Azcom Path Exam 2

Front 1

what are the steps in effective use of labs?

Back 1

•Perform a thorough history, physical exam-diagnosis will be evident 70+% of time

• Develop a differential diagnosis (DDx)

• Order appropriate disease- specific, targeted “screening” tests

• Assess results for necessity of additional tests

Front 2

What is Osler’s rule regarding lab results?

Back 2

• If patient is under age 50, look for one etiology (cause) of all abnormal results

Front 3

When is general screening appropriate?

Back 3

- targeted screening of high risk groups

Front 4

List and know biologic variability of test results with time.

Back 4

• Circadian rhythm (24 hr. rhythm) - cortisol - pronounced diurnal variation

• Rhythms less than or greater than 1 day

• Timed tests - with relationship to meals --glucose: reference range given fasting --triglycerides - drugs: related to dose

Front 5

What are the effects on lab results of: Caffiene

Back 5

- increased catecholamines, glucose - elevated lipids w/ chronic consumption

Front 6

What are the effects on lab results of: Alcohol

Back 6

- casual use increases triglycerides - gamma glutamyl transferase / GGT (transpeptidase) --increased due to induction in moderate and heavy drinkers (w/ or w/o liver dis.) - no other consistent changes

Front 7

What are the effects on lab results of: Nicotine/tobacco smoke

Back 7

• Increased: glucose, catecholamines, cortisol, free fatty acids

• Increased WBC’s

• Increased: CEA, carcinoembryonic antigen, a cancer marker

• Increased carboxyhemoglobin- carbon monoxide content

• Increased hemoglobin

Front 8

What changes in labs occur in the elder?

Back 8

• Albumin, protein decrease starting mid-adult

• Creatinine decreased : lower muscle mass • Muscle-related enzymes decreased

• Lymphocytes reduced

Front 9

What changes in labs occur in young children?

Back 9

• Lymphocytes must exceed 2500/μ ( adult normal is greater than 1500/ μ)

• Alkaline phosphatase increased above adult reference range - enzyme product of osteoblasts

Front 10

How does exercise effect lab results?

Back 10

• Strenuous exercise (marathon, etc.) - enzymes from muscles elevated - lactic acid increases

• Well-trained athletes - lower mean cell hemoglobin (MCH), glucose, WBCs

• Increased basal levels of muscle enzymes

• Higher bilirubin; BUN

Front 11

What is the reference interval for lab tests?

Back 11

• Gaussian distribution - occurs in tests with random fluctuations - usual interval is 2 SD from test mean; 95% --95% of persons w/o disease will have analyte result in this range

• NonGaussian distribution is common - interval is set from 3rd to 97th percentile

• Overlap between patients with disease and without disease

• The larger the battery of tests ordered, the more likely one or more results will be abnormal (unreliable)

Front 12

Define: accuracy and contrast with precision. What is the “gold standard”?

Back 12

• Accuracy: Reliability of the test method

• Gold standard: recognized methodology against which new tests are compared

• Precision: reproducibility of a result

Front 13

negative predictive value

Back 13

TN/TN+FN

Front 14

positive predictive value

Back 14

TP/(TP+FP)

Front 15

Sensitivity

Back 15

Sensitivity % = (TP/(TP + FN))x100

Front 16

specificity

Back 16

Specficity % = (TN /(TN + FP))x100

Front 17

what causes elevated BUN?

Back 17

• Increased BUN ( with creatinine = Azotemia) - Almost all renal disease and - Poor renal perfusion -- dehydration, shock, heart failure, etc • Nonrenal causes of increased BUN - Catabolism - fever, burns, diabetes, intensive exercise - GI bleeding

Front 18

what causes elevated creatinine?

Back 18

• Elevated-most renal disease – late ; poor renal perfusion, dehydration, etc

• Insensitive but specific for renal impairment

Front 19

what causes elevated bilirubin?

Back 19

• Jaundice= tissue accumulation of bilirubin - Prehepatic - hemolysis - Intrahepatic - liver disease: hepatitis, cirrhosis - Posthepatic - gallstone in bile duct

Front 20

what causes elevated alkaline phosphotase?

Back 20

• Major sources: - liver -- canalicular (biliary) system - bone – osteoblasts - placenta - others include intestine (genetically variable); production by some cancers

Front 21

What causes elevated LD?

Back 21

Glycolytic pathway enzyme • Widely distributed; elevated nonspecifically with a variety of tissue damage • Isoenzyme profile may be specific • Significant plasma elevation occurs with small amounts of tissue injury • High plasma levels associated with break-down of erythrocytes (hemolysis); platelets

Front 22

what casuses elevated AST?

Back 22

- hepatocyte injury (“hepatitis”) - cardiac, skeletal muscle injury - hemolytic and megaloblastic anemias - renal and pulmonary infarction and other tissue necrosis

Front 23

what casuses elevated ALT?

Back 23

Liver is the major source

• Lesser amounts released in renal infarction and very little from other tissues

Front 24

what is the chemistry profile of disease in muscle?

Back 24

• Muscle: - CK (creatine kinase) - AST - LD - Aldolase - Nonenzyme proteins: myoglobin

Front 25

what is the chemistry profile of disease in bone?

Back 25

• Enzymes elevated in bone disease - Alkaline phosphatase

Front 26

what is the chemistry profile of renal disease?

Back 26

BUN, late disease creatinine, AST, little ALT

Front 27

what is the chemistry profile of hepatic disease?

Back 27

• Synonym: Liver function tests or LFTs

• Transaminases/aminotransferases - AST-aspartate aminotransferase (SGOT) - ALT- alanine aminotransferase (SGPT)

• Alkaline phosphatase- ALP or Alk Phos

• Gamma glutamyl transferase- GGT

• LH or LDH -lactate dehydrogenase

Front 28

what is the chemistry profile of cardiac disease?

Back 28

• Troponin I (and T) -- highly sensitive and specific -- currently the single, preferred test for lab confirmation of MI; elevated 1 wk.

• Creatine kinase, CK - MB isoenzyme = “CK-MB” is cardiac specific; elevated before troponin

• AST – nonspecific

• LD – nonspecific • Myoglobin - nonspecific

Front 29

what is the chemistry profile of hemolytic anemia?

Back 29

• LD markedly elevated

• AST elevated

• Indirect bilirubin increased

• Haptoglobin decreased

Front 30

What does prealbumin assess?

Back 30

• Sensitive indicator of - malnutrition - alterations in liver function

• Short half-life of two days

• Includes transthyretin (TTR): minor transport of thyroxine and vitamin A (complexes with retinol binding protein)

Front 31

What are causes of hypoalbuminemia?

Back 31

• Very common

• Impaired synthesis : malnutrition, malabsorption, hepatic dysfunction

• Increased loss - renal disease, esp. nephrotic syndrome - protein-losing gastroenteropathy - ascites

Front 32

What are the origin and correlates of changes in gamma globulins?

Back 32

• Increased globulin is due to increase in gamma globulins, gammopathy

• Types of gammopathies - Polyclonal gammopathy: due to prolonged infection or inflammation - Monoclonal gammopathy: neoplastic Decreased Gamma Globulins

• Indicative of B-cell immunodeficiency, congenital or acquired

• Risk for development of pyogenic infections

Front 33

List and know acute phase responses given in lecture.

Back 33

Neutrophilia -Thrombocytosis (platelets increased) -Fibrinogen, other coagulation factors inc. -Alpha-2-macroglobulin increased -C-reactive protein increased -Haptoglobin increased -Albumin decreased -Erythrocyte sedimentation rate increased -Procalcitonin increased

Front 34

What are the clinical correlates of alpha-1 and alpha-2 globulins listed?

Back 34

Alpha-1 globulins: Alpha-1 antitrypsin

• α-1 antitrypsin is the major component of α-1 globulins - Protease inhibitor, PI, counters effects of leukocyte elastase

• Acute phase reactant

• Deficiency causes: - pulmonary emphysema - cirrhosis of the liver (misfolded protein is retained within hepatocyte) Alpha-2 globulins

• Includes most of the “Acute phase reactants”: blood elements that are altered in response to acute inflammation

• Alpha-2 macroglobulin: kinin inhibitor

• Haptoglobin-carrier of free hemoglobin

• C-reactive protein

Front 35

What are the uses of CRP?

Back 35

• History: protein that reacts to C-substance of streptococci

• General scavenger molecule

• Acute phase reactant -rises fast in response to bacteria, necrosis: doubles q 6 hours -elevated in inflammatory response to autoimmunity; disease progression in RA, SLE

• Correlates with risk of MI, stroke

Front 36

What is ESR and how is it used?

Back 36

• Definition: length of fall of RBCs in a column of blood in a given time interval, mm/hr

• Increased globulins, fibrinogen; decreased albumin favor accelerated sedimentation

• Interpretation: - increased ESR is a nonspecific indicator of inflammation - used to follow rheumatoid arthritis, diagnose temporal arteritis and r/o inflammation

Front 37

What are the uses of procalcitonin?

Back 37

• <0.15ng/dL, bacterial infection is unlikely

• Between 0.15 and 2.0, localized infection cannot be excluded - elevation in autoimmune disease rarely exceeds 0.5 ng/dL

• >2.0 highly favors severe bacterial infection: pneumonia, meningitis, sepsis correlates with progression to septic shock

• Transient elevation also occurs: severe trauma, major surgery, severe burns

Front 38

Compare/contrast exudates with transudates as to causes and lab findings.

Back 38

• Arise via increased vascular permeability • Exudates : high in protein, >3gm/dl; fibrin and other large molecules present - WBCs increased; LD (lactate dehydrogenase) often increased

• Causes- -- infections/inflammations -- repair : angiogenesis -- malignancy : angiogenesis

• Usually localized; generalized in septic shock

• Low protein content; few cells; LD (lactate dehydrogenase) does not exceed plasma level

• Causes: - Hydrostatic pressure increased: eg. heart failure - Osmotic pressure decreased: eg, liver disease, kidney disease, esp. nephrotic syndrome - Lymphatic obstruction - Primary retention of sodium (and water) --eg. renal disease; CHF / poor renal perfusion

Front 39

Table 4-1, Causes of edema:

Back 39

see picture

Front 40

What are some locations and what are the causes of local edema due to increased hydrostatic pressure?

Back 40

• Edema due to impaired venous outflow. Examples, localized increased pressure: - dependent edema - deep venous thrombosis

• Generalized (heart failure)

Front 41

What is the cause of hydrostatic pressure-related generalized edema?

Back 41

Generalized: Congestive Heart Failure

• Right ventricular dysfunction increases venous hydrostatic pressure

• Plasma volume expands 2o to signals from poorly perfused kidneys

Front 42

Describe the pathogenesis of edema in heart failure (figure 4-2, Robbins)

Back 42

see picture

Front 43

mechanisms of edema in renal disease

Back 43

Salt and Water Retention

• Expands plasma volume - increases hydrostatic pressure - decreases colloid osmotic pressure by dilution

• Retention most related to renal impairment - primary renal disease or secondary to renal hypoperfusion

Front 44

mechanisms of edema in liver failure

Back 44

• Decreased protein/albumin production-

Front 45

mechanisms of edema in malnutrition

Back 45

• Decreased protein/albumin production-

Front 46

List causes of decreased colloid osmotic pressure.

Back 46

• Increased protein loss: nephrotic syndrome, ascites, protein-losing enteropathy

• Decreased protein/albumin production- - Severe liver disease (cirrhosis or other liver failure) - Malnutrition

• Exacerbated by salt and water retention

Front 47

What is a frequent initial manifestation of edema related to decreased osmotic pressure?

Back 47

Periorbital swelling

Front 48

Define lymphedema. List causes. What is the description given to advanced lymphedema? What are complications of lymphedema?

Back 48

• Primary: inherited or developmental defect of lymph vessels or nodes, eg Milroy dis. - onset may be at birth or delayed for yearsTrauma to lymphatic channels - removal of lymph nodes- cancer surgery - hip replacement

• Radiation injury to lymphatics

• Cancer metastatic to lymph nodes • Extrinsic pressure on lymphatics- tumor

• Infections of lymphatics: “Elephantiasis” Wucheria bancrofti and other filariasis • Obesity

• Peau d’orange in breast cancer: sign of late disease; poor prognosis

• Complications of longstanding lymphedema - Secondary infection - Lymph vessel cancer (lymphangiosarcoma)

Front 49

What are the causes and morphology of pulmonary edema?

Back 49

• Causes - left ventricular failure--common cause - renal failure - adult respiratory distress syndrome - pulmonary infections and other

• Morphology, evolves from congestion - lungs 2-3x increase in weight - frothy, blood tinged fluid - Microscopic- see separate slides Clinical: hypoxia; risk for bacterial infection

Front 50

Define hyperemia and describe pathogenesis. What is the synonym and what are some causes?

Back 50

• Hyperemia so known as erythema erythros = red; erythemia = flush - local increased volume of blood - active arteriole dilation red color due to increased oxygenated blood

Front 51

Describe passive congestion. What are some causes?

Back 51

• Congestion - passive process due to impaired venous outflow from tissues - tissues are blue red (cyanosis); hypoxic - commonly associated with edema

Front 52

What is the morphology of chronic pulmonary congestion?

Back 52

- Lung: rubbery, brown

Front 53

What is the morphology of chronic lower extremity edema? What complication may occur?

Back 53

- Lower extremities: brown induration

Front 54

What is the cause and morphology of chronic hepatic congestion?

Back 54

• Chronic passive congestion: Nutmeg liver fig 4-3 - Due to congestive heart failure - Centrilobular hemorrhagic necrosis - gross: red-brown depressed areas - may progress to “cardiac cirrhosis”- fibrosis

• AST, ALT elevated due to necrosis of hepatocytes

Hint 54

fig 4-3

Front 55

What are causes of congestive splenomegaly?

Back 55

- right heart failure - hepatic cirrhosis - portal vein occlusion

Front 56

Hematoma

Back 56

Mass of blood confined within an organ, tissue or internal space

Front 57

Contusion

Back 57

• Contusion-bruise/ecchymosis: - Blunt force injury damages small blood vessels w/o disruption of continuity of tissue

Front 58

Ecchymosis

Back 58

• Ecchymosis: large areas >1-2cm - changes over time from red-blue, to -- blue green: heme converted to bilirubin -- to gold-brown: hemosiderin

Front 59

Purpura

Back 59

• Purpura: confluent petechiae. >3 mm - similar causes to above, plus vascular inflammation, trauma

Front 60

Hemarthrosis

Back 60

bleeding into a joint

Front 61

Epistaxis

Back 61

nosebleed

Front 62

Hemoptysis

Back 62

coughing up blood

Front 63

Hematemesis

Back 63

vomiting up blood

Front 64

Hematochezia

Back 64

bright red blood in stool

Front 65

Melena

Back 65

black/digested blood in stool

Front 66

Hematuria

Back 66

blood in urine

Front 67

Abnormal uterine bleeding (formerly menorrhagia, metromenorrhagia, etc)

Back 67

excessive menstrual bleeding

Front 68

What are signs and symptoms of defects primary hemostasis?

Back 68

• “ Superficial bleeds” • Epistaxis-nosebleeds • Bleeding from gums • Bleeding from/ into GI (gastrointestinal) tract and skin (typically multiple) - Petechiae (punctate hemorrhages) - Purpura: confluent petechiae - Ecchymosis: large areas >1-2cm • Bleeding from GU (genital urinary) tract

Front 69

Compare and contrast primary hemostasis deficiencies with signs and symptoms of coagulation factor deficiencies

Back 69

• Primary hemostasis - Immediate response to vascular injury - Vascular wall- Endothelial cells and underlying connective tissue - Platelets • Secondary hemostasis - Blood proteins- procoagulants - Anticoagulants, fibrinolytic agents

Front 70

What are the prothrombotic effects of endothelium?

Back 70

see picture

Front 71

Describe and know in order, the events involved in primary hemostasis (figure 4-4, A and B). List mediators involved in each step and actions of each.

Back 71

Front 72

What are the hereditary platelet diseases? Be familiar with the clinical features (refer to signs and symptoms of diseases of primary hemostasis)

Back 72

- Glansmann thrombasthenia, hereditary defect of GpIIbIIIa Additional Acquired defects in platelets

• Thrombocytopenia- decreased numbers. - Decreased production in bone marrow - Increased peripheral destruction: eg. autoimmune - ITP; HIV Sepsis

• Dysfunctional platelets - Uremia (kidney failure) -Drug induced

Front 73

Clopidogrel (Plavex); Cangrelor

Back 73

ADP receptor PY2 inhibitors (anti-platelet)

Front 74

GpIIbIIIa inhibitors

Back 74

GpIIbIIIa inhibitors(antiplatelet)

Front 75

Aspirin, nonsteroidal anti-inflammatory drugs (NSAIDS)

Back 75

- Block cyclo-oxygenase to prevent production of TxA2 (thromboxane)

Front 76

What are other acquired, nonpharmaceutical defects of platelets?

Back 76

• Thrombocytopenia- decreased numbers. (details to be discussed in a later lecture) - Decreased production in bone marrow - Increased peripheral destruction: eg. autoimmune - ITP; HIV Sepsis

• Dysfunctional platelets - Uremia (kidney failure) - DRUGS (antiplatelet)

Front 77

Review and recognize lab results likely to occur in defects of primary hemostasis?

Back 77

• CBC including platelet count - reference range 150,000-350,000/μL (mm3)

• Platelet function analyzer - measures time to form a platelet plug - analogous to bleeding time • Bleeding time: not used in most labs

• Ristocetin agglutination test for vonWillebrand disease

• Platelet aggregation studies

Front 78

Review coagulation (secondary hemostasis).

Back 78

• Successive amplifying enzymatic reactions (“cascade”) terminating in activated thrombin

• Thrombin proteolyzes fibrinogen to fibrin monomers.

• Fibrin monomers polymerize into insoluble gel that encases platelets, other cells, to form definitive secondary hemostatic plug.

• Factor XIII cross-links and stabilizes fibrin polymers.

• Antithrombotic mechanisms limit extent

Front 79

Memorize vitamin K dependent factors.

Back 79

-- procoagulants II, VII, IX, X -- anticoagulants proteins C and S

• Coumadin/warfarin (“blood thinner”): -Vitamin K antagonist

Front 80

Prolonged PT only

Back 80

Factor VII defects

Front 81

Combined prolonged aPTT and PT

Back 81

Medical conditions: anticoagulants, DIC, liver disease, vitamin K def., massive transfusion Rare: dysfibrinogenemia; factor X, V or II defect

Front 82

Prolonged aPTT only

Back 82

Associated with bleeding: VIII, IX and XI defects Not assoc. with bleeding: XII, prekallikrein (PK), HWMK and lupus anticoagulant

Front 83

What does Prothrombin time (PT) measure?

Back 83

• Time to clot measured ~ 12-14 seconds

• Prolonged in: - extrinsic factor and common pathway factor deficiencies VII, X, V, II, I

• Used to monitor coumadin therapy - INR: ratio of patient to control

Front 84

What doesPartial thromboplastin time , aPTT measure?

Back 84

Time to clot formation is measured: usually < 40 seconds

• Prolonged in - deficiencies of intrinsic system and common pathway factors: XII, XI, XI, VIII, X, V, II, I - circulating anticoagulants, eg. heparin

• Monitors unfractionated heparin therapy (LMW heparin therapy requires no labs)

Front 85

What is the inheritance pattern of von Willebrand disease?

Back 85

Autosomal Dominant

Front 86

What would thrombin time tests look like in Von Willebrand deficiency?

Back 86

PT:unaffected aPTT: prolonged or unaffected bleed time: prolonged

Front 87

What is the inheritance pattern of Factor VIII deficiency?

Back 87

X-linked

Front 88

What thrombin times are seen in Factor VIII deficiency?

Back 88

Hemophilia A PT: Normal aPTT:prolonged bleed time: normal

Front 89

What is the inheritance pattern of factor IX deficiency?

Back 89

X-linked hemophilia b

Front 90

What thrombin times are seen in Factor IX deficiency?

Back 90

hemophilia Bprolonged or normal aPTTNormal PT, and bleed times

Front 91

Other than von Willebrand, factor VIII, and IX deficiencies; what is the inheritance pattern of most clotting factor deficiencies?

Back 91

Autosomal Recessive

Front 92

Defects with Prolonged aPTT only and bleeding

Back 92

VIII, IX and XI defects

Front 93

Defects with Prolonged aPTT only and NO bleeding

Back 93

XII, prekallikrein (PK), HWMK and lupus anticoagulant

Front 94

Defects with only prolonged PT

Back 94

Factor VII defects

Front 95

defects with combined prolonged aPTT and PT

Back 95

Medical conditions: anticoagulants, DIC, liver disease, vitamin K def., massive transfusion Rare: dysfibrinogenemia; factor X, V or II defect

Front 96

What are the antithrombotic effects of endothelium?

Back 96

- Physically inhibits platelet adhesion - PGI2 (prostacyclin) , NO, ADPase

• Fibrinolytic - Source of tPA (tissue plasminogen activator)

• Heparin-like molecule- cofactor for antithrombin

• Thrombomodulin binding – inhibits thrombin and activates protein C

• Tissue factor pathway inhibitor - Inactivates TF; factor VIIa - Protein S in a co-factor

Front 97

What is anttithrombin?

Back 97

aka antithrombin 3, it inhibits the activity of thrombin and other serine proteases (IXa, Xa, XIa, XIIa), it is activated by when endolethial cells bind it with heparin-like molecule… (heparin activates this)

Front 98

What are proteins S and C?

Back 98

Vitamin K dependent proteins that form a complex that inactivates factors Va and VIIIa. Process begins when thrombmodulin activates protein C.

Front 99

What is tissue factor pathway inhibitor?

Back 99

secreted by endolethial cells, inactivate factors Xa and tissue factor-factor VIIa complexes.

Front 100

What condition is associated with deficiency or defect of a natural anticoagulant?

Back 100

Thrombophilia; thrombosis

Front 101

Describe fibrinolysis

Back 101

• Action: breakdown of fibrin to yield fibrin split products, FDPs (degradation products) and d-dimer - Inhibits fibrin polymerization; limits coagulation

• Major activators - Factor XIIa dependent pathway - tPA (tissue plasminogen activator) - Urokinase-like plasminogen activator - Streptokinase, bacterial product

Front 102

what labs measure fibrinolysis?

Back 102

fibrin degradation products(FDPs) --- d-dimer

Front 103

what are the inhibitors of fibrinolysis?

Back 103

fibrolysispicture

Front 104

Define thrombosis.

Back 104

pathologic process-formation of a clot within intact vascular system

Front 105

What is Virchow’s triad? Refer to examples of thrombosis related to each of the three components of the triad.

Back 105

see figure 4-12

Front 106

What do increased levels of factors VIII,IX,XI, or fibrinogen cause?

Back 106

a common type of thrombophilia

Front 107

What does a G20210A mutation lead to?

Back 107

Prothrombin mutation that leads to increased prothrombin levels;

• Increased prothrombin drives more fibrinogen--> fibrin

Front 108

What are the rare thrombophilias?

Back 108

Antithrombin III deficiency, Protein C deficiency, Protein S deficiency

Front 109

What are the features of Factor V Leiden?

Back 109

ARG to GLU subsitution in amino acid 506 leads to resistance to activated Protein C; factor V Leiden

Front 110

What are features of hyperhomocysteinemia?

Back 110

- Mutation in methyltetrahydrofolate reductase occurs in 3-5% of Caucasians, E. Asians --Elevated homocysteine inhibits: ATIII and thrombomodulin --- 2-5x risk for thromboembolism -- Increased risk for atherosclerosis - Homozygous deficiency of cystathione β- synthetase

Front 111

When would you suspect an inherited thrombophilia

Back 111

Under age 50 Recurrent thrombosis unusual thrombosis sites (peripheral arteries) Thrombosis in pregnancy no apparent predispostion preceding thrombosis

Front 112

Risks for secondary/acquired hypercoagulable disorders.

Back 112

Prolonged bed rest; immobilization

•Myocardial infarction; atrial fibrillation

• Tissue damage: surgery, esp orthopedic; fracture, burns, crush injury

• Cancer: procoagulant tumor products

• Prosthetic heart valves

• Disseminated intravascular coagulation

• Antiphospholipid antibody syndrome

• Prior thrombosis at any time

Front 113

Which aquired hypercoagulable disorders confer the highest risk for thrombosis?

Back 113

highriskthromb.png

Front 114

Describe HIT including pathogenesis and clinical features.

Back 114

Heparin-induced Thrombocytopenia,

• Antibodies form to unfractionated heparin -Recognize complexes of heparin-platelet factor 4 - Binding activates platelets: formation of platelet rich thrombi

-Thrombocytopenia due to platelet consumption - suspect when platelets drop by 50%

• May (rarely ) occur with low molecular wt. heparin and fondaparinux (factor X inhibitor)

Front 115

Define antiphospholipid antibody syndrome, listing clinical associations

Back 115

• May be primary: solitary autoimmune defect; or 2o to systemic lupus erythematosus

• Fatal thromboembolic events occur in 7%

• Recurrent venous or arterial thrombi, eg. - Arterial thrombosis: stroke, MI, bowel infarct - DVT with pulmonary emboli; pulmonary HTN - Renovascular hypertension - Renal microangiopathy renal failure

Front 116

Describe and recognize morphology of thrombi. Refer to figures 4-13 and similar examples.

Back 116

figure 4-13

Front 117

What are the most common cause of arterial thrombosis and what are the consequences?

Back 117

• Atherosclerosis is most common cause

• Locations in order of frequency:

• Coronary artery --> myocardial infarction (MI)

• Cerebral artery thrombosis --> stroke

• Femoral artery --> gangrene of the leg

• Mural thrombus (w/in a chamber of heart) -> systemic emboli

• Aneurysms also predispose to thrombosis

Front 118

What are the symptoms of DVT?

Back 118

Asymptomatic in half

• Found as consequence of pulmonary emboli

• May result in edema, swelling of leg

• Homan’s sign- pain in calf on dorsiflexion of foot

Front 119

Define terms that describe the fate of thrombi.

Back 119

fate of thrombi picture

Front 120

What is the most common type of embolus?

Back 120

Thrombi- cause of 99% of all emboli

Front 121

What are the causes and consequences of superficial saphenous vein thrombosis?

Back 121

Associated with varicosities

• Varicosities result in stasis; thrombosis

• Thrombi produce local congestion, pain, swelling

•Rarely embolize

• Predispose to venous insufficiency;

Front 122

What are symptoms, morphology and consequences of pulmonary thromboembolism? Recognize figure 4-15 or equivalent.

Back 122

Saddle embolus, large - Large embolus that occludes the bifurcation of the main pulmonary artery - Produces electrical mechanical dissociation (EKG activity with no pulse)

• Massive simultaneous emboli involving 60% of pulmonary circulation - causes obstructive shock

Hint 122

fig 4-15

Front 123

Which site is most vulnerable for systemic emboli?

Back 123

- Brain - 10% : stroke

Front 124

Which site is most common for systemic emboli?

Back 124

- Lower extremities-75%: gangrene

Front 125

Traumatic fat embolism, figure 4-16

Back 125

• Occurs with trauma, usually fracture of long bones (marrow) - shortness of breath followed by confusion, coma, 1-3 days after fracture; rash and thrombo-cytopenia; fatal in 10%

Hint 125

figure 4-16

Front 126

Air embolism

Back 126

• Clinical settings: exogenous air - Obstetric procedures-delivery/abortion contractions force air into injured vessels - pneumothorax -- Lung/chest wall injury opens large vein admitting air during inspiration - Clinically significant with >100cc air

Front 127

Amniotic fluid embolism, figure 4-17

Back 127

• Infrequent complication of delivery, 1/40,000

• Mechanism: infusion of amniotic fluid into maternal circulation via tear in membranes and uterine wall

• Morphology: Fetal squames, hair, vernix fat and meconium in pulmonary vessels

• Clinical: shortness of breath, shock, followed by seizures, coma, DIC; fatal up to 80%

Hint 127

figure 4-17

Front 128

Causese of infarction

Back 128

Vascular lesions causing ischemia Thromboembolic disease causes 99% of infarctions Other: Vasospasm Expansion of atheroma Compression (tumor, tourniquet) Twisting of vessels: intestinal volvulus, testicular or ovarian torsion Edema, entrapment in hernia sac with vessel strangulation Vessel inflammation or rupture

Front 129

Red infarct

Back 129

hemoragic infarct pic Venous occlusions: twisted ovaries, testes

• Arterial occlusions in loose tissues (lungs) - blood collects in infarcted zone

• Arterial occlusion in tissues with dual circulations: lungs, intestines

• Occlusions in tissues previously congested

• Occlusions where the blood flow is re-established

Front 130

White infarct

Back 130

takes place in "solid" organs heart spleen

Front 131

bland infarct

Back 131

no infection

Front 132

Septic infarct

Back 132

presence of infection

Front 133

What conditions predispose for DIC?

Back 133

Acute DIC

• Occurs in obstetrical accidents, sepsis Chronic DIC

• Presentation typically is venous thrombi - nonbacterial thrombotic endocarditis

• Example: Trousseau syndrome - Migratory thrombophlebitis in a patient with pancreatic cancer

Front 134

Define DIC.

Back 134

Thrombo-hemorrhagic disorder - consumptive coagulopathy: systemic activation of coagulation pathways leads to thrombi throughout the microcirculation

• Secondary complication of variety of diseases

Front 135

What laboratory tests are used to assess patients for DIC?

Back 135

--- platelets, coagulation factors are consumed --- fibrinolysis is activated

Front 136

Define shock (refer to consequences).

Back 136

systemic hypoperfusion from reduction in cardiac output or reduced effective circulating blood volume

Front 137

Shock:What pH alteration occurs and what are its consequences?

Back 137

Acidemia (increased serum lactic acid/ lactic acidosis)• Reversible cell injury that may progress to irreversible cell injury, death

Front 138

What is the mechanism of cell injury in shock?

Back 138

Hypoxia-->reduced ATP--> increased latic acid

Front 139

signs and symptoms of shock.

Back 139

• Related to increased catecholamines; vasoconstriction

• Skin: pallor (pale color); cool, clammy (exception: initial response in septic shockis warm, dry skin)

• Cyanosis, esp. around mouth; acrocyanosis (blue hands, feet)

• Tachycardia with weak, rapid pulse

• Tachypnea

• Altered sensorium

Front 140

Cardiogenic shock

Back 140

• “pump failure” primary myocardial impairment • Causes - Myocardial infarction -- common; in up to 15%; 70-90% mortality - Inflammation (myocarditis), intrinsic disease of myocardium(cardiomyopathy) - Arrhythmias, ventricular

• Cardiac output decreased due to systolic anddiastolic dysfunction; arterial pressure reduced

Front 141

Obstructive shock

Back 141

Often included in classifications of cardiogenic

• Causes: - Massive pulmonary embolism - Cardiac tamponade (compression of heart due to fluid in pericardium) - Tension pneumothorax (air in pleural space that increases with each inspiration) - Mass lesions in chamber of heart

• Cardiac output decreases because of decreased blood returning to left ventricle

Front 142

Septic shock

Back 142

Common cause of death in hospitals: ~ 200,000/year;

• Mortality: 20-50%

• Causes: overwhelming microbial infections - Gram positive bacteria - Gram negative bacilli- endotoxic shock - Fungi

• Other causes - superantigens/toxic shock syndrome - trauma, burns, pancreatitis

Front 143

Anaphalatic shock

Back 143

• Type I hypersensitivity: IgE mediated

• Histamine mediates vasodilation; increasedvascular permeability

• Symptoms - dyspnea, tachypnea, swelling of airways - GI disturbances - tachycardia - altered sensorium

• Common causes include peanut allergy; bee stings

Front 144

Hypovolemic/hemorrhagic shock

Back 144

Occurs with acute loss of >20% of circulating blood or plasma volume

• Cause: Hemorrhage - Trauma: wounds; fractures; perforations - Gastrointestinal bleeding - Aortic rupture

• Cause: fluid loss –diarrhea, burns, dehydration

• Cardiac output is decreased due to decreased blood volume (preload)

Front 145

With regard to septic shock, what are the pathogenesis (see also figure 4-20), clinical features unique from other shock, complications and sequelae?

Back 145

see 4-20

Front 146

Morphology of shock

Back 146

Kidneys: acute tubular necrosis/AKI

• Lungs : diffuse alveolar damage- morphology of ARDS/shock lung

• Liver: steatosis (fatty change); ischemic necrosis • Heart and CNS: ischemic necrosis

• GI: hemorrhagic necrosis

• Adrenal cortical lipid depletion

• Disseminated intravascular coagulation:tissue ischemia; bleeding

Front 147

Nonprogressive phase of shock

Back 147

eg blood loss that has ceased

• Neurohumoral and renal mechanisms maintain cardiac output; blood pressure - fluid retention by kidneys - sympathetic stimulation-eg norepinephrine acts on α1 receptors on arteriole smooth muscle vasoconstriction (heart/brain spared)

• Effects: - tachycardia - peripheral resistance increases

Front 148

Progressive shock

Back 148

• Widespread tissue hypoxia yields lactic acid

• Acidosis blunts the vasomotor response

• Local arteriolar dilation; blood pooling - cardiac output reduced - renal insufficiency-injury develops - endothelial damage: endovascular clotting - increasing tissue hypoxia: organ failure - vascular permeability leads to edema

Front 149

Irreversible shock

Back 149

• Lysosomal enzymes leak through damaged membranes- add to dysfunctions

• Renal shutdown from acute kidney injury/acute tubular necrosis (ATN)

• Myocardial contractility deteriorates

• Ischemia of viscera often occurs: - GI flora enter circulation

Front 150

What is the most common cause of familial hypercholesterolemia?

Back 150

• Heterozygotes - Plasma cholesterol increased from birth 2-3X

• Homozygotes - Plasma cholesterol 5-6X normal (>500mg/dL

Front 151

what are the lab findings of hypercholestolemia?

Back 151

Suspect familial hypercholesterolemia if: - Adults: Cholesterol > 350; LDL >270 - Children: Cholesterol > 270; LDL > 220

Front 152

What is the defect, its clinical, including morphologic findings?

Back 152

Heterozygotes - May exhibit cutaneous/tendinous xanthomas - Premature atherosclerosis develops in adults

• Homozygotes - Skin and tendinous xanthomas in childhood - Coronary, cerebral and peripheral vascular atherosclerosis in childhood; adolescence

Front 153

What genetic defect is associated with hypertriglyceridemia?

Back 153

- Hypertriglyceridemia various causes, including hepatic lipase deficiency

Front 154

endothelial dysfunction

Back 154

potentially reversible changes in functional state of endothelium in response to environmental stimuli

Front 155

Define endothelial activation

Back 155

11-2chart

Front 156

Describe the three steps involved in healing damaged intima (Figure 11-3)

Back 156

Migration of smooth muscle cells (SMC) from media to intima or SMC derived from circulating precursor cells –SMC proliferation (mitosis) –Elaboration of ECM by SMC

Hint 156

11-3

Front 157

What are the two major hemodynamic variables regulating normal blood pressure? (Figure 11-4)

Back 157

11-4

Front 158

Define the terms essential, secondary, benign and malignant hypertension. Which is the most common? (Table 11-1)

Back 158

11-1

Front 159

What are the mechanisms of essential hypertension?

Back 159

• Inherited variations may depend on cumulative effects of polymorphisms in several genes that effect blood pressure

• Environmental factors may initiate in genetically predisposed individual – Stress, obesity, smoking, physical inactivity

• Vasoconstrictive influences

• Reduced renal sodium excretion

Front 160

What form of hypertension is associated with hyperplastic arteriolosclerosis?

Back 160

– Related to acute, severe elevations of blood pressure, characteristic of malignant hypertension – Onionskin, concentric, laminated thickening of walls of arterioles with progressive narrowing of lumen

• May see necrotizing arteriolitis - deposits of fibrinoid and acute necrosis of vessel wall

Front 161

What form of hypertension is associated with hyaline arterilolsclerosis?

Back 161

– Common in diabetes – Major characteristic of benign nephrosclerosis – Homogenous, pink, hyaline thickening of the walls of arterioles with loss of underlying structural detail and narrowing of the lumen

Front 162

What are the three patterns of aterioslcerosis? Which pattern is the most frequent and clinically important?

Back 162

Atherosclerosis (dominant pattern) - intimal fibrous plaques with lipid rich core – Monckeberg’s medial calcific sclerosis - calcification of the media of muscular artery

• Usually adult older than 50, no clinical significance – Arteriolosclerosis - proliferation or hyaline thickening of walls of small arteries and arterioles

Front 163

What is the lesion that characterizes atherosclerosis? Describe the major components. (Figure 11-7)

Back 163

11-7

Front 164

What are the constitutional risk factors for ischemic heart disease? (Table 11-2) What are the modifiable risk factors? (Table 11-2)

Back 164

11-2

Front 165

Describe the response to injury hypothesis (Figure 11-10)

Back 165

11-10

Front 166

Using figure 11-11 as a model describe the major mechanisms of atherogenesis

Back 166

11-11

Front 167

What is a fatty streak? At what age do they appear? Do all fatty streaks become fibrous plaques?

Back 167

– Multiple yellow, flat spots, coalesce into elongated streaks – Lipid-filled foam cells – May appear before 1 yr, always present in older than 10 yrs – Not a clear cut relation to atheromas

Front 168

Recognize and describe the gross and microscopic findings (Figures 11-14, 11-15) Plaques

Back 168

11-14

Front 169

What are the three principle components of an atherosclerotic plaque?

Back 169

– Cells - SMC’s, macrophages, T lymphocytes – ECM – Lipids - intra and extracellula

Front 170

What clinically important complications/changes can happen to a plaque?

Back 170

– Rupture/fissuring

• Exposes thrombogenic plaque – Erosion/ulceration

• Exposes thrombogenic subendothelial BM to blood – Hemorrhage into the atheroma

Front 171

Atherosclerotic stenosis

Back 171

– Small vessels, plaque gradually occlude vessel lumen = ischemic injury – Critical stenosis

• Chronic occlusion significantly limits flow, demand exceeds supply

• Typically occurs at 70% fixed occlusion

• Patients develop angina

Front 172

Acute plaque change (Figure 11-15)

Back 172

11-15

Front 173

Thrombosis

Back 173

Most serious = superimposed thrombus on partially stenotic plaque converts lesion to total occlusion – Pieces can embolize – Potent activator of growth-related signals in SMC’s

Front 174

Vasoconstriction

Back 174

Adrenergic stimulation = increased BP, local vasoconstriction • Waking and rising = BP spikes = increased acute MI (6 am to 12 noon)

Front 175

How do atherosclerotic lesions cause disease?

Back 175

-Gradual narrowing of lumina with ischemia of tissues – Site for thrombosis and embolization – Sudden occlusion of vessel by hemorrhage or superimposed thrombosis – Weakens vessel wall, leads to aneurysm or rupture

Front 176

What are the four major clinical consequences of atherosclerosis?

Back 176

Myocardial infarction (heart attack) – Cerebral infarction (stroke) – Aortic aneurysms – Peripheral vascular disease (gangrene of legs)

Front 177

Be able to describe the pre-clinical and clinical phases of atherosclerosis (Figure 11-16)

Back 177

11-16

Front 178

What is the difference between and true and a false aneurysm (Fig. 11-18)?

Back 178

11-18

Front 179

What factors with respect to the connective tissue in the vascular wall can lead to an aneurysm?

Back 179

inherit weakness in connective tissue (marfans, etc) also inflamation-->increased mmp/decreased TIMP production scarring loss of smooth muscle

Front 180

Describe cystic medial degeneration. (Figure 11-19)

Back 180

11-19 a b

Front 181

What are the two major disorders which predispose to aortic aneurysms?

Back 181

• Atherosclerosis – abdominal aortic aneurysm (AAA)

• Hypertension – aneurysms of ascending aorta

Front 182

What is a mycotic aneurysm?

Back 182

- infection of a major artery that weakens wall

• Originate from: – Septic embolus lodges in vessel – Extension of adjacent infection – Circulating organisms directly infecting

Front 183

Where do aneurysms associated with atherosclerosis most commonly occur?

Back 183

abdominal aorta

Front 184

Who is more likely to get a AAA (age, sex, lifestyle)

Back 184

smokers, men, after 50

Front 185

What is a major cause of AAA?

Back 185

atherosclerosis

Front 186

Where are AAA’s usually located?

Back 186

below renal arteries above bifurcation of aorta

Front 187

Describe the gross appearance of a AAA (Figure 11-20)

Back 187

11-19actualy

Front 188

What are the five clinical consequences of AAA’s?

Back 188

Rupture into peritoneal cavity, retroperitoneal tissue = potentially fatal hemorrhage

– Impingement on adjacent structure

– Occlusion of branch vessel = ischemia downstream

– Embolism from atheroma or mural thrombus – Creation of abdominal mass – often palpably pulsating

– Most are aymptomatic

Front 189

At or above what size are AAA’s at greatest risk for rupture?

Back 189

>6cm >5cm managed surgically

Front 190

What are the clinical symptoms associated with a thoracic aortic aneurysm?

Back 190

– Respiratory difficulties, encroaches on lungs, airways – Difficulty swallowing, compresses esophagus – Persistent cough, pressure on recurrent laryngeal nerve – Pain caused by erosion of bone – Cardiac disease – Rupture

Front 191

What disease is a TAA associated with?

Back 191

hypertension

Front 192

What two groups of patients do dissections occur in?

Back 192

– Men 40 to 60 years old, 90% with hypertension – Patients with abnormality of connective tissue that affects aorta (Marfan syndrome)

Front 193

What is the major predisposing factor for dissections?

Back 193

– Cystic medial degeneration

Front 194

What is the most frequent detectable microscopic lesion? (Fig. 11-21)

Back 194

11-20

Front 195

What is the DeBakey classification for dissections (Figure 11-22)?

Back 195

11-20

Front 196

What are the classical clinical symptoms for a dissection?

Back 196

– Sudden onset of excruciating pain, anterior chest, radiating to back, moving downward – Confused with acute MI

Front 197

What is the most common cause of death with dissections?

Back 197

rupture of dissection into any of three major body cavities (pericardial, pleural or peritoneal)

Front 198

What are the two most common mechanisms for vasculitis? Why is it important to distinguish between the two?

Back 198

– Infectious pathogens - direct invasion – Immune-mediated inflammation

• Need to distinguish for therapeutic reasons – Immunosuppressive therapy for immune

Front 199

What are the common clinical findings in vasculitis?

Back 199

Fever, myalgias, arthralgias, malaise –Tissue ischemia

Front 200

What are the three main mechanisms which initiate noninfectious vasculitis?

Back 200

– Antineutrophil cytoplasmic antibodies

• Patients serum reacts with cytoplasmic antigens in neutrophils – Anti-endothelial cell antibodies – Autoreactive T cells

Front 201

In what two ways can ANCA’s be useful clinically?

Back 201

1. Certain types of vasculitis have specific association (eg c-ANCA=Polyangitis, P-ANCA=microscopic polyangitis, Churg-Strauss syndrome

2.Useful for diagnosis and following disease activity

Front 202

What is an ANCA? What are the two types?

Back 202

(Antineutrophil Cytoplasmic antibodies)

• Anti-myeloperoxidase (MPO-ANCA) – Old p-ANCA

• Anti-proteinase-3 (PR3-ANCA) – Old c-ANCA

Front 203

Giant cell (temporal) arteritis affects what size vessels?What age group is it seen in?

Back 203

medium arteries, typically in head, over age 50

Front 204

What is the major morphologic finding of giant cell arteritis? (Fig. 11-24)

Back 204

Segments of affected arteries develop nodular intimal thickenings with reduction of the lumen

• Granulomatous inflammation, giant cells and fragmentation of internal elastic lamina

Hint 204

11-24

Front 205

what are the symptoms of giant cell arteritis?

Back 205

– Rare before age 50

– May have insidious presentation (fever, fatigue, weight loss) or sudden onset of headache, tenderness with swelling and redness, facial pain – Can often see polymyalgia rheumatica

– Ocular symptoms serious (ophthalmic artery involved), occur in 50% of patients

Front 206

how is giant cell arteritis diaginosed definitively?

Back 206

– Biopsy may be diagnostic but 1/3 are negative due to segmental nature of lesion, need 2-3 cm length of vessel

– Negative biopsy doesn’t rule out disease

Front 207

what diseases are associated with giant cell arteritis?

Back 207

polymyalgia rheumatica (PMR), which is characterized by sudden onset of pain and stiffness in muscles

Front 208

how is giant cell arteritis treated?

Back 208

steroids

Front 209

what size vessel does Takayasu arteritis affect?

Back 209

medium and large arteries

Front 210

what is another name of Takaysu arteritis?

Back 210

granulomatous vasculitis, pulseless disease

Front 211

what are the two main symptoms of Takaysu arteritis?

Back 211

Ocular disturbance and weakening of upper-extremity pulses

Front 212

what are the major morphological findings of Takaysu arteritis?

Back 212

– Classically involves aortic arch, but 1/3 involve remainder of aorta and branches – ½ have pulmonary arteries involved – Irregular thickening of vessel wall with intimal hyperplasia – Aortic arch involvement = great vessels lumen decreased = pulseless disease – Mononuclear inflammation, granulomatous inflammation, then collagenous fibrosis

Front 213

what age group does Takaysu arteritis affect?

Back 213

under age 50

Front 214

what is the course of disease for Takaysu arteritis?

Back 214

Course of disease variable, rapid progression or quiescent stage after 1or 2 yrs

Front 215

PAN affects what size vessels?

Back 215

small or medium

Front 216

PAN affects renal and visceral vessels, what does it spare?

Back 216

pulmonary

Front 217

What are the morphologic features of PAN? (Fig. 11-26)

Back 217

– Segmental transmural necrotizing inflammation – Three stages (all may coexist): • Acute - fibrinoid necrosis, neutrophils, eosinophils, mononuclear cells • Healing - transmural scarring, continuing necrosis • Healed - fibrotic thickening

Hint 217

11-26

Front 218

Do PAN patients get glomerulonephritis?

Back 218

NOrenal artery involved, but not small renal vessls

Front 219

what age group does PAN affect?

Back 219

30-49 young adults

Front 220

what are common manifestations of PAN?

Back 220

Fever of unknown origin, weight loss, hypertension, abdominal pain, melena, muscle aches and pains, peripheral neuritis

Front 221

What is the course of disease for PAN with treatment? Without?

Back 221

Fatal if untreated, corticosteroids and cyclophosphamide result in 90% remission/cure

Front 222

How is PAN treated?

Back 222

corticosteroids and cyclophamide

Front 223

What other vasculitis has the same characteristic lesion as Churg-Strauss syndrome?

Back 223

PAN

Front 224

What are the three features of Churg-Strauss syndrome?

Back 224

Granulomas, infiltration of vessels and perivascular tissue with eosinophils

Front 225

What ANCA is Churg-Strauss syndrome associated with?

Back 225

– P-ANCA present in 50%

Front 226

What is the other name for Kawasaki disease? What arteries does it involve?

Back 226

Mucocutaneous lymph node syndrome involves corornary arteries

Front 227

What are the symptoms of mucocutaneous lymph node syndrome?

Back 227

• Fever, conjunctival and oral erythema and blistering, edema of hands and feet, erythema of palms and soles and later desquamation

• Cervical lymphadenopathy

Front 228

Patients with MLNS develop what complications? What are the morphologic features?

Back 228

aneurysm that rupture or thrombose-->MI in children under 4 Transmural necrosis, inflammation like PAN but not as severe necrosis

Front 229

How does microscopic polyangiitis present?

Back 229

palpable purpura involving skin or involvement of mucous membranes, lungs, brain, heart, GI tract, kidneys and muscle

Front 230

What size vessels are affected in microscopic polyangiitis?

Back 230

Arterioles, capillaries, venules

Front 231

Major clinical features of microscopic polyangitis?

Back 231

hemoptysis, hematuria, proteinuria, arthralgias, bowel pain, muscle pain/weakness, hemorrhage

Front 232

How is a definitive diagnosis or microscopic polyangitis made?

Back 232

•P-ANCA (MPO-ANCA’s) in 70%

•Skin biopsy often diagnostic

Front 233

What two features distinguish microscopic polyangitis from PAN?

Back 233

pulmonary involvement (pulmonary capillaritis) and glomerulonephritis

Front 234

Morphologic features of polyangitis(Fig. 11-27A)

Back 234

Segmental fibrinoid necrosis or infiltration with neutrophils which fragment - leukocytoclasia

Front 235

What is the triad that characterizes Wegener Granulomatosis?

Back 235

– Acute necrotizing granulomas of upper (ear, nose, sinus ,throat) and/or lower respiratory tract(lung)

– Necrotizing or granulomatous vasculitis of small to medium size vessels mostly in lung and upper airway, can have other sites

– Renal disease – focal necrotizing, often crescentic, glomerulonephritis

Front 236

What are the major morphological features of Wegener Granulomatosis?

Back 236

Probable T-cell mediated hypersensitivity reaction - ? Inhaled infectious agent, environmental agent

Front 237

Wegener Granulomatosis affects what ages and sex?

Back 237

Male >female, 40 yrs average

Front 238

What are the clinical features of Wegener Granulomatosis?

Back 238

Pneumonitis with bilateral nodular and cavitary infiltrates, chronic sinusitis, ulceration of nasopharynx, evidence of renal disease

Front 239

What is the natural course of disease in Wegener Granulomatois?

Back 239

– Untreated – 80% die within one year

Front 240

What ANCA is Wegener Granulomatosis associated with?

Back 240

– C-ANCA (PR3-ANCA) in 95% - good marker for disease activity

Front 241

What is the other name for thromboangiitis obliterans?What group of people get it?

Back 241

–Buerger Disease –Heavy cigarette smokers • Used to be predominantly male –Usually before age 35

Front 242

What are the morphological features of thromboagiitis obliterans?

Back 242

–Acute and chronic inflammation with luminal thrombosis

–Microabscesses within thrombus, wall of granulomatous inflammation

Front 243

What can be done to prevent further attacks of thromboangiitis obliterans?

Back 243

Stop smoking early in disease = relief from further attacks

Front 244

Clinical features? (Fig. 11-29)

Back 244

– Paroxysmal pallor or cyanosis of digits of hands or feet

– Involved digits show red, white, blue color changes, proximal to distal

Front 245

What is Raynaud phenomenon?

Back 245

Exaggerated vasoconstriction of digital arteries and arterioles; Red, White, and Blue

Front 246

Who gets primary Raynaud phenomonen? What precipitates the attack?

Back 246

– Exaggeration of normal central and local vasomotor responses to cold or emotion

– Prevalence 3% to 5%, young female

Front 247

What is secondary Reynaud phenomonen?

Back 247

– Vascular insufficiency of extremities, secondary to arterial narrowing from various processes

• SLE, scleroderma, atherosclerosis and Buerger disease – Raynaud may be first manifestation of condition, rule out underlying cause

Front 248

What is the natural course of Raynaud phenomenon?

Back 248

– Usually benign course

Front 249

What are varicose veins?

Back 249

Abnormally dilated, tortuous veins due to increased intraluminal pressure and loss of vessel wall support

Front 250

What veins typically become varicose?

Back 250

superficial leg veins

Front 251

what are predisposing factors for developing varicose veins?

Back 251

Obese individuals and women (pregnancy) at risk

• Familial tendency may be due to defective venous wall development

Front 252

what are the sequelae of varicose veins?

Back 252

– Persistent extremity edema – Trophic skin changes

• Stasis dermatitis

• Ulcerations

• Poorly healing wounds and infections may become chronic varicose ulcers

• Vulnerable to injury – Embolism or other serious complications very RARE

Front 253

what are the clinical symptoms associated with varicose veins?

Back 253

Venous stasis –Congestion –Edema –Pain –Thrombosis

Front 254

What veins account for majority of cases of thrombophlebitis and phlebothrombosis?

Back 254

– Deep leg veins account for >90% of cases

Front 255

What is migratory thrombophlebitis' other name?

Back 255

Trousseau sign

Front 256

What factors predispose one for thrombophlebitis and phlebothrombosis?

Back 256

• Prolonged immobilization resulting in decreased blood flow through veins, most important

• Congestive heart failure, neoplasia, pregnancy, obesity

• Postoperative state

• Systemic hypercoagulability

Front 257

What are the local manifestations of thrombophlebitis and phlebothrombosis?

Back 257

– Edema distal to occluded vein – Dusky cyanosis – Dilation of superficial veins – Heat, tenderness, redness, swelling, pain

Front 258

what are serious complications of thrombophlebitis and phlebothrombosis?

Back 258

Pulmonary embolism serious complication of DVT

• Pulmonary embolus may be first sign of DVT

Front 259

Clinical features superior vena caval syndrome ?

Back 259

–Dusky cyanosis, –Marked dilation of veins of head, neck and arms

Front 260

The superior vena caval syndrome is cause by what?

Back 260

Usually caused by neoplasms that compress or nvade superior vena cava

• Primary bronchogenic carcinoma

• Mediastinal lymphoma

Front 261

Clinical features inferior vena caval syndrome?

Back 261

• Marked leg edema

• Distention of superficial veins of lower abdomen

• Massive proteinuria (renal veins involved)

Front 262

The inferior vena caval syndrome is caused by what?

Back 262

– Neoplasms compress or penetrate walls of vena cava or thrombus may propagate upwards

• Hepatocellular carcinoma and renal carcinoma have propensity to grow within lumens of veins with ultimate extension to vena cava, may cause obstruction

Front 263

When does systolic dysfunction occur?

Back 263

•Ischemic injury, pressure/volume overload, dilated cardiomyopathy

Front 264

When does diastolic dysfunction occur?

Back 264

•Massive LV hypertrophy, myocardial fibrosis, deposition of amyloid, constrictive pericarditis

Front 265

What three mechanisms does the cardiovascular system use to maintain pressure and perfusion in the face of damage or excess burden?

Back 265

•Frank-Starling

•Myocardial hypertrophy with/without cardiac chamber dilation

•Activation of neurohumoral systems

Front 266

What two features characterize CHF?

Back 266

•Diminished cardiac output - forward failure •Damming back of blood - backward failure

Front 267

What are the three most common underlying disease states for CHF? (Fig. 12-2)

Back 267

12-2

Front 268

What are the two patterns of hypertrophy in the heart? (Fig. 12-2)

Back 268

12-2

Front 269

What four morphologic features are seen in the heart in CHF? (Fig. 12-1)

Back 269

-Increased heart weight -Progressive wall thinning -Chamber dilatation -Microscopic changes of hypertrophy

Hint 269

12-1

Front 270

What are the four most common causes of left-sided heart failure?

Back 270

•Ischemic heart disease

•Hypertension

•Aortic and mitral valvular disease

•Nonischemic myocardial diseases

Front 271

What happens to the left atrium in left heart failure?

Back 271

•Atrial enlargement occurs, leads to atrial fibrillation

•May cause blood stasis with thrombus formation, especially in appendages

•Leads to increased risk for embolic stroke

Front 272

What three changes occur in the lungs with left heart failure?

Back 272

•Pressure in pulmonary veins increases, transmitted retrogradely leads to pulmonary congestion and edema

•Perivascular and interstitial transudate •Edematous widening of alveolar septa

Front 273

What are heart failure cells?

Back 273

- hemosiderin containing macrophages in alveoli

Front 274

What are the possible clinical manifestations of the lung changes?

Back 274

•Dyspnea - breathlessness

•Orthopnea - dyspnea on lying down relieved by sitting/standing

•Paroxysmal nocturnal dyspnea - attacks of extreme dyspnea bordering on suffocation •Cough

Front 275

What is the most common cause of right heart failure?

Back 275

Most commonly right sided heart failure is caused by left sided failure

Front 276

Pure right-sided heart failure occurs with what? What is it called in this case?

Back 276

called cor pulmonale

•RV pressure overload due to intrinsic disease of lungs or pulmonary vasculature

Front 277

What four changes occur in the liver in CHF?

Back 277

•“Nutmeg” liver - chronic passive congestion, congested red centers of liver lobules surrounded by paler peripheral regions •Centrilobular necrosis

•Central hemorrhagic necrosis - severe, rapidly developing failure leads to rupture of sinusoids •Cardiac sclerosis - long standing severe failure, central areas become fibrotic

Front 278

What happens to the spleen in CHF?

Back 278

•Splenic congestion - enlarged, firm spleen, may weigh 500 to 600 gm (150 nl), fibrous thickening of sinusoidal walls = congestive splenomegaly

Front 279

What is ascites?

Back 279

transudate in peritoneal cavity

Front 280

What is anasarca?

Back 280

Massive and generalized peripheral edema

Front 281

What five categories of heart disease account for almost all cardiac mortality?

Back 281

•Ischemic heart disease (80 to 90%) •Hypertensive heart disease and pulmonary hypertensive heart disease

•Certain valvular disease

•Congenital heart disease

•Nonischemic (primary) myocardial disease

Front 282

What category of heart disease accounts for 80-90% of deaths?

Back 282

ischemic heart disease

Front 283

In 90% or more of cases what is the underlying cause of myocardial ischemia?

Back 283

90% of cases related to perfusion deficiency due to reduction in coronary blood flow (atherosclerosis of arteries)

Front 284

What is another name for IHD?

Back 284

•Coronary artery disease (CAD) •Coronary heart disease (CHD)

Front 285

What four syndromes describe the clinical manifestations of IHD?

Back 285

Angina pectoris (three variants)

•Myocardial infarction

•Chronic ischemic heart disease

•Sudden cardiac death

Front 286

What two things have led to a decrease in death due to IHD?

Back 286

•Prevention by changed lifestyle, decreases risk •Diagnostic and therapeutic advances

Front 287

What is acute plaque change?

Back 287

abrupt plaque change followed by thrombosis

Front 288

What disruptions may occur in IHD?

Back 288

•Hemorrhage

•Rupture and fissuring

• Erosion/ulceration

Front 289

What are the acute coronary syndromes?

Back 289

•Unstable angina,

•Acute MI

•Sudden cardiac death

Front 290

Define angina

Back 290

•Paroxysmal attacks of substernal or precordial chest discomfort caused by:

• transient (15 seconds to 15 minutes) myocardial ischemia

Front 291

What are the 3 angina patterns called?

Back 291

•Stable or typical angina

•Prinzmetal’s or variant angina

•Unstable or crescendo angina

Front 292

What are the symptoms and underlying cause for stable angina?

Back 292

•Due to reduction of coronary perfusion to a critical level by chronic stenosing atherosclerosis •Relieved by rest and nitroglycerin and calcium channel blockers

Front 293

What are the symptoms and underlying cause for prinzmetal's angina?

Back 293

•Pattern of episodic angina that occurs at rest •Due to coronary artery spasm

•Elevation of ST segment on EKG

•Responds to nitroglycerin and calcium channel blockers

Front 294

What are the symptoms and underlying cause for unstable angina?

Back 294

•Pain occurs with progressively increasing frequency, precipitated with less effort, often occurs at rest, of prolonged duration

•Induced by fissuring, ulceration or rupture of plaque with superimposed (partial) thrombus and possibly embolization

•Often prodrome of MI = preinfarction angina

Front 295

What is an MI?

Back 295

Heart Attack

•Death of cardiac muscle resulting from ischemia

Front 296

What are the two types of MI and how do they differ?

Back 296

•Transmural (more common) -Ischemic necrosis involves the full or nearly full thickness of ventricular wall in distribution of single coronary artery

•Subendocardial -Ischemic necrosis limited to the inner on-third or at most one half of the ventricular wall, extends laterally beyond perfusion area of single artery

Front 297

Which sex is protected from MI until middle age?

Back 297

Women have less MI until middle age

Front 298

What sequence of events occurs with an MI?

Back 298

•Sudden change in morphology of plaque (hemorrhage, fissuring/rupture, ulceration/erosion)

•Platelet exposed to collagen and plaque, leads to platelet activation, aggregation with formation of platelet mass - may give rise to emboli or occlusive thrombosis

•Vasospasm due to mediators released by platelets

•Activated platelets release factors predisposing to coagulation and favoring vasospasm

•Often, within minutes thrombus evolves to become completely occlusive

Front 299

What other three possible events unrelated to atherosclerosis may occur causing an MI?

Back 299

•Vasospam +/- atherosclerosis may cause deficit •Emboli from left mural thrombosis, vegetative endocarditis, paradoxic emboli from right •Unexplained – no atherosclerosis or thrombosis

Front 300

What seven things account for the location, size and morphologic features of an MI?

Back 300

•Location, severity and rate of development of coronary occlusion

•Size of vascular bed perfused by vessel •Duration of occlusion

•Metabolic/oxygen needs of at risk myocardium

•Extent of collaterals

•Presence site and severity of coronary arterial spasm

•Alterations in blood pressure, heart rate and cardiac rhythm

Front 301

How does a transmural infarct differ from a subendocardial infarct?

Back 301

12-12

Front 302

Describe the sequence of events grossly and microscopically for an MI (Table 12-5)

Back 302

12-5

Front 303

How may reperfusion to an infarct occur?

Back 303

-Thrombolysis -Ballon Angioplasty -Coronary arterial bypass graft -Stent

Front 304

What pathologies may occur in an infarct with reperfusion?

Back 304

•Reperfusion-induced arrhythmias

•Myocardial hemorrhage with contraction bands •Irreversible cell damage due to the reperfusion itself

•Microvascular injury

•Prolonged ischemic dysfunction – Stunned myocardium

Front 305

What two laboratory measurements are useful to diagnose an acute MI? (Fig. 12-17)

Back 305

12-17

Front 306

What four factors are associated with a poor prognosis after an MI?

Back 306

• Diabetes, female, advanced age, previous MI

Front 307

What are the 11 possible complications following an MI? (Fig. 12-18)

Back 307

– Cardiac arrhythmia's

- conduction disturbances or myocardial irritability

– Contractile dysfunction

– Cardiac rupture syndromes - occur 3-7 days post MI

– Infarct extension - new necrosis adjacent to old

– Infarct expansion - stretching, thinning dilatation of infarct region

– Ventricular aneurysm - late complication

– Papillary muscle dysfunction

– Mural thrombus

– Progressive late heart failure

– Right ventricular infarction

– Pericarditis

Front 308

With regards to myocardial rupture which type is most common and when is it most likely to happen after an MI?

Back 308

3-7 days after MI ventricular free wall most common and typically means death

Front 309

What happens with papillary muscle rupture?

Back 309

Papillary muscle rupture = acute mitral regurgitation

Front 310

What three things determine complications and prognosis after an MI?

Back 310

– Infarct size – Site – Transmural extent

Front 311

What age group is affected by Chronic Ischemic Heart disease?

Back 311

elderly

Front 312

What is the clinical history of Chronic Ischemic Heart disease?

Back 312

– Usually elderly, often prior MI, previous CABG – Insidious development of CHF as a result of ischemic damage - posinfarction cardiac decompensation

Front 313

what is the morphology of Chronic Ischemic Heart disease?

Back 313

• Usually enlarged and heavy due to LV hypertrophy and dilation

• Scars of previous infarcts, coronary vessel disease

Front 314

What is sudden cardiac death?

Back 314

– Unexpected death from cardiac causes early (within 1 hour) after or without onset of symptoms

Front 315

What is the ultimate mechanism of death in sudden cardiac death?

Back 315

lethal arrythmia

Front 316

What are the minimum criteria for diagnosing systemic hypertensive heart disease?

Back 316

– Left ventricular hypertrophy (concentric) in absence of other causative pathology – History or pathologic evidence of hypertension

Front 317

What is the morphology of systemic hypertensive heart disease? Clinical ? (Fig. 12-20)

Back 317

12-20

Front 318

Pulmonary hypertensive disease is referred to as what?

Back 318

cor pulmonale

Front 319

What are the two types of cor pulmonale?

Back 319

– Acute - RV dilation due to massive pulmonary embolism – Chronic - RV hypertrophy and later dilation secondary to prolonged pressure overload from obstruction of pulmonary arteries or compression of septal capillaries

Front 320

What are the four groups of disorders predisposing to cor pulmonale? (Table 12-7)

Back 320

12-7

Front 321

what is the gross morphology of cor pulmonale?

Back 321

– Right ventricular enlargement secondary to pulmonary hypertension caused by disorders that effect lungs or pulmonary vasculature

Front 322

What is valvular stenosis? Insufficiency?

Back 322

– Stenosis - failure of valve to open completely – Insufficiency (regurgitation) - failure of valve to close completely

Front 323

Two causes of regurgitation?

Back 323

– valve incompetent due to dilation of ventricle or dilation of aortic or pulmonary artery

Front 324

Mitral stenosis

Back 324

rheumatic heart disease

Front 325

Mitral insufficiency

Back 325

myxomatous degeneration (mitral valve prolapse)

Front 326

Aortic stenosis

Back 326

calcification of anatomically normal and congenitally bicuspid aortic valves

Front 327

Aortic insufficiency

Back 327

dilation of ascending aorta, related to hypertension and aging

Front 328

What are the two types of calcific aortic stenosis?Which is more common?

Back 328

senile calcific aortic stenosis (majority cases) and congenital bicuspid aortic valve

Front 329

What does the term senile calcific aortic stenosis refer to?

Back 329

wear and tear due to age

Front 330

What is the hallmark lesion of calcific aortic stenosis? (Fig. 12-21)What is the gross morphology?

Back 330

Heaped up nodular masses of calcium within sinuses of Valsalva, primarily at base, no commissure fusion

Front 331

What is the anatomic change in the heart associated with mitral valve prolapse?(Fig. 12-22)

Back 331

Myxomatous 'degeneration of the mitral valve – One or both valve leaflets are enlarged, redundant or floppy

Hint 331

12-22

Front 332

What are the serious complications of MVP?

Back 332

– 3% develop complications

• Infective endocarditis

• Mitral insufficiency

• Stroke of systemic infarct from thrombi that form on valve

• Arrhythmias, sudden death uncommon

• Most common cause for mitral valve surgery

Front 333

Who is at increased risk of having MVP?

Back 333

Common condition, >/= 3% of population, young women

Front 334

Describe acute rheumatic fever of childhood - Jones criteria, labs (Fig. 12-23)

Back 334

• RF – Jones Criteria

–Major manifestations

• Migratory polyarthritis of large joints

• Carditis

• Subcutaneous nodules

• Erythema marginatum of skin

• Sydenham’s chorea - neurologic disorder –

--Minor

• Fever

• Arthralgias

• Acute phase reactants

• Diagnosis by Jones criteria – Evidence of streptococcal infection, presence of 2 major or 1 major and 2 minor

Front 335

What are the morphologic features of acute rheumatic pancarditis? Pathogenesis?

Back 335

– Aschoff bodies

• Collagen surrounded by lymphocytes and plump macrophages – Myocardium - Aschoff bodies – Pericardium - fibrinous pericarditis – Endocardium - fibrinoid necrosis with small vegetations (verrucae)

Front 336

What is the most important consequence of acute rheumatic carditis?

Back 336

most important is develop ment of chronic rheumatic heart disease – Deforming fibrotic valve disease (mitral stenosis)

• Severe, sometimes fatal, cardiac dysfunction decades later

Front 337

What are the features of chronic RHD?

Back 337

Valvular stenosis and regurgitation (predominantly stenosis) – Most frequesnt cause of mitral stenosis (99%) – Mitral valve alone, 70% cases – Combined mitral, aortic 25% – Tricuspid less common, pulmonic very rare

Front 338

Define infective endocarditis (IE).

Back 338

Microbial infection of heart valves or mural endocardium that leads to formation of vegetations composed of thrombotic debris and organisms

Front 339

What are the predisposing factors for subacute bacterial endocarditis? What organisim? What complications?

Back 339

Clinical course of weeks/months

• Previously damaged valves in half

• Low virulence organisms are usual - Streptococcus viridans group (oral source) --most common cause: 60% of cases - Staphylococcus epidermidis infects prostheses - HACEK group, oral commensals - Streptococcus bovis (GI tract infections) - Enterococci (GU tract)

Front 340

What are the predisposing factors for acute bacterial endocarditis? What organisim? What complications?

Back 340

-Heart valve usually normal prior to infection - Abrupt onset of fever and chills, lassitude - New murmur due to vegetations, valve destruction • Early complications of bacteremia and embolization of vegetations(metastatic infection) • Causes: virulent organisms - eg. Staphylococcus aureus in IV drug users

Front 341

What valves are most commonly affected by endocarditis?

Back 341

-mitral and/or aortic are most common: source of systemic emboli - tricuspid in 50% of IV drug-use related IE : source of pulmonary emboli

Front 342

What are the clinical features of systemic septic embolization?

Back 342

Janeway lesions

Front 343

What are usual cause and types of complications related to tricuspid endocarditis

Back 343

Lung abscess: may be due to embolization from tricuspid vegetations

Front 344

Describe the cardiac morphology and cardiac complications of infective endocarditis.

Back 344

• Vegetations on heart valves are bulky, friable (easily reduced to powder)

• Localization of vegetations on valves - atrial side of AV valves - ventricular surface of semilunar valves

• Valves involved: - mitral and/or aortic are most common: source of systemic emboli - tricuspid in 50% of IV drug-use related IE : source of pulmonary emboli

Front 345

What are the associations of NBTE?

Back 345

Associated with debilitation: cancer; wasting (hypercoaguable states)

Front 346

Define Libman Sacks endocarditis and know associations.

Back 346

LUPUS

• Uncommon; due to current therapies

• Small, sterile warty vegetations most commonly seen on undersurface of mitral/tricuspid valves

• Micro: granular, fibrinous eosinophilic material with cellular debris/remnants - fibrinoid valvulitis of valve substance due complement activation; Fc-receptor cells

• Thrombotic lesions may also be assoc. with antiphospholipid antibody syndrome

Front 347

What are the cardiac morphology and cause of carcinoid heart disease?

Back 347

Cardiac lesion: Fibrous intimal thickening of right ventricle, pulmonic/tricuspid valves - acid mucopolysaccharide matrix deposited - tricuspid insufficiency is most common - pulmonic stenosis may occur - left side usually spared except when carcinoid tumor is in the lung or cardiac shunt present

Front 348

What other substances are associated with similar morphology to carcinoid heart disease?

Back 348

Lesion on left due to drugs: ergots, phen-fen (fenfluramine) metabolized in lung to serotonin

Front 349

What ar the clinical feature of carcinoid syndrome?

Back 349

- Episodic flushing, diarrhea, dermatitis andbronchoconstriction due to bioactive compounds such as serotonin released by carcinoid tumors

Front 350

What are the complications of artificial heart valves?

Back 350

• Thromboembolic disease

• Infective endocarditis - uncommon

• Structural deterioration is the major cause of bioprosthesis failure

• Nonstructural dysfunction - hemolytic anemia- shear forces - inadequate healing with paravalvular leak - exuberant healing with fibrosis

Front 351

How are bioprosthetic and mechanical type valves different? Need for anticoagulation?

Back 351

• Mechanical - tilting disks; semicircular flaps - requires life long anticoagulation

• Bioprosthetic- treated; largely nonviable - treated animal tissue: porcine aortic valve; bovine pericardium or human cadaver valve - graft rejection does not occur - prone to failure and requiring replacement

• Serious complications occur in 60% w/in 10 yrs

Front 352

What is cardiomyopathy?

Back 352

heterogenous group of diseases of myocardium…usually exhibit inappropriate ventricular hypertrophy or dilation …variety of causes…frequently genetic…confined to heart or part of systemic disease…often lead to cardiovascular death

Front 353

What causes hypertrophic cardiomyopathy?

Back 353

- Hypertrophic: diastolic dysfunction

Front 354

What causes dilated cardiomyopathy?

Back 354

Dilated (DCM): systolic dysfunction

Front 355

What causes restrictive cardiomyopathy?

Back 355

Restrictive: diastolic dysfunction

Front 356

Is hypertrophic cardiomyopathy a systolic or diastolic dysfunction?

Back 356

diastolic

Front 357

Is dilated cardiomyopathy a systolic or diastolic dysfunction?

Back 357

systolic

Front 358

Is restrictive cardiomyopathy a systolic or diastolic dysfunction?

Back 358

systolic

Front 359

what is the morphology of hypertrophic cardiomyopathy? Recognize 12-32; 12-34

Back 359

• Heavy muscular hypercontracting heart developing in the absence of identifiable extrinsic stress

• Incidence 1 /500; heterogenous; genetic

• Left ventricular ejection fraction 50-80% (normal)

• Mechanism of failure: impaired compliance; diastolic dysfunction; reduced filling

• Intermittent ventricular outflow obstruction in 1/3

Front 360

what is the morphology of dilated cardiomyopathy? Recognize 12-32; 12-34

Back 360

Globular shaped regurgitation Hypertrophy fibrosis

Front 361

what is the morphology of restrictive cardiomyopathy? Recognize 12-32; 12-34

Back 361

ventricles normal size or slightly enlarged and firm; ***biatrial dilation***

Micro: variable fibrosis or specific infiltrate

Front 362

what are the clinical findings of hypertrophic cardiomyopathy?

Back 362

• Impaired diastolic filling of left ventricle: reduced size; poor compliance “ heart failure with preserved ejection fraction”

• Intermittent left ventricular outflow obstruction • Reduced output; increase in pulmonary venous pressure--> exertional dyspnea

• Harsh systolic ejection murmur • Myocardial ischemia with angina • Ventricular arrhythmias

Front 363

what are the clinical findings of dilated cardiomyopathy?

Back 363

• Age, any: peak 20-50

• Progressive CHF- shortness of breath, etc

• Half die in 2 yrs. - heart failure - arrhythmia; secondary mitral regurgitation - pulmonary/systemic emboli

• Systolic dysfunction: ejection fraction < 25% in terminally ill patients ( normal ~60%)

• Treatment: ventricular assist; transplantation

Front 364

what are the clinical findings of restrictive cardiomyopathy?

Back 364

• Heart failure due to diastolic dysfunction

• Ejection fraction near normal

• Morphology on echocardiogram; radiography - Ventricles: may demonstrate mild wall thickening; may be normal

**** Atria are dilated****

Front 365

what are the causes of dilated cardiomyopathy?

Back 365

•Idiopathic--cause unknown

• Previous myocarditis - viral; Chagas’ disease

• Alcohol abuse; other toxicity

• Peripartum cardiomyopathy: pregnancy

• Supraphysiologic stress

• Genetic/familial cause

Front 366

What chemotherapies are associated with cardiomyopathy?

Back 366

Doxorubicin (Adriamycin), Tyrosine kinase inhibitors Her-2 neu (trastuzumab; Herceptin) blocker

Front 367

What is the morphology of cocaine/other stimulant and reperfusion myocardial injury?

Back 367

Morphology: focal myocyte necrosis; contraction bands, sparse inflammatory cell infiltrate (Contraction band necrosis also occurs in reperfusion injury)

Hint 367

layla

Front 368

What cardiac pathology is associated with iron overload?

Back 368

Cardiomyopathy due to Iron Overload

• Mechanism of injury - Iron interference with metal-dependent enzyme systems - Reactive oxygen species

Front 369

What cardiac pathology is associated with hyperthyroidism?

Back 369

Cardiomyopathy due to Supraphysiologic Stress (similar morphology to cocaine induced cardiomyopathy)

Front 370

What are the features of senile cardiac amyloidosis?

Back 370

--- amyloid type is transthyretin; accumulates with aging (nonmutant) and when mutated --- African Americans > Caucasians

Front 371

What are the causes of restrictive cardiomyopathy?

Back 371

- Amyloidosis- protein accumulates between cells - Radiation fibrosis; metastatic tumor - Sarcoidosis (inflammatory disease) - Inborn errors of metabolism (Pompe, Fabry and glycogen storage dis. III., Hurler syndrome)

Front 372

List 3 uncommon, distinctive causes of restrictive cardiomyopathy.

Back 372

• Endomyocardial fibrosis - children; young adults in Africa; mural thrombus

• Loeffler endomyocarditis - fibrosis associated with eosinophilia - PDGFR activation from myeloproliferative disorder causes fibrosis; Tx imatinib

• Endocardial fibroelastosis - childhood; congenital cardiac anomalies-1/3 - mutation mitochondrial gene; prenatal virus - thickened LV endocardium: insignificant to fatal

Front 373

Define myocarditis

Back 373

***Inflammatory*** involvement of heart muscle characterized by a leukocyte infiltrate not secondary to ischemia; causes nonischemic degeneration of myocytes

Front 374

What are the most common causes of myocarditis? figure 12-35

Back 374

- Infections are the most common cause - Immune-mediated reactions

Front 375

What type of myocarditis has the worst prognosis?

Back 375

Chronic Chagas disease?? (Trypansoma cruzii)

Front 376

What are complications of heart transplantation (page 572)?.

Back 376

• Graft rejection

• Complications of immunosuppression

• Graft arteriopathy- coronary artery stenosis occurs at accelerated pace

Front 377

What alterations in laboratory tests are seen in heart failure?

Back 377

• Creatinine, BUN increased - initially due to poor renal perfusion - prolonged failure --> permanent renal damage

• Elevated AST, ALT from hepatic congestion/ nutmeg liver

• N Terminal pro B natriuretic peptide; B natriuretic peptide: cardiac distension/ stretch • Galectin-3: marker for fibrosis; 40-50% of HF; predicts slower recovery; disease progression

• ST2: interacts with IL-33; marker of inflammation,stretch. Correlates with poorer prognosis

Front 378

What are the clinical features of pericarditis?

Back 378

• May be asymptomatic; present as enlarged heart on chest radiograph due to effusion

• May resemble ischemic heart disease

• Intense chest pain, accentuated on inspiration, relieved by sitting up

• Pain may radiate to shoulder, trapezius ridge

• Effusion - Slow accumulation tolerated - Rapid, as little as 200ml --cardiac tamponade

Front 379

What is the likely outcome of serous pericarditis? Morphology?

Back 379

• Causes - Noninfectious inflammatory conditions - Viral infections eg, Coxsackie virus extension from myocarditis

• Morphology: mild infiltrates of lymphs in epipericardial fat

• Organization and adhesions uncommon

Front 380

What is the likely outcome of fibrinous pericarditis? Morphology?

Back 380

Causes:

• Acute myocardial infarction

• Postinfarction (Dressler’s) syndrome: autoimmune reaction to MI several days to weeks later

• Autoimmune disease- rheumatic fever; rheumatoid arthritis; SLE

• Morphology: “bread and butter” granular roughening

• Friction rub may be heard on auscultation

• Sequelae - Organization into adhesions is common

Front 381

What is the likely outcome of purulent pericarditis? Morphology?

Back 381

• Due to bacterial infection

• Examples: - Extension from pneumonia; - Ring abscess of endocarditis - Surgical introduction

• Clinical findings same as fibrinous pericarditis

• Sequelae - organization into adhesions; mediastinopericarditis or constrictive pericarditis

Front 382

What is the likely outcome of caseous pericarditis? Morphology?

Back 382

Causes: Tuberculosis; some fungi

• Outcome: Fibrocalcific, chronic constrictive pericarditis is likely

Front 383

What are the clinical features of cardiac tamponade?

Back 383

• Triad of: - Hypotension (see obstructive shock) - Jugular venous distension - Muffled heart sounds • Pulsus paradoxus: systolic blood pressure during inspiration drops >10mmHg

Front 384

Describe adhesive mediatinopericarditis

Back 384

• Healed pericarditis following suppurative or caseous pericarditis or cardiac surgery

• Parietal pericardium adheres to heart and surrounding structures

• Results in cardiac hypertrophy and dilatation

Front 385

What are causes, clinical features of constrictive pericarditis?

Back 385

• Heart encased in fibrous or fibrocalcific scar

• Diastolic expansion limited

• Concretio cordis: extreme type- thick layer of calcification • Follows tuberculosis, suppurative infection or hemorrhage; may be idiopathic

• Clinical: heart failure, quiet heart with reduced output; - cardiac hypertrophy/dilation cannot occur

Front 386

What are the morphologic features of 22q11 deletion?

Back 386

"Catch 22" --Cleft palate (other facial abnormalities) - Absent Thymus or hypoplastic thymus - Cardiac anomalies--outflow tract --truncus arteriosus; double outlet RV; tetralogy of Fallot and others - Hypoplasia of parathyroids; hypoparathyroidism--> hypocalcemia

Front 387

Describe the findings in right to left shunts

Back 387

• “Cyanotic (blue) congenital heart disease” • Inadequate oxygenation of blood= cyanosis of skin/mucous membranes • Consequences - Paradoxical emboli - Hypertrophic pulmonary osteoarthropathy (clubbing of fingers) - Polycythemia- increased Hct/increased RBCs with risk of cerebral thrombosis

Front 388

Describe the findings in left to right shunts, including Eisenmenger syndrome

Back 388

• Cyanosis initially absent

• Increased pulmonary blood flow--> pulmonary hypertension - limits surgical correction of defects

• Eisenmenger’s syndrome - “late cyanotic congenital heart disease” or cyanose tardive - L-to-R shunt becomes a R-to-L shunt due to pulmonary hypertension

Front 389

List causes of left to right shunts

Back 389

• Ventricular septal defect VSD - most common heart defect

• Atrial septal defect ASD

• AV septal defect

• Patent ductus arteriosus PDA

• (note “D” in name)

Front 390

What are complications of CHD in general?

Back 390

• Cardiac hypertrophy and dilatation with heart failure

• Infective endocarditis from jet stream injury

• Retarded development/ failure to thrive

• Increased complications of infectious diseases of childhood

Front 391

What type of atrial septal defect is most common?

Back 391

1- Septum secundum 90%

2- Septum primum assoc w/ cleft mitral valve

3- Sinus venosus

4- Coronary sinus (rare)

Front 392

What are the features including complications of atrial septal defect (ASD)?

Back 392

Left-to-right shunt• May be isolated or associated with other defects

• Presentation of isolated ASD- May be asymptomatic into adulthood- Large defects may present with neonatal CHF - Pulmonic valve murmur due to excessive blood flow- Pulmonary hypertension uncommon, <10%

• Treatment: - Closure to prevent complications, eg. paradoxical emboli; infective endocarditis

Front 393

What are the frequency and significance of patent foramin ovale in adults?

Back 393

• Fuses in 80% of neonates

• Remaining 20% may re-open due to pulmonary hypertension - eg, multiple or recurrent PEMay lead to emboli formation

Front 394

What are the frequency, most common location and outcomes of VSD?

Back 394

• Left to right shunt

• 20-30% isolated defect; other defects in rest

• Defect types- Membranous septum- common- Muscular -- may close spontaneously -- may be multiple, “Swiss-cheese septum”

Front 395

What are the features of PDA? How is patency maintained; how might it be closed w/o surgery? Why maintain patency?

Back 395

• Left-to-right shunt

• Usually an isolated defect

• Presentation- Machinery murmur- Normal cardiac function at birth

• Maintain patency (for survival in some defects): administer prostaglandin E

• To close: give indomethacin or ibuprofen (nonsteroidal anti-inflammatory drugs)

• Closed becomes the ligamentum arteriosum

Front 396

What heart defect is associated with Down syndrome? What is the embryology?

Back 396

Atrioventricular septal defect, AVSD; results from failure of fushion of endocardial cushions (neurocrest)

Front 397

What are the components of tetralogy of Fallot?

Back 397

-VSD- Subpulmonary stenosis- Aorta overrides VSD; dextroposition-shifted rt.- Right ventricular hypertrophy

Front 398

What is the morphology of tetralogy of Fallot?

Back 398

Boot-shaped heart--enlarged right ventricle

Front 399

What are the clinical features of tetralogy of Fallot?

Back 399

• Degree of subpulmonary stenosis determines direction of shunting, outcomes

Front 400

What is the morphologic determinant of severity of disease for tetrology of Fallot?

Back 400

Clinical Features of Tetralogy of Fallot dependent upon size of subpulmonic stenosis

Front 401

What genes are associated with tetrology of Fallot?

Back 401

NOTCH pathway genes implicated

Front 402

Define transposition of great arteries

Back 402

• Cyanotic at birth

• Ventriculoarterial discordance - Aorta arises from right ventricle; is anterior and right of the pulmonic artery - Pulmonic artery arises from LV • Embryology: Abnormal formation of truncal and aortopulmonary “ spiral” septa

Front 403

Define persistent truncus arteriosus

Back 403

• Rt to L; early cyanosis

• Single great artery overiding both ventricles; associated VSD • Embryology: Failure of separation of the truncus arteriosus into 2 vessels

Front 404

What syndrome is associated with truncus arteriosus?

Back 404

Most common association: 22q11.2 deletion syndrome

Front 405

What is the association of tricuspid atresia?

Back 405

hypoplasia of right ventricle

Front 406

Define TAPVC

Back 406

Right-to-left shunt; cyanosis common

• Pulmonary veins don’t enter L. atrium - Half feed into left innominate veins; coronary sinus

• Patent foramen ovale or ASD always present

• Volume and pressure hypertrophy of right heart

• Left atrium is hypoplastic

Front 407

Define coarctation of the aorta

Back 407

Obstructive anomaly; narrowing or constriction of aorta

Front 408

What are sex associations of coarctation of the aorta?

Back 408

2x more common in males

Front 409

Describe adult form of coarctation of the aorta, including major, bolded associations.

Back 409

- Valve defects: ***bicuspid aortic*** - ASD, VSD - Mitral regurgitation - ***Berry aneurysm***, circle of Willis

Front 410

What are the clinical features of coarctation of the aorta?

Back 410

• Upper body hypertension

• Hypotension of the legs - Cold/cyanotic legs - Claudication, intermittent--pain and limping brought on by walking

• Characteristic x-ray finding: Rib notching

• Clinical: Murmur throughout systole; Thrill

• Cardiomegaly due to LV hypertrophy

Front 411

What are complications of coarctation of the aorta?

Back 411

• Complications related to hypertension: ruptured cerebral aneurysm, stroke, heart failure

• Infective endocarditis – of coarctation, bicuspid valve

• Treatment: Surgical resection with anastamosis or prosthetic graft

Front 412

What is the most common type of valvular aortic stenosis?

Back 412

Bicuspid aortic valve

Front 413

What is the associated gene of the most common type of valvular aortic stenosis?

Back 413

Bicuspid aortic valve, NOTCH2

Front 414

What are complications of the most common type of valvular aortic stenosis?

Back 414

Predisposes to premature calcific aortic stenosis; infective endocarditis

Front 415

Define hypoplastic left heart syndrome.

Back 415

Severe stenosis or atresia of aortic valve

• Underdeveloped left ventricle and aorta

• Endocardial fibroelastosis

• PDA necessary for life

• Fatal first week of life if PDA closes

Front 416

List clinical features of Williams Syndrome

Back 416

• Thickened ascending aorta; lumen of aorta is constricted = supravalvular stenosis

• Multiple organ system disorder

• Facial abnormalities: elfin, flat nose • Hypercalcemia in infancy (colic, vomiting, risk for metastatic calcifications)

Front 417

What is the genetic defect in Williams Syndrome?

Back 417

Deletion chromosome 7 -- includes elastin gene (ELN) and other genes assoc. with brain development