Easy Dr. Abdelrahman Khalifa[ HEART DISEASES) Rheumatic fever Autoimmune collagen disease, following streptocoocal infection, affecting multiple systems Predisposing factors:_Children 5-15 y. ‘+ URTinfection by group A Beta-hemolytic strept., + genetic factor fonsillitis (low immunity crowding) Pathogenesi: + After 2-3 weeks of URTI by group A bet hem strept. > elevated ASO antibody ‘+ Cross reaction: © Ab attacks bacterial (M protein) in cardiac muscle > Complement activation > Activation of macrophages © CDAT cell attack cardiac muscle > cytokine mediated inflammation , Ashoff's nodule ; the pathognomonic lesion + Sites: Heart — Joint -Skin - CNS ‘+ Gross: rounded ~ small (pin head) ~ pale grey - firm © Micro: o Early: + Fibrinoid necrosis (dmamged collagen + fibrin deposts) + Inflammatory cells (lymphocyte & macrophages) + (Anitskow or Caterpillar cell) Activated macrophage with nuci containing cylinder beaded chromatin + Aschoff's giant cells (multinucleated giant cell, pale acidophilic) + Fibroblasts © Chronic lesion (in heart only) : Fibrosis + CaleificationEee [ HEART DISEASES) Acute Rheumatic heart disease: (Pan-carditis) common site is posterior wall of left atrium, para vascular and left valves (M, A) eer Enlarged & thickened Multiple Aschoff nodules (describe) between muscle fibers Lac Sero-fibrinous inflammation , splitting of 2 layers (Bread & Butter) Fate: -Resolution -or Fibrosis > Thick white patch (milky patches) > Adhesions ECT ‘Mural endocarditis: ‘Ashoff body + swollen endocardium-> Irregular rough patch (Mc Callum patch) > mural thrombosis Valve: 75% mitral and aortic = swollen valve , endothelial damage Vegetations: Gross: multiple - Small~ pale ~ adherent on top of the valve along line of closure micro: platelets + fibrin subendothelial ashoff nodules Chronic Rheumatic Heart disese: © Aschoff body > fibrosis * Valve > fibrosis > thick, white & deformed * Commissural adhesion > Fish mouth or button hole * Cordae tendenae > thick & short > Funnel shaped valve © Valve stenosis , or incompetence , or both (double lesion) Complications: AFSH ‘Arrhythmia (Atrial fibilation in case of mitral stenosis) N.B. Embolism if occurs (from mural thrombosis ~ NOT from Rhuems Fibrosis Subacute Bacterial Endocarditis (SBE) Heart failure (ave to chronic valve lesion) - Lung congestion & pulmonary hypertension vegetations) 3 Dr. Abdelrahman Khalifa , MD., PhO.[ HEART DISEASES) Rheumatic Arthri + Sitez Large joints & muscle , Migratory, fleeting poly-arthritis ‘+ Morphology: acute inflammation with eff «Fate: Self limiting (Acute only>no chronic joint lesion, no joint damage) Rheumatic Skin lesion: + Subcutaneous nodules: over bony prominence + Erythema marginatum: red borders and pale center Rheumatic Chorea + Rheumatic lesion of Basal ganglia ‘+ Involuntary, purposeless, sudden movement, > self limited NB. © Other Rheumatic lesions:- Arterial nodules, Plurisy, peritoni © Jone's chriteria for diagnosis : 2major signs or major + 2 minor signs Major: Carcitis, Arthritis, Chorea, Skin nodules, Erythema _ Minor: Fever, ASO, ESR, Arthralgia ndocarditi Inflamm )n of mural & valvular endocardium, with formation of vegetations Types of Endocarditis = Types of cardiac vegetation: % Non infective RAT © Bheumatic endocarditis * Atypical verrucous endocarditis (Libman-sack endocarditis of SLE) + Thrombotic non bacterial endocarditis (D/C, chronic diseases, metastatic cancer } Or Associated with any Valve lesion : Valve trauma - Carcinoid syndrome “ Infective acute - sub-chronic © Acute bacterial endocarditis (ABE) © Subacute bacterial endocarditis (S86) 4 Dr. Abdelrahman Khalifa , MD., PhO.Eee [ HEART DISEASES) rrr > 50y (lower immunity) RYT era 1 endocarditis young Highly virulent bacteria (pyogenic) > septicemi enray Fungal (with AIDS patients or low immunity) Tow virulent bacteria (strept. veridance) > bacteremia PF: Dental procedures seased valve (e.g. Rheumatic valve ~ congenital - artificial) Defective shunt (ASD, vsb, PDA) rug abuse (mainly right sided SBE) Pyogenic bacteria ~ proliferate on healthy valve > Suppurative inflammation > ‘Suppurative vegetations Co ooo ‘weak bacteria > proliferate inside vegetations of diseased valve -> non Suppurative inflammation Valve: -suppurative inflammation ulceration > perfor Vegetation: -Large bulky “Yellow -Friable (2) “Micro: “upper zone: platelet middle zone: bacteria ‘ower zone: inflammatory cells ~ Neutrophils & pus cells Eons Valve: = non supp. inflammation Vegetations: -Medium sized -less Friable “upper zone: platelets - fib iddle zone: bacteria ower zone: inflammatory cells -valve Fibrosis Cardia -Viave perforation ~ acute heart failure Abscess in myocardium, pericardium Extra-cardiac: - Emboli> pyemia - Toxin > Toxemia ee ad Cardia “Viave stenosis incompetence > Heart failure Extra-cardiac: - Emboli> infarctions -Cerebral, retinal, cardiac, Splenic, renal -very small emboll in vasa vasorum of Arteries - > mycotic aneurism “Toxin > Toxemia Allergic vasculitis (Ag-Ab mediated) & microemboli: Focal embolic GN (flea bitten kidney) (hematurea, proteinurea & R.F.) Finger lesions (osler nodule ~ splinter hemorrhage] -Peticheal hemorrhage in skin & retina Dr. Abdelrahman Khalifa , MD., PhO.Eee [ HEART DISEASES) Compare between different types of cardiac vegetations Rheumatic ABE Ed re neae Neercil iene Leftvalves | leftvaives | Leftvalves | Mitral & tricuspid ‘Any valve Upper surface | Upper surface | Upper surface | Upper & lower surface | Upper surface Rheumatic | Septicemia | Bacteremia SLE DIC (eg. mucoid aur] fever carcinomas) Deblitating disease (marantic) Damaged valve by trauma describe —_| describe describe _| Similar to rheumatic | Similar to rheumatic Oa + but: Fibrinoid necrosis | Larger (1-5 mm) Loose (embolism) Deformity | Pyemia Embolism | Deformity Embolism SBE SBE SBE Carcinoid syndrome: -GIT carcinoid secretes 5-HT > leads to Flushing & dermatitis ~ Diarrhea - Ashma -In case of hepatic metastasis > 5-HT reaches right side thick tricuspid & pulmonary valves (smooth muscle + collagen + mucopolysaccarid matrix) - in case of septal defect or Lung carcinoid ~ affects left Dr. Abdelrahman Khalifa , MD., PhD,Eee [ HEART DISEASES) alvular diseases| rece rca acca) = Rheumatic = Rheumatic = Rheumatic ~ Rheumatic. “SBE “SBE “SBE SBE Congenital Congenital (ea. marfon, | -Congenital Congenital (Marfan) valve prolapse) Senile calcific | -Syphilitic aneurism -Ruptured papillae or | stenosis) chorda Teft atrium dilatation | left side dilatation& Teft ventricle Teft side dilatation& ‘& hypertrophy > hypertrophy > left sided | dilatation & hypertrophy > left sided Lungeongestion > | heart failure > hypertrophy heart failure ~ right pulmonary sided heart failure hhypertension -> Right | Lung congestion > coronary & vent dilatation & pulmonary hypertension | cerebral hypertrophy > Right | > Bight vent dilatation & | insufficiency sided heart failure | hypertrophy > Bight sided heart failure ‘Sudden death (vr) All valvular diseases are complicated by: Thrombosis ~ SBE & Heart failure Degenerative valve disea: Calcific Aortic stenosis: -Old age -Caused by atherosclerosis > calcification Valve fibrosis & calcific nodules ~ valve stenosis -Lead to IHD & effects of valve stenosis (enumerate) Myxomatous mitral valve prolapse: -0.5 to 2.4 % of adults , Asymptomatic Causes: Marfan (Fibrilin-1 mutation) or hemodynamic injury {abnormality in myofibroblast) Morphology: Ballooned cusp, thin cordae. Fibrosa layer is thin. Spongiosa layer is myxomatous Complications: 3% Thrombosis & embolism ~>infarctions or stroke) Papillary SBE muscles Sudden death (due to VF) Dr. Abdelrahman Khalifa , Mi PhO.Eee [ HEART DISEASES) Myocarditis © Suppurative (© Pyogenic bacteria © Pus in interstetial tissue + muscle becrosis * Parenchymatous © Toxic (bacterial or chemical) , or parasitic (e.g. Ticheniosis) (© Degenerated muscle + mixed inflammation with eosinophils + necrosis in severe cases © Interstetial (© Immune response against Viral infection (coxsacki, CMV) © Focal muscle necrosis + mixed inflammation with excess lymphocytes © Granulomatous © Rheumatic, TB of septum , Sarcoidosis, Syphilis, Fungal (Cryptococcus, Asprigilus, Moniliasis), © Microscopic picture of causative granuloma (describe) © Idiopathic giant cell myocarditis: rare "Affects young adults, idiopathic, some of them are rheumatic,or ‘thymoma patients Ventricular necrosis = Chronic inflammatory cells and elongated giant cells Hypertensive heart} ‘Systemic Hypertension Pulmonary hypertension (cor pulmonale) “ry or 2ry ‘Acute (massive pulmonary emboli) chronic (idiopathic — Eisenmenger - Lung fibrosis — Emphysema ~ Lung congestion due to left sided HE) “Increased size >500 g, ~ Increased size -Left ventricle is thick >2cm ~ Right ventricle is thick -Neuclear enlargement + fibrosis, -¢ilatation and failure -Left side dilatation and failure associated with pulmonary atherosclerosis associated with coronary atherosclerosis Degenerative Heart diseases : Brown atrophy ~ Cloudy swelling ~ Fatty changes — Amyloidosis — Glycogen storage (Von Gierk's disease) Dr. Abdelrahman Khalifa , MD., PhO.[ HEART DISEASES) Cardio-myopathy| Pathological changes of myocardium, not caused by ischemia, inflammation, or valve disease Aetilology ry s inherited genetic abnormality _2ry Sarcoidossi ~ Amyloidosis ~ Leukemia - Toxins ~ Storage diseases (glycogen) , "SALTS" Morphological types = pilated ‘0 The most common type of cardiomyopaty 0° Congenital, or 2ry to Toxins (Alcohol, Cobalt Chemotherapy ,viral, iron, Beri Beri) © Allichambers are dilated with thin muscle, some fibers are hypertrophied 3 Hypertrophic ‘© Congenital autosomal dominant (B-myosin , C protein ,Troponin T) 0 Asymmetrical hypertrophy of left ventricle & ventricular septum> banana shaped distorted ventricle> Diastolic dusfunction & Mitral regurge & HLF. © Haphazard myocytes & fibrous tissue > Restrictive ‘o Rare type © Idiopathic fibrosis , or 2ry to Amyloidosis, endomyocardial fibrosis, Lofflers dis (© Thickening of endocardium -> limitation of diastolic filing © Endomyocardial fibrosis : caused by starvation or eos © _Lofflers: endocardial fibrosis due to eosinophilia Ischemic Heart diseases (IHD) Angina — Chronic IHD - Myocardial infarction - Sudden cardiac death causes: Aortic aneurism (syphilitic, Dissecting) | -Coronary Atherosclerosis ~ Hypotension (shock) “Aortic calcific stenosis “Coronary Thrombosis — -Hypertension -Aortic viave stenosis & Coarctation —_| embolism -Hypoxemia (Anemia, CO ) -Coronary spasm -Valve diseses -Vasculitis (PAN) Dr. Abdelrahman Khalifa , MD., PhO.Eee [ HEART DISEASES) Angina Chronic IHD T Stable: crushing or squeezing induced by effort | Progressive H.F. due to occlusion of > 70% of lumen old infarction Causes _| 2-Prinzmetal: Vasospasm giving pain during rest 3-Unstable (crescendo): increasing pain intensity , caused by low effort + occlusion of 290% morphology | No morphological changes until infarc Gross: dilated, gr. White Micro: fibrosis + hypetrophy+ degenerated vacuolated cells Myocardial Infarction Coagulative necrosis of myocardium due to ischemi Incidence; Most commen cause of disease induced death. Male > female, P.F.: causes of IHD, mainly Complicated atherosclerosis, Sites; h Wi Mi all) + Leftanterior coronary occlusion (40-50%) - infarction of anterior wall of left ventricle, ant 2/3 of septum & apex + Right coronary occlusion (30 -40%) > infarction of posterior wall of left ventricle , right ventricle, post 1/3 of septum. * Left circumflex occlusion (15-20%) infarction of lateral wall of left ventricle Pathogenesis: + Coronary ischemia by stenosis (atherosclerosis) or occlusion (thrombosis, spasm) “Hypoxia > lack ATP >Los of contractility (in one minute) + Lactic acidosis + Necrosis > release of enzymes CK, LDH, myocardial protein Troponin | (c-Tn-i) * Ischemia 20-40 min is irreversible, while during 3-6 hours intervention can prevent. extension of infarction. Patterns: ‘Sub-endocardial Transmural Microscopic =1/3 thickness, multifocal “Full thickness “small areas -stenosis but not occluded: caused | -caused by occlusion— _| -small vessel occlusion by effort, or occurs during -Archythi ht | more complications {e.g.vasculitis) -less complicated 10 Dr. Abdelrahman Khalifa , MD., PhD.Eee [ HEART DISEASES) Morphology: Cert creo ees) Dark, mottled Gross: none Fone Dts alr ees month Pale yellow Grayish white Red margins Firm Coagulative necrosis -gosinophilic fibers + pyknosis -neutrop! Micro: Wavy fibers E/M: glycogen loss smitochondria swollen MQ appear 3-7 days Granulation Collagen scar tissue at margin (describe) Complications: cH AMP # Congestive heart failure Hemopericardium (Tamponade) : due to ruptured pap. muscle > acute H.F. Aneurismal dilatation (due to fibrosis) > thrombosis & embolism Arrhythmia (ischemia of conduction system) Myocardial rupture (left vent, papillary muscle, or vent septum) during 7 days (muscle is weak and infiltrated by inflam. cells , before granulation tissue) + Pericarditis, Tumors of the Heal Myxoma of left atrium(the most common) - Rhabdomyoma ~ Lipoma ~ Fibroma- Angiosarcoma (the most common Iry malignant) ~ metastatic (e.g.leukemia, lymphoma, Lung carcinoma , melanoma) (oy a XTal itl aes diseases} + Incidence; 10% of heart diseases in children, starts in Sth to 8th gestational week © Stenotic diseases : Aortic coarctation © Shunt diseases : + Non cyamotic left-right shunts (ASD, VSD, POA) + Cyanotic right->left shunts (Fallot tetralogy, Transposition of 11 ‘Teratogenic Drugs- Trisomies (e.g. Trisomy 21) ~ D.M.- viral (Rubella, coxaci)- Dr. Abdelrahman Khalifa , MD., PhO.Eee [ HEART DISEASES) Aortic Coarctation: Focal stenosis in the wall of Aorta, 2 types: Pre-ductal Post-ductal “Proximal stenosis (before PDA) Distal stenosis -Associated with PDA -No PDA -Eatal in early life (infantile) -Not fatal (Adult ) , complicated with upper limb hypertension, lower body hypotensi ‘Shunt diseases: Left Dright shunt (non cyanotic) Right > left shunt (cyanotic) “ASD patent foramen ovale {the most common) “Tetralogy of Fallot -VSD Large defect- Small defect of Roger Transposition of great vessles (A-P) “PDA Effects: “Right s. dilation > rt. S.H.F. (congestive H.F.) “SBE - Reversal of shunt (Eisnemenger)> Cyanotic. -Hypoxia > Cyanosis & polycythemia & clubbing of fingers PDA In normal infants DA is closed after 8 week of birth due to low Pg E2, & hypoxia, Tetralogy of Fallot ; P.s.- Right ventr hypertrophy - Overriding of Aorta- VSD PROV Transposition : Aorta arises from right, and pulmonary arises from left. Lora) 12 Dr. Abdelrahman Khalifa , MD., PhD.Eee [ HEART DISEASES) a Maintained impairment of cardiac function, with insufficient cardiac output ulmonary embolism ~ Hemopericardium (tamponade) - Myocardia disease (2) eStats Uae a ‘Causes: CAMPS Cause: “Congenital {right > left shunts enumerate?) Congenital (left-right shunts enumerate?) “Aortic diseases PS. brown induration? Chronic generalized venous congestion ? -Right sided heart failure Congestive Heart Failure = Left sided heart failure + Right S. H. F Pericard Acute © Serous: infection (viral) immunological (Rhumatic, SLE) — idiopathic (© Filbrinous (same causes + uremia) - heal by organization -> adhesion © Suppurative (direct, blood, lymphatic) > marked adhesions 0 Hemorrhagic fibrinous or suppurative + blood (TB, tumors, Trauma, blood diseases) -> marked adhesions Chronic ° Adhesive: adehesions obliterate pericardial sac > limited complications © Constrictive: fibrous calcific scar around the heart (defective diastole) and may obliterate orifices of vena cava > generalized congestion 9 Tuberculous (fibrinous + GT and fibrosis) > adhesive or constrictive Hemopericardium (tamponade) is caused by: General causes of bleeding Local causes (injury ~ tumor ~ ruptured cardiac or aortic aneurism). Effect > limited diastole > HE Pneumopericardium: Air in pericardium (Lung trauma — or gas forming organisms) 13 Dr. Abdelrahman Khalifa , MD., PhD.Eee [ HEART DISEASES) McQ Q1: Regarding rheumatic vegetation all are true except: a) Appeared on the ventricular surface of the mitral valve b) Multiple beaded thrombi. ) The thrombi are pin head size d) Never give embolic manifestation, Q2: The type of necrosis that develops in Aschoff nodule is: a) Coagulative necrosis b) Fibrinoid necrosis, ©) Liquifactive necrosis d) Zenker necrosis Q3: Mycotic aneurysm that may develop in cerebral vessels due to low grade infected emboli is a complication of: a) Acute bacterial endocarditis b) Acute rheumatic valvulus c) Subacute bacterial endocarditis d) Libman-Sacks endocardi Q4: Male patient 23 years old developed sudden severe chest pain, with no any relevant past history, followed by death, postmortem examination revealed enlarged congested heart with friable necrotic foci, microscopic examination revealed inflamed myocardium with mononuclear cellular infiltrate rich in giant cells and areas of necrosis, the most likely diagnosis of this case is a) Acute myocardial infarction b) Giant cell myocarditis. c) Acute Rheumatic myocarditis d) Acute bacterial endocarditis Q5: in a case of myocardial infarction, well developed phagocytosis with prominent granulation tissue formation. Appeared at: a) 2-24h b) 1-3 days c) 4-7 days d) 7-14 days 14Eee [ HEART DISEASES) Q6: Infarction in the posterior wall of left ventricle and posterior part of interventricular septum is caused by occlusion of: a) Descending branch of left coronary b) Right coronary c) Left circumflex d) Left coronary Q7: Pericarditis that developed 2 to 6 weeks after myocardial Infarction is believed to be a) Infectious b) Immunological mediated c) Traumatic d) Toxic Q8: Regarding tuberculous pericarditis, a) Inflammatory exudate rich in neutrophil-, is detected b) It can be hemorrhagic but complete resolution is the usual fate ) Itis a primary tuberculou d) None of the above Q9: Cardiac tamponade is a) Aneurysmal dilatation of myocardial infarction b) Mural thrombosi c) Cardiac perforation with accumulation of blood in pericardial sac that interfere with normal hear contraction. d) None of the above embolization Q10: Fallot's tetralogy includes all except a) Hypertrophy of left ventricle b) Pulmonary stenosis. ¢) Shift of aorta to right side d) High ventricular septal defect Q11: Regarding coarctation of the aorta, it is accompanied with a) Right to left shunt b) Left to right shunt c) No shunt d) None of the above 15 Dr. Abdelrahman Khalifa , MD., PhD.Eee [ HEART DISEASES) Q12: Monckeberg's medial calcific sclerosis shows a) Calcification in vessel wall with narrowing of the lumen b) Strong relationship to atherosclerosis ©) No clinical manifestations d) Affection of young people Q13: The most common cause of death in essential benign hypertension is a) Congestive heart failure b) Cerebral vascular accident (hemorrhage) c) Renal failure d) None of the above Q14: Fibrinoid necrosis is a common pathological feature seen in a) Atherosclerosis b) Benign hypertension c) Malignant hypertension d) None of the above Q15: Regarding Buerger's disease a) It commonly affects the large vessel b) The vessel wall shows mixed acute and chronic inflammatory cells ¢) It is limited to the arterial wall d) It has no clinical significance Q416: Hepatitis B virus antigens incorporated in which of the following diseases a) Giant cell arteritis b) Rheumatic arteritis c) Buerger's disease d) Polyarteritis nodosa Q17: The vegetations that give aseptic emboli occur with a) Non-bacterial thrombotic endocarditis. b) Acute Rheumatic endocarditis c) Acute bacterial endocarditis Q18: Regarding Von Gierke's disease, the cardiac muscle fibers are enlarged and vacuolated due to a) Accumulation of lipid b) Accumulation of amyloid material 16 Dr. Abdelrahman Khalifa , MD., PhD.Eee [ HEART DISEASES) ©) Accumulation of glycogen d) None of the above Q19: Concerning suppurative pericarditis, all are true except a) It is yellow creamy in appearance b) It showed increase neutrophils and pus cells ¢) It ends by resolution d) It may be haemorrhagic Q20: Secondary hypertension can be caused by all except a) Conn's disease b) Cushing syndrome c) Pheochromacytoma d) None of the above Q21: Dissecting Aortic aneurysm can be seen in a) Myxomatous degeneration of aortic media b) Polyarteritis nodosa c) Atherosclerosis d) None of the above Q22: Glomangioma (Glomus tumour) is a) Malignant vascular neoplasm b) Benign vascular neoplasm c) Hamartoma d) None of the above. Q23: Phlebothrombosis means a) Thrombosis of non-inflammatory origin b) Thrombosis initiated by inflammation c) Thrombosis with or without inflammation d) None of the above Q24: If a trauma leads to fistulous communication between the wall of artery and vein via a hematoma, the patient is considered to have: a) Vascular malformation b) False aneurysm c) Vascular tumour d) None of the above 17 Dr. Abdelrahman Khalifa , MD., PhD.Eee [ HEART DISEASES) Q25: Hyalinosis and elastosis are diagnostic findings in the arterial wall affected by: a) Atherosclerosis b) Benign hypertension c) Malignant hypertension d) None of the above. Q26: A male patient 10 years old presented of fever and malaise, clinical examination revealed inflamed knee with skin rashes. On auscultation, murmur is heard over his mitral valve. History is taken and is suggestive tor the diagnosis of his condition. What is the most important test that should be done to confirm the diagnosis? a) ECG b) B- Antistreptolysin O titre c) Creactive protein d) ESR 18Eee [ HEART DISEASES) Case 1 A male patient 65 years old heavy smoker, obese and hypertensive, died from embolic brain infarction. Postmortem examination revealed rough aortic intima with confluent ulcerated yellowish patches. 1- What is the aortic lesion that present in this patient? 2- What are the risk factors for his condition? 3- What is the pathogenesis of his disease? 4- List two complications for this disease? Case 2 During postmortem examination of a cadaver who died in car accident, the heart showed thickened wall about 2.5 cm in thickness, kidneys were contracted with fine granularity on their outer surface,otherwisenoany other gross abnormality appeared in the examined internal organs. 1- What do you expect the patient had before death? 2- What do you expect to see in the small vessels on microscopic examination? 3- How is this disease classified, give examples. Case 3 A 12 years old boy was brought to the physician with a sore throat and fewer 3weeks ago. On examination, the child is afebrile but audible murmur on the mitral valve is found. The child is admitted in the hospital, over the next 2 days the child develops manifestations of left ventricular failure. 1-What is your. 2- What is the pathogenesis of this disease? 3- List two complications for this disease. 4- In your opinion, what is the cause of left ventricular failure in this patient? Case 4 Male patient 55 years old with hyperlipidemia and hypertension developed a sever attack of chest pain that was not responding to repeated sublingual nitroglycerine treatment. The patient died. Postmortem examination revealed yellow soft wall of the wall of the left ventricle, apex and the anterior part of interventricular septum. Dissection of one of the coronaries revealed thrombotic occlusion. 1 What is the cause of death in this patient? 2- What is the occluded coronary? 3- According to the gross appearance of the left ventricular wall how long did it take this lesion to occur and what do you expect to see microscopically? 4- Enumerate four complications that would develop if this patient was still alive? 19 Dr. Abdelrahman Khalifa , MD., PhD.Easy Dr. Abdelrahman KhalifaEee [ VASCULAR DISEASES] Atherosclerosis} Progressive disease, affecting small and large arteries, and characterized by lipid deposition Incidence: in intima followed by thickening and calcification of vascular wall males > females. Age > 45 y. Predisposing factors (risk factors): + Non modifiable © Age © Sex: male > female. incidence in female is increased after menopause © Family history of atherosclerosis (e.g. familial hypercholesterolemia) + Modifiable factors © Major (4) Pathogenesis exact mechanism s unknown + Insudation theory (Response to endothelial injury) + Hyperlipidemia (LDL) with low HDL: due to Obesity, high intake of animal fat, nephrotic syndrome, hypothyroidism + Hypertension Hyperglycemia (DM) : leads to hyperlipidemia Heavy smoking: proved to induce endothelial damage Hyperlipidemia & smoking increase the risk in age <40 years Minor (45) Sugar intake "Steroid intake (anabolic steroids) + Stress (Type A personality) * Sedentary life (lack of exercise) oe Endothelial injury > deposition of LDL due to high blood pressure Attraction of macrophage > phagocytosis of Lipid (Foam cells) lipid oxidation > more endothelial damage Platelets & macrophage secrete -> cytokines & GF (PDGF, FGF, TNf) Proliferation of smooth muscles & Matrix protein in intima Excessive vascularization of the wall Endothelial injury > Thrombosis ‘Thrombus organization -> incorporation (retraction) of thrombus into the wall Atheroma is the retracted thrombus. Lipid content is derived from cells forming thrombus, and not from LDL in blood. Dr. Abdelrahman Khalifa , MD, PhD.Eee [ VASCULAR DISEASES] Sites: Large & small arteries: Aorta - coronaries — cerebral - carotid - mesenteric — Renal - Popletial More common in the ostium of artery (due to hemodynamic current-> endothelial stress) Morphology: © Fatty streaks_ (progressive from young age up to 20 years age) © Gross: yellow, flat streaks (common in aortic orifice) © Micro.: Clear fat clefts- Foam cells (macrophage & smooth muscles containing fat) © Atheroma plaque © Gross: White firm cap - yellow soft core Fibrous cap: © Macrophages + Proliferated smooth muscle & Collagen in intima Lipid core: + Foam cells & needle shaped cholesterol clefts ‘© Dystrophic Calcification Basal zone : smooth muscle & connective tissue + vascularization + Atrophy of the media * Acute Complicated Atheromatous plaques © Thrombosis on top of atheroma (due to end injury & ruptured pleat (© Ulceration & detachment (ruptured plaque) cholesterol emboli © Hemorrhage inside atheroma (due to weak vascularization and thi oe fibrous cap} sudden occlusion or detachement Complications: © Large Arteries (e.g. Aorta) > Aneurism & mural thrombosis © Small & medium sized arteries (eg. coronary) > ischemia > infarction Lower limb arteries > ischemia >claudications > dry gangrene of the limb BPO] Dr. Abdelrahman Khalifa , MD, PhD.Ea roe [ VASCULAR DISEASES) Hypertension (Arteriolo-sclerosis) Progressive elevation of blood pressure >140 systolic, and >90 diastolic, with subsequent thickening of arterioles. Type: * According to Aetilology © 1ry (idiopathic) >95% of cases are benign hypertension ‘Sensitivity to Angiotensin > V.C. & vascular thickening # Salt intolerance (increased renal tubular Reabsorption) «Secretion of normal Aldosteron > abnormal metabolism Predisposing factors: Stress, Salt intake & Smoking © 2ry (80% benign ~ 20% malignant) + Nurogenic (increased intra cranial pressure) © Endocrinal (Cushing, Conn's, pheochromocytoma) + Renal (Nephritis, congenital dis, vascular cis. tumors) Vascular & blood dis ( Aortic coarctation, A-V shunt, polycythemia) * Eclampsia & pre-eclampsia (Renal Toxemia of pregnancy) * According to course © Benign (hyaline arteriolosclerosis) : gradual onset, long duration © Malignant (Hyperplasic arteriolosclerosis) : rapid onset, short duration Dr. Abdelrahman Khalifa , MD, PhD.[ VASCULAR DISEASES) Peay acai Neuen eacuniel Au Ceca rer >50 <30 Onset gradual sudden COTE) long ‘Short (fatal) id Less than 200/100 High 280/180 Arteries: Atherosclerosis & its complications | Arterie: therosclerosis & its complications with aortic dissection with aortic dissection Dea . Arterioles: ‘Gross very thick wall, multiple layers (onion skin) Arterioles have thick wall, narrow lumen crosconi Microscopi Microscopic: -Hyperplasia of SM. & basement membrane alastesls -Fibrinoid necrosis + perm “Ayatinosis Proremarsprearird -Ruptured vessels Malignant nephrosclerosis, Gross: Pere sour contracted kidney Red spots (flea -bitten) Micro: Micro: Arterioles: (as described above) Afferent Arterioles: (as described above) Glumeruli & tubules : hemorrhage st sided hypertrophy > congestive _| Left ventricular hypertrophy is mi Brain: Cerebral hemorrhage (strokes) Cerebral hemorrhage (strokes) Retinal hem & papilloedema Causes of death Congestive H.F. (45%), Mainly by Renal failure 95.% IHD (45%), Cerebral hemorrhage (5%), Renal IHD & H.F,, cerebral hemorrhage failure (5%) Dr. Abdelrahman Khalifa , MD, PhD.Eee [ VASCULAR DISEASES) A Sia) Focal abnormal dilatation of cardiac wall or arterial wall True Aneurisms Leads to weak media, and detached Compression atrophy , Ruptu hemorrhage) , Thrombosis, coronary occlusion Atherosclerotic | Syphilitic aneurism Mycotic Congenital aneurism i aneurism aneurism Sites Sites Sites Sites coronary, cerebral, Aorta (abdominal) | Aorta (ascending mesenteric Cerebral arteries ‘thoracic)mainly_ transverse arch Circle of Willis Causes ‘Causes Atherosclerosis, Congenital Morphology ‘Spherical (berry aneurism) > cerebral hemorrhage False Aneurisms Pulsating hematoma : Treumatic hematoma, The wall is formed by surrounding compre tissue A-V Fistula : Developmental - Traumatic — Inflammatory necrosis ~ Surgical in hemodyalisis| Complication: High output H. Dr. Abdelrahman Khall Shunt of blood from arteries > veins > increased venous return > MD, PhD.Eee [ VASCULAR DISEASES} Congested, dilated, elongated, tortuous veins Aetiology : Weak veins (Age related) more in females * High pressure (e.g, prolonged standing, portal hypertension) Sites : * Superficial veins of the lower limb + Porto-systemic anastomosis Complications * Edema © Ruptured venules > hemorrhage © Thrombosis > embolism 1n > thrombophele! Vascular tumors} Benign Malignant © Trophic skin lesions > varicose ulcer > inf Hemangioma (capillary & cavernous) _| Kaposi sarcoma caused by HHV-8 Gross: red or purple lesion Spindle malignant cells extravascular RBCs jlomangioma Classic Europian type: Lower limb skin. In Old age (Occurundenfingerinaia African endemic type:tN. in young age Vascular spaces + glomus cells 5 Post -transplantation type : LN & viscera Angiosarcoma Skin, Liver, breast In Liver: caused by chemicals (e.g. arsenic) Communicating vascular spaces, lined with 7 7 7 Dr. Abdelrahman Khalifa , MD, PhD.[ VASCULAR DISEASES] ascu Pathogenesis: Immunological © Immune complex type Ill hypersenset.(e.g. SLE, PAN, drug) © Anti-neutrophil cytoplasmic Ab ANCAs (e.g. Wegener) © Anti endothelial Ab (e.g. Kawasaki) Infections © Direct by organism ©. Indirect > immune mediated reaction Other causes (e.g. radiation, Trauma, Chemicals) Complications: Ischemia Thrombosis - Ruptured vessels > hemorrhage Types: Large to small vessel & * Giant cell (temporal) arteritis T-cell mediated - Temporal & ophthalmic — Old males - granuloma with giant cells * Takayaso Aortic arch and its branches - middle age - granuloma Medium vessel * Poly Arteritis Nodosa PAN Multiple arteries mostly renal (not affecting pulmonary vessels) Immune complex reaction , may be associated with HBV infection gross: multiple nodules - multiple aneurisms micro: necrotizing inflammation + excess neutrophils > chronic & fibrosis Clinical: (Fever + hypertension + abdominal pain) « Kwasaki le vessels— Children - necrotizing inflammation with mucocutaneous & LN syndrome & strawberry tongue Small vessel «Wegner granulomatosis respiratory tract & Kidney- cANCA - granuloma & necrotizing vasculitis © Churg-straus respiratory tract- Asthma- pANCA - granuloma & eosinophils * Microscopic polyangitis respiratory tract & Kidney— ANCA or no immune deposit - necrotizing Dr. Abdelrahman Khalifa , MD, PhD.Eee [ VASCULAR DISEASES] Burger's disease Raynaud phenomena Male smokers Females > males (genetic, immune, effect of tobacco on endothelium) exposure to cold or emotion ‘Small & medium vessels of Limbs ‘Small arteries Granulomatous Inflammation of small & medium ‘Ary: exaggerated vasospasm arteries veins& nerves > thrombosis with 2ry: to arterial diseases (SLE, burger) microabscesses > fibrosis or aneurism Cold sensitivity & pain Cold senesetivity & pain Claudications Cyanosis of fingers, nose, ear Trophic ulcers / Gangrene S.V.C. syndrome Lung carcinoma or Mediastinal lymphoma ~ invade S.V.C. >Obstructio Congestion & cyanosis of head and arms 1.V.C. syndrome Cancer or thrombus > Obstruction > L.L. edem + renal congestion & proteinurea + dilated abdominal veins Lymphangitis: inflamed lymphatic vessels (red streaks) with painful enlarge: (lymphadenitis) lymphedema: discussed in general pathology (circulatory) Chylus effusion: Milky fluid (lymph) in serous sacs due to ruptured lymphatics Congenital vascular diseases: ‘A-V fistula - Congenital berry aneurism - Fibromuscular dysplasia (Thick wall of large and medium sized arteries) Monckeberg disease: Senile idiopathic dystrophic Calcification of Media in muscular arteries . Without narrowing of lumen. No symptoms. Dr. Abdelrahman Khalifa , MD, PhD.Eee [ VASCULAR DISEASES] Match 1. Benign Hypertension 2. Aortic atherosclerosis 3. Burger's disease 4. Monckberg's disease 5. Giant cell arteritis 6. Wegner's vasculitis 7. Renauld’s disease 8. Mycotic aneurism 9. Malignant hypertension 10. Glomangioma 11. Kaposi sarcoma 12. Kawasaki vasculitis ‘A. Benign vascular tumor B. Vascular inflammation related to smoking C. Elastosis & hyalinosis D. Temporal arteritis E, Idiopathic calcification of media F, Glomerulonephritis, mucosal ulceration , ANCA G. Malignant spindle cells H. Strawberry tongue 1 Foamcells J. Arteriolar vasospasm K. SBE L._ Onion skin hyperplasia 10 Dr. Abdelrahman Khalifa , MD, PhD.Eee [ VASCULAR DISEASES] Complete A. Foam cells are lipid-laden.. B. Most common site of aortic atherosclerOsis ws... sneer C. Hemorrhage of atheromatous plaque is cause by.. D. Atheromatous plaque with thin fibrous cap is liable to E, The etiology of Monckberg disease is.... F. Mechanism of Kawaski vasculitis is mediated by The commonest cause of death in benign hypertension iS....c.cmnnnene zo The commonest cause of death in malignant hypertension Large artery vasculitis iNCIUdE..eonmnernee & snnnmnensinnnnnennne J. Excessive perivascular eosinophils is pathognomonic for. onevasculitis K. Dissecting hematoma is Caused bY «...cscnenes OF senses nnn L. Causes of A-V fistula include...... is a malignant vascular tumor lined by malignant endothelium .&. M. N. Pitutary causes of hypertension include. °. ). Renal causes of 2ry hypertension includes. .. but less P. Blood pressure in essential hypertension is more than... re 4 Dr. Abdelrahman Khalifa , MD, PhD.ERS [ VASCULAR DISEASES] Cases Patient with history of attacks of wheezy chest and dry cough, is complaining of ulcerative lesions in the nose and upper respiratory tract. Biopsy revealed vasculitis with striking perivascular eosinoph 1- Most possible diagnosis 2- Give reason: ulceration of respiratory tract 3- Lab investigation to support diagnosis Male patient 55 years old is complaining of weak pulse in lower limb. Recent transient ischemic attacks are reported. History of smoking and high lipid LDL profile. 1- Possible diagnosis 2- Microscopic findings of arteries 3- Possible complications? Male patient 60 years old is complaining of progressive headache and visual disorders. Blood pressure is 160 / 100 . Abdominal ultrasound revealed contracted kidneys. 1- Possible diagnosis 2- Microscopic findings of the kidney? 3- Possible complications? 12 Dr. Abdelrahman Khali