S3 Week 3 Pathology

Front 1

What two changes can result in interstitial edema?

Back 1

1) Increased capillary pressure
2) Reduced colloid osmotic pressure

Front 2

What is transudate?

Back 2

Edema fluid as a results of volume or pressure overload, or under conditions of reduced plasma protein.

Front 3

What is exudate?

Back 3

The result of an inflammatory edema due to increased vascular permeability.

Front 4

Increased hydrostatic pressure as a cause of edema:

Back 4

1) localized increases in pressure can result from impaired venous return
2) generalized increases in venous presure occur most in CHF. Reduced renal perfusion makes the problem worse by upping aldosterone and volume retention --> even more fluid for the failing heart to deal with --> generalized edema.

Front 5

Reduced plasma osmotic pressure as a cause of edema:

Back 5

Albumin is the protein responsible for maintaing osmotic pressure. Albumin loss can occur with nephrotic syndrome, liver disease or protein malnutrition.
Renal hypoperfusion leads to high aldosterone and salt retention; but these cannot correct the problem --> makes the edema worse.

Front 6

Lymphatic obstruction as a cause of edema:

Back 6

Impaired lymphatic drainage and consequent lymphedema are usually localized; can result from inflammation or neoplastic obstruction.

Front 7

Sodium and water retention as a cause of edema:

Back 7

Increased salt with the obligate retention of water causes both increased hydrostatic pressure and reduced vascular osmotic pressure.
Salt retention can occur with any compromise of renal function, as in poststreptococcal glomerulonephritis or acute renal failure.

Front 8

Summary of the causes of edema:

Back 8

1) increased hydrostatic pressure caused by a reduction in venous return
2) Decreased colloid osmotic pressure, due to reduced albumin
3) Lymphatic obstruction
4) Primary renal sodium retention
5) Increased vascular permeability

Front 9

Pulmonary edema:

Back 9

A common problem seen with left ventricular failure, but it also occurs in renal failure, ARDS, pulmonary infections and hypersensitivity reactions.
The lungs typically weight 2-3 x than normal, and contain a frothy blood tinged fluid containing some red cells.

Front 10

Acute pulmonary and hepatic congestion:

Back 10

1) Congestion is a passive process resulting from impaired venous return out of a tissue.

2) Acute pulmonary congestion is characterized by alveolar capillaries engorged with blood .
3) In acute hepatic congestion the central vein a sinusoids are distended with blood --> liver hypoxia --> fatty change

Front 11

Chronic pulmonary and hepatic congestion:

Back 11

1) Chronic pulmonary congestion is characterized by alveolar spaces containing numerous hemosiderin-laden macrophages (heart failure cells).

2) In chronic hepatic congestion you get "nutmeg" liver

Front 12

General characteristics of shock:

Back 12

1) Shock is the final common pathway for severe hemorrhage, extensive trauma or burns, large MI, massive pulmonary embolism and microbial sepsis.
2) Shock gives rise to systemic hypoperfusion; it can be caused either by reduced cardiac output or by reduced effective circulating volume. The end results are hypotension, impaired tissue perfusion and cellular hypoxia.

Front 13

Five types of shock:

Back 13

1) Cardiogenic shock resulting from failure of the cardiac pump.
2) Hypovolemic shock resulting from loss of blood or plasma volume
3) Septic shock caused by microbial infection
4) Neurogenic shock as a result of anesthetic accident or spinal cord injury
5) Anaphylactic shock caused by an IgE hpersensitivity reaction.

Front 14

What kind of bacteria cause most cases of septic shock?

Back 14

Endotoxin-producing gram negative bacilli

- Endotoxins are bacterial wall LPS

Front 15

What cellular effects does LPS have on immune cells and endothelial cells?

Back 15

- LPS attaches to a circulating LPS binding protein which then binds to the CD14 receptor on monocytes, macrophages and neutrophils
- Activation of CD14 results in activation of mononuclear cells and production of cytokines IL-1 and TNF
- These cytokines act on endothelial cells to reduce synthesis of anticoagulation factors such as tissue factor pathway inhibitor and thrombomodulin.

Front 16

The effects of LPS on the immune system and vasculature are dose dependant:

Back 16

1) At low doses, LPS activates monocytes, macrophages and neutrophils; activates compliment - leading to local eradication of bacteria.
TNF and IL-1 induce endothelial cells to express adhesion molecules. These responses enhance LOCAL acute inflammatory responses and clearance of the infection.

2) With a moderate level of LPS, endothelium express NO and platelet activating factor. In addition, systemic effects of TNF and IL-1 induce fever, increased acute-phase reactants and increased production of neutrophils. The endothelium is tipped toward a procoagulant state.

3) At very high levels, the same cytokine and secondary mediators, now at high levels, result in:
Systemic vasodilation
Diminished myocardial contractility
Widespread endothelial injury and activation, causing systemic leukocyte adhesion and diffuse alveolar capillary damage in the lung.
- Activation of the coagulation system, resulting in DIC.

Front 17

Three phases of shock:

Back 17

1) An initial nonprogressive stage during which reflex compensatory mechanisms are activated and perfusion of vital organs is maintained.
2) A progressive stage characterized by tissue hypoperfusion and onset of worsening circulatory and metabolic imbalances.
3) An irrerversible stage that sets in after the body has incurred cellular and tissue injury so severe that even if the hemodynamic defects are corrected, survival is not possible

Front 18

Compensatory mechanisms activated in the initial phases of shock:

Back 18

Neurohumoral mechanisms help maintain cardiac output and blood pressure.
These include baroreceptor reflex, activation of RAA, antidiuretic hormone release and sympathetic stimulation.

The net effect is tachycardia, peripheral vasoconstriction and renal conservation of fluid.

Front 19

Mechanisms activated during the progressive stage of shock:

Back 19

- Tissue hypoxia becomes widespread. Anaerobic glycolysis produces excessive lactic acid.
Metabolic acidosis lowers the tissue pH and blunts the vasomotor response; arterioles dilate and blood pools in the microcirculation.

Front 20

Characteristics of irreversible stage shock:

Back 20

- Widespread cell injury results in lysosomal leakage further aggravating the shock state.
- Myocardial contractile function worsens, in part due to NO synthesis.
- Ischemic bowels may allow intestinal flora to enter the circulation, worsening endotoxic shock.
- Patient has renal shutdown due to ischemic tubular necrosis.

Front 21

Cellular and tissue changes in shock:

Back 21

- Fibrin thrombi in kidney glomeruli
- Adrenal gland lipid depletion
- Acute tubular necrosis in the kidneys
- GI tract may manifest focal mucosal hemorrhages and necrosis
- Lung alveolar damage may occur in bacterial sepsis

Front 22

Diagram of the effects of varying levels of LPS:

Back 22

Front 23

Diagram of hypovolemic shock effects:

Back 23

Front 24

The cytokine cascade in sepsis:

Back 24

Front 25

Effects of cytokines/LPS on the permeability of vessels:

Back 25

- Permeability:
Fluid seeps through the endothelium via open pores creating edema and reducing available intravascular volume
- Vasodilation:
LPS has direct effect on iNOS in endothelium which leads ot local ↑NO and, through cGMP causes vasodilation

Front 26

Metabolic disturbances during sepsis:

Back 26

Hyperglycemia will temporarily increase urine output; until fluids are depleted.

Front 27

What is the management for septic shock?

Back 27

- Antibiotics
- Insulin for hyperglycemia
- Fluids to reinstate intravascular volume and replace interstitial losses
- Correction of adrenal insufficiency is often required;
corticosteroids may be needed

Front 28

What is the relationship between lactate levels and survival in shock?

Back 28

- Normal levels of lactate are between 0-4.

- The higher the level of lactate, the worse the outcome

Front 29

The role of the interstitial space in shock:

Back 29

Front 30

Treatment of cardiogenic shock:

Back 30

Front 31

Key points 1 from the shock lecture:

Back 31

Front 32

Key points 2 from the shock lecture:

Back 32

Front 33

Lipid Levels:

Back 33

Front 34

What is the calculation for determining LDL?

Back 34

Total cholesterol = HDL + LDL + TG/5

Front 35

Risk factors for coronary heart disease:

Back 35

Front 36

LDL level goals correlated with risk factors:

Back 36

Drug of choice to prescribe is a statin!

Front 37

Order of therapy goals for dyslipidemia:

Back 37

- Treat TG over 500 first to prevent pancreatitis
- Then treat LDL to goal level
- Then treat HDL to goal level

Front 38

What is the recommended age to start screening for lipids?

Back 38

Recommended age to start screening for high cholesterol/LDL is at age 20! Should screen every 5 years.

Front 39

Current guidelines for the use of aspirin:

Back 39

Front 40

Back 40

Goal is 160; she is at 140 so she does not need any treatment.

Front 41

Back 41

Three risk factors (diabetes counts as two?)
LDL goal of 100

Front 42

Back 42

Multiple risk factors
LDL goal is less than 70

Front 43

What is a serious side effect of an extremely low cholesterol level?

Back 43

Violence; cholesterol is necessary for cell membranes and nerve myelination.

Front 44

What is the definition of cardiac failure?

Back 44

The inability of the heart to pump blood forward at a sufficient rate to meet the metabolic demands of the body (forward-failure)
OR
The ability to do so only if the cardiac filling pressures are abnormally high (backward failure)
OR BOTH

Front 45

What is the effect of stretching on heart muscle fibers?

Back 45

Stretching the muscle before stimulation optimizes the overlap and interaction of myosin and actin filaments, increasing the number of cross bridges and the force of contraction.
Stretching cardiac muscle fibers also increases the sensitivity of the myofilaments to calcium, which further augments force development.

Front 46

What is the Frank-Starling relationship?

Back 46

Ventricular output increases in relation to the preload.

(The larger the ventricular volume during diastole, the more fibers are stretched before stimulation and the greater the force of the next contraction)

Front 47

What is cardiac output equal to?

Back 47

Stroke volume x Heart rate

The three major determinants of stroke volume are preload, afterload and myocardial contractility.

Front 48

What is the equation for stroke volume?

Back 48

End diastolic volume - End systolic volume

Front 49

What is the equation for ejection fraction?

Back 49

EF = stroke volume / end diastolic volume

Normal range is 55-75%

Front 50

What is Compliance?

Back 50

Intrinsic property of a chamber that describes its pressure-volume relationship during filling. Reflects the ease or difficulty with which the chamber can be filled.

Compliance = Change in volume/change in pressure

Front 51

Random observation:

Back 51

So if CO = HR x SV and stroke volume is determined by preload, afterload and contractility....

A decrease in preload will result in a lower CO and vice-versa.
A decrease in contractility will also result in a lower CO.
An increase in afterload will result in a lower CO.

Front 52

Afterload:

Back 52

Afterload is equal to P x r / 2h

P=ventricular pressure
r = ventricular chamber radius
h = ventricular wall thickness

So... An increase in ventricular pressure or chamber radius will increase wall stress/afterload.
AND
An increase in ventricular wall thickness will decrease wall stress/afterload.

Front 53

Contractility:

Back 53

When contractility is enhanced pharmalogically, the ventricular performance curve is displaced upward such that at any given preload, the stroke volume is increased.

Conversely, when a drug that reduces contractility is administered or the ventricle's contractile function is impaired, the curve shifts in a downward direction, leading to reductions in stroke volume and cardiac output at any given preload.

Front 54

Three important concepts on heart physiology from Lilly:

Back 54

1) Ventricular stroke volume is a function of preload, afterload and contractility. SV rises when there is an increase in preload, a decrease in afterload or augmented contractility

2) Ventricular end-diastolic volume is often used as a representation of preload. The end-diastolic volume is influenced by the chamber's compliance

3) Ventricular end-systolic volume depends on the afterload and contractility but not the preload

Front 55

Causes of heart failure may be grouped into three broad catagories:

Back 55

1) Impaired ventricular contractility (systolic)
2) Increased afterload (systolic)
3) Impaired ventricular filling (diastolic)

Heart failure that results from an abnormality of ventricular emptying (due to impaired contractility or excessive afterload) is called systolic disfunction.
BUT
Heart failure caused by abnormalities of diastolic relaxation or ventricular filling is termed diastolic dysfunction.

* Most patients have systolic problems.

Front 56

Consequences of systolic dysfunction:

Back 56

- Ventricle has diminished capacity to eject blood (may be due to destruction of myocytes, abnormal myocyte function or fibrosis; pressure overload increases resistance to flow)
- Stroke volume falls --> increased end systolic volume. When coupled with the normal return from the lungs --> increase in preload.
- Stroke volume increases but the myocardium is still impaired so the end systolic fraction remains high.
- Elevated LV pressure --> increased LA pressure --> elevated pulmonary capillary pressure resulting in the transudation of fluid into the interstitium --> pulmonary congestion.

Front 57

Consquences of diastolic dysfunction:

Back 57

Causes of diastolic dysfunction are; impaired diastolic relaxation (an energy dependant process), increased stiffness of the ventricular wall, or both.

Acute MI can transiently inhibit energy delivery and diastolic relaxation.

LV hypertrophy, fibrosis or restrictive cardiomyopathy causes the LV walls to become chronically stiffened.

* Patient with diastolic dysfunction often present with signs of vascular congestion because the elevated diastolic pressure is transmitted retrograde to the pulmonary and systemic veins.

Front 58

Special characteristics of Right-Sided heart failure:

Back 58

The RV is highly susceptible to failure in situations that present a sudden increase in afterload, such as acute PE.

The most common cause of right sided HF is actually the presence of left sided HF. This is due to increased pulmonary pressure.

Isolated right HF is less common and is due to increased RV afterload owing to diseases of the lung parenchyma or pulmonary vasculature.

* Right sided heart disease that results from a primary pulmonary process is called "cor pulmonale"!!!

Front 59

Causes of "Cor Pulmonale"

Back 59

- COPD
- Interstitial lung disease (sarcoidosis)
- ARDS
- Chronic lung infection or bronchiectasis
- PE
- Primary pulmonary hypertension

Front 60

The Frank-Starling mechanism as a compensatory change in HF:

Back 60

Increased end systolic volume + normal diastolic filling volume = higher than normal LV volume.

At the higher volume, there is an increased stretch on the myofibers, which induces a greater stroke volume on subsequent contraction --> preservation of forward cardiac output.

* This mechanism only works up to a certain point...if contractility decreases then this ceases to be effective.

Front 61

Neurohormonal alterations as a compensatory mechanism in heart failure:

Back 61

1) Adrenergic nervous system: decreased perfusion pressure is sensed by barorecptors in the carotid sinus and aortic arch. Sympathetic outflow is increased --> increased HR, increased contractility and a-mediated vasoconstriction

2) RAA system: Decreased renal perfusion leads to release of renin. Angiotensin II constricts arterioles and increases TPR. It stimulates thirst centers and increases aldosterone secretion.

3) ADH: Conserves water and increases blood volume --> augment preload

* Although initially beneficial, all these can worsen symptoms by exacerbating congestive pulmonary symptoms. Increased TPR may impair stroke volume and reduce CO.
An increased HR augments metabolic demand and can further reduce the performance of a failing heart.

Front 62

Benefits of Natriuretic peptides:

Back 62

Are secreted in response to increased intracardiac pressures.
ANP: store in atrial cells and released when needed.
BNP: Not normally produced by a healthy heart; only when subjected to hemodynamic stress.

ANP and BNP act to excrete sodium and water, vasodilate, inhibit renin secretion and antagonize the effects of ATII.

Front 63

Ventricular hypertrophy and remodeling as a compensatory mechanism in heart failure:

Back 63

Increased wall stress stimulates the development of hypertrophy and deposition of extracellular matrix.
This increased mass of muscle serves as a compensatory mechanism that helps to maintain contractile force. However, because of increased stiffness, this results in high diastolic ventricular pressures which are transmitted to the LA and lungs.

Front 64

Eccentric hypertrophy:

Back 64

A result of chronic chamber dilation owing to volume overload.
New sarcomeres are synthsized in series with the old, causing the myocytes to elongate.

Front 65

Concentric hypertrophy:

Back 65

Caused by chronic pressure overload; results in the synthesis of sarcomeres in parallel with the old - thickening the myocytes.

Front 66

Precipitating factors that elicit symptoms of HF:

Back 66

- Conditions of increased metabolic demand; fever, infection, anemia, hyperthyroidism, etc...
- Increased circulating volume
- Conditions that increase afterload
- Conditions that impair contractility
- Failure to take medications
- Excessively slow heart rate

Front 67

Most common symptoms and physical findings in left-sided heart failure:

Back 67

Symptoms: dyspnea, orthopnea, PND, fatigue

Physical findings: Diaphoresis, tachycardia, tachypnea, pulmonary rales, loud P2 and S3 gallop

Front 68

Most common symptoms and physical findings in right sided heart failure:

Back 68

Symptoms: Peripheral edema, hepatomegaly (RUQ discomfort)

Physical findings: JVD, hepatomegaly and peripheral edema

Front 69

How do pleural effusions develop in heart failure?

Back 69

The pleural veins drain into both the systemic and pulmonary venous beds.

The presence of pleural effusion is suggested on PE by dullness to percussion over the posterior lung bases.

Front 70

Five main goals in the treatment of patients with heart failure:

Back 70

1) Identification and correction of the underlying condition causing heart failure.
2) Elimination of the acute precipitating cause of symptoms. (treat acute infection, remove excessive salt intake, changing medications)
3) Management of heart failure symptoms:
a. Treatment of pulmonary and systemic vascular congestion (restrict Na+ and give diuretics)
b. Measures to increase forward cardiac output (vasodilators and + inotropic drugs)
4) Modulation of the neurohormonal response (slows progression of LV dysfunction)
5) Improvement of long term survival

Front 71

Diuretics in the treatment of heart failure:

Back 71

- Diuretics reduce preload --> decreased pulmonary congestion
- Judicious use of diurectics does not cause a decrease in CO, but exessive use can!
- Diuretics should only be used if there is evidence of pulmonary congestion or edema.
- Electrolyte imbalances (hyper or hypokalemia) may cause dangerous arrythmias

Front 72

Vasodilators in the treatment of heart failure:

Back 72

- Vasodilator drugs such as ACE inhibtors counteract the detrimental effects of neurohormonal compensatory mechanisms.

- Venous vasodilators (nitrates): result in decreased LV pressure and a relief of pulmonary congestion. Just watch out for an undesired fall in SV, CO and BP.

- Arteriolar vasodilators (hydralazine): reduce TPR and LV afterload. This augments stroke volume. Blood pressure decrease not usually a problem due to compensatory mechanisms.

- ACE inhibitors: result in dilation of both venous and arteriolar circuits. Reduce sodium and water retention and vasoconstriction --> reduced intravascular volume and decreased pulmonary congestion. ACEI also limit the maladaptive ventricular remodeling in patients with heart failure and following acute MI.

- ARB's : These drugs provide a more complete inhibition of the system via blockade of the actual AII receptor. BUT ARB's don't produce a serum rise in bradykinin like ACEI do. Usually prescribed when ACEI are not tolerated because of cough.

- Combination Nitro/Hydralazine: indicated when patient cannot take an ACEI or ARB (because of renal insufficiency or hyperkalemia) or when the patient is African American.

- Nesiritide: A human recombinant B-type natriuretic peptide. It is a rapid vasodilator given IV when the patients cannot take IV nitroglycerin or nitroprusside. It has many other beneficial effects detailed on another note; however it is associated with increased mortality.

Front 73

Intotropic drugs used in the treatment of heart failure:

Back 73

- These drugs increase the availability of intracellular calcium and enhances the force of ventricular contraction. These agents are useful in treating patients with systolic dysfunction, but NOT those with pure diastolic failure.

- B-adrenergic agonist (dobutamine and dopamine): Administered IV for support of critically ill patients - receptors are quickly downregulated leading to resistance

- Phosphodiesterase inhibitors (amrinone and milrinone): used for IV treatment of CHF in acutely ill patients.

- Digitalis: IV or Oral. Enhance contractility, reduce cardiac enlargment, improve symptoms and increase CO in patients with systolic HF. Also blunts the baroreceptor response, slows AV node conduction --> helps patients with atrial fibrillation.
Last line therapy and/or for patient with atrial fibrillation.
NOT useful in the treatment of LV diastolic dysfunction.

Front 74

B-blockers used in the treatement of heart failure:

Back 74

Carvedilol and Metoprolol:
Augment cardiac output, reduce hemodynamic deterioration and improve survival.
Use cautiously so that the negative inotropic effect doesn't outweigh the positive CO effect.
* Regimens should be started at low dosages and augmented gradually.

Front 75

Aldosterone antagonist in treatment of heart failure:

Back 75

Spironolactone and Eplerenone: Reduce the negative remodeling effects on the heart, reduce water retention and volume overload.

* Monitor heart failure patient's therapy carefully to prevent hyperkalemia, especially if there is renal impairment or concomitant ACE inhibitor therapy.

Front 76

Additional beneficial therapies for treatment of heart failure:

Back 76

- Anticoagulation: to prevent intracardiac thrombus formation if LV systolic function is impaired.

- Treatment of atrial and ventricular arrythmias: Amiodarone is the most effective and least likely to provoke dangerous arrythmias in HF patients. BUT implantation of a cardioverter-defibrillator is preferred; reduces the likelihood of sudden death.

Front 77

Cardiac Resynchronization therapy:

Back 77

- Biventricular pacing to correct bundle branch blocks and widened QRS complexes common in advanced heart failure.
- Will augment LV systolic function, reduce LV size, improve exercise tolerance and reduce mortality
- CRT is used for patients with LV EF of less than 35% with prolonged QRS and continued symptoms despite drug therapy.

Front 78

Treatment of diastolic dysfunction:

Back 78

- Treatment of underlying disorder, if possible; Pericardiectomy for restrictive pericarditis, or therapy for coronary artery disease if transient ischemia is the mechanism of diastolic dysfunction.

- Diuretics may be used cautiously to reduce pulmonary congestion and edema; careful not to compromise CO.

Front 79

Acute pulmonary edema:

Back 79

- A severe, acute form of left sided heart failure, in which elevated capillary hydrostatic pressure causes rapid accumulation of fluid within the interstitium and alveolar spaces of the lungs.
- This condition is frequently accompanied by hypoxia.
- Patients experience severe dyspnea and anxiety while struggling to breathe.
- Patient will be tachycardic with cold clammy skin owing to sympathetic stimulation. Tachypnea and coughing of frothy sputum represent alveolar transudate. Rales are present at the lung bases and then throughout the lung fields.

- Management of acute PE (lmnop):
LASIX: a rapid acting diuretic to reduce LV preload and pulmonary pressure.
MORPHINE: to reduce anxiety and as a venous dilator
NITRATES: To reduce preload
OXYGEN
POSITION: upright to facilitate pooling of blood in the lower body, reducing venous return to the heart.

Front 80

What is the histologic difference between physiologica and pathogenic cardiac hypertrophy?

Back 80

In physiologic, there is an increase in the number of capillaries.
In pathologic there is not...leading to ischemia.

Front 81

Table of differences between physiological and pathological causes of hypertrophy:

Back 81

Front 82

Molecular factors involved in cardiac hypertrophy:

Back 82

Front 83

Concentric vs. Eccentric hypertrophy characteristics:

Back 83

Front 84

Pathologic hypertrophy can lead to fibrosis over time:

Back 84

Front 85

What are the 3 top causes of development of heart failure?

Back 85

In order; Coronary artery disease, valvular disease and hypertension

Front 86

Causes of systolic and diastolic heart failure diagram:

Back 86

Front 87

Differential diagnosis between systolic and diastolic heart failure:

Back 87

The small LV cavity and concentric LV hypertrophy will eventually end up being the large dilated heart with time.

Front 88

What are two signs of end-stage HF?

Back 88

Cheyne-stokes respirations (rapid breathing followed by a period of not breathing)
Pulsus alternans (alternating normal and depressed pulses)

Front 89

The pathophysiology of dyspnea:

Back 89

Front 90

Pathophysiology of PND:

Back 90

Front 91

Pathophysiology of edema:

Back 91

Front 92

New York classes of Heart Failure:

Back 92

Front 93

Stages of CHF:

Back 93

Front 94

Kerley lines on chest X-ray in pulmonary edema:

Back 94

Kerley B lines = linear markings at the periphery of lungs that represent interlobular edema
Kerley A lines come from the periphery toward the mediastinum at an angle (engorgement of the lymphatics)

Front 95

Guidelines for therapy in systolic heart failure:

Back 95

Loop diuretics are the most effective.

Front 96

Treatment types according to manifestations of CHF:

Back 96

Front 97

Causes of secondary pulmonary hypertension:

Back 97

1) Chronic obstructive or interstitial lung disease, which is accompanied by destruction of lung parenchyma and consequent reduction in alveolar capillaries. This causes increased pulmonary arterial resistance and secondarily, elevated arterial pressure.

2) Recurrent pulmonary emboli, which lead to a reduction in the functional cross-sectional area of the pulmonary vascular bed, in turn, leading to increased vascular resistance.

3) Antecendent heart disease, for example, mitral valve stenosis, which increases LA pressure leading to higher pulmonary venous pressures and ultimately pulmonary arterial hypertension.

* Congenital left to right shunts are another cause of secondary pulmonary hypertension

Front 98

Primary or idiopathic pulmonary hypertension:

Back 98

The vast majority of cases are sporadic and only 6% have the familial form with an autosomal dominant mode of inheritance.

Front 99

Pathogenesis of PH:

Back 99

- Pulmonary endothelial cell and/or vascular smooth muscle dysfunction is the probable underlying basis.

- In secondary PH, endothelial dysfunction occurs due to the underlying disorder. Endothelial cell dysfunction reduces production of vasodilatory agents while increasing synthesis of vasocostrictors. In addition there is production of growth factors and cytokines that induce the migration and replication of vascular smooth muscle and elaboration of the extracellular matrix.

- In primary PH, especially the familial form, the TGF-B signalling pathway mediates endothelial and SMC dysfunction. Germ line mutations of BMPR2 lead to loss of inhibition of proliferation of endothelial and SMC's.

Front 100

Clinical course of PH:

Back 100

- Features of secondary PH: can develop at any age. Respiratory insuffinciency and right-sided heart strain.

- Primary PH: mostly in younger persons, common in women. Marked by fatigue, syncope, dyspnea upon exertion and sometimes chest pain. These persons usually develop severe respiratory insufficiency and cyanosis, and death usually results from right-sided heart failure in 2-5 years.

Front 101

Pulmonary hypertensive heart disease (cor pulmonale):

Back 101

Cor pulmonale consists of right ventricular hypertrophy and dilation due to pulmonary hypertension caused by primary disorders of the lung parenchyma or pulmonary vasculature.
Cor pulmonale may be acute or chronic, depending on the tempo by which the pulmonary hypertension develops.
Acute most commonly follows massive pulmonary embolism with obstruction of over 50% of the pulmonary vascular bed.
Chronic occurs secondary to prolonged pressure overload caused by obstruction of the pulmonary vasculature, or compression or obliteration of septal capillaries (resulting from emphysema, interstitial pulmonary fibrosis, or primary pulmonary hypertension)

Front 102

Pathology of cor pulmonale:

Back 102

- In acute, the RV is usually dilated but does not show hypertrophy; if an embolism causes sudden death the heart may be of normal size.
- Chronic is characterized by RV and often RA hypertrophy. In some cases the thickness of the RV wall may exceed that of the LV. When ventricular failure develops the RV and RA may also be dilated.

* Because chronic occurs in the setting of chronically elevated pulmonary arterial pressure, the pulmonary arteries often contain atheromatous plaques and other lesions reflecting long standing pulmonary hypertension.

Front 103

When cardiac output increases, what keeps the resistance low in the lungs?

Back 103

Recruitment of previously unused vessels and distenstion of vessels to handle an increase in flow.

Front 104

What pulmonary pressures are required for a diagnosis of pulmonary hypertension?

Back 104

> 25 mmHg at rest
> 30 mmHg at with exercise.

Front 105

How is pulmonary artery pressure measured?

Back 105

Echocardiography with doppler

Right Heart catherization

Front 106

Diagram of normal pressure through the vasculature:

Back 106

Front 107

Pathobiology of primary pulmonary hypertension:

Back 107

Front 108

Two hit hypothesis in BMRP2 gene mutation:

Back 108

Front 109

Histology of pulmonary hypertension:

Back 109

Front 110

Gross appearance of heart in pulmonary hypertension:

Back 110

The heart on the left shows RV hypertrophy indicative of cor pulmonale

Front 111

What is Eisenmenger's syndrome (ventricular septal defect)?

Back 111

This refers to a condition in which an intraventricular left to right shunt results in such severe pulmonary hypertension that right-sided pressures eventually exceed systemic pressures, and the intracardiac shunt is reversed (becoming right to left). 

Front 112

What is pulmonary artery wedge pressure?

Back 112

A catheter is inserted into the pulmonary artery until the tip occludes one of the branches. The pressure measured at that point in the vessel is equal to the pressure in the left atrium.
Normal value is about 8.

But how does this relate to LV pressure? An increase in LA pressure usually means LV dysfunction.

Front 113

Pathophysiology of cor pulmonale:

Back 113

Front 114

Physical exam signs of pulmonary hypertension:

Back 114

Jugular venous distension
Triscupid regurgitation murmur
Loud P2
Right sided S4
Pedal edema
Ascites
Para-sternal heave
Cyanosis
Digital clubbing

Front 115

Diagnostic tests for pulmonary hypertension:

Back 115

Front 116

Flowchart for the workup of pulmonary hypertension:

Back 116

Front 117

Degrees of severity of PH:

Back 117

Front 118

General treatment of pulmonary hypertension:

Back 118

- Anti-coagulate with Coumadin
To prevent thrombosis
- Calcium channel blockers in patients with responsive pulmonary vasculature
- Diuretics and Digoxin for Right sided heart failure
- Oxygen therapy

Front 119

Characteristics of left to right shunts:

Back 119

- The most common type of congenital cardiac malformation
- Include atrial and ventricular septal defects and patent ductus arteriosus.
- Cyanosis is not an early feature of these defects but can manifest after pulmonary hypertension has developed enought to produce right to left shunting (Eisenmenger syndrome).

Front 120

Atrial septal defects:

Back 120

- ASD's initially cause left to right shunts, as a result of the lower pressures in the pulmonary circulation and right side of the heart.
- Defects are well tolerated if small in diameter.
- With time, pulmonary vascular resistance can increase, resulting in pulmonary hypertension.

Front 121

Ventricular septal defects:

Back 121

- The most common congenital cardiac anomaly at birth.
- Left to right shunt
- Most close spontaneously in childhood.
- Large defects cause a left to right shunt, often complicated by pulmonary hypertension and CHF.
- PH with resultant reversal of the shunt and cyanosis occurs earlier and more frequently in patients with VSD than in those with ASD.

Front 122

Patent ductus arteriosus:

Back 122

- Ductal closure is often delayed or absent in infants with hypoxia resulting from respiratory distress or heart disease.
- PDA's are high pressure left to right shunts, audible as harsh "machinery like" murmurs.

Front 123

Right to left shunts:

Back 123

- Distinguished by cyanosis at or near the time of birth.
- Two important right to left shunts are tetrology of Fallot and transposition of the great vessels.
- Clinical findings associated with severe, long standing cyanosis include clubbing of the fingertips and polycythemia.
- Right to left shunts permit venous emboli to bypass the lungs and directly enter the systemic circulation.

Front 124

Tetrology of Fallot

Back 124

The four features are:
1) VSD
2) Obstruction to the right ventricular outflow tracts
3) An aorta that overrides the VSD
4) Right ventricular hypertrophy

- The hemodynamic consequences of TOF are right to left shunting, decreased pulmonary blood flow and increased aortic volumes.
- The lungs are protected from hemodynamic overload by the pulmonary stenosis, so that PH does not develop.

Front 125

Transposition of the great arteries:

Back 125

- The aorta arises from the RV and the pulmonary artery arises from the LV.
- Patients with a VSD tend to have a relatively stable shunt.
- Patients with only a patent foramen ovale or PDA tend to have unstable shunts that need to be corrected in the first days of life.

Front 126

Aortic coarctation:

Back 126

- Narrowing or constriction of the aorta; a form of obstructive congenital heart disease.

- Preductal coarctation with a PDA usually manifests immediately after birth. The delivery of poorly oxygenated blood through the DA produces cyanosis localized to the lower half of the body.

- Postductal coarcation without a PDA is usually asymptomatic. Typically there is upper extremity hypertension, due to poor perfusion of the kidneys, but weak pulses and a lower blood pressure in the lower extremities. Adults tend to show exuberant collateral circulation around the coarctation involving markedly enlarged intercostal and internal mammery arteries.

Front 127

Types of abnormalities seen in congenital heart disease:

Back 127

Front 128

Normal circulation:

Back 128

Front 129

Normal oxygen saturation levels:

Back 129

Front 130

Diagram of a left to right shunt:

Back 130

Making some parts of the blood volume get lost in this circular loop means the heart has to work harder because it gets more volume returned to it. More blood being put through the lungs means that lungs are subject to pulmonary overcirculation.

Front 131

What is bad about a left to right shunt?

Back 131

- HEART is subjected to excess blood volume
- LUNG is subjected to excess “overcirculation”

-- this puts a strain on these organs

*Pulmonary arteries are thinner, more compliant and have a thinner medial layer than other body artery types.
They are more subject to damage occurring from overcirculation.

Front 132

Clinical manifestations of a left to right shunt part 1:

Back 132

Front 133

Clinical manifestations of left to right shunts part 2:

Back 133

* Will start to see cyanosis in the patient at this point; is an irreversible condition with poor prognosis.

Front 134

Patent ductus arteriosus:

Back 134

Front 135

Consequences of a PDA:

Back 135

Shunt direction?
- Left-to-right shunt
O2 step-up/down?
- O2 step-up in the pulmonary artery
Effect on heart and lungs?
- Heart: volume overload
- Lungs: pulmonary overcirculation
Clinical Manifestations?
- Congestive heart failure
- Pulmonary hypertension leading to Eisenmenger’s

Front 136

Consequences of an atrial septal defect:

Back 136

Shunt direction?
- Left-to-right shunt
O2 step-up/down?
- O2 step-up in the right atrium
Effect on heart and lungs?
- Heart: Volume overload
- Pulmonary overcirculation
Clinical Manifestations:
Pulmonary hypertension, Eisenmenger’s

Front 137

Consequences of a ventricular septal defect:

Back 137

Shunt direction?
- Left-to-right shunt
O2 step-up/down?
- O2 step-up in the right ventricle
Effect on heart and lungs?
- Heart: Volume overload
- Pulmonary overcirculation
Clinical Manifestations:
Congestive heart failure
Pulmonary hypertension, Eisenmenger’s

Front 138

Therapy options to manage left to right shunts:

Back 138

MEDICAL
Medicines to manage CHF (digoxin, diuretics, ACE inhibitors)

SURGICAL
Repair the anatomic defect, thus normalize the circulation

Front 139

Epidemiology of Congenital Heart Disease:

Back 139

5% of CHD cases are associated with known chromosomal anomalies

Front 140

Congenital heart disease in Down's syndrome:

Back 140

Front 141

What's bad about a right to left shunt?

Back 141

- Decreased oxygen in the blood (hypoxemia)
- Decreased oxygen delivery to tissues (hypoxia)
- Increased hemoglobin (polycythemia)
- Hypercoagulability, thrombosis

Front 142

Clinical manifestations of a right to left shunt:

Back 142

Exercise intolerance
Cyanosis
Cyanotic episodes, aka: “tet spells”
Squatting
Clubbing
Stroke (due to hypercoagulability)
Brain abscess (due to infective embolism)
Premature death

Front 143

Diagram of tetrology of Fallot:

Back 143

1) Narrowing of the pulmonary valve can lead to higher pressure in the right ventricle
2) Thickening of RV occurs secondary to higher pressure in RV.
3) Interesting, but not that important…
4) VSD is the most important

Front 144

The right to left shunt in tetrology of Fallot:

Back 144

Front 145

Consequences of TOF:

Back 145

Shunt direction?
- Right-to-left shunt
O2 step-up/down?
- O2 step-down in the left ventricle
Effect on heart and lungs?
- Pulmonary blood flow decreased (due to obstruction)
- RV hypertrophy

Front 146

Therapy for TOF:

Back 146

Close the VSD
Relieve obstruction above, at and below the small pulmonary valve

Front 147

What is coarctation of the aorta?

Back 147

A narrowing of the aorta just beyond the arch

Front 148

Angiography images of coarctation of the aorta:

Back 148

Front 149

Diagram of coarctation blood flow:

Back 149

All the processes of internal organs and muscle growth still occur due to development of collateral circulation.
Top half has high BP and is pink
Bottom half has low BP and is blue

Front 150

Consequences of coarctation of the aorta:

Back 150

- Ventricular hypertrophy leading to dysfunction
In long run: hypertension
May persist after repair
- “critical narrowing”: shock, ventricular failure, renal failure

Front 151

Overview of aneurysm locations and causes:

Back 151

Front 152

Cardiac aneurysms:

Back 152

Cardiac aneurysms actually pouch outward while the rest of the myocardium contracts during systole.
These aren’t likely to rupture, but they do caused decreased function of the heart.

Front 153

Pathogenesis of an aneurysm:

Back 153

Front 154

Back 154

Front 155

Rules for QT intervals:

Back 155

Front 156

Review of the cause of Torsades de Pointes:

Back 156

Front 157

Example of prolonged QT:

Back 157

Front 158

Example of WPW syndrome:

Back 158

Recognizable because of the "delta wave" which is the slight upward slope on the QRS complex.

Front 159

Example of AV nodal re-entrant tachycardia:

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Recognized by a narrow QRS complex with a rate of 150-200 along with some P waves buried in QRS complexes.

Front 160

Example of atrial fibrillation:

Back 160

Recognized by very fast chaotic P waves with QRS complexes coming at different rates; ventricular rate irregular due to variable AV node block

Front 161

Example of ventricular tachycardia:

Back 161

Characterized by wide QRS complex tachycardia. Can be regular or irregular.

Front 162

Example of a STEMI:

Back 162

Front 163

Correlation of lead abnormalities to damaged part of the heart:

Back 163

Front 164

Example of 3rd Degree AV block:

Back 164

Front 165

Example of 1st degree AV block:

Back 165

What do you tell your patient?
* No restrictions

Front 166

Cardiac Output in Ventricular Fibrillation:

Back 166

Best next step if this patient passed out on the street is chest compressions.

Front 167

Another example of atrial fibrillation:

Back 167

Front 168

Example of atrial flutter:

Back 168

Re-entrant circuit localized to the RA.
Classic saw-tooth pattern

Front 169

Example of 2nd Degree AV block Mobitz Type I:

Back 169

Front 170

Example of Ischemia:

Back 170

Front 171

Example of sinus tachycardia:

Back 171

What would best explain the patient's HR?
* Fever

Front 172

Another example of atrial fibrillation:

Back 172

Front 173

Example of a 2nd Degree AV block Mobitz Type II

Back 173

Randomly dropped QRS complex.