Maturing Granulation Tissue Vessels decreasing Fibrocytes decreasing Type III replaced by Type I collagen Inflammation resolved Epithelium

helium restored Wound Strength Primary intention: 10% when sutures removed (4-10 days) Rapid increase 4 weeks Granulation tissue remodeling 70-80% strength plateau 3 months Synthesis > degradation first 2 months Collagen III replaced by collagen I Cross- binding and increase in fiber size strengthen Secondary intention: Wound contraction up to 95% at 6 weeks Myofibroblasts and Elastin remodeling participate

Test q: The principal cells of granulation tissue are: fibroblasts and endothelial cells,

Scars never have the same tensile strength, even when healed back by primary intention. Remodeling Scar By the end of 3 months: Vessels absent Fibrocytes few Type III replaced by Type I collagen Contraction complete Inflammation resolved Epithelium restored
Test q: A 22y/o female succumbs to peer pressure and has her ears pierced. Two months later, the sites of piercing develop firm nodules that are the same color as the surrounding skin. There is no evidence of infection. You would expect the histopathology to show: Broad bands of collagen. Test q: A well-healed scar that is 6mo old contains primarily collagen type: I

Above: FIGURE 326 Repair, regeneration, and fibrosis after injury and inflammation.

FIGURE 320A Healing of skin ulcers. A, Pressure ulcer of the skin, commonly found in diabetic patients. The histologic slides show: B, a skin ulcer with a large gap between the edges of the lesion; C, a thin layer of epidermal re-epithelialization and extensive granulation tissue formation in the dermis; and D, continuing reepithelialization of the epidermis and wound contraction. FIGURE 321B A, Granulation tissue showing numerous blood vessels, edema, and a loose ECM containing occasional inflammatory cells. Collagen is stained blue by the trichrome stain; minimal mature collagen can be seen at this point. B, Trichrome stain of mature scar, showing dense collagen, with only scattered vascular channels.

 FIGURE 32 Role of the extracellular matrix in regeneration and repair. Liver regeneration with restoration of normal tissue after injury requires an intact cellular matrix. If the matrix is damaged, the injury is repaired by fibrous tissue deposition and scar formation.
Test q: A 50y/o female develops lobar pneumonia secondary to Streptococcus pneumoniae infection. Neutrophils are numerous and the ECM is destroyed locally. The patient recovers after antibiotic treatment. The involved area of the lung will exhibit: Fibrosis. Test q: A 45y/o female is hospitalized for Pneumococcal pneumonia (caused by Streptococcus pneumoniae). The isolated bacteria is resistant to penicillin and the pneumonia persists for several weeks, but she recovers. At discharge, many of the alveoli in the patients lung would exhibit: Granulation tissue and fibrosis. Test q: What is the most frequent reason acute inflammation may result in replacement of the tissue by collagen scar: Damage to ECM. REPEATED TWICE. Test q: An 18y/o man lacerated his left hand and required sutures. The sutures were removed 1 wk later. Wound healing continued, but the site became disfigured by a prominent raised, nodular scar that developed over the next 2 months. Which of the following terms best describes the process that occurred during this 2mo period? Keloid formation.

Pathologic Wound Healing Deficient scar Dehiscence resulting from tension or infection Nonhealing ulcer In diabetes or peripheral vascular disease Excessive repair Granulation tissue excess Pyogenic granuloma, proud flesh Keloid (mostly Af Am) Fibromatoses Desmoid, aggressive fibromatosis Uncertain whether neoplastic Contracture at flexor surfaces Palms, soles, anterior chest wall

Keloid and Contracture FIGURE 323A Keloid. A, Excess collagen deposition in the skin forming a raised scar known as keloid. B, Note the thick connective tissue deposition in the dermis. FIGURE 324 Wound contracture. Severe contracture of a wound after deep burn injury. Learning Objectives (w/answers): 1. Regeneration versus replacement Stable or labile cells, BM & ECM preserved 2. 3 Surface receptor types IK mitogenic, CK cytokines, GPCR hormones 3. Cell cycle, 4 cyclins, 2 checkpoints G0G1SG2M; Cyclins DEAB; midG1(Rb) G2M(p53) 4. 2 unique basement membrane molecules Collagen IV, Laminin 5. Collagen synthesis & structure ProOHProGlycosSelect3LysOx/ C,N peptidase to tropocollagenLysOxagg 6. 5 Growth factors EGF Ep mitogenic, PDGF MpEn mito/tactic, FGF En angio SkmsLung maturing, VEGF En angio, TGF Ep inhibits Fb collagen synthesis-collagenase inhib. 7. Wound healing & maturation, zinc function Angiogenesis, Fibroblast invasion/mitosis, ECM synthesis, Remodeling (Zn metalloproteinase)

Hemodynamics Topics: Homeostasis - Water/Compartments Edema Congestive Heart Failure Congestion/Hyperemia Hemostasis: Hemostasis - Normal Hemostasis - Thrombosis Atherosclerosis Thrombosis/Embolism Infarct Shock Vascular Fluid Hemodynamics Body Compartments: Body Water (60% of body weight) Intravascular Space: 5% Cellular Space: 40% Interstitial (Extracellular) Space: ~ 15% Lymphatic Space: small % Blood Flow: Blood Pressure Maintenance Cardiac Output Vascular Perfusion Pressure - Vascular Tone Vascular Resistance - Organs

Fri. 08/27/10

Increased Hydrostatic Pressure Impaired Venous Return Congestive Heart Failure Constrictive Pericarditis Ascites (liver cirrhosis) Venous Obstruction Thrombosis External pressure mass Lower extremity inactivity

Congestive Heart Failure: Left Sided CHF: Decreased Cardiac Output Etiology: Myocardial dysfunction Atherosclerosis, Infarcts, Hypertension, Aortic/Mitral valve diseases, Myocarditis, Constrictive Pericarditis Findings: Decreased Cardiac Output - Decreased tissue perfusion Reactive vasoconstriction (increased vascular tone) Peripheral and Pulmonary Edema Organ Congestion: Liver, Spleen, Kidneys, GI, etc. Effusions: Pleural, Peritoneal (ascites) Symptoms/Findings: Dyspnea, decreased activity level PND (paroxysmal nocturnal dyspnea) Orthopnea Jugular-venous distention Increased BNP (B type nutriuretic peptide produced by distended ventricle) Peripheral edema Pulmonary rales Right Sided CHF: Etiology: Left sided failure most common cause, pulmonary hypertension, pulmonary/tricuspid valve disease, myocarditis Findings: Similar to Left Sided except no pulmonary edema Congestive Heart Failure Mechanisms:

Below: Congestive Heart Failure - Vascular Pressures

Test q: A 74y/o woman w/left heart failure develops pulmonary edema. This accumulation of fluid is best explained by which of the following mechanisms? Increased hydrostatic pressure. Test q: The most common cause of right-sided congestive heart failure is: left-sided heart failure. Test q: Which of the following is seen predominantly in acute left heart failure? Pulmonary edema. Test q: A 50y/o male w/a history of previous MI develops shortness of breath and dies after 2wk in the hospital. At autopsy the patient exhibits necrosis of hepatocytes surrounding the central veins. The most likely cause is: congestive heart failure.

Myocardial Infarction: Decreased Cardiac Output

Constrictive Pericarditis: Decreased Cardiac Output

Above: fibrous bands constrict the pericardium to heart surface.

Sodium Retention: Increased Plasma Volume

Test q: Choose the best answer concerning congestive heart failure (CHF): May result in increased sodium retention from increased aldosterone action. (Other choicesPeripheral edema seen w/CHF is the result of decreased osmotic/oncotic vascular pressure; Pulmonary edema seen w/CHF is the result of increased right ventricular pressure; Left ventricular failure is commonly the result of pulmonary embolisms; Is most often a complication of portal hypertension.)

Pulmonary Congestion and Edema:

Congestive Heart Failure:

Pulmonary Edema:

Pulmonary edema: fluid/transudate w/few RBCs

Exaggeration of pulmonary vasculature. Filling of air spaces w/fluid.

Frothy/blood-tinged edema fluid

Test q: On day 3 after an acute MI, the patient developed congestive heart failure and died. The lungs would show: congested capillaries and transudate in alveoli.

Peripheral Edema:

Reduced Osmotic/Oncotic Pressure:

Above: pitting edema. Discoloration = chronic venous stasis.

Test q: A 48y/o man w/alcoholic cirrhosis has ascites and dependent pitting edema in the lower legs. Fluid accumulation in the peritoneal cavity and legs occur by which of the following mechanisms? Decreased plasma oncotic pressure.

Reduced Osmotic/Oncotic Pressure: Reduced Plasma Colloid Osmotic/Oncotic Pressure Protein losing states: nephrotic syndrome (glomerulonephritis), protein losing enteropathies Cirrhosis/Malnutrition: decrease albumin production (protein has strong effect of pulling H2O back into vascular system) Effect: Peripheral edema Non-dependent edema, periorbital/facial Effusions: Ascites (Peritoneal), Pleural Sodium and H2O Retention: Increased Plasma Volume Acute/Chronic Renal Failure Abnormal Renin-Aldosterone

Test q: The mechanism for the production of anasarca is: extensive loss of albumin in the urine. (Anasarca = extreme generalized edema) REPEATED TWICE

Lymphatic Obstruction Lymphatic Obstruction Neoplasms, Infections, Post-surgery, Post-Rad Tx Lymphomas - neoplasms Filarisis - infection Mastectomy - post surgery Abdominal lymph node obstruction - Rad Tx Localized Edema Inflammation, vessicle/bullae, injury, etc

Reduced Lymphatic Flow:

Lymphatic Obstruction: Filarial Infection

Local Edema: Inflammation

Cerebral Edema Cerebral Edema: Localized from Trauma: Localized or Diffuse: Localized - Trauma, Infections/abscess Diffuse - Hypertensive Crisis, Venous obstruction, CSF Obstruction, Trauma Effects: Decreased Mental Status Tissue destruction, infarct, paralysis Brain stem herniation - death Cerebral Edema: Diffuse Swelling Herniation: Hyperemia/Congestion: Active vs Passive:

Inflammation Active Exercise Active Heat Active Above: herniation of cerebellum. Compresses midbrain/spinal cord. Congestive Heart Failure Passive Venous Obstruction Passive

Congestion: Increased amount of blood in capillaries, venules Active Hyperemia: Increased blood flow to area due to inflammation or vascular control Inflammation: Vasodilatation, increased vascular permeability Exercise: Increase muscle tissue blood flow Heat: Increase skin blood flow Passive Congestion: Reduced venous return/obstruction, Edema, Common with CHF Lung Congestion: Edema, extravasated RBCs, interstitial thickening (chronic), heart failure cells = hemosiderin laden macrophages Liver Congestion: Centrilobular congestion, centrilobular necrosis/fibrosis (chronic, i.e. cardiac cirrhosis) Spleen Congestion: Splenomegaly, fibrosis (chronic) Localized, venous thrombosis

Pulmonary Congestion:

Test q: A 62y/o male is found dead at home. At autopsy, the alveolar wall capillaries are congested w/RBCs and alveoli contain macrophages that exhibit brown, granular material. This patient most likely has a history of: Left heart failure.

Hepatic Congestion:

Centro-lobular Congestion/Atrophy

Test q: Nutmeg liver is a descriptive term for liver changes due to: chronic passive congestion.

Hemostasis: Coagulation/Fibrinolytic Pathways Bleeding/Hemorrhage vs Hemostasis/Clotting Dynamic Equilibrium: bleeding vs clotting Vascular Endothelium/Platelets/Coagulation Factors/Fibrinolytic Factors Primary Hemostasis - Vascular Seal = Platelets Vasoconstriction Platelet Adhesion Platelet Aggregation Secondary Hemostasis - Coagulation Pathway Endothelial/Platelet Activation Coagulation Cascade Thrombolytic/Fibrinolytic Elements Regulatory Factors for Clotting vs Clot Lysis

Hemostasis Vascular Injury:

Primary Hemostasis Hemostasis - Platelet Adhesion/Aggregation: Clotting: Platelets Platelet adhesion (Von Willebrand Factor (vWF), collagen) Platelet shape change (discoid) Platelet release of aggregation factors: ADP, Thromboxane A2 Aspirin inhibits production of Thromoboxane A2 Platelet recruitment/aggregation New anti-platelet drugs inhibit aggregation Platelet hemostatic plug Anti-platelet aggregation/adhesion Prostaglandin I2, nitric oxide, ADPase (derived from endothelium) Platelet Adhesion Mechanism: (Gp1b receptor)
Test q: A 35y/o woman takes acetylsalicylic acid (aspirin) for arthritis. Although her joint pain is reduced w/this therapy, the inflammatory process continues. The aspirin therapy alleviates her pain mainly through reduction in the synthesis of which of the following mediators? Prostaglandins. REPEATED TWICE. Test q: A 59y/o obese woman w/a history of diabetes mellitus had an MI 3mo ago. She is now taking a low dose of aspirin to reduce the risk of arterial thrombosis. On which of the following steps in hemostasis does aspirin have its greatest effect? Aggregation of platelets. REPEATED TWICE.

Inadequate Platelet Function or #: Platelet - Inadequate Primary Hemostasis: Petechiae - pinpoint loss of blood into tissues, ex. Skin Purpura - larger loss of blood into tissues, ex. Skin Hemorrhage - severe bleed (Brain, GI, etc) Inadequate Platelet #/Function: Petechiae less than 2 mm hemorrhage: Congestion/Hemorrhage: Bowel, Brain:

Purpura: Platelets and Coag Factors > 3 mm hemorrhage:

Ecchymosis: Subcutaneous Hemorrhage Platelets/Coag Factors > 1-2 cm hemorrhages

Secondary Hemostasis Coagulation System

Above: Tissue factor is primary driving factor.

Coagulation Cascade: The function of the extrinsic pathway is measured by PT. Vascular injury activates Factor VIIa + TF, which activate the conversion of Factor X to Factor Xa. Factor Xa is the central area within the clotting cascade.

Coagulation Pathway - Platelet Surface:

Fibrin Generation:

Hemostasis Equilibrium: Clotting Stimulating Factors (Pro-coagulants): Exposed collagen, vWF = Platelet activation Platelet aggregation factors = ADP, Thromboxane A2 Tissue Factor (Thromboplastin) = tissue injury Activated Factors = XIIa, XIa, IXa, Xa, VIIa, IIa Plasminogen Activator Inhibitor (PAI) = antifibrinolytic Alpha-2-antiplasmin = anti-fibrinolytic Anti-coagulation Factors: Antithrombin III (ATIII) : Inactivates Xa, IXa, IIa Protein C (+Protein S): Inactivates Va, VIIIa Thrombomodulin: activates Protein C Tissue Factor Pathway Inhibitor (inactivates VIIa+Xa) Clot Lysis Factors: Tissue Plasminogen Activator (tPA) Plasminogen = Plasmin: Degrades Fibrin ATIII is a key anti-coagulant.

Coagulation Control

Anti-coagulants: Test q: The clotting factors that are produced in the liver and Anti-coagulants use in blood tubes to yield whole blood or plasma: are vitamin K dependent are: II, VII, IX, X. EDTA (lavender top) binds Ca++, used for hematology tests Test q: A 33y/o female presents to the ER w/a deep vein thrombosis in her left leg. She is treated w/heparin until Citrate (blue top) binds Ca++, used for coagulation testing stable. On discharge, you wish to change her anticoagulant Oxalate (grey top) binds Ca++, used for some whole blood to Coumadin (Warfarin). What lab test should you order to testing monitor drug effectiveness after discharge? PT. Heparin (green top) inhibits AT III Therapeutic Anticoagulants: Heparin, Unfractionated: Binds to Anti-thrombin III and inhibits Thrombin (II) and Factor Xa; Monitor with Partial Thromboplastin time aPTT or activated clotting time Heparin, Low molecular weight: Binds to Anti-thrombin III and inhibits Factor Xa mostly; Monitor with Anti-Xa assay Warfarin (coumadin): Decreases factors II, VII, IX, X, production (Vitamin K factors); Monitor with Prothrombin Time (PT, INR) Direct Factor Xa Inhibitors; effects PT, aPTT, and Anti-Xa assay Direct Thrombin Inhibitors Thrombin Equilibrium Thrombosis vs Anti-thrombosis: Thrombin effect on thrombosis: Fibrinogen to Fibrin reaction Activates XIII to cross-link fibrin Activates VIII, V Stimulates Platelet Aggregation and Secretion Endothelial leukocyte adhesion molecules Thrombin effect on anti-thrombosis = Fibrinolytic Process Stimulation: Tissue Plasminogen Activator (tPA) Vasoactive - NO, PGI2 (inhibits Platelet aggregation) Cytokines Heparin + Antithrombin III inhibits Thrombin Thrombolysis/Fibrinolysis Tissue Plasminogen Activator (tPA) released from adjacent normal endothelium: Activates Plasminogen to Plasmin Plasmin lyses fibrinogen with release of d-dimers (d-dimer assay used to ruleout DVT or Pulmonary Embolus) Fibrinogen breakdown products inhibits coagulation Thrombomodulin released from endothelial cells inhibits coagulation by inaction with thrombin in activating Protein C Anti-fibrinolysis actions Alpha2-Anti-plasmins Plasminogen Activator Inhibitors Fibrinolytic System: Activation and Regulation

Test q: Lysis of a thrombus is enhanced by which of the following mechanisms? Thrombin stimulation of tPA release. Test q: A 66y/o woman comes to the ER 30 min after the onset of chest pain that radiates to her neck and left arm. She is diaphoretic and hypotensive; the serum troponin I level is elevated. Thrombolytic therapy is begun. Which of the following drugs is most likely to be administered? Tissue plasminogen activator.

Hemodynamics/Hemostasis Lecture # 2 Thrombosis/Embolism Atherosclerosis Infarcts Shock Pathologic Causes of Thrombosis: Genetic Disorders: Hyper-coagulable States Mutations in Factor V (Leiden Mutation): 2-15% of whites; reduced degradation of Factor V by Protein C (decreased aPC) Antithrombin III Deficiency: Autosomal dominant (1:2-5000); or acquired (i.e. nephrotic syndrome or DIC) Protein C or S Deficiency: Anti-coagulant Allelic Variations in Prothrombin: 1-2% Population; Increased Levels (3 xs risk) but not structural change. D5, 10 Methylenetetrahydrofolate reductase mutation (C677T homozygous) increased homocysteine Fibrinolysis defects Homocysteinemia - genetic disorder or folate deficiency Acquired: Hyper-coagulable States Tissue damage (release of activating factors) Cancer (pro-coagulant factor release) Trousseaus Syndrome: Pancreatic Ca, Thrombi Disseminated Intravascular Coagulation (DIC): Diffuse endothelial injury (sepsis, toxins) Anti-Phospholipid Syndrome (Lupus Anticoagulant) Systemic Lupus Erthyematous, Pregnancy (causes miscarriages and stillbirths), Viral Infections Antibodies to cardiolipin, beta-2 glycoprotein I, phosphotidylserine Heparin induced thrombocytopenia (HIT) 10 % of patients; Antibodies to heparin bound to platelet factor 4 results in platelet activation and initiation of thrombus formation Endothelial Cell Injury Necrotic Tissue - Infarct Valve Disease - Rheumatic Fever Atherosclerosis - Plaques Traumatic Injury Vasculitis - Autoimmune Disorders Infections - Endotoxins Other
Test q: An athletic, 51y/o man w/a history of diabetes mellitus goes to the ER because he has had left-sided chest pain that radiates to the arm for the past 5 hr. Serial measurements of serum creatine kinase-MB levels show an elevated level 24hr after the onset of pain. Partial thromboplastin time and prothrombin time are normal. Coronary angiography shows occlusion of the left anterior descending artery. Which of the following mechanisms is the most likely cause of thrombosis in this patient? Damage to endothelium.

Thrombosis Formation:

Test q: An elderly man presents w/multiple deep vein thromboses over the past several months with one episode of pulmonary embolism. Which of the following is the most likely underlying condition? Adenocarcinoma of the pancreas. (Not cirrhosis, Von Willebrands disease, FH, or renal cell carcinoma w/lung metastases) Test q: A 55y/o former baseball player presents to his doctor w/a small thrombus in his lower leg and 1mo later is hospitalized for a pulmonary embolus. Further workup reveals a malignancy. Which is most likely? Adenocarcinoma, pancreas. Test q: A 45y/o present w/multiple venous thromboses in his legs and also in the mesentery of his intestinal tract. He most likely has a history of: Pancreatic cancer. Test q: A 45y/o white male is mildly overweight, but otherwise healthy. During the past year he has developed thromboemboli in his lower extremities. The most likely cause is Leiden mutation. REPEATED TWICE. Test q: The Leiden mutation of the gene for Factor V is commonly seen in persons who: have history of thombosis of the deep veins. REPEATED TWICE. Test q: A 25y/o woman has had multiple episodes of deep venous thrombosis during the past 10 years and one episode of pulmonary thromboembolism during the past year. Prothrombin time, partial thromboplastin time, platelet count, and platelet function studies are all normal. Which of the following risk factors has most likely contributed to the patients condition? Factor V mutation.

Disseminated Intravascular Coagulopathy Etiology: Diffuse activation of Thrombin/Coagulation System, example: Diffuse endotoxin injury of endothelium Findings: Diffuse clotting in small vessels Ischemic injury to organs, especially brain, lung, heart, kidneys Consumption of clotting factors (Platelets, Factor VIII, V, etc) bleeding can result (increased aPTT and decreased platelet count) Activation of Fibrinolytic System = dissolution of clots and subsequent bleeding (fibrinolytic products inhibit clotting); increased d-dimers

DIC - Small Vessel Thrombi:

Test q: Choose the best answer concerning Disseminated Intravascular Coagulation (DIC): It is often seen with septicemia and endotoxin release. (Other choices- It is commonly assocd w/an increased platelet count, Fibrin split products are increased which enhance clotting, Thrombi in small vessels commonly result in pulmonary emboli.) Test q: A 32y/o female gives birth to a 10lb male infant at 42 weeks gestation after induction and stressful delivery. She develops multiple clots as well as large hematomas and hematuria. Lab studies would show: Elevated D-dimer. Test q: A 13mo old male presents to the ER w/a swollen right knee. The family reports that the child bruises easily. There is no family history of bleeding disorders. Lab results: PT: 12s (10-14s). APTT: 43s (21-35s). Bleeding time: 5min (3-6min). Platelet count: 300,000 (150-450,000). Mixing studies: APTT corrected to normal. What is the diagnosis? Factor VIII deficiency. (Did not specifically discuss this?)

Hemodynamics: Abnormal Blood Flow Turbulence - Arterial/Cardiac Thrombosis Abnormal Valves - Abnormal surface, Stasis with Mitral Stenosis Atherosclerosis - Plaques/Nodules Ulcerated Plaques Aneurysms (stasis and abnormal surfaces) Atrial Fibrillation - irregular atrial contraction Turbulence can directly injure endothelial cells Stasis - Venous Thrombosis Reduced circulation: CHF, Obstructions, Varicose Veins, immobility, etc Failure to dilute out activated clotting factors Failure to bring fresh anti-coagulant factors Promotes endothelial cell activation Sickle Cell Anemia, Hyperviscosity States, polycythemia rubra vera Genetic and acquired etiologies:

Atherosclerotic Plaque:

Above: Top aorta is severe atherosclerosis. There is a large ulcer overlying the atherosclerotic plaque. The middle aorta represents moderate atherosclerosis. The bottom aorta is smooth and normal.

Plaque Formation:

Atherosclerotic Plaque:

Fate of Atherosclerotic Plaques:

Atherosclerosis:

* = thrombus overlying plaque

Coronary Artery

Coronary Artery Thrombosis

Ulcerated Plaque - Coronary Artery

Ulcerated Plaque: Coronary Artery - Thrombus

Aorta Mural Thrombus

Blood clot, a cause of MI.

Can break off embolus tissue infarction.

Test q: A 50y/o male presents to the ER w/crushing chest pain. A stress test 2 months ago was suspicious. Cardiac catheterization one month ago showed 25% occlusion of the left circumflex artery. The patient was given a prescription for Atorvastatin (Lipitor) and told to take 81mg of aspirin daily. He did neither. What is the likely cause of his MI? Acute thrombus over an ulcerated plaque.

Atherosclerosis Consequences

Thrombi - Organized/New Channel

Blood going through channel (but not enough!)

Deep Vein Thrombosis and Pulmonary Emboli Predisposing Factors: Venous Stasis/Immobilization especially of lower extremities Hypercoagulable States Surgery or Trauma, especially orthopedic and pelvic surgery Pregnancy Oral Contraceptive Pills 3 fold (higher with cigarette use) Malignancy Identified in 17% of thrombo-embolism

Test q: A 76y/o woman is hospitalized after falling and fracturing her left femoral trochanter. 2wk later, the left leg is swollen, particularly below the knee. She experiences pain on movement of the leg; on palpation, there is tenderness. Which of the following complications is most likely to occur after these events? Pulmonary thromboembolism. Another year- same story, diff question: What is the diagnosis for her current problem? Deep vein thrombosis. Test q: A 42y/o obese male suffers a compound fracture of his tibia playing soccer. He is placed in traction and bed rest. He is at high risk for: Pulmonary embolus. Test q: A 75y/o woman has had discomfort and swelling of the left leg for the past week. A venogram shows thrombosis of deep left leg veins. Which of the following mechanisms is most likely to cause this condition? Long-term bedrest.

Emboli 20-25/100,000 hospital patients = 200-600,000 deaths/year (third most common cause of hospital death) Most from dislodged thrombus (Thrombo-embolism) Pulmonary Embolus (venous thrombi) - common Most are small and clinically silent (may lead to pulmonary hypertension over time) Large emboli infarct or cardiac collapse/death Commonly arise in large veins in legs or pelvic area i.e. DVT (60-80% will have emboli) Systemic/Arterial Emboli: Infarction Most from mural thrombus in heart: due to MI or Mitral Stenosis, atrial fibrillation, endocarditis, Aneurysms, ulcerated plaques, valve diseases Result = Organ Injury: Lower Extremities, Brain, GI, Kidneys, Spleen Rare forms: Fat, Air/Nitrogen, Atherosclerotic debris (angioplasty), amniotic fluid, bone marrow

Venous Thrombus: Fate

Pulmonary Emboli Symptoms: May not have any symptoms if small Dyspnea, pleuritic chest pain Hemoptysis especially with infarction Cardiac decompensation Sudden death Thromboembolus:

Pulmonary Embolus:

Saddle Embolus:

deposition of fibrin

Above: Saddle embolus crossing where the pulmonary artery branches to go to two lungs.

Thrombus - Lines of Zahn (alternating bands of fibrin)

Organizing Thrombus:

Organizing Thrombus:

Can see fibroblasts growing into thrombus

Post-Mortem Clot Not organized; not adherant (gel-like). Currant jelly Passive settling out of RBCs and plasma. No Lines of Zahn.

Test q: A pathologist is asked to perform an exam of a diabetic woman who died suddenly w/a history of thrombophlebitis of the left lower leg. He finds a clot in the pulmonary artery. Which of the following findings would indicate that this clot is a thromboembolus? Presence of Lines of Zahn. REPEATED x3!!

Test q: Features consistent w/a post-mortem clot are: Jelly-like.

Hemodynamics: Infarcts Post-mortem Clot: Infarct Determinates: Nature of vascular system (alternative blood supply) Rate of occlusion Vulnerability to hypoxia (cell type) Oxygen content of blood/cardiac output Use of thrombolytic therapy (tPA tissue plasmingen activator or streptokinase) Red Infarct: Loose tissues (lung) and/or 2 vascular systems (lung, liver) Venous infarcts (ovarian torsion) Previously congested organs (spleen) Re- establishment of blood flow (lysis of thrombus in MI after angioplasty or thrombolytic treatment) White Infarct: Solid Organs with single vascular system (kidney, heart, spleen (later))
Test q: A 60y/o hospitalized woman has sudden onset of dyspnea, pleural pain, and cough productive of frothy, blood-tinged sputum. Ventilationperfusion scintigraphy indicates a perfusion defect in the left lung. Which of the following would most likely be present in section of the lung? Hemorrhagic (red) infarct.

Coronary Artery Occlusion MI

Infarct Course:

Biochemical Markers Myoglobin increased at 2-4 hours; non-specific skeletal muscle injury also increases myoglobin Cardiac Troponin I or Troponin T increased at 4-6 hours; primary criteria for myocardial infarct elevated for > 3 days Creatine Kinase (MB) increased at 6 hours, not as sensitive as troponin I or T for MI Elevated for 1-2 days Lactate Dehydrogenase (LDH), especially isoenzyme 1 increased at 6 hours+; not commonly used today Elevated for > 3 days Myocardial Infarct: 6 18 hours Can see contraction bands (arrow) MI: Inflammation Coag Necrosis 24-48hr
Test q: The main disadvantage of the serum myoglobin test for acute MI is its: poor specificity. Test q: A 57y/o man has just returned from an overseas trip and reports having had severe substernal chest pain 3 days ago. Which of the following is the most appropriate lab test to order for this patient? Troponin I.

See some loss of nuclei.

Complete loss of nuclear and cytoplasmic detail.

Myocardial Infarct: 1-2 days Loss of nuclei and PMNs:

Congestion at edge of infarct:

MI: Complete loss of nuclei (48hr)

Myocardial Infarct: Recent (several days old) Infarct: softening; pale, hyperemic border

MI: Myocardial Rupture 1-2 wks

Below: MI: 2-3 weeks Macrophages and fibroblasts

Myocardial Infarct: months/years

Lung Infarct: (wedge-shaped)

Pulmonary Infarct - Coagulative Necrosis w/tissue congestion/hemorrhage; loss of alveolar septae

Extravasated blood in damaged area.

Test q: An organ from a 70y/o woman at the time of autopsy showed a focal, wedge-shaped area that was firm and accompanied by extensive hemorrhage, giving it a red appearance. Choose the best answer w/the organ and the situation that resulted in this lesion: Lung with pulmonary embolism. (Other choices: heart w/coronary thrombosis, liver w/hypovolemic shock, kidney w/septic emboli, and brain w/hypertensive stroke.)

Kidney Infarct

Kidney Infarct Coagulative Necrosis

Kidney Infarct

Wedge-shaped. More tan/white in character.

Loss of cellular detail in infarcted area.

Renal Infarct: Healed (organized w/fibrous scar)

Extremity Infarct: Infarct of foot (from embolus or thrombus)

Brain Infarct Liquefactive necrosis

Can be from systemic arterial emboli.

Shock: Hypotension/Diffuse Organ Damage Cardiogenic: High Mortality MI, Ventricular Rupture, Arrhythmia, Tamponade, Pulmonary Embolism Hypovolemic: Hemorrhage, Fluid Loss (burns, vomiting/GI, trauma) Septic: 100,000 deaths/year; High Mortality Overwhelming Infections (septicemia) Endotoxic Shock: Release of bacterial cell wall components (LPS) Neurogenic: anesthesia Anaphylactic: IgE mediated hypersensitivity
Test q: Platelets are: Created from whole blood donations or collected from donors using apheresis machines. Other choices: Stored for 14 days on a rotator at room temp Treated w/multiple antibiotics to prevent the growth of bact and fungi Are the first line therapy for patients the TTP (what?? typo?) Frozen at -70*C for later use Test q: Disorders of primary hemostasis include all of the following except: hypofibrinogenemia. (Other choices: Aspirin or Plavix (acquired); Von Willebrands disease; Hereditary platelet defects)

= lipopolysaccharide Septic Shock:

(Not sure that these qs were covered maybe the tests are outdated compared to our pptsor maybe I skipped over these while reading?)