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141 Cards in this Set

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Blood diseases-white cells:
---->Leukocyte neoplasms

What are the four main categories?
1) Acute lymphoid leukemia
2) chronic lymphoid leukemia
3) Acute myeloid leukemia
4) chronic myeloid leukemia
Blood diseases-white cells:
---->Leukocyte neoplasms

What are acute leukemias (general description)?
-uncontrolled proliferations of immature (blast) cells -->**lymphoblasts or **myeloblasts
-these blast cells have lost their ability to differentiate into mature functional cells.
-they have a high mitotic index (proliferate rapidly)
-replace the normal hematopoiesis production of red cells (erythrocytes), white cells (leukocytes) and platelets (megakaryocytes)
Blood diseases-white cells:
---->Leukocyte neoplasms

What are some clinical features of acute leukemias?
-bleeding (decreased platelets)
-infection (neutrophils)
-fatigue--anemia (red cells)

these are aggressive and untreated patients normally live only a few months (hence "acute")
Blood diseases-white cells:
---->Leukocyte neoplasms

What is the difference between Acute lymphoid leukemia (ALL) and Acute myeloid leukemia (AML)?
-Acute lymphoid leukemia (ALL)
1) is more common in children
2) lymphoblasts replace the bone marrow
3) 80% cure w/ chemo

Acute myeloid leukemia (AML)
1) more common in adults
2) myeloblasts replace the normal bone marrow
3) prognosis is worse than the lymphoid type
4) about 50% of cases are cured w/ chemo and bone marrow transplant
Blood diseases-white cells:
---->Leukocyte neoplasms

What is remission?
-post therapy state, in which there is no evidence of leukemia
-bone marrow has resumed normal hematopoiesis, but patient not necessarily cured
-AML remission=small # of malignant myeloblasts (stem cells), when chemo stops, they again proliferate and cause a relapse.
Blood diseases-white cells:
---->Leukocyte neoplasms

What are chronic leukemias? (general definition)
-uncontrolled proliferation of mature cells (note: they are mature, unlike acute): lymphocytes, neutrophils, red cells, or platelets.
-generally functional cells, w/ slow proliferation (indolent=present for a long time before symptoms appear)
Blood diseases-white cells:
---->Leukocyte neoplasms

How would you describe chronic myeloid leukemia?
-classified by the predominante cell type seen in the blood.
-most common type: neutrophil proliferation.
-characterized by high neutrophil count with *immature* cells, basophilia, hypercellular bone marrow and an enlarged spleen.
-most common cause of death is evolution to acute leukemia
**Philadelphia chromosome is the defining characteristic
Blood diseases-white cells:
---->Leukocyte neoplasms

How would you describe chronic lymphoid leukemia?
-proliferations of *mature* lymphocytes, occurs slowly, over years.
-most common type in the U.S. is **"B-cell chronic lymphocytic leukemia"
Blood diseases-white cells:
---->Leukocyte neoplasms

What is multiple myeloma?
-uncontrolled **proliferation of plasma cells.
-these plasma cells produce large amounts of a single immunoglobulin (antibody)--may cause kidney damage
-displaces the bone marrow and erodes bone, causing bone pain
Blood diseases-white cells:
---->Leukocyte neoplasms

What are lymphomas?
What are the 2 classifications?
-uncontrolled proliferations of lymphocytes *outside* of the bone marrow---primarily in the lymph nodes (hence the name).
-classified as either Hodgkin's disease or Non-Hodgkin's lymphoma
Blood diseases-white cells:
---->Leukocyte neoplasms---> lymphomas

How do Hodgkin's disease and Non-hodgkin's lymphoma differ?
Hodgkin's disease--malignancy **specifically of the Reed-Sternberg cell
-the more the lymph node groups involved, the worse the prognosis.

Non-Hodgkin's lymphoma-- **heterogeneous group of malignant lymphocyte proliferations---low, intermediate, or high grade based on cell size and pattern of lymph node involvement.
Blood diseases-Diseases of platelets

From where are platelets derived?
What is the normal adult platelet count?
-Platelets are fragments broken off of megakaryocytes.
Normal adult: 150,000-400,000 microliters
increased platelet count= thrombocytosis
decreased platelet count= thrombocytopenia
Blood diseases-Diseases of platelets

What is thrombocytopenia and what are its causes?
-large decrease in platelet count, resulting in spontaneous bleeding/tiny hemorrhages (petechiae)
Causes:
1) destruction (from antibodies to platelets)
2) consumption (with a coagulation disorder... platelets used in disease process)
3) decreased production (due to marrow replacement or damage)
Blood diseases-Diseases of platelets

What is thrombocytosis?
-increased platelet count
-leads to abnormal clotting
Coagulation and bleeding disorders: Hemostasis

What is hemostasis? (What does it do?)
-prevents bleeding
-keeps blood fluid
-is continuous and dynamic
-interaction of blood vessels, platelets, and coagulation factors
Coagulation and bleeding disorders: Hemostasis

What components/processes are involved?
-blood vessels and supporting structures
-platelets
-fibrin formation by coagulation system
-coagulation factor inhibitors
-fibrinolytic system
-remodeling and repair of injury site
Coagulation and bleeding disorders: Hemostasis

How is hemostasis divided? (3 things)
-primary: platelet plug formation
-secondary: coagulation system
-fibrinolysis: removal of clot
Coagulation and bleeding disorders: Hemostasis

How are endothelial cells involved?
-Vasodilation by nitric oxide (NO)
-vasodilation by prostacyclin (PGI2)
-anticoagulant properties:
(come back if need be)
Coagulation and bleeding disorders: Hemostasis

Characteristics of platelets:
-produced in bone marrow (megakaryocytes)
-lacks nucleus
-discoid shape
-size: 1-2 microns in diameter
-normal range: 125-300,000 plts/uL
-Life span: 12-15 days
-removed by spleen
Coagulation and bleeding disorders: Hemostasis

How do the platelets function in primary hemostasis? (i.e. steps of action)
1) contact
2) adhesion
3) aggregation
4) coagulation
Coagulation and bleeding disorders: Hemostasis

What are the bleeding symptoms in disorders affecting Primary Hemostasis?
-Petechiae (pinpoint, nonraised intradermal hemorrhage)
-Easy bruising
-Epistaxis
-Menorrhagia
-Unexpected per or post operative bleeding
-Severe spontaneous bleeding
Coagulation and bleeding disorders: Hemostasis

What are (3) disorders of primary hemostasis?
-Thrombocytopenias (lower **quantity)
-Platelet Dysfunction (lower **quality)
-Von Willebrand's disease
Coagulation and bleeding disorders: Hemostasis

What are some general characteristics of von Willebrand disease (VWD), and what does VW factor do?
-**most common inherited bleeding disorders
-incidence: .1-1%
-Functions of VW factor:
Adhesion of platelets to site of injury
Binds, "protects" factor VIII in the circulation
Coagulation and bleeding disorders: Hemostasis

VWD--symptoms and diagnosis
Clinical symptoms:
-mucosal bleeding, especially epistaxis and menorrhagia
-postoperative bleeding
-bleeding from oral cavity
-gastrointestinal bleeding

For diagnosis of VWD:
-personal history of bleeding
-Family history of bleeding
-laboratory evidence of VWD
Coagulation and bleeding disorders: Hemostasis

Coagulation factors vs. Inhibitors: name them
Coagulation factors:
-tissue factor (TF)
-Thrombin
-Factors VIII, V

Inhibitors:
-Tissue factor pathway inhibitor (TFPI)
-Antithrombin
-Protein C and S
Coagulation and bleeding disorders: Hemostasis

What are the vitamin K dependent factors and inhibitors?
What does vitamin K do, and what drug blocks its function?
-Factors II, VII, IX, X, protein C, protein S

-Vitamin K serves to bind the factors to phospholipid surfaces.
-The recycling of vitamin k is blocked by warfarin (Coumadin)
Coagulation and bleeding disorders: Hemostasis

What are the inhibitors of coagulation, and what do they do?
-Tissue factor pathway inhibitor (TFPI): binds to factor VIIa
-Protein C serine protease: cleaves and destroys factors Va and VIIIa, cofactor protein S is crucial for its function
-Antithrombin is a serine protease: binds and inactivates all serine proteases of the coagulation cascade, is augmented by heparin
Coagulation and bleeding disorders: Hemostasis

Describe the process of fibrinolysis:
-breaks down blood clots
-Plasminogen (a serine protease, produced by the liver, cleaves both fibrin and fibrinogen)
-Specific fragments are produced (collectively called "fibrinogen-fibrin degradation products FDP)
-the crosslinked fibrin gives different fragments
Coagulation and bleeding disorders: Hemostasis

Describe the regulation of fibrinolysis:
-Plasminogen is activated by tissue plasminogen activator (tPA)
1) is synthesized in endothelial cells
2) has a half-life of about 5 min.
3) is inhibited by plasminogen activator inhibitor (PAI-1) and alpha2-antiplamin
Coagulation and bleeding disorders: Hemostasis

Blood coagulation analysis: pre-analytical variables
-patient identification
-Peripheral stick preferred for coag tests
-tubes (must be completely filled)
Coagulation and bleeding disorders: Hemostasis

Blood coagulation analysis:
Anticoagulant in tube
-3.2% Na Citrate binds Calcium--coagulation cannot occur
-During testing samples are recalcified
-More citrate in tube, more will complex to calcium--less calcium available to promote clotting--process slowed--prolonged PT and APTT
Coagulation and bleeding disorders: Hemostasis

Blood coagulation analysis:
Prothrombin time (PT)
-What is is used for, what does it do?
-Measures the time from VIIa forming a complex with TF to clot formation
-Tissue thromboplastin added to plasma=TF+PL
-Prolongation of PT only means factor VII deficiency, which can be congenital or acquired (vit. k deficiency, liver disease, DIC)
-***is used to monitor warfarin therapy
Coagulation and bleeding disorders: Hemostasis

Blood coagulation analysis:
International Normalization Ratio (INR)
-INR=(patient PT/normal PT)^ISI
where ISI is the International Sensitivity Index (specific for each batch of commercial reagent)
-The INR is the standardized PT
-provides more accurate monitoring of warfarin therapy
Respiratory Diseases:

3 leading causes of death in the world/U.S.
1) Heart diseases
2) Cancer (lung most prom.)
3) Cerebrovascular disease (CVAs=strokes)
Respiratory Diseases:

Main function of respiratory tract (3 things)
Gas exchange between blood & air
-02 in, CO2 out

Ventilation
-air into and out of lungs (inspiration and expiration)

Perfusion
-blood comes through alveolar capillaries
Respiratory Diseases:

Acute Respiratory infections
(where do they come from, what part of respiratory tract do they affect?)
-majority are due to a virus or mycoplasma
-usually involve the upper respiratory tract
-only 10% of these are pneumonias
Respiratory Diseases:

Pneumonia
(what is is, how many americans does it affect/year, how does it rank as a killer?)
Inflammation of the lungs
-usually implies an inflammation secondary to an infection by an organism ex) bacteria

-2.5 million Americans contract pneumonia each year

-#1 cause of infectious death
-#6 cause of all deaths
Respiratory Diseases:

Pulmonary Symptoms
-cough
-hemoptysis (coughing produces blood in sputum)
-pain (pain fibers in pleura)
-dyspnea (shortness of breath, difficulty breathing)
Respiratory Diseases:

Major types of inflammation or pneumonia in the lung
-Bronchopneumonia (bacteria--patchy)
-Lobar pneumonia (bacteria--confluent=a part fully covered, i.e. not patchy)
-Interstitial pneumonia (virus or mycoplasma)
-Granulomatous inflammation (TB or fungus)
Respiratory Diseases:

Acute Pneumonias (2 types, where acquired)
Community acquired (in relatively healthy adults)
-viruses
-mycoplasma pneumonia
-streptococcus pneumonia (usually lobar pneumonia)
--note: bacterial pneumonia often is secondary to viral pneumonia

Hospital acquired
-staphylococcus aureus (gram +)
-gram negative enteric bacteria (e.coli, kiebsiella, pseudomonas)
--note: often, bacterial infections need to be treated empirically=using strong antibiotic which kills all possible types of bacterial causes
Respiratory Diseases:

Acute Community-acquired pneumonias (2 categories)
1) "viral-like illness"
-**virus or mycolpasma
-prodrome--systemic illness
-dry cough

2) "bacterial illness"
-**pneumococcus
-sudden onset
-productive cough
-chest pain
-leukocytosis
Respiratory Diseases:

Viral infections of Respiratory tract (4)
-"common cold"
-laryngotracheobronchitis
-acute bronchiolitis
-interstitial pneumonia
Respiratory Diseases:

Tuberculosis (3 stages/types)
Primary Tuberculosis
-95% have asymptomatic infection (=don't know they have it, until they become immuno suppressed)

Secondary Tuberculosis
-destructive process in apices of lung
-reactivation of old or new

Miliary Tuberculosis
-spread to other organs through blood stream
Respiratory Diseases:

Opportunistic pathogens
Organisms
-that cause serious disease only in patients with an abnormal immune response
-that are relatively harmless to individuals with normal immune systems
Respiratory Diseases:

Predisposing factors for Opportunistic infections
-immunosuppressive agents (especially with transplants)
-chemotherapeutic agents (for malignancies)
-immune deficient patients (AIDS)
-corticosteroids
Respiratory Diseases:

Pneumocystis (what is it, where is it localized?)
-fungus or protozoal parasite
-intra-alveolar infection in immunosuppressed patients (especially in AIDS patients)
-silver stain --cyst walls
Respiratory Diseases:

Chronic Lung Disease
Obstructive=problem getting air out

restrictive=lung too stiff

COPD (chronic obstructive pulmonary disorder)= irreversible airflow obstruction (as opposed to asthma, reversible)

Diffuse pulmonary fibrosis
Respiratory Diseases:

Asthma (general description, prevalence, 3 key features)
Prevalence--3-6% of general population (10 million individuals in U.S.)

Characterized by hyper-reactive airways, leading to episodic reversible bronchoconstriction (owing to increased responsiveness of the tracheobronchial tree to various stimuli

results in widespread narrowing of airways

clinical --episodic occurrence of coughing, dyspnea (breathlessness), and wheezing.

3 key features:
1) reversible airflow obstruction
2) chronic airway inflammation
3) bronchial hyperreactivity
Respiratory Diseases:

Types of asthma (2 categories)
Extrinsic or allergic asthma
-presents in childhood
-hereditary
-allergic to antigens, often inhaled (pollen, dust, foods, drugs, etc.)
-25-50% remission

Intrinsic or idiosyncratic asthma
-presents in adults
-not hereditary
-episodes related to viral infections, exercise, cold, cigarette smoke, etc.
-usually don't go into remission
Respiratory Diseases:

Chronic Obstructive Pulmonary Disease (COPD)
Centrilobular Emphysema

Chronic Bronchitis
-large airway disease
-small airway disease
Respiratory Diseases:

Cancer deaths (most prevalent-->least)
1) Lung
2) Colon-Rectum
3) Breast
4) Prostate
Respiratory Diseases:

Classification of Lung Carcinoma (2 classifications)
Small cell carcinoma

Non-small cell carcinoma
-squamous cell carcinoma
-adenocarcinoma (denotes a lesion in which the neoplastic epithelial cells grow in gland patterns--as opposed to an undifferentiated pattern)
-large cell carcinoma
Respiratory Diseases:

Spread of lung carcinoma (to where does it spread/how?)
Local spread

Distant metastases
-lymphatic or blood-borne spread
Respiratory Diseases:

Pulmonary Embolism (origin, pathway of spread)
-Originate in thrombi in deep leg veins (>95%) or pelvic veins
-break off & travel through right heart into pulmonary arteries
-occlude small or large pulmonary arteries
-can cause pulmonary infarct
-may be a cause of sudden death
Respiratory Diseases:

Asbestos--related disease
Pleural plaques
-benign bilateral, symmetrical fibrous thickening of parietal pleura

Malignant mesothelioma
-lethal malignant tumor arising from pleura

Asbestosis
-diffuse interstitial fibrosis

Lung carcinoma
-all types of lung carcinoma
Cardiovascular disease:

Atherosclerosis: (general description)
-Major cause of death/morbidity in developed/industrialized world (50% of deaths in U.S.)
-roots in early childhood
-Manifests in later life
-involves:
aorta, coronary cerebral
arteries
-leads to:
infarction of heart and brain
aortic aneurysm
limb gangrene
gut infarction
sudden cardiac death
Cardiovascular disease:

Atherosclerosis: Definition (what does it affect, what is it composed of?)
-Disease of the arterial intima (interior of artery)
-affects muscular arteries (elastic=large, and medium-sized)
-characterized by formation of a fibrofatty intimal plaque (composed of lipid core-- mainly cholesterol--covered by a fibrous cap)

small arteries:
-intimal thickening narrows the lumen

Large arteries:
-aneurysm formation and atheroembolism
Cardiovascular disease:

Atherosclerosis: Major risk factors (1st of 2 types..you can't do anything about it)
Non-modifiable risks
-**Age (increases w/ aging)
-**Gender (MALES--damn!)
-**Family history
-**Genetic abnormalities
Cardiovascular disease:

Atherosclerosis: Major risk factors (2nd of 2 types)
Modifiable risk factors
-**hyperlipidemia
-**hypertension
-**cigarette smoking
_**Diabetes mellitus
Cardiovascular disease:

Atherosclerosis: Lesser / uncertain or non-quantitated risk factors
-obesity, physical inactivity
-stress (type A personality)
-**Hyperhomocysteinemia (Elevation of the plasma homocysteine concentration --->linked to diet)
-Post-menopausal estrogen reduction
-infection (**Chlamydia pneumoniae)
Cardiovascular disease:

Atherosclerosis: Precursor lesions and atherosclerotic lesions
Initial lesion:
-a few foam cells
-a fatty streak in the intima

Intermediate lesion:
-extracellullar lipid pools, or "progressing fatty streak"

Atheroma:
-characterized by a core of extracellular lipids

Fibroatheroma:
-has a lipid core/fibrous layer, or is mainly fibrotic or calcific

Complicated lesions have:
-superimposed thrombus
-surface defect (due to atheroembolism--loss of part of the plaque)
-hemorrhage
-calcification
Cardiovascular disease:

Atherosclerosis: Hypothetical pathogenesis (fig. p.170, notes)
1) endothelial damage / dysfunction (caused by the major risk factors)
2) platelets and monocytes adhere to injured sites and monocytes migrate into the intima from the media
3) PDGF (growth factor) released from platelets attracts smooth muscle cells from the media and causes them to proliferate
4) smooth muscle cells form extra-cellular matrix (produce collagen, proteoglycans)
5) foam cells are derived from monocytes and SMCs.
6) Extra-cellular lipid is derived:
-from foam cell death
-from influx of serum cholesterol
---this gives plaque a soft base and a fibrous cap
Cardiovascular disease:

Atherosclerosis: Complications of an atheromatous plaque
-luminal **stenosis (obstruction of blood flow across the aortic valve)
-ulceration, **thrombosis, atheroemboli
-hemorrhage into a plaque
-wall weakening (**aneurysm)
-calcification (making the plaque, and thus artery, brittle)
Cardiovascualar disease:

Ischemic heart disease: (What is it, what are the 4 clinical patterns?)
Result of excess O2 demand compared to sypply -atherosclerosis accounts for 90%
-increased demand also in excercise, pregnancy, decreased O2 transport (anemia, lung disease)

Clinical patterns
1) angina pectoris (chest pain)
2) Acute myocardial infarct (AMI)
-Sudden death
-Congestive heart failure (loss of muscle/pumping function)
Cardiovascualar disease:

Myocardial Infarction (MI)
-statistics (U.S. population)
-(heart attack) is the leading cause of death in developed nations
-1.5 million die annually in U.S. (1 of every 3 heart attacks is fatal)
-250,000 die annually before reaching a hospital
Cardiovascualar disease:

Myocardial Infarction (MI):
-definition, description
-death of myocytes due to interruption of blood supply
-takes 20 to 45 minutes to occur (until muscles are dead)
-ischemia may produce sudden death before an infarct is established
-commonly males over 45 yrs old
Cardiovascualar disease:

Myocardial Infarction (MI):
-2 pathologic forms
Regional, Transmural infarct:
-due to coronary artery thrombosis on atherosclerotic plaque
-infarct of full thickness of ventricular wall

Global, subendocardial infarct:
-diffuse, severe narrowing (without thrombosis) of all 3 major coronary arteries
-produces ischemia of entire inner portion of LV myocardium (limited to the inner 1/3 to 1/2 of myocardium)
Cardiovascualar disease:

Sequence of coronary artery thrombosis:
1) Tear (fissure) in fibrous cap
2) Platelets/fibrin adhere to exposed collagen/atheroma
3) Tissue thromboplastin activates extrinsic coagulation pathway
4) Activated platelets release factors causing arterial spasm, further thrombosis
5) occlusive thrombus formed in only minutes
Cardiovascualar disease:

Ischemic heart disease: (What is it, what are the 4 clinical patterns?)
Result of excess O2 demand compared to sypply -atherosclerosis accounts for 90%
-increased demand also in excercise, pregnancy, decreased O2 transport (anemia, lung disease)

Clinical patterns
1) angina pectoris (chest pain)
2) Acute myocardial infarct (AMI)
-Sudden death
-Congestive heart failure (loss of muscle/pumping function)
Cardiovascualar disease:

Myocardial Infarction (MI)
-statistics (U.S. population)
-(heart attack) is the leading cause of death in developed nations
-1.5 million die annually in U.S. (1 of every 3 heart attacks is fatal)
-250,000 die annually before reaching a hospital
Cardiovascualar disease:

Myocardial Infarction (MI):
-definition, description
-death of myocytes due to interruption of blood supply
-takes 20 to 45 minutes to occur (until muscles are dead)
-ischemia may produce sudden death before an infarct is established
-commonly males over 45 yrs old
Cardiovascualar disease:

Myocardial Infarction (MI):
-2 pathologic forms
Regional, Transmural infarct:
-due to coronary artery thrombosis on atherosclerotic plaque
-infarct of full thickness of ventricular wall

Global, subendocardial infarct:
-diffuse, severe narrowing (without thrombosis) of all 3 major coronary arteries
-produces ischemia of entire inner portion of LV myocardium (limited to the inner 1/3 to 1/2 of myocardium)
Cardiovascualar disease:

Sequence of coronary artery thrombosis:
1) Tear (fissure) in fibrous cap
2) Platelets/fibrin adhere to exposed collagen/atheroma
3) Tissue thromboplastin activates extrinsic coagulation pathway
4) Activated platelets release factors causing arterial spasm, further thrombosis
5) occlusive thrombus formed in only minutes
Cardiovascualar disease:

Ischemic heart disease: (What is it, what are the 4 clinical patterns?)
Result of excess O2 demand compared to sypply -atherosclerosis accounts for 90%
-increased demand also in excercise, pregnancy, decreased O2 transport (anemia, lung disease)

Clinical patterns
1) angina pectoris (chest pain)
2) Acute myocardial infarct (AMI)
-Sudden death
-Congestive heart failure (loss of muscle/pumping function)
Cardiovascualar disease:

Myocardial Infarction (MI)
-statistics (U.S. population)
-(heart attack) is the leading cause of death in developed nations
-1.5 million die annually in U.S. (1 of every 3 heart attacks is fatal)
-250,000 die annually before reaching a hospital
Cardiovascualar disease:

Myocardial Infarction (MI):
-definition, description
-death of myocytes due to interruption of blood supply
-takes 20 to 45 minutes to occur (until muscles are dead)
-ischemia may produce sudden death before an infarct is established
-commonly males over 45 yrs old
Cardiovascualar disease:

Myocardial Infarction (MI):
-2 pathologic forms
Regional, Transmural infarct:
-due to coronary artery thrombosis on atherosclerotic plaque
-infarct of full thickness of ventricular wall

Global, subendocardial infarct:
-diffuse, severe narrowing (without thrombosis) of all 3 major coronary arteries
-produces ischemia of entire inner portion of LV myocardium (limited to the inner 1/3 to 1/2 of myocardium)
Cardiovascualar disease:

Sequence of coronary artery thrombosis:
1) Tear (fissure) in fibrous cap
2) Platelets/fibrin adhere to exposed collagen/atheroma
3) Tissue thromboplastin activates extrinsic coagulation pathway
4) Activated platelets release factors causing arterial spasm, further thrombosis
5) occlusive thrombus formed in only minutes
Cardiovascular diseases:

Non-atheromatous coronary arterial occlusion:
-frequency, causes
-is <10% of cases (90%=thrombosis on atheromatous plaque)

causes:
-embolism
-dissecting aneurysm
-vasospasm
-congenital anomaly
-trauma
Cardiovascular disease:

Macroscopic dating of MI:
-what does tissue (myocardium) look like over time?
18 hrs: Pale, edematous or mottled
36 hrs: opaque/yellow center w/ red border
4-10 days: yellow due to neutrophils
1 week: slight shrinkage
3 weeks: myocardium thinned
4-6 weeks: good scar
Cardiovascular disease:

Microscopy of MI:
-what is happening, on microscopic level?
4-12 hrs: coagulative necrosis (CN) starts, edema, hemorrhage
12-24 hrs: ongoing CN, nuclear pyknosis (nuclear shrinkage, DNA condensed), hypereosinophilia, edge contraction bands, neutrophils appear
1-3 days: CN with loss of striations & nuclei. Neutrophils are in interstitium
3-7 days: myocyte disintegration, neutrophils die, hisiocytes at edge
7-10 days: advanced phagocytosis, early granulation tissue
10-14 days: advanced granulation tissue, early fibrosis
>2 weeks: dense scar
Cardiovascular disease:

Results/complications of myocardial infarction:
-% of cases
-no complications (10-20%)
-arrhythmias, heart block, sudden death
-cardiac failure (60%) or shock (10%)
-mural thrombus, embolism (15-40%)
-cardiac aneurysm
-pericarditis; local or autoimmune
-rupture (1-5%) of external, septum or papillary muscle.
Cardiovascular disease:

Infarct modifications by cardiology or surgery:
-how is the problem solved?
Outside help:
-angioplasty
-stent (holds artery open)
-coronary bypass surgery (vein grafts, internal mammary artery)

Body does this
-thrombolysis
-altered morphology: limited coagulative necrosis, more contraction bands, hemorhhage
Cardiovascular disease:

Cardiomyopathy (heart muscle disease):
-most common type?
Idiopathic (primary) cardiomyopathy:
-heart muscle disease of unknown cause
(unless qualified, the term cardiomyopathy is commonly taken to mean idiopathic cardiomyopathy)
Cardiovascular disease:

Classification of Idiopathic cardiomyopathy:
(4 types)
1) Dilated cardiomyopathy (DCM)
2) Hypertrophic cardiomyopathy (HCM)
3) Restrictive cardiomyopathy (RCM)
4) Arrhythmogenic right ventricular dysplasia / cardiomyopathy (ARVCM)
Cardiovascular disease:

Dilated Cardiomyopathy (DCM):
-general characteristics
-is the most common ICM (idiopathic cardyomyopathy)
-Globular shaped heart=contracts poorly
-50,000 cases annually in USA
-affects young people
-die of CHF, embolism, arrhythmia
Cardiovascular disease:

Dilated cardiomyopathy:
-what is it associated with? (i.e. possible causes)
-idiopathic in most cases
-alcoholism, malnutrition
-peripartum (post partum=after childbirth)
-myocarditis
-Adriamycin therapy (dose related)
-cobalt added to beer
-genetic: 20-30% familial. From dystrophin gene
Cardiovascular disease:

Criteria for diagnosis of DCM:
-(4) negative criteria
(must not be present for dagnosis)
1) no major coronary artery disease/anomaly
2) no valvular disease or anomaly
3) no systemic hypertension
4) no shunts within or outside the heart
Cardiovascular disease:

Microscopy of DCM:
-what is seen?
-**myocyte hypertrophy
-myocardial fibrosis (variable)
-sybendocardial ischemia due to poor CO (due to DCM itself)
Cardiovascular disease:

Hypertrophic cardiomyopathy:
-general description (superb athletes may have this)
-is a diastolic disorder in a super-contracting heart=atria battles to fill against VH
-blood is trapped within the massively hypertrophied LV
-sudden death due to obstruction or arrhythmia related to myocyte disarray
-50% due to autosomal dominant gene
Cardiovascular disease:

Genetic abnormalities in HCM:
-what type of abnormality, on what chromosome?
-most often due to a 403 Arg--Gln mutation in beta-myosin heavy chain on chromosome 14q
Cardiovascular disease:

Restrictive Cardiomyopathy (RCM):
-description
-is a primary decrease in ventricular compliance, resulting in impaired ventricular filling during diastole
(may appear like HCM or constrictive pericarditis/pericardial effusion)
Cardiovascular disease:

Forms of Restrictive cardiomyopathy:
-amyloidosis: proteinaceous material abnormally deposited in tissue interstitium
-sarcoidosis: noncaseating granulomas in tissues and organs
-hemochromatosis (iron)
-interstitial fibrosis
-radiation therapy
Cardiovascular disease:

Gross pathology of RCM:
Heart appears **normal or **small

specific cause may be seen
-ex) amyloid
Cardiovascular disease:

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVCM):
-general info
-4th new category of idiopathic cardiomyopathy
-associated with sudden unexpected death in young persons/athletes
-many cases have a genetic basis
-thinned, increased adipose tissue in RV free wall
Cardiovascular disease:

Myocarditis:
-general characteristics
-inflammation of myocardium, often viral, with myocyte necrosis
-often a primary heart disease
-onset may be sudden, at any age
-most virus caused inflammations are Coxsackie A, B, or enterovirus
-symptoms are fatigue, SOB, palpitations, pain, sudden death
-most resolve OK
Cardiovascular disease:

Cardiac Tumors:
-2 types and their characteristics
Primary (rare--> originates in area)
-Myxoma -most common in adults and in general
-Rhabdomyoma (common in children)
-Malignant primary include angiosarcoma, Malignant fibrous histiocytoma

Secondary:
-**20 times more common (metastatic)
-from lung, breast, lymphoma, melanoma
Cardiovascular disease:

Left Atrial Myxoma (Primary cardiac tumor):
-general characteristics
-most common Primary heart tumor in adults
-clinically mimics mitral stenosis or infective endocarditis
-danger of embolism
-emergency surgery necessary after ECHO diagnosis
Cardiovascular disease:

Sclerotic lesions in arteries: Arteriosclerosis:
-defn' + 4 pathologic causes
-is a clinical term for arterial thickening/hardening that may have 4 different pathologic causes:
1) senile arteriosclerosis (aging)
2) Monckeberg (medial) sclerosis/calcification (solid "rock" of calcium)
3)Hypertensive arteriolosclerosis (lumen not narrowed)
4) Atherosclerosis (is the most important)
Cardiovascular disease:

Aging changes in arteries: (senile) arteriosclerosis
-gradual diffuse distention and tortuosity (elongation) of large elastic arteries.
-intimal thickening in muscular arteries
-loss of medial muscle and fibrosis
Cardiovascular disease:

Monckeberg Medial calcific sclerosis:
-Is a medial lesion only, so no intimal thickening or luminal narrowing occurs
-affects medium sized muscular arteries
-is age related
-may co-exist with atherosclerosis
Cardiovascular disease:

Hypertensive arteriosclerosis:
-what are the 2 forms?
Hyaline form:
-results from leakage of plasma components, SMCs produce extracellular matrix
--systemic ("benign") hypertension
-(aging may produce same changes)
-(Diabetes mellitus may produce same changes)

Hyperplastic Form:
-shows concentric lamellar fibrosis, fibrinoid necrosis (=much more severe)
-"malignant" hypertension is usual cause.
Cardiovascular disease:

Aneurysms:
-defn' + etiology
-an Aneurysm is a localized, abnormal dilation of part of the vascular system, commonly an artery

etiology:
-wall weakening
-excessive dilating force (hypertension)
Cardiovascular disease:

Classification of aneurysms:
-2 groups
True aneurysm
-contains a remnant of the original arterial wall

False aneurysm
-(pseudoaneurysm) is a pulsating (evacuated) hematoma that communicates with the lumen of an artery (=no arterial wall, only clotting)
Cardiovascular disease:

Shape of aneurysm may give clue as to etiology: Fusiform
Fusiform (cylindroid) aneurysm is due to atherosclerosis
-**entire arterial circumference dilates
-most common aneurysm in the elderly
-abdominal aorta commonly
-familial in males
Cardiovascular disease:

Shape of aneurysm may give clue as to etiology: Saccular
-results from weakening of only a small portion of the circumference of an artery
-Ostium connects aneurysm to artery

causes:
-aortic medionecrosis (most common)
-syphilitic aortitis (rare)
-Berry aneurysm of circle of Willis
-arteritis
Cardiovascular disease:

Berry Aneurysm (can cause saccular aneurysm)
Etiology:
-medial muscle gaps near branching points of circle of Willis
-Systemic hypertension favors aneurysm development
Cardiovascular disease:

Mycotic aneurysm:
what causes it?
-aneurysm due to infection
Cardiovascular disease:

Microaneurysms:
-common with diabetes mellitus in retina, heart
-Charcot-Bouchard "aneurysms" (associated with incr. b.p.)
Cardiovascular disease:

Dissecting aneurysm: Aortic dissection
-what is the etiology of aortic dissection?
-Medionecrosis
-hypertension
-trauma
-(rarely pregnancy)
Cardiovascular disease:

Dissecting aneurysm: Aortic dissection
-what are the complications of aortic dissection? Commonest cause of death?
-external rupture=opposite site of initial tear, thus hemopericardium, cardiac tamponade
-occlusion of branches
-re-entry tears (pulse re-appears)
-dissection down aortic branches (ex) coronary arteries

External aortic rupture into pericardial space (=most common cause of death in aortic dissection)
Cardiovascular disease:

Complications of arterial aneurysms:
(4)
1)**pressure on adjacent structures
2)**rupture with massive hemorrhage
3)**thrombosis with occlusion of branches
4)**thromboembolism
Cardiovascular disease:

Cardiac Aneurysms:
-2 groups
-usually result from myocardial infarction

1) True Cardiac Aneurysm
-results from healed regional, transmural infarct
-virtually never ruptures
-problems due to heart failure or arrhythmia

2) False Cardiac Aneurysm
-ruptured infarct with adherent pericardium=aneurysm wall consists of pericardium (very rare!)
-very prone to rupture
Cardiovascular disease:

Congenital heart disease:
-general characteristics
-developmental abnormalities of heart & great arteries present from birth
-may have serious consequences
-heart formed during 3-8 weeks gestation
-incidence 6-8/1000 live births
-cause unknown in >90%
-2-10 times increased incidence in siblings or child of affected parent
-two major categories of structural abnormalities:
1)Shunt abnormal communication
2)Obstruction
-stenosis=partial narrowing
-atresia=complete obstruction
Cardiovascular disease:

Frequency of types of heart disease:
Ventricular septal defects (VSD):
30%
Atrial septal defects (ASD): %7
**Tetralogy of Fallot: 5%
Coarctation of aorta: 5%
Aortic stenosis: %5
Pulmonary stenosis: 10%
Patent ductus arteriosus (PDA): 10%
Cardiovascular disease:

Ventricular septal Defect (VSD):
-characteristics
-defect in ventricular septum which allows flow between left and right left ventricle
-functional significance depends on size of defect
-L to R shunt is acyanotic (increased pulmonary flow): high presure, high flow
-pan-systolic murmur
-50% close spontaneously in 1st year
-classified by size and location
--perimembranous/infracristal 90%
--muscular
--supracristal
Cardiovascular disease:

Atrial Septal Defect (ASD):
-abnormal communication in atrial septum (AS) allows blood flow between LA & RA
-Classified by size & location in AS
--ASD at fossa ovalis (secundum)=90%
--primum ASD (low in septum)=5%
--Sinus venosus (high in septum)=5%

-functional result
--Left to right shunt: acyanotic
--increased pulmonary flow

-systolic murmur
-may be diagnosed in adults >30 years old (low pressure, low flow)
-less than 10% develop pulmonary hypertension
Cardiovascular disease:

Coarctation of Aorta:
-localized obstruction due to curtain-like fold or aortic media that narrows lumen
-often sited just beyond origin of LSA
-may be associated with other CV abnormalities
-may give symptoms in infancy
-lower blood pressure in legs than arms
Cardiovascular disease:

Tetralogy of Fallot (TOF):
-Most common form of **cyanotic heart disease
-4 components
1) VSD (ventricular septal defect)
2) pulmonary stenosis
3) overriding aorta
4) RV hypertrophy (due to PS)

-functional consequences
--right to left shunt
--decreased pulmonary flow

-clinical murmur
Cardiovascular disease:

Acquired Abnormalities of heart Valves: 2 main
Stenosis: valve does not open fully, flow obstruction results

insufficiency: valve does not close completely, backward flow occurs

Mixed: Most valves have a combination of the two above

According to degree, duration, etiology, valvular abnormalites may produce secondary changes in heart, blood vessels, or other organs

numerous causes of valve disease, may affect one or more valves
Cardiovascular disease:

Acquired aortic valve stenosis:
-most are age related degenerative calcification or changes
-70 yrs old for tricuspid, 40-60 yrs old for calcified congenital bicuspid aortic valve
-gross: heaped up calcific masses within aortic cusps
-symptoms: ischemic chest pain, fatigue, fainting, sudden death
-LVH may develop
-treatment: AV replacement or balloon angyoplasty
Cardiovascular disease:

Mitral valve prolapse:
Present in 7% of US population, but few have functional disease / symptoms
-most often 20-40 yrs old
-Gross: inter-chordal hooding (ballooning) of posterior leaflet
-symptoms: nil 95%; fatigue, palpitations
-signs: mid-systolic click, late diastolic murmur
-predisposes to infective endocarditis, mitral insufficiency, arrhythmias, sudden death
Cardiovascular disease:

Infective Endocarditis (IE):
-serious disease: colonization / invasion of valves/mural endocardium by microbial agent

epidermiology / pathogenesis:
-usually on abnormal valves (subacute IE vs acute IE on normal valves)
-most often: streptococci 65%, staphylococci 20-30%, gram negative/other %5
-fungal or viral too
-bacteremia from oral cavity by dental procedures, surgery or IV drug use

-gross bulky vegetations
-may affect prosthetic valves
Cardiovascular disease:

Clinical course of IE:
-subacute vs acute bacterial endocarditis
Subacute bacterial endocarditis:
-low virulence organism; untreatd die later than 6 weeks
-nonspecific symptoms: fatigue, wt loss
-may or may not have a fever
-may have a new heart murmur

Acute bacterial endocarditis:
-virulent organism (untreated die less than 6 weeks)
-fever, chills, weakness, loud murmur
-infects normal valve
-embolic complications (sepsis), positive blood cultures
-5 yr survival 50-90% with treatment
-antibiotics convert acute into subacute course
Cardiovascular disease:

Rheumatic heart disease:
Acute rheumatic fever (RF)
-Acute, recurrent inflammatory disease in children, 5-15 yrs old (rarely adults)
-occurs 10-20 days after untreated throat infection by group A, Beta-hemolytic streptococcus
-almost vanished in USA due to antibiotics, now re-appearing
Cardiovascular disease:

Pathogenesis of RF (rheumatic fever)
-increased immune response to streptococcal antigens elicits antibodies to form that cross-react with heart & valve tissue
-similar antigenic groups are shared by streptococcus and heart/valve tissues
Cardiovascular disease:

Morphology of acute rheumatic fever:
-Pancarditis (inflammation of endocardium, myocardium, pericardium); verrucous vegetations on MV contact area
-Aschoff body: proliferative phase is diagnostic of RF
--focal fibrinoid necrosis of collagen alongside blood vessl in interstitium
--elicits cardiac histiocytes (Anitschkow cells) and lymphocytes locally
-inflammation of valves leads to deformity (is self-perpetuating and leads to chronic valve deformity)
Cardiovascular disease:

Rheumatic Heart Disease (RHD):
-permanent valve deformity due to post-inflammatory fibrosis; may occur 10-30 yrs after repeated attacks of acute RF
-Cusps thickened, shortened; chordae (MV, later TV) shortened, fused
-MV is hardest working heart valve affected 1st (70%); fish mouth then button hole orifice
-mitral plus aortic valves affected 25%
Cardiovascular disease:

Long-term outcome of RHD:
-depends on severity of chronic valve changes
-may develop heart failure due to mitral stenosis, mitral incompetence or mixed mitral valve disease; AS/AI, TS/TI, PS/PI
-Right-sided heart valves only affected after right-sided pressure rises due to left sided valve disease
-infective endocarditis
-left atrial thrombus formation
-Rx-valvuloplasty or valve replacement
Cardiovascular disease:

Non-Bacterial thrombotic (marantic) endocarditis:
-occurs in acute rheumatic fever, any serious illness (e.g. cancer, TB) and in systemic lupus erythematosus
The role of the autopsy:

Definitions: 1)autopsy 2)underlying cause of death, 3)proximate cause of death
1)literally means "to see with your own eyes"
2)is the disease or injury that initiated the train of morbid events leading to death
3)the immediate ("last straw") event associated with death
The role of the autopsy:

Instigators of autopsy:
Galen: the first
Andreas Vesalius: wrote 1st textbook on anatomy
Giovanni Batista Morgagni: Correlated clinical & anatomic findings
The role of the autopsy:

Diseases discovered by autopsy:
-TB (cause)
-appendicitis (how to treat)
-coronary thrombosis (cause of MI)
-Alzheimer's disease (existence)
The role of the autopsy:

Forensic vs. hospital autopsies:
Forensic (med. examiner / coroner's) autopsy is concerned with 'unnatural' causes of death.
-suicide, homicide, child abuse, intra-operative death

Hospital (academic) autopsy is concerned with 'natural' causes of death. drugs and new therapies may also produce morbidity and/or death.
The role of the autopsy:

Stages in the performance of a hospital autopsy:
1) signed permit (authorization) and consultation request
2) gross dissection: preliminary anatomic diagnoses (<24 hrs)
3) Microscopic examination
4) final report includes final anatomic diagnoses, summary & interpretation
The role of the autopsy:

Traditional purposes of an autopsy:
-Discover new diseases, causal relationships, complications.
-educate medical students, residents.
-CME for MDs: continuing medical education=learn from mistakes.
-evaluate new technologies, therapies, interventions.
-research
-source of spare parts
The role of the autopsy:

Additional purposes of an autopsy:
-genetic counseling (molecular diagnostics)
-diagnose unsuspected contagious disease ex)TB
-identify occupational diseases
-hospital quality control=detect major and minor discrepancies between pre- and postmortem diagnoses
-reinforce the importance of medical uncertainty
-improve accuracy of death certificates
-insurance and death benefits
-reduce feelings of guilt/anger in relatives
The role of the autopsy:

Reasons for falling autopsy rates:
-doctors may graduate without seeing an autopsy
-JCAHO has not required autopsies for hospitals to be licensed since 1971
-fear of litigation
-Medical arrogance: MRI, CT scans, etc.
-Lack of training in requesting an autopsy
The role of the autopsy:

Economic factors affecting autopsy rates:
-no reimbursement received for the performance of an autopsy on hospital patients.
-however, hospital patients have pre-paid for an autopsy via the Medicare system.
The role of the autopsy:

How often does autopsy reveal an unexpected finding?
-40% reveal at least one major unexpected finding (diagnosis is wrong in 2/5 patients)
-1/3 of the misdiagnoses (13%) the patients would have lived if proper treatment had been given.
The role of the autopsy:

Major vs. Minor discrepancy:
-major affects primary diagnosis (if diagnosis had been made patient would have lived e.g. undiagnosed but treatable)
-minor has no adverse effect on survival