Heart Murmurs

Heart Murmurs
By: David Leder

Outline

I. Basic Pathophysiology
II. Describing murmurs
III. Systolic murmurs
IV. Diastolic murmurs
V. Continuous murmurs
VI. Summary

Basic Pathophysiology
Murmurs = Math
Describing a heart murmur

1. Timing
o murmurs are longer than heart sounds
o HS can distinguished by simultaneous palpation of the carotid arterial pulse
o systolic, diastolic, continuous
2. Shape
o crescendo (grows louder), decrescendo, crescendo-decrescendo, plateau

3. Location of maximum intensity
o is determined by the site where the murmur originates
o e.g. A, P, T, M listening areas
4. Radiation
o reflects the intensity of the murmur and the direction of blood flow

5. Intensity
o graded on a 6 point scale
+ Grade 1 = very faint
+ Grade 2 = quiet but heard immediately
+ Grade 3 = moderately loud
+ Grade 4 = loud
+ Grade 5 = heard with stethoscope partly off the chest
+ Grade 6 = no stethoscope needed

*Note: Thrills are assoc. with murmurs of grades 4 - 6

6. Pitch
o high, medium, low
7. Quality
o blowing, harsh, rumbling, and musical
8. Others:
i. Variation with respiration

+ Right sided murmurs change more than left sided

ii. Variation with position of the patient

iii. Variation with special maneuvers

+ Valsalva/Standing => Murmurs decrease in length and intensity

EXCEPT: Hypertrophic cardiomyopathy and Mitral valve prolapse

Systolic Murmurs
* Derived from increased turbulence associated with:

1. Increased flow across normal SL valve or into a dilated great vessel
2. Flow across an abnormal SL valve or narrowed ventricular outflow tract - e.g. aortic stenosis
3. Flow across an incompetent AV valve - e.g. mitral regurg.
4. Flow across the interventricular septum

Early Systolic murmurs
1. Acute severe mitral regurgitation
2. Congenital, small muscular septal defect
3. Tricuspid regurg. with normal PA pressures

Midsystolic (ejection) murmurs
* Are the most common kind of heart murmur
* Are usually crescendo-decrescendo
* They may be:
1. Innocent
2. Physiologic
3. Pathologic

Aortic stenosis
* Loudest in aortic area; radiates along the carotid arteries
* Intensity varies directly with CO
* A2 decreases as the stenosis worsens
* Other conditions which may mimic the murmur of aortic stenosis w/o obstructing flow:

1. Aortic sclerosis
2. Bicuspid aortic valve
3. Dilated aorta
4. Increased flow across the valve during systole

Hypertrophic cardiomyopathy
Pansystolic (Holosystolic) Murmurs
1. Mitral valve regurgitation
2. Tricuspid valve regurgitation
3. Ventricular septal defect
Diastolic Murmurs
* Almost always indicate heart disease
* Two basic types:

1. Early decrescendo diastolic murmurs
2. Rumbling diastolic murmurs in mid- or late diastole

Aortic Regurgitation
* Best heard in the 2nd ICS at the left sternal edge
* High pitched, decrescendo
* Blowing quality => may be mistaken for breath sounds
* Radiation:

Mitral Stenosis
* Two components:
1. Middiastolic - during rapid ventricular filling
2. Presystolic - during atrial contraction; therefore, it disappears if atrial fibrillation develops
Continuous Murmurs

1. Cervical venous hum
2. Mammary souffle
3. Patent Ductus Arteriosus
4. Pericardial friction rub
Back to the Basics
1. When does it occur - systole or diastole
2. Where is it loudest - A, P, T, M
I. Systolic Murmurs:
1. Aortic stenosis - ejection type
2. Mitral regurgitation - holosystolic
3. Mitral valve prolapse - late systole

II. Diastolic Murmurs:
1. Aortic regurgitation - early diastole
2. Mitral stenosis - mid to late diastole

Summary
A. Presystolic murmur
o Mitral/Tricuspid stenosis
B. Mitral/Tricuspid regurg.
C. Aortic ejection murmur
D. Pulmonic stenosis (spilling through S20
E. Aortic/Pulm. diastolic murmur
F. Mitral stenosis w/ Opening snap
G. Mid-diastolic inflow murmur
H. Continuous murmur of PDA

Heart Murmurs.ppt

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Valvular Heart Disease

Valvular Heart Disease

Medical Surgical I
Types
* Mitral Stenosis
* Mitral Regurgitation
* Mitral Valve Prolapse
* Aortic Stenosis
* Aortic regurgitation
* Tricuspid valve is affected infrequently
o Tricuspid stenosis – causes Rt HF
o Tricuspid regurgitation –causes venous overload

Tricuspid Valve
Rheumatic Heart Disease
* Inflammatory process that may affect the myocardium, pericardium and or endocardium
* Usually results in distortion and scarring of the valves
* Subjective symptoms
o Prior history of rheumatic fever
o General malaise
o Pain – may or may not be present
* Objective symptoms
o Temperature
o Murmurs
o Dyspnea
o polyarthritis
* Diagnosis
o H/P
o WBC and ESR
o C-reactive protein
o Cardiac enzymes
o EKG
o Chest x-ray
o Echo
o Cardiac cath
o Cardiac output
* Nursing Care
o Vital signs
o Rest and quiet environment
o Give antibiotics, digitalis, and diuretics
o Provide adequate nutrition
o Monitor I/O
o Explain treatment and home care

Mitral Stenosis
* Usually results from rheumatic carditis
* Is a thickening by fibrosis or calcification
* Can be caused by tumors, calcium and thrombus
* Valve leaflets fuse and become stiff and the cordae tendineae contract
* These narrows the opening and prevents normal blood flow from the LA to the LV
* LA pressure increases, left atrium dilates, PAP increases, and the RV hypertrophies
* Pulmonary congestion and right sided heart failure occurs
* Followed by decreased preload and CO decreases
* Mild – asymptomatic
* With progression – dyspnea, orthopneas, dry cough, hemoptysis, and pulmonary edema may appear as hypertension and congestion progresses
* Right sided heart failure symptoms occur later
* S/S
o Pulse may be normal to A-Fib
o Apical diastolic murmur is heard

Mitral Regurgitation
* Primarily caused by rheumatic heart disease, but may be caused by papillary muscle rupture form congenital, infective endocarditis or ischemic heart disease
* Abnormality prevents the valve from closing
* Blood flows back into the right atrium during systole
* During diastole the regurg output flows into the LV with the normal blood flow and increases the volume into the LV
* Progression is slowly – fatigue, chronic weakness, dyspnea, anxiety, palpitations
* May have A-fib and changes of LV failure
* May develop right sided failure as well

Mitral Valve Prolapse
* Cause is variable and may be associated with congenital defects
* More common in women
* Valvular leaflets enlarge and prolapse into the LA during systole
* Most are asymptomatic
* Some may report chest pain, palpitations or exercise intolerance
* May have dizziness, syncope and palpitations associated with dysrhythmias
* May have audible click and murmur

Aortic Stenosis
* Valve becomes stiff and fibrotic, impeding blood flow with LV contraction
* Results in LV hypertrophy, increased O2 demands, and pulmonary congestion
* Causes – rheumatic fever, congenital, arthrosclerosis
* Atherosclerosis and calcification is primary cause in the elderly
* Complications – right sided heart failure, pulmonary edema, and A-fib
* S/S – Early: dyspnea, angina, syncope

Aortic Regurgitation
* Aortic valve leaflets do not close properly during diastole
* The valve ring that attaches to the leaflets may be dilated, loose, or deformed
* The ventricle dilates to accommodate the ^ blood volume and hypertrophies
* Causes: infective endocarditis, congenital, hypertension, Marfan’s
* May remain asymptomatic for years
* Develop dyspnea, orthopnea, palpitations, ,and angina
* May have ^ systolic pressure with bounding pulse
* Have a high pitch, blowing, decrescendo diastolic murmur

Assessment for Valve Dysfunction
* Subjective symptoms
o Fatigue
o Weakness
o General malaise
o Dyspnea on exertion
o Dizziness
o Chest pain or discomfort
o Weight gain
o Prior history of rheumatic heart disease
* Objective symptoms
o Orthopnea
o Dyspnea, rales
o Pink-tinged sputum
o Murmurs
o Palpitations
o Cyanosis, capillary refill
o Edema
o Dysrhythmias
o Restlessness

Diagnosis
* History and physical findings
* EKG
* Chest x-ray
* Cardiac cath
* Echocardiogram

Medial Treatment
* Nonsurgical management focuses on drug therapy and rest
* Diuretic, beta blockers, digoxin, O2, vasodilators, prophylactic antibiotic therapy
* Manage A-fib, if develops, with conversion if possible, and use of anticoagulation

Interventions
* Assess vitals, heart sounds, adventitious breath sounds
* ^ HOB
* O2 as prescribed
* Emotional support
* Give medications
* I/O
* Weight
* Check for edema
* Explain disease process, provide for home care with O2, medications

Surgical Management of Valve Disease
* Mitral Valve
o Commissurotomy
o Mitral Valve Replacement
o Balloon Valvuloplasty
* Aortic Valve Replacement

Mechanical Valve
Porcine Valve
Tissue Valve

Valvular Heart Disease.ppt

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Developmental Toxicology

Developmental Toxicology

* Structural malformations
* Growth retardation
* Functional impairment
* Death of the organism
4 manifestations of developmental toxicity

Teratology
1. the study of malformations or serious deviations from the normal type in organisms

2. the branch of science concerned with the production, development, anatomy, and classification of malformed fetuses.

* Teratogen
o Any agent that causes a birth defect
o After Greek “monster creating”
* Environmental conditions (1200)
* Maternal nutritional deficiencies (1930)
* Rubella virus infection (1941)
* Thalidomide (1961)

Adverse Outcomes in Pregnancy
Cause of human birth defects
Chemical teratogenicity
Pregnancy Risk Categories
Therapeutic Drugs Teratogenic to Humans
* Anticonvulsants
o Phenytoin, primidone, trimethadione, valproic acid, carbamazepine
* Anticancer agents
o Alkylating agents –busulfan, cyclophosphamide, chlorambucil, mechlorethamine
o Antimetabolites-aminopterin, methotrexate, cytarabine
* Androgenic hormones-danazol
* Coumarin anticoagulants-warfarin
* Retinoids-accutane, isotretinoin, etretinate, acitretin
* Antihyperlipidemic agents-lovastatin, atorvastatin
* Other drugs-diethystilbestrol, thalidomide, penicillamine, lithium, fluconazole, misoprostol
Thalidomide
Diethylstilbesterol (DES)
Alcohol (Ethanol)
Fetal Alchohol Syndrome (FAS)
Fetal Alchohol Effects (FAE)
* Cranial facial dysmorphism
* Intrauterine and postnatal growth retadation
* Retarded psychomotor and intellectual development
* IQ 68

Tobacco smoke
* Spontaneous abortions
* Perinatal deaths
* Lower birth weight
* Increased risk of
o Sudden infant death syndrome
o Behavioral attention disorders
o Orofacial cleft (particular xenobiotic gene polymorphisms)
o Gastroschisis (with variant alleles N053, ICAM1, NPPA)
o Branching morphogenesis and maturation of the lung
* Nicotine-related adverse nerodevelopmental outcomes
Cocaine
* At risk for premature labor, spontaneous abortion, increased perinatal mortality and fetal death.
* intrauterine growth retardation, microcephaly, altered presencephalic development, decreased birth weight, a neonatal neurologic syndrome of abnormal sleep, tremor, poor feeding, irritability, and occasional seizures.
* Genitaouinary tract malformation
* Impaired uditory process

Retinoic Acid
Retinoic acid is the active ingredient in “Accutane”, a drug used to treat severe acne. Since its introduction in September of 1982, an estimated 160,000 women of child bearing age have ingested the drug. Between 1982 and 1987, approximately 900-1300 malformed children, 700-1000 spontaneous abortions and 5000-7000 elective abortions are due to Accutane exposure. Exposed children may have hydrocephaly, ear malformations, cardiovascular defects and decreased IQ. Accutane carries a pregnancy category X warning, meaning it is a known human teratogen.
c acid
Retinoids
* Malformations of the face, limbs, heart, CNS, and skeleton
* RXR α receptor
* Schizophrenia
Retinoid Therapies
Tretinoin/ATRA (Vesanoid)
Leukemia
Adapalene (Differin),
Tretinoin (Renova),
Isotretinoin (Accutane)
Acne
Tazartene (Zorac),
Etritinate (Tegison)
Psoriasis
Drugs
RAR and RXR (Simple Version)
* Nuclear Receptors (like ER, PPAR, VDR and others)
* RXR/RAR Heterodimer is functional unit
* Bind selectively to REs in genome
* Act as transcription factors
* Up-regulate or Repress the expression of particular genes

Valproic acid was released in 1967 in Europe and in 1978 in the United States to treat epilepsy. Approximately 11,500 epileptic women become pregnant each year, many of which use valproic acid. By 1980, publications began linking malformed children to in utero exposure to valproic acid (greater than 500 mg/day).

Valproic Acid
* spina bifida with menigomyelocele or menigocele
* The proposed mechanism of action is that valproic acid influences folate metabolism

Angiotensin Converting enzyme inhibitors and angiotensin antagonists
* 2-3 trimester
* related reduced amniotic fluid volume and impaired fetal renal function
o Oligohydromnios
o Fetal growth retardation
o Pulmonary hypoplasia
o Renal failure
o Hypotension
o Death
* First trimester
o Congenital malformation

Wilson’s General Principles of Teratology (Table 10-2)
* Susceptibility to teratogenesis depends on the genotype of the conceptus and the manner in which this interacts with environmental factors.
* Susceptibility to teratogenic agents varies with the developmental stage at the time of exposure.
* Teratogenic agents act in specific ways (mechanisms) on developing cells and tissues to initiate abnormal embryogenesis (pathogenesis).
* The final manifestations of abnormal development are death, malformation, growth retardation, and functional disorder.
* The access of adverse environmental influences to developing tissue depends on the nature of the influences (agent).
* Manifestations of deviant development increase in degree as dosage increases from the no-effect to the totally lethal level.
Critical periods of susceptibility and endpoints of toxicity
* Gametogenesis and Fertilization

Mechanism unclear, may be related to imprinting
Cytosine methylation and change in chromatin conformation ethylene oxide, ethylmethane sulfonate, ethylnitrosourea→malformed fetus

DNA Methylation vs Genomic Imprinting
Mechanisms and pathologenesis of developmental toxicology

* Mutations
* Chromosomal breaks
* Altered mitosis
* Altered nucleic acid integrity or function
* Diminished supplies or precursors of substrates
* Decreased energy supplies
* Altered membrane characteristics
* Osmolar imbalance
* Enzyme inhibition
Example of cyclophosphamide (CP)
Single strand DNA break
A teratogenic chemotherapeutic agent
CP induces DNA damage
Advances in the Molecular basis of dysmorphogenesis
1.Using either singly or double gene knockout Retinoic acid receptor family (syndactyly)
2. Antisense oligonucleotide Wnt-1, Wnt-3a (mid and hindbrain malformation)
3. Reporter transgenes

Pharmacokinetics and metabolism in pregnancy
1.Changes in maternal physiology
hepatic metabolism, GI tract, cardiovascular system, excretory system, respiratory system
2.Overall decrease in hepatic xenobiotic transformation
3.Roles of placenta in influence embryonic exposure help to regulate blood flow
-offer a transport barrier-pH gradient, weak acid rapidly transfer
-metabolize chemicals
2-acetylaminofluorene (proteratogen)
7-hydroxyl metabolites(proximate teratogen)
4.Maternal metabolism of xenobiotics 2-methoxyethanol 2-methoxyacetic acid

Placental toxicity
* Metals, Cd, As, Hg, ethanol, cocaine, cigaratte, sodium salicylate
* Maternal injection vs fetal injection of Cd
* Production of metallothionein
* Interaction with Zn

Maternal toxicity-
* acetazolamide inhibits carbonic anhydrase forelimb ectrodactyly

* diflunsial results in anemia skeleton defects in rabbits
* phenytoin affects folate metabolism and heart rates
* metallothionein synthesis inducer-urathane, mercaptopurine, valproic acid Zn deficiency

Develpmental toxicity of endocrine-disrupting chemicals
Definition of endocrine-disrupting chemicals
“Exogenous agent that interferes with the production, release, transport, metabolism, binding, action, or elimination of natural hormones responsible for the maintenance of homeostasis and the regulation of developmental processes.”
Endocrine-disrupting chemicals
Four modes of action
1. Serving as steroid receptors ligands
2. Modifying steroid hormone metabolizing enzymes
3. Perturbing hypothalamic-pituitary release of trophic hormones
4. Uncharacterized proximate modes of action

Fetal Basis and Transgenerational Transmission of Reduced Fertility
Environmental Epigenetics
Decreased spermatogenic capacity and decreased fertility ..as well as increased prevalence of other diseases transferred via MALE germ line

Summary
* A transient embryonic exposure to endocrine disruptors at the time of gonadal sex determination can cause epigenetic transgenerational disease state of subfertility and spermatogenic defects in F1 through F4 generations
* Transgenerational disease phenotype was primarily transmitted through the male germ line
* Exposure appears to have caused an epigenetic reprogramming of the germ cell line that is “permanent” and transferred transgenerationally to subsequent generations

Modern safety assessment
* Regulatory guidelines for in vivo testing
* Multigeneration tests
* Children’s health and the food quality protection act
o Tenfold safety factor for children
* Alternative testing strategies
* Epidemiology
* Concordance of data (among species)
* Elements of risk assessment
use-in pregnancy rating: A, B, C, D, X

In Vivo Regulatory Protocol Guideline
The 17 intercellular signaling pathways by most metazoans
* Early development and later
* 1. Wnt pathway
* 2. Receptor serine/threonine kinase (TGFb) pathway
* 3. Hedgehog pathway
* 4. Receptor tyrosine kinase (small G proteins) pathway
* 5. Notch/Delta pathway
* Mid-development and later
* 6. Cytokine receptor (cytoplasmic tyrosine kinases)
* pathway
* 7. IL1/Toll NFkB pathway
* 8. Nuclear hormone receptor pathway
* 9. Apoptosis pathway
* 10. Receptor phosphotyrosine phosphatase pathway
* Larval/adult physiology
* 11. Receptor guanylate cyclase pathway
* 12. Nitric oxide receptor pathway
* 13. G-protein coupled receptor (large G proteins) pathway
* 14. Integrin pathway
* 15. Cadherin pathway
* 16. Gap junction pathway
* 17. Ligand-gated cation channel pathway

Sonic Hedge-hog signal pathway
cyclopamine
jervine
Holoprosencephaly
Cholesterol synthesis inhibitor
Consequences of Folate Deficiency
* Result of low dietary intake, genetic error of folate metabolism, lifestyle exposures
* DNA Hypomethylation
o Gene overexpression, uncontrolled cell growth, genomic instability
* Hyperhomocysteinemia
o Excessive accumulation of Hcy
* Base Misincorporation
o Decrease in thymine synthesis; replaced by uracil
o DNA strands prone to nicks, breaks and vulnerable to mutagen insertion
Homework

1. Describe the possible mechanisms for teratogenic effects of the following chemicals.
a. aminoglycosides
b. ethylene oxide
c. captopril
d. danazol
e. aminopterin
f. Accutane

Developmental Toxicology.ppt

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