Exam 1 Flashcards
cardiac hypertrophy or cardiomegaly
any increases in size or particularly in increases in masses
Left ventricular hypertrophy
A nything that should exceed that, so say more than 15mm, (normal is 13-15)
a cellular, structural response to a variety of insults.
consequences of both pumping against increased pressure and you also reduce the cardiac output because of reduced stroke volume
right ventricular hypertrophy
anything above that 5mm threshold (normal is 3-5mm)
cor pulmonale: primary pulmonary hypertension will lead to right sided changes in the heart.
Pulmonary arteries hypertrophy, constrict, and sclerose
Persistent elevations in pressure result in right to left shunt (Eisenmenger syndrome)
After birth, blood flow from right to left results in hypoxemia and cyanosis
Bypasses the pulmonary circulation
Emboli from veins to the systemic circulation (paradoxical emboli)
Cardiac dilation or dilatation
increase chamber size often related to disease state
Microscopic consequence of systemic hypertension
increased production of sarcolemma proteins and markedly enlarged, what we call boxed car nuclei, with thickened myofibrils
Three major coronary arteries
Left anterior descending (breaks into diagonal branches)
Left circumflex (Marginal branches)
Right Coronary
Pathologic changes of the valves
Damage to collagen that weakens the leaflets
Nodular calcification
Fibrotic thickening
Secondary changes:
Ventricular dilation
Tendinous cord rupture
Papillary muscle dysfunction
Left to right shunts
result in an increase in pulmonary blood flow
Elevate both volume and pressure in the low-pressure, low- resistance pulmonary circulation
Most common congenital heart disease
Symptoms vary from asymptomatic to fulminant heart failure
Ventricular septal defects
o incomplete closures of the ventricular septum, allowing free communication of blood between the left and right ventricles
o most common form of congenital heart disease
o 90% occur in the region of the membranous interventricular septum (membranous VSD)
o 10% occur below the pulmonary valve (infundibular VSD)
o Functional consequences of a VSD depend on the size of the defect and associated right-sided malformations
o Lead to early right ventricular hypertrophy and pulmonary hypertension
o Irreversible pulmonary vascular disease, shunt reversal, and death
o 50% CLOSE SPONTAEOUSLY
Atrial septal defects
o Abnormal, fixed openings in the atrial septum caused by incomplete tissue formation
o Usually asymptomatic until adulthood
o left to right shunts, increased pulmonary blood flow, and murmurs
o Pulmonary hypertension is unusual
o Secundum ASD (90%) results from a deficient septum secundum formation
o Primum anomalies or sinus venosus defects (10%) occur adjacent to the AV valves or the entrance of the SVC
Patent Ductus Arteriosus
o The ductus arteriosus arises from the pulmonary artery and joins the aorta just distal to the origin of the left subclavian artery
o PDAs cause a characteristic continuous harsh “machinery-like” murmur
o Large defects can lead to volume and pressure overloads in the small pulmonary arteries, reversal, and associated consequences
o May be life saving for infants with other congenital abnormalities that obstruct pulmonary or systemic outflow tracts (TOF)
Tetralogy of Fallot
o RIGHT TO LEFT SHUNT*
o Four features
VSD
Obstruction of the right ventricular outflow tract (pulmonary stenosis)
Overriding aorta
Right ventricular hypertrophy
o Boot shaped heart
o Severity = based on the ability of the right heart to pump blood and adequate amount of blood into the pulmonary circulation
pink tetralogy: you may only have a left-to-right shunt because you haven’t built up pressures sufficiently to cause the right to left; mild and may not require surgery
most infants are symptomatic at birth and will require immediate surgery right after birth.
Transition Of The Great Arteries
o produces ventriculoarterial discordance
o Aorta arises from the right ventricle/ Pulmonary artery arises from the left ventricle
o Atrium-to-ventricle connections are normal
o Early survival depends on accompanying shunting defects
Obstructive Lesions
o Congenital obstruction can occur at the level of the heart valves, within a great vessel, or within a chamber
Aortic or pulmonary valve stenosis or atresia
Outflow obstruction in TOF
Coarctation of the aorta
• constricting or narrowing of the aortic arch
• Infantile
o Often symptomatic in early childhood with tubular hypoplasia of the aorta arch proximal to the ductus
• Adult
o Discrete, ridge-like infolding of the aorta just opposite of the closed ductus
• with PDA usually manifests early in life due to the delivery of unsaturated blood through the lower part of body
• without PDA often goes unrecognized until adulthood
o Hypertension of the upper extremities
o Hypotension of the lower extremities
o Development of collateral circulation
Six principal mechanisms of Cardiac Dysfunction
- Pump failure
- Flow obstruction
- Regurgitant flow
- Shunted flow
- Disorders of cardiac conduction
- Rupture of the heart or a major vessel
Congestive heart failure
occurs when the heart is unable to pump blood at a rate sufficient to meet the metabolic demands of the body tissues
Malignant hypertension
o a rapidly rising blood pressure that if left untreated will die within 1 -2 years
o Systolic BP above 200 mm Hg/Diastolic BP above 120 mm Hg
o Renal failure/ Retinal hemorrhages
Arteriosclerosis
hardening of the arteries
Hyaline Arteriolosclerosis
Pink hyaline thickening with associated luminal narrowing
Plasma protein leakage across injured endothelial cells leading to increased smooth muscle matrix synthesis
Hyperplastic Arteriolosclerosis
Concentric, laminated, onion- skinning thickening of the walls with luminal narrowing
Consists of smooth muscle cells with thickened, reduplicated basement membranes
May lead to necrotizing arteriolitis in malignant hypertension, particularly in the kidneys
Atherosclerosis
o form of arteriosclerosis caused by the build up of fatty plaques within the arterial walls
o underlying pathology of coronary artery, cerebral, and peripheral vascular disease (the main driver for end organ damage within the cardiovascular system)
a chronic inflammatory and healing response of the arterial wall to endothelial injury
Lesion progression occurs due to complex interactions of lipoproteins, macrophages, T- cells, and smooth muscle cells
Modifiable Risk Factors for Atherosclerosis
Diabetes mellitus Unhealthy diet Inactivity Obesity Alcohol use Smoking Hyperlipidemia Low-density lipoproteins Systemic inflammation Hyperhomocystinemia Metabolic syndrome Insulin resistance, hypertension, dyslipidemia, hypercoagulability, and a proinflammatory state
Pathophysiology of Atherosclerosis
Endothelial injury or dysfunction
Accumulation of lipoproteins
Monocyte adhesion to the endothelium
Platelet adhesion
Factor release
Smooth muscle cell proliferation
Lipid accumulation
What percent decrease in luminal diameter is needed to reach critical stenosis in the coronary arteries?
70% decrease in the luminal diameter for critical stenosis and subsequent tissue ischemia
Angina pectoris
“chest pain” in response to reaching the point of critical stenosis and the vessels are not able to respond in times of increased demand
FANCY ANSWER: paroxysmal and usually recurrent attacks of substernal or precordial chest discomfort caused by transient myocardial ischemia that is insufficient to induce myocyte necrosis
Stable angina
“Chest pain with exertion”
A stable plaque that’s 70-80% occluded, so, when your heart requires, because of the activity, more oxygen delivered – increased contractility – your vessel cannot respond to that by delivering increased amount of blood and oxygen causing pain
Unstable angina
“Chest pain at rest”
You’re probably well above the 70% mark, approaching 80-90%. Even at base line contractility of the heart, the coronary arteries are not able to deliver as much oxygen as necessary.
plaque disruption can then result in thrombosis and vasoconstriction without total occlusion, so you can develop a thrombus in that area as a response to plaque disruption.
A person can go from unstable to stable
Plaque Disruption
Plaques erode or rupture when they are unable to withstand mechanical stresses generated by vascular shear forces
Plaque rupture results in the release of the necrotic lipid core, and rapid recruitment of platelets
Plaque rupture is typically promptly followed by partial or complete vascular thrombosis
Myocardial Infarction
heart attack
Death of cardiac muscle due to prolonged and severe ischemia
The incidence of MI strongly correlates with genetic and behavioral predispositions to atherosclerosis
most common cause of death in older women
Ischemic heart disease
Epi of MI
45% occur in people younger than 65
10% of MIs occur in people younger than 40
Blacks and white are equally affected
In middle age, men have a higher relative risk
Women are generally protected during reproductive years
Postmenopausal decline in estrogen production is usually associated with accelerated coronary artery disease
Process of a Heart Attack
Coronary artery atheromatous plaque undergoes an acute change
When exposed to subendothelial collagen and necrotic plaque contents, platelets adhere, become activated, and aggregate
they are going to vasospasm and constrict further in response to these local mediators (so instead of dilating, they constrict).
Tissue factor activates the coagulation cascade, adding the bulk of the thrombus
Occlusion can occur within minutes
Obstruction diminishes the blood flow to the region of the myocardium.
Within seconds the oxygen will be depleted and without oxygen, aerobic metabolism will stop
Noxious metabolites (lactate) accumulate
Myocardial contractility ceases
Ultrastructural changes occur in the myocyte
Myofibrillar relaxation, glycogen depletion, mitochondrial swelling
(Reversible!!)
In about 20 – 30 minutes, myocyte necrosis begins
2 – 3 hours of half thickness
6 hours for transmural
(Irreversible!!)
MI Timeline
Within 30 minutes Relaxation of myofibrils Glycogen loss Mitochondrial swelling (Reversible injury)
30 minutes – 4 hours
Sarcolemmal disruption and mitochondrial densities
No gross findings
Subtle waviness of mycoytes at the border of the infarct
4 – 12 hours
Beginning to have dark mottling
Early coagulation necrosis, edema, and hemorrhage
12 – 24 hours Dark mottling Ongoing coagulative necrosis Pyknosis of nuclei Hypereosinophilia of myocytes Contraction band necrosis Early neutrophilic infiltrate
1 – 3 days
Mottling with yellow-tan infarct center
Coagulation necrosis with loss of nuclei and striations
Brisk neutrophilic infiltrate
3 – 7 days Hyperemic border with central yellow-tan softening Disintegration of dead myofibers Dying neutrophils Macrophages at infarct border
7 – 10 days peak of macrophages maximally yellow-tan & soft depressed tissue at the site of the infarct brisk phagocytosis Granulation tissue at the margins
10 – 14 days
Red-gray depressed borders
Well established granulation tissue with new blood vessels and early collagen deposition
2 – 8 weeks
Grey-white scar from border to center
Collagen deposition
Decreased cellularity
> 2 months
Complete scar
Dense collagen
When is the time period where you are most vulnerable to complication down the road, if you survive the heart attack and the heart is at its most weakened?
3 – 7 days
macrophages are chomping up on the dead myocytes and the nuclear debris.
Summarized Timeline
So the earliest change that we find is sort of this wavy, maybe hyper-eosinophilic area - these are the earlier microscopic changes that we see.
Next step in the process is the recruitment of neutrophils – this occurs in the 12-24 hour mark
As we progress, neutrophils will be replaced by macrophages
Macrophages[replaced] by smooth muscle cells & fibroblast depositing collagen
Ultimately you’re left with fibrosis in that area if you survive & the development of a collagenous scar (bottom right)
LAD supplies…
most of the apex, the anterior wall of the LV, and the anterior 2/3 of the ventricular septum
– The dominant artery perfuses the posterior 1/3
occlusions account for 40 – 50% of myocardial infarcts
RCa supplies…
the entire right ventricular free wall and the posterobasal wall of the LV
occlusions account for 30 – 40% of myocardial infarcts
LCx supplies…
the lateral wall of the LV
occlusions account for 15 – 20% of myocardial infarcts
Transmural infarction
Caused by occlusion of a vessel with full thickness necrosis of the myocardium
Usually caused by chronic coronary atherosclerosis, acute plaque changes, and thrombosis
Subendocardial infarction
Partial thickness, although that can occur in complete occlusions
The subendocardial zone is normally the least perfused region and is most vulnerable to disruptions in flow
May result from severe, prolonged reduction in systemic blood pressure in individuals with otherwise non-critical stenosis
Multifocal infarction
Typically seen with pathology involving the small intramural vessels
Microembolization, vasculitis, vasospasms like someone who uses cocaine
MI Presentation
Typically present with prolonged chest pain described as crushing, stabbing, or squeezing
Often associated with a rapid weak pulse, diaphoresis, and nausea and vomiting
25% may be entirely asymptomatic
– Diabetics
MI Diagnosis
diagnosed by clinical symptoms, laboratory tests, and characteristic EKG changes
Laboratory diagnosis exploits blood levels of proteins that leak out of irreversibly damaged myocytes
– Troponins, CK-MB, lactate
Troponins rise later than all the other proteins but STAY HIGH LONGER after an MI***
MI Treatment
Morphine to relieve pain Reperfusion Antiplatelet agents Anticoagulation Nitrates for induce vasodilation Beta blockers to decrease myocardial oxygen demand Antiarrhythmics to manage arrythmias Angiotensin converting enzyme to limit ventricular dilation Oxygen supplementation
Myocardial Rupture
3 – 5 days after an MI are most at risk
you can end up with rupture of the left ventricular free wall which leads to hemopericardium or blood within the pericardial sac.. That blood will compress the heart, reduce its ability to contract & that leads to condition called cardiac tamponade.
You can also develop ruptures of the ventricular septum if that’s the area that was infarcted.. This can develop a function ventricular septal defect & a left to right shunt & all of the complications that occur because of that.
The papillary muscles in subendocardial ischemia or transmural.. can rupture which can lead to an onset of severe mitral regurgitation
Chronic Ischemic Heart Disease
progressive congestive heart failure as the result of accumulated ischemic myocardial damage
usually appears after an infarction due to the functional decompensation of the hypertrophied, noninfarcted myocardium
Ischemic heart disease leads to the development of…
Left ventricular hypertrophy
Cardiac dilation
Cardiomegaly
Heart failure
Valvular Disease
most commonly stenosis, insufficiency, or some combination of both.
Valvular stenosis is a failure of the valve to open completely, which is going to impede FORWARD flow
Valvular Insufficiency results from a failure of a valve to CLOSE completely, so this leads to regurgitation or REVERSED flow, so pressure overload in the chamber prior to
Primary vs. Secondary Valvular Disease
Primary: defects & generation of the valvular tissue ITSELF
Secondary or functional insufficiency: often happens because of DILATION of one of the CHAMBERS of the heart, so dilation of the left ventricle may prevent the proper closure of an otherwise normal valve
Most common acquired valvular diseases
- Aortic stenosis
- Aortic insufficiency
- Mitral stenosis
- Mitral insufficiency
So left sided heart problems are the ones that are the most common, most frequently encountered.
Aortic stenosis
Calcification and sclerosis of anatomically normal or congenitally bicuspid aortic valves
Consequence of recurrent chronic injury due to factors similar to atherosclerosis in other areas
Hyperlipidemia
Hypertension
Inflammation
Chronic progressive injury leads to valvular degeneration and incites deposits of hydroxyapatite (same calcium found in bone)
Obstruction to the left ventricular outflow tract leads to gradual narrowing of the valve orifice and an increasing pressure gradient across the valve
Left ventricular pressures rise
Left ventricular hypertrophy
Systolic and diastolic dysfunction occur
Angina, congestive heart failure, and death
TXT: Valve replacement
Aortic insufficiency
Dilation of the ascending aorta secondary to hypertension or aging
Mitral stenosis
Rheumatic heart disease
Rheumatic fever is an acute, immunologically mediated, multisystem inflammatory disease classically occurring a few weeks following group A streptococcal pharyngitis
Results from a host immune response to GAS antigens that cross react with host proteins
Antibodies against streptococcal M proteins that cross react with cardiac self antigens
Leads to complement activation, cytokine production, and T-cell/macrophage activation
Mitral insufficiency
Myxomatous degeneration
Marked thickening of the spongiosa layer with deposition of myxomatous material
Attenuation of the collagenous fibrosa layer
Secondary changes
Fibrous thickening of the leaflets
Fibrous thickening of the left ventricular endocardial surface
Thrombi on the atrial surface of the leaflets
Mitral Annular Calcification
degenerative changes in the mitral valves typically affect the fibrous annulus
Leads to irregular, stony hard, sometimes ulcerated nodules at the base of the leaflets
Usually doesn’t affect valvular function
Regurgitation to due contraction of the valve ring
Stenosis by impairing valve opening
Arrhythmias due to penetration of calcium into the atrioventricular conduction system
These calcific nodules provide a site for thrombus formation
Increase risk of embolic stroke and infective endocarditis
Mitral Valve Prolapse
one or both of the mitral valve leaflets are floppy and balloon back into the left atrium during systole
Affects 2 – 3 % of individuals in the US
7:1 female to male ratio
Often benign, but may lead to sudden cardiac death
Leaflets are enlarged, redundant, thick, and rubbery
The tendinous cords may be elongated, thinned, or ruptured
Mitral valve annulus is dilated
What is found during Rheumatic Fever?
focal inflammatory lesions are found in various tissues
Aschoff bodies in the heart
Foci of T lymphocytes, occasional plasma cells, and activated macrophages
Anitschkow cells
Pathognomonic
Acute Rheumatic Fever
Diffuse inflammation and Aschoff bodies may be found anywhere in the heart
Inflammation of the endocardium and left-sided valves result in fibrinoid necrosis within the cusps or tendinous cords
Overlying these necrotic foci are small vegetations (verrucae)
Subendocardial lesions develop (MacCallum plaques
Valve most commonly seen effected by Rheumatic fever?
Mitral Valve
Pathologic changes in RF
a fish mouth deformity of the valve (fusion of the commissures here so the normal mitral leaflets start to thicken, they get fused here at the commissures)
Tight mitral stenosis
Progressive left atrium dilation
Pulmonary congestion and vascular changes
Right ventricular hypertrophy
Comparison between mitral prolapse and mitral stenosis from RF?
In contrast to mitral valve prolapse, where had thinning and elongation of the tendinous cords, we see thickening and reduplication of these cords which can cause further dysfunction
Rheumatic Fever Clinical
Characterized by
Migratory polyarthritis of the large joints
Pancarditis inflammation of the heart muscle
Subcutaneous nodules
Erythema marginatum of the skin
Sydenham chorea
Involuntary, rapid, purposeless movements
Infective Endocarditis
microbial infection of the heart valves or mural endocardium (just adjacent to the valves) that leads to the formation of (infected) vegetations
Often associated with destruction of the underlying cardiac tissues (as well as the valves themselves)
Most infections are bacterial (but there are a wide variety of causes)
Classified into acute and subacute forms
Acute endocarditis
typically caused by infection of a previously normal heart valve by a highly virulent organism (Staph aureus)
Rapidly produces necrotizing and destructive lesions
Difficult to cure with antibiotics alone
Subacute endocarditis
endocarditis is typically cause by organisms with lower virulence (Strep viridans) that cause insidious infections of deformed valves
most important predisposing factors to developing endocarditis
Obvious infection
Contaminated needle shared by IVDU
Dental or surgical procedures
Nonbacterial thrombotic endocarditis
Sterile vegetations characterized by deposition of small sterile thrombi on the leaflets of the cardiac valves
Single or multiple
Nondestructive
Illicit no inflammatory response
May embolize
Libman-Sacks endocarditis
Mitral or tricuspid valvulitis with small sterile vegetations
Occasionally encountered in systemic lupus erythematosus
Single or multiple
Located on the undersurfaces of the atrioventricular valves
Associated with intense valvulitis
INFLAMMATION!!!*
these are the only lesions that are located on the undersurface of valves**
Three major morphologic patterns of cardiomyopathy
Dilated cardiomyopathy
Hypertrophic cardiomyopathy
Restrictive cardiomyopathy
Dilated Cardiomyopathy (DCM)
most common (90% of cases)
Characterized by progressive dilation and systolic dysfunction, usually with concomitant hypertrophy
– Ejection fraction < 40%
Genetic factors, alcohol, peripartum, myocarditis, hemochromatosis, chronic anemia, doxorubicin toxicity, sarcoidosis
Enlarged, heavy, and flabby heart
– Dilation of all four cardiac chambers
Mural thrombi are common
May result in secondary valvular dysfunction
Typically affects those between 20 and 50
Presents with slowly progressive signs and symptoms of CHF
– Dyspnea, fatigue, poor exertional capacity
Hypertrophic Cardiomyopathy
common, clinically heterogenous, genetic disorder characterized by myocardial hypertrophy, poorly compliant left ventricular myocardium leading to abnormal diastolic filling, and intermittent ventricular outflow obstruction
Thick walled, heavy, and hypercontracting
Ejection fraction is 50 – 80%
Autosomal dominant disorder with variable penetrance
Banana-like left ventricular cavity
Central abnormality in HCM
reduced stroke volume due to impaired diastolic filling
Reduced chamber size
Reduced compliance of the ventricle
Those with significant outflow obstruction develop increased pulmonary venous pressures and dyspnea
hypertrophic obstructive cardiomyopathy
this is the characteristic young athlete, who had no problems but just died suddenly during the filed of play
Intramural arteries thicken Focal myocardial ischemia is common Atrial fibrillation Ventricular arrhythmias Mural thrombi and embolization Cardiac failure Sudden death
Restrictive Cardiomyopathy
characterized by a primary decrease in ventricular compliance resulting in impaired ventricular filling during diastole
– Ejection fracture 45 – 90%
Systolic function is usually unaffected
Causes of Restrictive Cardiomyopathy
Radiation Amyloidosis Sarcoidosis Metastatic tumors Inborn errors of metabolism
(secondary changes)
Myocarditis
a diverse group of pathologic entities in which infectious microorganisms and/ or a primary inflammatory process cause myocardial injury
May cause direct myocyte injury or elicit a destructive immune response
The intense cytokine response produces myocardial dysfunction out of proportion to the degree of actual myocyte damage
Myocarditis is a PRIMARY disease, and should be distinguished from secondary causes of inflammation (ie, ischemic heart disease)
Causes of Myocarditis
Viral infections are the most common cause of myocarditis in the US
Coxsackie A and B and other enteroviruses
Occasionally, CMV, HIV, and influenza may be implicated
Nonviral agents are common outside of the US
Trypanosoma cruzi, trichinella spiralis, toxoplasmosis, borrelia burgdorferi, and Corynebacterium diphtheriae
Pericarditis
inflammation can occur secondary to a variety of cardiac, thoracic, or systemic disorders, metastases, or cardiac surgical procedures
Primary pericarditis is rare (viral)
Serous pericarditis
Characteristically produced by non-infectious diseases (RF, SLE, scleroderma, tumors, and uremia)
Fibrinous pericarditis
Most frequent type of pericarditis
Serous fluid mixed with fibrinous exudate
Acute MI, postinfarction syndrome (Dressler syndrome), uremia, radiation, RF, SLE, and trauma
Primary cardiac tumors
Myxomas (most common tumor in adults) Fibromas Lipomas Papillary fibroelastomas Rhabdomyomas (most common pediatric tumor) Angiosarcomas
**Most common heart tumor is a metastasis**
respiratory epithelium
pseudostratified columnar with cilia and goblet cells
2 types of pneumocytes
Type 1- where gas exchange occurs and really hard to see.
Long thin cell with a very small nucleus. Gas exchange occurring across the cytoplasm.
As you breathe in the oxygen. they are at high risk of dying so they have a high turnover rate.
Type 2-can terminally differentiate and become type 1 cells. They also have macrophage functions. They also make surfactant.
Surfactant and newborns
what surfactant does is it follows La Place’s Law and it lines these airways. And it decreases surface tension. So by having a hydrophobic surface towards the center of the alveoli, the fluid is thinned out and surface tension is less. And that’s important because the second breath the child takes is against less resistance because the child is not born with great muscles, they’re thin as can be.
. So they realized that if you gave surfactant to a child born before 24 weeks, they could survive.
Also give steroids to the mother to jack up surfactant production by the type 2 pneumocytes.
Pulmonary function tests
TLC: total lung capacity (5 to 7 l)
VC: vital capacity (3 to 5 l) TV: tidal volume (1 to 2 l)
FVC: forced vital capacity (3 to 4 l)
FEV1: forced expiratory volume in 1 second (2 to 3 l) FEV1/FVC ratio (60 to 70%)
Three mechanisms to have obstructive lung disease
You can have obstruction because there’s something blocking the way (fluid or mucus)
You can have decreased diameter because the muscular hypertrophy or construction
You can have a loss of tether
Three types of obstructive lung disease with their definitions
Emphysema: abnormal permanent enlargement of airspaces without obvious fibrosis
Chronic bronchitis: persistent cough with sputum for at least 3 months in at least 2 consecutive years
Asthma: hyperreactive airways leading to episodic reversible bronchoconstriction
Emphysema
so you can breathe the air in. But you can’t get that carbon dioxide out which is bad for two reasons.
One, the carbon dioxide levels are going to rise in your blood. But number two you don’t have room for more oxygen.
Emphysema Supersimplified pathogenesis
tip the balancing act towards the elastases and the enzymes will destroy the lung and break down the lung. (Neutrophil elastase Proteinase 3 Cathepsins
Matrix metalloproteinases) and away from the “anti-enzymes” (1-Antitrypsin
Secretory leukoprotease inhibitor Elafin
Tissue inhibitors of matrix metalloproteinases)
Example is Tobacco blocks the antitrypsin and leads to the influx of a lot of neutrophils; and neutrophils stimulate the release of these proteins as well. So anything that leads to break down the lung and prevents the breakdown of lung, will lead to dissolving are melting of the lung tissue and that’s what causes emphysema.
Emphysema a1-antitrypsin deficiency
1-2% of patients with COPD
Autosomal recessive disorder
1AT is a serine protease inhibitor—elastase Made in the liver
Defective 1AT does not neutralize elastase—emphysema Defective 1AT accumulates in the liver—cirrhosis
Mutated SERPINA1 gene
PiZZ—panacinar emphysema at a young age
PiSS, PiMZ and PiSZ–reduced levels of normal—emphysema if smokers
Chronic bronchitis
You plug the airways with mucus . So a smoker is most risk of developing this because the tobacco smoke harms the respiratory epithelium and predisposes to infection. So then you keep getting infections of the airways you get bronchitis, you get pneumonia, you get bronchitis
Bronchiolar and bronchial injury leading the bronchospasm, and hypersecretion of mucus, infection.
Obstruction and airways continued in repeated injury, smoking, continued in repeated infection chronic bronchitis.
Asthma
You got more goblet cells than normal. You’ve got inflammatory cells. You’ve got thickened muscle and way too many seromucinous glands. So all of that is a response to whatever this immune trigger is. Bronchoconstriction leads to muscle thickening. Whatever the insult is damages the epithelium and leads to more seromucinous gland production of fluids and also hypertrophy of the seromucinous glands.
Asthma Focus on T-cells
Process of Asthma
an antigen being presented by a macrophage and then shit really hits the fan because the T cells get revved up and they stimulate the B cells which secretes the antibodies that cross link on the mast cell. That lead to lead mediator release of leukotrienes, cytokines, and histamines and cause bronchospasm and edema and airway inflammation and so on.
Still don’t have a way to stop the T cells, so we treat asthma the same old fashioned way with bronchodilators and steroids. Bronchodilators to help the airways stay open and steroids to try and knock down this inflammatory cascade.
Atelectasis
Incomplete expansion or collapse of lung (airless lung)
REVERSIBLE DISORDER
3 types
Resorption atelectasis: due to airway obstruction
Compression atelectasis: due to pleural cavity expansion hemothorax, pneumothorax
Contraction atelectasis: due to lung or pleural fibrosis
Restrictive lung diseases
Spinal disorders Neurologic disorders Sarcoidosis Hypersensitivity pneumonitis Pneumoconiosis Idiopathic
Hypersensitivity pneumonitis
Extrinsic allergic alveolitis
Immunologic reaction to inhaled antigens Antigens not identified in up to 66% of cases Acute and chronic presentations
ACUTE PRESENTATION
Single large bolus exposure to antigen
Dyspnea, cough, fever/chills 4-6 hours later
CXR: diffuse granular infiltrates Pathology: Pulmonary edema Pathogenesis: Type III hypersensitivity reaction (immune complex disease) Prognosis: Improvement in a day or so Reexposure: Recrudescence
CHRONIC PRESENTATION
Prolonged exposure to small amounts of antigen Insidious dyspnea, dry cough, fatigue
CXR: Mostly upper lobe interstitial reticulonodular infiltrates Lab: serum antibodies, skin tests?
BAL: Increased CD8+ lymphocytes
Pathology: Chronic bronchiolitis, interstitial pneumonia, and granulomas Pathogenesis: Type III and IV hypersensitivity reactions
Prognosis: Improvement in 33%, stable in 33%, worsening in 33% if antigen not removed
Hypersensitivity Pneumoconiosis
Pathologic response related to:
intensity of exposure
duration of exposure quantity of exposure size of particle
physiochemical properties of particle route of clearance
efficiency of clearance host response
interactions with other environmental pollutants
examples causing pneumoconiosis
Asbesto Silica Silicates (talc, kaolin, mica) Mixed dust Coal Metals
fluid filled skin lesions
Vesicle: a circumscribed collection of free fluid less than 0.5cm in diameter
Bulla: a circumscribed collection of free fluid greater than 0.5cm in diameter
Pustule: a circumscribed collection of purulent exudate that varies in size (pimples)
Cyst: a cavity containing fluid or semisolid material surroudned by an epithelial layer
Disorders of Pigmentation and Melanocytes
Freckle
Lentigo
Melanocytic Nevi
Melanoma
Freckles
small- Focal abnormality in pigment production
Hyperpigmentation: increased amount of melanin pigment. Normal density of melanocytes
Lentigo
Liver spots- age spots
They’re not related to sunlight exposure, they are stable in color that’s why they are very difficult to remove.
The pathology is unknown
Excessive melanotic maculae in the oral and perioral distribution related to which two diseases?
Addison’s disease
Peutz-Jeghers
Addison’s Disease
Adrenal failure
Activation of pituitary gland leading to increased ACTH and MSH .
Stimulate melanocytes in the skin and mucosa
Peutz-Jeghers
INHERITED!!! (they’re going to have a family history)
They’ll also have other things in the skin and GI tract too.
Neurofibromatosis
Café au lait spots
Histologically similar- larger and arise independently of sun exposure
Neurofibromatosis is more a genetic disease and this is only one of the manifestations of that because the location of the skin lesions, different types of tumors, and even manifestations on the eyes too.
Vitiligo
Hypopigmentation (loss of melanocytes or melanin production)
Melanocytes are destroyed
White patches of skin
May be an autoimmune disease
May be associated with another autoimmune disease
Melanocytic Nevus (Pigmented Nevus Mole)
Benign neoplasms
Numerous subtypes
Acquired are the most common type
Dysplastic Nevi
May be direct precursors of melanoma Many never progress Mutations or epigenetic changes NRAS and BRAF genes Inherited loss of function mutations in CDKN2A
Melanoma
Most deadly of all skin cancers
Strongly linked to acquired mutations caused by exposure to UV radiation in sunlight
Relatively common neoplasm
Some studies suggest that periodic sunburns early in life are the most risk factors
Predisposing factors/environmental factors
Mutations in cell cycle regulators
Blistering sunburn can double the chances of developing melanoma later in life
Strong dose-response relationship
ABCs of Melanoma
Asymmetrical Borders (irregular) Color Diameter (1/4in or 6mm) Evolving (changing)
Melanoma Therapy
Antibody Therapy
Chemotherapy
Compared to those who have never tanned indoors, indoor tanners….
have a 20% percent higher risk of melanoma
have an 87% higher risk of melanoma if they start tanning before 35
are 2.5 times more likely to develop SCC and 1.5 more likely to develop Basal cell carcinoma
Benign Epithelial Tumors
Seborrheic Keratoses
Acanthosis Nigricans
Fibroepithelial Polyp
Epithelial or Follicular
Inclusion Cyst
Tumors of the Dermis
Benign Fibrous Histiocytoma
Dermatofibrosarcoma Protuberans
Tumors of Cellular Migrants of the Skin
Mycosis Fungoides
Mastocytosis
Acanthosis Nigricans
Dark velvety patches
May be an important sign of underlying conditions
GI Adenocarcinomas- middle aged and older individuals
Type 2 diabetes
Fibroepithelial Polyp or intraoral Polyp
skin tag
intraorally associated with an area of trauma usually
Premalignant and Malignant Epidermal Tumors Related to Sun Exposure
Actinic Keratosis
Squamous Cell Carcinoma
Basal Cell Carcinoma
Actinic Keratosis
Sun damaged skin-hyperkeratosis
Exposure to ionizing radiation and arsenicals
It seems like the skin is very dry, but they’re going to have this type of ulcerations.. But these ulcerations are not healing
Squamous Cell Carcinoma
DNA damage induced by exposure to UV light
P53 dysfunction
Can progress from actinic keratosis, chemical exposure, thermal burn sites or in association with HPV infection in the sitting of immunosuppression
Cutaneous cell carcinoma has potential for metastasis but is less aggressive than squamous cell carcinoma at mucosal sites
Basal Cell Carcinoma
Locally aggressive tumor
Rarely metastasize
Pearly papules containing prominent blood vessels ( telangiectasias)
Advanced lesions may ulcerate
