Exam I Flashcards
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)
All of the above
- elastin replaced by collagen
- widened pulse pressure (SBP - DBP)
Preload is determined by
EDV
- proportional to Right Atrial Pressure
- Inc. RAP = Inc. preload (more blood pumped into the ventricle)
Purkinje fibers are specialized conducting fibers composed of electrically excitable cells larger than cardiomyocytes. What can be found in the cells of purkinje fibers?
-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
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?
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
The following describes what kind of capillaries?
- complete basal lamina
- pinocytotic vesicles
- no fenestrae
- continuous epithelium
Continuous (somatic) capillaries
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
Aortic regurgitation
*retrograde flow in LV during diastole
Pharmacology: Drugs for hypercholesterolemia include:
a. bile acid binding resins
b. Niacine
c. Ezetemibe
d. Fibrates
A-C
**NOT niacin
Hypertension: Calculate Mean arterial Pressure (MAP)
*Pressure against the arterial walls
CO x TPR (systemic vascular resistance)
1/3 SBP-DBP + DBP
[SBP + 2(DBP)]/3
Describe the Pacemaker (SA node) Action potential
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
Valvular disorders: What are the effects of pre-load and afterload on heart murmurs?
- Inc. preload
- Dec. preload
- Inc. afterload
- Dec. afterload
- 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
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”
Atypical exertional leg pain type II
*obturator stenosis type
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
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.
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?
anchoring filaments
(elastin)
–interstiatil fluid enters via openings
- backflow of lymph stopped by endothelial folds
- no tight jxns or fenestrations
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?
- 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)
Venules accompany arterioles. What are key features of venules
-broad, irregular lumen
- Intima: thin
- Media: thin; no SM
- Adventitia: thickest layer
- receives blood from capillaries
- responds to vasoactive agents (leukotrienes, 5HT, histamine)
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.)
Answer: all of the above
Weibel Palade bodies can be found in capillaries and play a role in what?
Endothelial blood clotting
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
Lymphedema
Single largest cause of death since 1900
Ischemic heart disease
Anti-hypertensive drugs: _______ 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
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
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
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)
- Stenosis
- -harsh sound - Regurgitation
- -blowing sound
*auscultation and echocardiogram for valvular diseases
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)?
- 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
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.
True
Anti-hypertensive Drugs: List the Dihydropyridine drugs (calcium channel blockers; direct vasodilators)
nifedipine, nicardipine, amlodipine
Pharmacology: Drugs for Hypercholesterolemia and Hypertriglyceridemia include:
a. Statins and Niacin
b. Statins and FIbrates
c. Fibrates and Niacin
Answer: A
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
Histology: Tunics of the Heart - The pericardium of the heart is composed of the
- Fibrous pericardium (tough CT)
- 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
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
Valvular disorders: Distinguish between acute aortic regurgitation and chronic aoric regurg.
- Acute:
-rapid valve failure
(dilatation secondary to dissection)
-dyspnea, crackles, CXR = fluid in lungs
- Chronic
- -gradual
- -asymptomatic (w/ compensation)
- -palpitations, SOB, Chest pain (inc. LV EDP; dec. coronary),
- sudden cardiac death
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”
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
Pharmacology: Bile acid binding resins are oral drugs that bind to bile acids in the GI tract and prevent their reabsorption. These include:
- colestipol
- cholestyramine
- cholesevelam
By binding bile acids, what does this cause?
- Increased utilization of cholesterol to form bile acids
- inc. LDL receptor expression
* inc. clearance of cholesterol out of b.v’s
NOTE: cholesterol is used to make bile acids (emulsifiers of fat)
Shock: Type of shock that normally occurs from massive blood loss (trauma, rupture vessel, ectopic pregnancy).
Physical exam findings include:
- decreased skin turgor (young patients)
- dry skin/axillae
- dry tongue/oral mucosa
- obvious trauma
Hypovolemic shock
- Dec. CO
- Inc. TPR (compensation; NE on a1)
- Dec. LVEDP (PCWP)
History:
-vomiting, diarrhea, hematomesis
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)
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
Hypertension: What role does Hypercalcemia play in secondary hypertension?
ex; Primary hyperparathyroidism
*increased contraction of arteriolar SM = TPR
Pharmacology: The following drugs may be used to treat what disorder?
- Dalteparin (LWWH)
- Enoxaparin (LMWH)
- Fondaparinux (Synthetic)
- Heparin
Acute Venous Thromboembolism
Cardiac atria have _____ endocardium, while ventricles have ____.
Thick endocardium
Ventricles: thin
Sensory nerve endings include:
- Baroreceptors
- Chemoreceptors
Where are these found?
- Baroreceptors: carotid sinus and aortic arch
- Chemoreceptors: carotid and aortic bodies
* bifurcation point of carotid
Hypertension: True/False: Damage to the baroreceptor reflex (e.g. autonomic neuropathy) can lead to extremely labile blood pressure
True
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
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
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
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)
Shock: The prime mediator of inflammatory response in sepsis and septic shock.
It causes decreased myocardial contractivlity, and increased vascular permeability (vasodilation).
TNF
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)
Anti-Hypertensive Drugs: Sympatholytic drugs are anti-hypertensives that act to relax SM and blunt the effects of NE.
There are 3 subclasses:
- α-Adrenoceptor antagonists (a1)
- β-Adrenoceptor antagonists
- Centrally acting Drugs
B-adrenoceptor drugs may be selective or non-selective. Distinguish b/t the two.
- Non-selective
- -affect B1 and B2 (heart and lung)
- -dec. b.p
- -bronchoconstriction
ex: propanolol
- B-1 Selective:
- -heart only
ex: atenolol (not 1st choice)
ex 2: metoprolol
- β and α selective
ex: carevdilol and labetalol
- -after heart attack
What is a foam cell?
Macrophage that ingests oxidized LDL
*tunica intima
Anti-hypertensives: ______ lower blood pressure by relaxing vascular SM
direct vasodilators
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
- Eismenger
- -switch to R to L shunting once pulmonary HTN develops
- -elevated RV pressure (straining; RVH) - Paradoxical embolus
- -DVT thrombus in the leg that crosses the ASD into the LA and enters systemic circulation
- -infarcts downstream
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
ANti-hypertensive Drugs: What are common adverse side effects of the following vasodilators? Also include contraindications.
- Calcium channel blockers:
- Dihydropyridine
- Diltiazam
- Verapamil - Other vasodilators
- Hydralazine
- Minoxidil
- Nitroprusside
- Fenoldopam
- Calcium channel blockers
- Dihydropyridine
- -reflex tachycardia
ContraX: Any anti-hypertensives
- Diltiazam
- -bradycardia
ContraX: any anti-hypertensives
etc.
- 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)
Hypertension: Baroreceptors are responsible for short term blood pressure regulation.
Describe what happens to the baroreceptors in the presence of increased blood pressure
- Inc. b.p
- arterial wall distends
- Stretch of mechanoreceptors (carotid sinus and aortic arch)
- electrical signal generated = sent to medulary brainstem nuclei
- –via CN 9 and CN 10 - Dec. sympathetic outflow
- Dec. blood pressure
*short term
Cardiomyopathy: A myocardial dysfunction associated with an enlarged heart, dilated ventricles (or just LV) and impaired systolic function (HFrEF).
Common pathophysiology includes:
- LV dilation
- Decreased pumping force (due to hyperextension,)
- dec. contractility
- dec. SV
- Inc. Ventricular filling Pressures
- Decreased forward Cardiac Output
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.
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
- Systolic dysfunctions
- -dilated cardiomyopathy - Diastolic dysfunctions
- -hypertophic cardiomyopathy
- -restrictive cardiomyopathy
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
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:
- Overriding aorta
- RV outflow tract obstruction (due to overriding aorta)
- VSD
- RV hypertrophy
Because poorly oxygenated blood is flowing into systemic circulation, the patient must have a protective shunt to survive. What are these shunts?
- Atrial septal defect (ASD)
- -inc. SaO2 in RA
- -blood shunted to L heart has higher SaO2 - Patent ductus arteriosus (PDA)
–shunts poorly ox blood from aorta to pulmonary artery for oxygenation in the lungs
(shunts blood toward lungs)
Hypertension: Severe HTN (DPB > 12ommHg) with end organ damage
HTN emergency
*eye: retinal hemorrhage, papilledema
*heart: MI, angina
Brain: cerebral infract; seizures
What is an example of a ligand that binds selectin? Where is it found?
Lewis S. antigen (endothelial cells)
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
- Large/Elastic
- Muscular
- Arteriole
vascular disorders: What are the symptoms of a rupture following an abdominal aortic aneurysm? What is the greatest predictor of rupture?
- sudden onset of severe flank pain (retroperitoneal bleed)
- hypotension (blood loss)
Greatest predictor: diameter of aneurysm (?5cm)
Tx: endovascular/open surgery
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)
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
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 delta (dense core) granules
- Delta (δ) [dense core granules]:
Mediate vascular tone:
Serotonin, Adenosine Diphosphate [ADP], and Calcium
Type of shock that normally occurs from cardiac failure of any cause (e.g. MI, valvular dysfunction, tamponade)
Physical exam findings include:
- diffuse crackles
- new murmur
- muffled heart sounds
- Inc. JVP? ECG abnormalities?
Cardiogenic shock
- impaired LV pump
- Dec. CO
- Inc. LVEDV (blood accumulates in ventricle)
-Inc. TPR (vasoconstrictors)
Shock: Confirmation of shock can be accomplished with measuring ______
Serum lactate
*build up of lactic acid due to anaerobic metabolism
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
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)
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
True/False: About 85% of people who have type 2 diabetes also have metabolic syndrome
True
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?
- pheochromocytoma (excess catechols)
- -myocardial necrosis leading to DCM - Takotsubo cardiomyopathy
- severe psychologic stress and LV contractile dysfunction
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
Thromboembolic Disorders: The coagulation cascade involves two pathways, the intrinsic and the extrinsic both of which involve several specialproteinsknown 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
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
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
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
The dichrotic notch on a curve represents
Aortic valve closing
Pharmacology Thromboembolic Disorders: The following Fibrinolytic drugs are Tissue plasminogen activators (t-PA)
- streptokinase
- anistreplase (Activator complex: streptokinase + plasminogen)
What is their mech of action?
Non-specific plasminogen binding; Increased bleeding risk
Valvular disorders: Describe what happens to the aortic and pulmonic vs. the Tricuspid and Mitral Valves during
- Systole
- Diastole
- Systole
- Aortic and Pulmonic: Stenosis
- Tricuspid and Mitral: Regurg. - Diastole
- Aortic and Pulmonic: Regurg.
- Tricuspid and Mitral: Stenosis
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
Lipoprotein disorders: There are 5 major classes of lipoproteins:
- Chylomicrons
- Very Low Density Lipoproteins (VLDL)
- Intermediate Density Lipoproteins (IDL)
- Low density Lipoprotein (LDL)
- 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
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
- 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) - Pericardial friction rub
- high pitched, scratchy sound (leaning forward and not breathing)
* differ from pleural rub = can’t hear when not breathing
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?
- Tetralogy of Fallot
- Transposition of the Great vessels
- Truncus arteriosus
- Total anomalous pulmonary venous return
NOTE: systemic complications - secondary polycthemia and infectious endocarditis
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
Valvular disorders: True/False: murmurs are due to abnormal flow across a valve
True
*auscultation = first clue
Pharmacology: What drugs may be used to Tx Pulmonary embolism?
Heparin Fibrinolytic drug (alteplase)
*catalyze formation of plasmin – lyses fibrin clot
Lipoprotein Disorders - Secondary Hypercholesterolemia:
True/False:
Secondary Hypercholesterlemia and formation of atherosclerotic plaques may be caused by several different factors including
True
Lipoprotein disorders: There are 5 major classes of lipoproteins:
- Chylomicrons
- Very Low Density Lipoproteins (VLDL)
- Intermediate Density Lipoproteins (IDL)
- Low density Lipoprotein (LDL)
- 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
Hypertension: Secondary HTN due to adrenal disorders including
- Primary aldosteronism (Hyperaldosteronism)
- Cushing syndrome
- Pheochromocytoma
Hyperaldosteronism is due to either an aldosterone-secreting adrenal adenoma or bilateral adrenal hyperplasia. What are the effects?
- excess aldosterone
- -inc. Na/H2O retention
- -inc. blood volume
- -inc. K+ and H+ excretion
NET: HTN, hypOkalemia, metabolic ALKalosis
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
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
Hypertension: What drugs can pose risk for secondary hypertension?
- oral contraceptives
- -inc. synthesis of angiotensinogen
* *most common HTN in young women - Cocaine (sympathomimetic)
- -sympathetic activity - ALcohol (dose related)
- Vasopressors
–Ang II
Catecholamines
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
Muscular arteries function as distributing vessels. Describe their functions
**handout page 8
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
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
Lipoprotein disorders: There are 5 major classes of lipoproteins:
- Chylomicrons
- Very Low Density Lipoproteins (VLDL)
- Intermediate Density Lipoproteins (IDL)
- Low density Lipoprotein (LDL)
- 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)
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
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)
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
Valvular disorders: _____mitral regurgitation features:
- increased LA size and compliance
- lower pulmonary venous pressures
- dec. cardiac ouput
Chronic mitral regurgitation
Pharmacology: A disorder involving elevated LDL (cholesterol)
Hypercholesterolemia
Normal LDL < 100
Hypertension: Secondary HTN due to adrenal disorders including
- Primary aldosteronism (Hyperaldosteronism)
- Cushing syndrome
- Pheochromocytoma
Cushing syndrome has mile _____ activity, while Pheochromocytoma is due to a _______-secreting tumor within the adrenal medulla.
- Cushing: mineralcorticoid
- Pheochromocytoma: Catecholamine-secreting tumor (inappropriate release of NE/E)
* pain,
* inc. pressure (a1; vasoconstriction and B1 ; HR and contractility)
* palpitation, perspiration
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)
What is the thickest layer of the aorta?
tunica media
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:
- Myxoma
- Angiosarcoma
- Rhambomyosarcoma
- 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:
- Angiosarcoma
- -rare
- -malignant (endothelial cells; may include heart) - Rhabdomyoma
- -benign
- -lethal arrhythmia (conduction pathways)
- -most common primary pediatric cardiac tumor
- -associated w/ tuberous sclerosis (hamartoma of cardiac myocytes)
*spontaneous regression
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
- Cimetidine (Histamin Rec. antagonist; ulcers)
- Aspirin (high dose)
- Cephalosporins (anti-bacterial, pneumonia)
- Heparin
- Hepatic Disease
Hypertension: Consistently elevated b.p. out of the office, but not elevated based on in-office readings. (b.p. appears normal)
Masked HTN
Lipoprotein disorders: There are 5 major classes of lipoproteins:
- Chylomicrons
- Very Low Density Lipoproteins (VLDL)
- Intermediate Density Lipoproteins (IDL)
- Low density Lipoprotein (LDL)
- 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]
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
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
Hypertension: _______ is due to acute injury to the kidneys resulting from severe HTN.
Pathologic findings include:
- fibrinoid necrosis of small arterioles
- hyperplastic arteriolosclerosis (onion skinning)
- increased serum creatinine (renal damage)
- 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
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?
- ACE inhibitors
- -No Ang I to ANg II
ex: captopril (6-12hrs), enalapril (IV form), lisinopril
- Angiotensin receptor antagonists (ARBs)
- -block Ang. II receptor binding
- -cardioprotective
ex: losartan, valsartan (recall)
- Direct Renin inhibitor
* *not for combo therapy with ACE inhibitors or ARBs
Pharmacology: The following accurately represents Statin pharmacokinetics, with the exception of what statin drugs?
- short half lives (2-3 hours)
- administer in the evening (peak effect during cholesterol synthesis)
- Atorvastatin (Lipitor)
- -long 1/2 life (11-14hr)
- -can be administered anytime - Rosuvastatin (19 hours)
The tunica intima is composed of
endothelial cells + CT (subendothelial)
List the steps in conduction of the heart
- SA nodal cells (specialized cardiac muscle cells)
- Internodal tract
- AV nodal cells
- AV bundle of HIS
- -purkinje like fibers - Right bundle
- -purkinje like
- -extend into moderator band - Left bundle
- -subendocardial purkinje like
Vascular disorders: Painful red subungal nodule that
arises from smooth muscle cells of the glomus body (an arteriovenous structure involved in thermoregulation)
Glomus tumor
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
________ 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)
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
Hypertension: Diastolic blood pressure primarily depends on ________
Peripheral vascular resistance (PVR; TPR)
- arteriolar vasoconstriction (a1 receptors)
- resistance = luminal radius ^4
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.
- Visceral pericardium
- Parietal pericardium
Fxns:
- cardiac efficiency (limit acute dilation)
- distribute hydrostatic forces
- reduce external friction
- barrier against infection/malignancy
Valvular disorders: Compensation for aortic stenosis
LVH, inc. LV pressure
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)
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
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?
- HDL transfers apo E and apo CII to the nascent chylomicron = mature chylomicron
- 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 - 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
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
Pharmacology: Cholesterol that is moved from peripheral cells to the liver. “good fat”
HDL
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
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
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
Hypertension: The following describes what disorder?
- Angiopathy of unknown etiology
- Involves medium size arteries (e.g. renal arteries)
- 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)
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
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
Vascular disorders: Arteriolosclerosis is commonly associated with Hypertension.
There are two general patterns:
- Hyaline
- Hyperplastic
______ is characterized by luminal obliteration and appears as “onion skinning”
Hyperplastic arteriolosclerosis
*Slide 7
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?
- Increased SaO2 in the pulmonary artery
- -L to R shunting
- -pulmonary HTN
- -LVH and dilatation - Machinery-like murmur
3.Differential “cyanosis”
–pink upper body
–cyanotic lower body
[Eismenger (shunt reverses): deox blood into aorta below subclavian)
Valvular disorders: The following describes what valvular disorder?
- Family History of sudden cardiac death
- Similar to other murmurs (maenuvers give it away)
- Louder w/ dec. preload
- Louder w/ decreased afterload
- Softer w/ inc. pre-load
- softer w/ inc. afterload
HOCM
*hypertrophic obstructive cardiomyopathy
Vascular Disorders: Hardening of the Arteries (arterial wall thickening and loss of elasticity).
Occurs in 3 general patterns:
- Arteriosclerosis
- Monckeberg medial sclerosis
- Atherosclerosis
*Image: slide 6
Arteriosclerosis
- Arterio…
- small arteries arterioles
- narrowed lumen - downstream ischemia
- hyaline vs. hyperplastic - Monckeberg
- -calcified muscular arteries
- -aging (no impaired flow) - Atherosclerosis
- -most frequent
* clinically important
Which phase of the SA node action potential sets the heart rate?
PHase 4
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
- Medications
- -Anthracyclin (doxorubicin; anti-neoplastic) – dose-related toxicity
- -Trastuzumab (recombinant monoclonal Ab to HER2) - Alcohol
- ->10% of heart failure
- -OH and acetaldehyde (metabolite) = cardiotoxins
- -reversible
- -issues: vacuolization of myocytes, Mt abnormalities, myocardial fibrosis
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
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)
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)
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
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
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)
When activated, platelets undergo a shape change that is induced by what structural elements?
MT’s, MF’s and myosin
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
Pharmacology: Low HDL-cholesterol can lead to an increased risk of developing what?
Inc. risk of Heart DIsease
Normal values: 40-60
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
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
Pharmacology Thromboembolic Disorders: The following are drugs used to Tx thromboembolic disorders:
- anti-coagulant drugs
- anti-platelet drugs
- 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
- Warfarin
- -inhibits synthesis of coagulation factors - Heparin (enoxaparin, Dalteparin, Fondaprinux)
- -indirectly inactivate coagulation factors - Bivalirudin, Rivaroxaban
- -directly inactivate coagulation factors
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
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
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
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
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:
- Hypovolemic
- Cardiogenic
- Distributive
Describe these
- Hypovolemic
- -decrease in volume
- -dec. CO (dec. SV)
*trauma, vomiting, diarrhea
- Cardiogenic
- -dec. cardiac function
- -dec. CO and hypotension
*myocardial infarction, acute valve dysfunction
- Distributive
- -loss of TPR (widespread vasodilation)
*sepsis (most common); PAMPS), anaphylaxis (Type I) neurogenic (loss of sympathetic tone)
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]
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
Pharmacology: What is the mechanism of action of statin drugs?
HMG-CoA reductase inhibitors
- prevent cholesterol formation (Liver)
- increase LDL receptor expression (inc. uptake/clearance of free LDL cholesterol)
- dec. serum total and LDL cholesterol
Lipoprotein Disorders - Fredrickson Classification:
True/False: For Type II (familial hypercholesterolemia), Homozygotes are more adversely affected than heterozygotes.
True
Values:
- Heterozygotes
- -one mutant LDL receptor
- -LDL b/t 200-400mg/dL - Homozygotes
- -rare
- -both mutant LDL receptors
- -CHD in early childhood
- -florid xanthamatosis