - abnormally large drop in systolic b.p. during inspiration (>10mmHg)
--inhalation constricts heart -- LV can't expand to pump blood out
351
Valvular disorders: THe following describes what valvular disorder?
1. Old age person
2. SAD (syncope, angina, dyspnea)
3. Commissural fusion (leaflets)
4. Crescendo-decrescendo
5. Calcified valve (hydroxyapatite; 1st step)
6. Radiates to carotids
7. Schistocytes (fragmented RBC's)
Aortic stenosis
* obstructs
* if due to rheumatic disease -- involves mitral valve
NOTE: most common valvular lesion to cause angina/syncope with exercise
352
Valvular disorders: Narrowing of the mitral orifice that results in increased workload on the left atrium.
Mitral stenosis
* LA enlargement
* upstream pressure into lungs
353
Hypertension: Narrowing of the vessel lumen and decreased blood flow resulting in patchy areas of renal ischemia that heal with scarring (fibrosis). This causes granulation of the renal cortex
Hyaline arteriolonephrosclerosis
* benign nephrosclerosis
* slide 32 images
354
What happens to the fatty acids that are released by lipoprotein lipase during lipid processing?
either oxidized in muscle or stored in adipose as Triacylglycerols
355
Congenital defects: Left to Right shunts involves shunting of blood from the left side of the heart to the right side of the heart (abnormally). Blood flows from high pressure to low pressure.
This causes overload of the right ventricle and elevated blood flow to the lungs.
In which disorders is it most commonly seen? What are the effects of L-R shunting?
Disorders: ASD, VSD, PDA
Effects:
- inc. flow to RA and lungs
- inc. pulmonary artery pressure and RV hypertrophy
- Once b.p. on R side > L side = reversal of shunt (Eisenmenger syndrome)
356
What is the most prominent cell in the tunica media of the arteriole?
SM cells
357
Hypertension: Which of the following is a risk factor for the development of HTN?
a. ethnicity (african americans)
b. Increasing age (inc. SBP)
c. Obesity (linear inc. w/ BMI; inc. RAAS)
d. High sodiium diet (>3000mg)
e. Excessive alcohol
f. Genetics
g. Sedentary lifestyle
All of the above
358
Histology: The following describes what kind of capillaries?
a. complete basal lamina
b. Fenestrae -- free exchange of molecules
- closed by diaphragm
- choroid plexus
Fenestrated capillaries
359
Lipoprotein Disorders: True/False: Elevated plasma concentrations of apo B-100 containing lipoproteins can induce the development of atherosclerosis even in the absence of other risk factors. Small LDL particles penetrate the endothelial barrier more easily than large LDL particles, however, all LDL particles regardless of size increase the risk of atherosclerotic cardiovascular events.
True
* cholesterol deposition within arteries leads to atherosclerotic plaque
* Primary (genetic) vs. Secondary Hypercholesterolemia
360
Pharmacology Thromboembolic Disorders: The following Fibrinolytic drugs are Tissue plasminogen activators (t-PA)
a. alteplase
b. reteplase
c. tenecteplase
What is their mech of action?
Activate clot-bound plasminogen
361
Lipoprotein Disorders - dislipidemias:
Type IIb lipidemia is familial combined hyperlipidemia. It is caused by overproduction of VLDL by the liver. It is characterized by elevated ____ and _____ .
Elevated LDL and VLDL
| --inc. atherogenicity
362
Congenital disorders: Transposition of the Great Vessels occurs when the RV drains into the aorta (instead of the pulmonary artery) and the LV drains into the pulmonary artery (instead of the aorta). Grossly, the RV is thickened due to inc. workload.
This disorder is incompatible with life unless a shunt is present. What are the shunts needed?
1. ASD
- -inc. SaO2 in RA (RV and aorta)
- -L to R.
2. VSD
- -shunts blood into LV for oxygenation by lungs
- -R to L shunt
or
3. PDA
- -shunts blood into pulmonary artery for oxygenation in lungs
- -L to R
363
Anti-hypertensive drugs:
Loop diuretics are appropriate for patients with SEVERE renal insufficiency, cardiac failure or cirrhosis, marked sodium retention, severe HTN w/ multiple other anti-hypertensives being used, and/or when multiple drugs with sodium-retaining properties are used.
What are examples of loop diuretics?
Furosemide, bumetanide and ethcynic acid
***most POTENT and powerful diuretics, but marginal anti-hypertensive effects
364
Pharmacology Thromboembolic Disorders:
True/False - Heparin can induce hemorrhage and thrombocytopenia (dec. platelet #'s) by causing an initial increase in blood clots.
True
Type 1: mild
--PLT aggregation
Type 2: severe
- -Ig--mediated PLT activation
- -Abs to Heparin
365
Hypertension: Renavascular HTN is the secondmost common cause of secondary HTN. It results in decreased renal blood flow due to atherosclerosis and stenosis of the renal artery. How is RAAS involved?
NOTE: More common in males w/ advancing age
Dec. flow through renal artery = inc. plasma renin in ypsilateral vein = vasoconstriction = HTN
NOTE: Abdominal bruit indicative of Renovasc. HTN; atrophy of kidney
NOTE 2: Angiography or plasma renin within ypsilateral renal vein
366
Hypertension: Hyaline arteriolosclerosis in the brain and the kidney due to HTN
SMall vessel strokes (lacunar infarct)
*slide 28 images
367
Vascular disorders: Stasis dermatitis refers to blockage of venous drainage that leads to congestion of the dermal vessels. Ultimately, increased intraluminal pressure leads to extravasation of RBC's into the dermis.
When these RBC's breakdown, they release ____ from Hb which deposits within the dermis.
-release iron from Hb
--iron deposits (hemosiderin) within dermis
*may lead to ischemia; ulcers
368
Congenital Disorders: List the Steps of Fetal Circulation before birth
1. Oxygenated blood from the placenta travels through the _____ vein to the fetus. This blood either travels through the _______ to bypass the liver, or into the portal vein to the liver.
2. Blood then flows to the RA via the IVC
3. Most of the blood returning to the RA goes through the _____ into the Left Atrium (bypassing the lungs) and then into the LV to the aorta.
4. The remaining blood (esp. returning to RA via SVC) enters the RV and then goes out the pulmonary artery.
1. Umbilical Vein; Ductus venosus
3. Foramen ovale
NOTE: Lungs only get 8% of CO
NOTE 2: Normal features in fetus:
- patent foramen ovale (RA to LA)
- patent ductus arteriosus (PDA; pulmonary artery into aorta)
369
Pharmacology Thromboembolic Disorders: Clopidogrel and Prasugrel are anti-platelet drugs that act by blocking ______ receptors, thus reducing the expression of GP receptors and inhibiting platelet aggregation.
block ADP (P2Y12) receptors
370
Capillaries are composed of ___ layer(s) of endothelium. What are their other componenets?
1 endothelial layer
- vimentin
- microfilaments
* -zonula occludens, desmosomes, gap jxns between endothelial cells
* some fenestrated
371
Anti-hypertensives: True/False - If a single drug does not adequately control b.p., drugs with different sites of action are combined to lower blood pressure ("stepped care"). If diuretic isn't used at first, it is added 2nd. If three drugs are needed, a sympatholytic or ACE inhibitor, and a direct vasodilator are combined. Alpha-agonists may be added if HTN is still refractory.
True
372
The basic constituents of the walls of blood vessels are:
endothelial cells and smooth muscle cells
-E.C. matrix (elastin, collagen, GAG)
3 layers: tunica, media and adventitia
*most prominent in arteries
373
Vascular disorders: A rare, highly malignant tumor of the endothelial cells.
1. Hepatic: vinyl chloride exposure
2. Cutaenous: radiation injury
Angiosarcoma
374
The process by which bleeding is stopped, keeping blood within a damaged vessel. (opposite of hemorrhage)
--Hemostasis
1. Vasospasm reduces bleeding (platelet aggregation and blood coagulation)
2. Platelet plug
3. Fibrin clot formation
- -Tissue factors:
- -clotting factors: serine proteases
4. Repair and fibrinolysis (remove plug)
375
Diseases of vessel walls and valves includes Marfan sydrome. What kind of disorder is Marfan syndrome?
Marfan’s Syndrome:
-fibrillin disorder-faulty tunica media = vessels dissect
- Mitral valve disorders = prolapse or redundant
- changes in chordae tendinae
376
_______ lower blood pressure by reducing peripheral vascular resistance and blunting the Na+ handling effects of aldosterone
Indirect vasodilators
*prevent production or action of Ang II
377
Atherosclerosis is a disease associated with endothelial dysfunction of what structures? It is caused by progressive accumulation within what layer of SM cells, lipids and CT?
- large; muscular arteries (medium)
- progressive accumulation within the INTIMA
Signs:
1. Fatty streak (lesions in intima)
- Lipids
- Foam cells
* initial structural abnormality
Characteristic lesion:
2. fibrofatty plaque
- Fibrous cap w/ foam cells, SM cells, & lymphocytes
378
Valvular disorders: List the locations of the:
1. Aortic valve
2. Pulmonic valve
3. Tricuspid valve
4. Mitral valve
1. Aortic: 2nd - 3rd R. Interspace (R. Upper sternal border)
2. Pulmonic
- 2nd-3rd L. Interspace
- L. Upper sternal border
3. Tricuspid:
- L. Sternal border (L. Lower sternal border)
4. Mitral:
- apex
NOTE: tricuspid and mitral: open during diastole, closed during systole
379
Hypertension: Most patients with significantly elevated BP (SBP ≥ 180 mm Hg and/or DBP ≥120 mm Hg) have no acute, end-organ injury. This is referred to as severe asymptomatic hypertension.
However, those with elevated b.p and signs of acute target organ damage are said to have _______ which can develop in patients with or without known pre-existing HTN.
Hypertensive emergency
* DBP ≥120 mm Hg
* no threshold
380
Anti-Hypertensive Drugs: Direct vasodilators include calcium channel blockers and Nitroprusside (IV).
What are the actions of these drugs?
1. Calcium channel blockers
- -dec. peripheral vasc. resistance of arteries
ex: Dihydropyridines (vascular effects)
ex 2: Non-dihydropyridine (vascular and cardiac)
--can inc. renin (edema)
2. Hydralazine
- -Inc. CO, Blood volume, plasma renin
3. Minoxidil, Nitroprusside (IV), and Fenoldopam (IV)
- --severe HTN or HTN emergency
- -inc. CO, blood volume, plasma renin
381
Congenital Heart Defects: Right to Left Shunts are MC seen in babies. They present with early cyanosis and needto maintain the PDA (Prostaglandins).
What is responsible for closure of the PDA?
Indomethacin
NOTE: R to L shunt = 5T's (truncus arteriosus, Transposition, Tet of Fallot, Tricuspid atresia, total anomalous...)
382
Congenital heart defects: _______ is often associated with failure of aoticopulmonary septum formation and thus failure of the trunk to divide into the aorta and pulmonary artery. VSD is present.
Truncus arteriosus
* Neural crest cells
* Right to Left
383
Congenital heart defects: _____ occurs when the aorta is attached to the RV and the pulmonary trunk is attached to the LV. It occurs as a result of failure of the aorticopulmonary trunk to spiral.
Transposition of great vessels
* R to Left shunt
* neural crest cells
* Maternal diabetes
384
Congenital heart defects: _____ is absence of the tricuspid valve and presence of hypoplastic RV. It requires ASD and VSD
Tricuspid atresia
385
Congenital heart defects: _____ is the MCC early cyanosis in childhood. Patients present with pulmonary infundibular stenosis, right ventricular hypertophy (boot shaped heart), and overriding aorta.
Symptoms include "tet spells" or cyanosis induced by crying, fever and/or exercise (RV outflow obstruction). Cyanosis improves with squatting. Presence of crescendo-decrescendo murmur.
Tet of fallot
386
Congenital heart defects: Pulmonary veins drain into the right heart circulation (instead of the LA). Results in necessity of ASD or PDA
total anomalous pulmonary venous return
387
Congenital heart defects: Displacement of the tricuspide valve leaflets downward into the right ventricle leading to "atrialization" of the ventricle
Ebstein anomaly
* lithium use
* tricuspid regurg
388
Congenital heart defects: Patients with Left to Right shunts tend to be older. They present as acyanotic early. Left to Right shunting is a later presentation
These include:
1. ASD
2. VSD
3. PDA
4. Eisenmonger syndrome
_____ is the MC congenital cardiac defect. Patient presents with harsh holosystolic murmur that is loudest at the tricuspid area
VSD
389
Congenital heart defects: Congenital heart defects: Patients with Left to Right shunts tend to be older. They present as acyanotic early. Left to Right shunting is a later presentation
These include:
1. ASD
2. VSD
3. PDA
4. Eisenmonger syndrome
_______ is a defect in the inter-atrial septum. Patients present with a wide, fixed split S2.
ASD
*ostium secundum
390
Congenital heart defects: Patients with Left to Right shunts tend to be older. They present as acyanotic early. Left to Right shunting is a later presentation
These include:
1. ASD
2. VSD
3. PDA
4. Eisenmonger syndrome
Patient who presents with a "machine-like murmur"
Patent ductus arteriosus
*maintain latency with PGE
391
Congenital heart defects: Patients with Left to Right shunts tend to be older. They present as acyanotic early. Left to Right shunting is a later presentation
These include:
1. ASD
2. VSD
3. PDA
4. Eisenmonger syndrome
Eisenmenger syndrome is a result of switch from a left to right shunt to a R to L shunt due to inc. pressure
True
392
Congenital heart defects: A patient presents with HTN in the upper extremity, but normal bp in the lower extremities.
Rib notching is noted on X-ray. Systolic murmur is heard in the back between the scapula
Coarctation of the aorta
*aortic narrowing near ductus arteriosus
393
Heart murmurs: True/False - Normal Physiologic splitting occurs when there is a delay in pulmonic valve closure due to inc. venous return. It is heard on inspiration.
True
394
Heart murmuers: _______ splitting occurs from delayed RV emptying (pulmonic stenosis and RBBB). It is exaggerated with deep inspiration
Wide splitting (PeRsistent S2)
* right side
* delayed pulmonici valve
395
Heart murmurs: _______ splitting is heard in ASD due to increased blood flow to the right heart. It is caused by delayed pulmonic valve closure, but is independent of inspiration.
Fixed splitting
*does not widen
396
Heart murmurs: _______ splitting occurs as a result of delayed aortic valve closure (aortic stenosis, LBBB). The split disappears on inspiration.
ParadoxicaL splitting
*Left side
397
Heart murmuers: When do we hear an ejection click?
Bicuspid aortic valve
*before carotid pulse
398
Heart murmurs: When would we hear a non-ejection click?
Mitral valve prolapse
399
Heart murmurs: On auscultation you hear a crescendo-decrescendo ("ejection") murmur
Aortic stenosis
* pulsus parvus et tardus (weak and small carotid pulses)
* soft quiet S2
* SAD - syncope, angina, dyspnea
400
Heart murmurs: On auscultation you hear a holosystolic, high pitched "blowing" murmur
Mitral/Tricuspid regurg
401
Heart murmurs: On auscultation you hear a late systolic crescendo with a mid-systolic click
mitral valve prolapse
*MC females, Marfan
402
Heart murmurs: You hear a harsh, holosystolic murmur that is loudest at the tricuspid area
VSD
403
Heart murmurs: You hear an early diastolic decrescendo murmur "Water hammer pulse"
Aortic regurgitation
*wide pulse pressure
404
Heart murmurs: On auscultation you hear a diastolic rumbling murmur preceded by an opening snap
mitral stenosis
*high left atrial pressure
405
Heart murmurs: On auscultation you hear a continuous, "machine" like murmur
PDA
