Arterial Vessel Pathology Tutorial
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Arterial Vessel Pathology Tutorial

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A tutorial of blood vessel pathology for 5th year medical students at Cambridge University.

A tutorial of blood vessel pathology for 5th year medical students at Cambridge University.

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Arterial Vessel Pathology Tutorial Arterial Vessel Pathology Tutorial Presentation Transcript

  • Histopath Tute 3: Things to do with(blood)Vessels Christiane Riedinger 21/03/14
  • Today’s Contents ● Introduction ○ What your revision should cover ○ Reminder of the structure of blood vessels ○ Acquired changes of arterial vessels ● Atherosclerosis ● Hypertension ● Interim Summary ● Vasculitides ● Tying it in with last week: effects on the Kidney
  • Today’s Contents ● Introduction ○ What your revision should cover ○ Reminder of the structure of blood vessels ○ Acquired changes of arterial vessels ● Atherosclerosis ● Hypertension ● Interim Summary ● Vasculitides ● Tying it in with last week: effects on the Kidney
  • Path: What your pathology revision should cover ● Definition ● Aetiology ● Risk factors ● Epidemiology ● Pathogenesis ● Macroscopic Features ● Microscopic Features ● Investigations ● Clinical Features ● Treatment ● Prognosis ● Cancer: also Staging and Routes of Spread
  • Back to Basics: The Structure of Blood Vessels ● Tunica intima ○ endothelium ○ basement membrane ○ connective tissue ● Internal elastic lamina ● Tunica media ○ smooth muscle (arterioles), collagen, elastin (large arteries) ● External elastic lamina ● Tunica adventitia ○ supporting tissue, innervation, vasa vasorum
  • !Acquired Changes of Arterial Vessels! Arteriosclerosis = hardening of medium and large sized arteries by any process. Subtypes: ● Atherosclerosis - chronic process of accumulation of fatty deposits in intimal lesions of arterial vessels. ● Arteriolosclerosis - hardening and loss of elasticity in arterioles. ○ hyaline arteriolosclerosis* - hyaline (glassy) deposits in media. (T2DM, hypertension, drugs) ○ hyperplastic arteriolosclerosis - large deposits => narrowing of lumen ● Medial calcific sclerosis** - deposition of Calcium in the media. ○ clinical significance unclear
  • Today’s Contents ● Introduction ○ What your revision should cover ○ Reminder of the structure of blood vessels ○ Acquired changes of arterial vessels ● Atherosclerosis ● Hypertension ● Interim Summary ● Vasculitides ● Tying it in with last week: effects on the Kidney
  • Atherosclerosis:Contents ● Definition ● Risk factors ● Pathogenesis ● Macroscopic Features ● Microscopic Features ● Treatment
  • Atherosclerosis:Definition Chronic acquisition of fatty deposits in intimal lesions of arterial vessels.
  • Atherosclerosis: Risk factors ● genetic ○ FH (LDLR mutations) or common polygenic ○ gender ● acquired ○ age ○ hypertension ○ diabetes ○ smoking, lifestyle, stress ● measured in the lab ○ hyperlipidaemia/hypercholesterolaemia (LDL) ○ raised CRP ○ hyperhomocysteinaemia ○ procoagulants ● a good buzz word: metabolic syndrome
  • Atherosclerosis: Pathogenesis Many theories: ● Response-to-injury hypothesis ○ injury causes chronic inflammatory response and sm.m. proliferation ● Encrustation hypothesis: ○ sm.m. reaction to mural thrombus ● Monoclonal hypothesis ○ mutation in sm.m. to increased proliferation / chronic inflammation ● ... ● Unifying hypothesis
  • Atherosclerosis: Pathogenesis Toxins Turbulence Inflammation Injury Macrophage infiltration Lipid Insudation* Foam cells ┼ lipid release T-cell infiltration aneurysm dissection Sm.m. hyperplasia Fibrous tissue Platelet adhesion remodelling vascularisation weakening of vessel wall** stenosis rupture, embolisation clotting, thrombus occlusion
  • Atherosclerosis: Macroscopic Features Common Locations ● Abdominal aorta ● Coronary arteries ● Popliteal arteries ● Internal carotid arteries ● Circle of Willis ● At any ostia and branching points
  • Atherosclerosis:Macroscopic Features Increasingly severe lesions: ● fatty streaks - acquired by 10y, mainly IC lipids ● intermediate lesions - IC and EC lipid ● atheroma - core of EC lipid ● fibroatheroma - multiple lipid cores with fibrotic/calcific layers ● complicated lesions - haemorrhage/thrombosis at surface defects 70% occlusion means critical stenosis!
  • Atherosclerosis:Microscopic Features
  • Atherosclerosis:Treatment ● in order to prevent cardiovascular disease: ischaemia/infarcts, IHD, periph. vascular disease, sudden cardiac death ● Lifestyle changes ● Statins ○ indication ○ action: ■ HMG-CoA reductase inhibitor (cholesterol synthesis in the liver) ■ anti-thrombotic, anti-inflammatory, plaque stabilising, endothelium ○ side-effects: ■ muscle aches, myositis, rhabdomyolysis (esp. if + fibrates) ■ abdominal discomfort ■ raised transaminases (e.g. ALT), CK
  • Today’s Contents ● Introduction ○ What your revision should cover ○ Reminder of the structure of blood vessels ○ Acquired changes of arterial vessels ● Atherosclerosis ● Hypertension ● Interim Summary ● Vasculitides ● Tying it in with last week: effects on the Kidney
  • Hypertension:Content ● Definition ● Aetiology ● Pathogenesis ● Macroscopic Features ● Microscopic Features ● Treatment
  • Hypertension: Definition systolic >140mmHg - diastolic >85mmHg Above these levels, medical intervention is of benefit. 25% of the population affected!!! Distinguish: ● 1* (essential, idiopathic) vs. 2* hypertension ● benign (slow onset) vs. malignant hypertension (fast onset) ○ note: outdated terms ○ malignant hypertension = hypertensive crisis/emergency (>180/>110), acute impairment of organs and potential irreversible organ damage.
  • Hypertension: Aetiology ● 1* essential, idiopathic - 90% of cases ○ complex multifactorial ○ genetic combination of polymorphisms ○ nutrition salt, caffeine, alcohol, obesity ○ lifestyle stress (=> increased sympathetic discharge?) ○ hormonal RAAS ○ environmental ● 2* - 10% of cases ○ renal 1* or 2* (e.g. renal artery stenosis) ○ adrenal Phaeo, Cushing’s, Conn’s, CAH ○ thyroid hyper AND hypo ○ pituitary acromegaly ○ parathyroid hyper (how ?) ○ cardiovascular AVM, coarctation ○ drugs OCP, steroids, sympathomimetic ○ pregnancy ○ genetic Liddle syndrome (ENaC), aldosterone metabolism
  • Hypertension: Pathogenesis of benign hypertension increased pressure leakage of plasma components across vessel valls sm.m.↑ ECM ↑ hypertrophy of media hyaline arteriolo- sclerosis worsening of atherosclerosis!* rupture, embolisation clotting, thrombus occlusion 5% progress to malignant hypertension!
  • Hypertension: Macroscopic Features of benign hypertension http://www.sclerodermasociety.co.uk/Theheartandscleroderma1.php ● nephrosclerosis ● “cobblestone” kidney
  • Hypertension: Pathogenesis of malignant hypertension sudden increase in pressure acute destructive forces in vessels fibrous thickening of intima* heavy arteriolosclerosis thrombosis fibrinoid necrosis in arterioles
  • Hypertension: Macroscopic features of malignant hypertension http://www.sclerodermasociety.co.uk/Theheartandscleroderma1.php http://sweetclipart.com/womens-green-eyes-474 https://www.auanet.org/education/modules/pathology/renovascular- disease/malignant-hypertension.cfm
  • Hypertension: Microscopic Features hyaline arteriolosclerosis hyperplastic arteriolosclerosis fibrinoid necrosis
  • Hypertension: Treatment ● measure BP: if high in clinic AND during ambulatory/home blood pressure monitoring A/HBPM (24h/>4d am) ● rule out 2* causes ● when to treat: ○ consider treatment if > 140(135 A/HBPM), treat if + IHD, TIA, CKD, T2DM ○ start treatment if >160(150 A/HBPM) ○ immediate treatment if >180/110 ● lifestyle modifications: ○ lower salt and alcohol intake ○ lose weight ○ increase exercise ○ stop smoking ○ healthier diet
  • Hypertension: Treatment ctnd. ● single agent unlikely to be sufficient ● aim for <140/90 unless comorbidities (then lower) ● drug choice depends on age and race ● 4 step therapy depending on when target is reached 1: <55 non-black: ACE-i/ARB* >55 or black: ACE-i/ARB* and Ca2+-channel blocker 2: ACE-i/ARB* and Ca2+-channel blocker 3: ACE-i/ARB* and Ca2+-channel blocker and thiazide diuretic 4: optimise doses in resistant hypertension ● * beta blocker if younger, want children, IHD, LVF, intolerance
  • Today’s Contents ● Introduction ○ What your revision should cover ○ Reminder of the structure of blood vessels ○ Acquired changes of arterial vessels ● Atherosclerosis ● Hypertension ● Interim Summary ● Vasculitides ● Tying it in with last week: effects on the Kidney
  • Interim (extended) summary Hyaline arteriolosclerosis ↔ Benign Hypertension Hyperplastic arteriolosclerosis Intimal Thickening ↔ Malignant Hypertension ↔ Malignant Hypertension (Atherosclerosis) ↔ Hypertension (Atherosclerosis)Hypertrophy of media Fibrinoid necrosis ↔ Malignant Hypertension, Vasculitis ↔ Atherosclerosis, hypertension, aneurysm, dissection (see supervision 1) Thinning of media This is up for discussion!
  • Today’s Contents ● Introduction ○ What your revision should cover ○ Reminder of the structure of blood vessels ○ Acquired changes of arterial vessels ● Atherosclerosis ● Hypertension ● Interim Summary ● Vasculitides ● Tying it in with last week: effects on the Kidney
  • Vasculitis ● Definition and Aetiology ● Organising Vasculitides ● Pathogenesis ● Clinical Features ● Overview
  • Vasculitis:Definition and Aetiology Inflammation of blood vessels (or a vessel) that is either non-infectious or infectious. Non-infectious: ● mainly autoimmune, chronic inflammatory ● idiopathic Infectious: ● bacterial e.g. treponema pallidum causing aortitis in syphilis! ● fungal e.g. Aspergillus, Mucor spp. ● 2* e.g. due to systemic infection, endocarditis
  • Vasculitis: Organising Vasculitides BY SIZE!!!! (and not complete) ● Large: Giant cell arteritis, aortitis, Takayasu’s arteritis* ● Medium: Polyarteritis nodosum PAN, Kawasaki’s disease ● Medium-small: Wegener’s granulomatosis, Churg-Strauss ● Small: Henoch-Schoenlein purpura, microscopic polyangiitis, (Goodpasteure’s) Behcet’s ● Any size: Immune complex deposition
  • Vasculitis: Pathogenesis ● Mechanisms in autoimmune reactions causing vasculitis ● Immune complex deposition ○ hypersensitivity (type 3 and type 4!) ● Antineutrophil cytoplasmic antibodies ANCAs (type 2 hypersensitivity?) ○ c-ANCA ■ against PR3 proteinase 3 granule of PMNLs ■ = critically important, specific for Wegener’s ○ p-ANCA ■ against MPO myeloperoxidase in PMNL granules ■ = pretty useless ANCA as unspecific ● Anti-endothelial antibodies (Kawasaki) ● Autoreactive T-cells
  • Vasculitis: Clinical Features ● generic, systemic => consider if any unidentified multisystem disorder ● myalgia, tiredness, loss of appetite ● fever ● arthritis ● specific symptoms see upcoming overview ○ kidneys: GN, kidney failure, hypertension! ○ lungs: haemoptysis ○ nerves: neuritis, pain ○ skin: rash, ulcers, purpura ○ .. and more! ● investigations: ○ ESR/CRP raised ○ ANCA? ○ U&E and creatinine ● FBC ● urinalysis ● angiography
  • Vasculitis: Overview
  • PAN l Necrosis of blood vessels leads to formation of characteristic nodules in the blood vessels of the kidney
  • Kawasaki’s ● mimics Scarlet Fever ● diagnostic criteria: fever > 5d + 4 out of ● conjunctivitis ● mouth changes: dry, swollen lips or tongue, strawberry tongue ● cervical lymphadenopathy ● erythema and desquamation of palms and soles of feet ● erythematous rash ● complications ● coronary aneurysm => MI (prevent with aspirin)
  • Vasculitis: Summary ● Giant cell arteritis emergency, eyesight at risk ● PAN kidney nodules, part of HepB ● Kawasaki affects children, strawberry tongue, CA aneurysm ● Wegener’s midline, lung, kidneys, nose, c-ANCA ● Churg Strauss allergic, lung, p-ANCA ● Microscopic Polyangiitis many organs, necrotising, p-ANCA
  • Case A 53y-old man presents with cough (ongoing for the past few months), SOB, fever, weight loss, as well as haemoptysis, joint pain, sinusitis and recent otitis media. CXR shows cavitation, urinalysis shows red cells + casts. No response to antibiotics and sputum cultures -ve. What is the diagnosis? Why? What do you test for?
  • Casectnd. What if there was multiorgan involvement, including CNS and GI? What if he had eosinophilia and asthma? What if it was only lung and renal involvement?
  • Today’s Contents ● Introduction ○ What your revision should cover ○ Reminder of the structure of blood vessels ○ Acquired changes of arterial vessels ● Atherosclerosis ● Hypertension ● Interim Summary ● Vasculitides ● Tying it in with last week: effects on the Kidney
  • How this affects the kidney ● tying things in with the 2nd supervision (see http://www.dr-cee.net/? page_id=1431) ● Atherosclerosis ○ renal artery stenosis ● Hypertension ○ arterionephrosclerosis ○ hyalinisation of glomeruli => renal failure ● Vasculitis ○ immunocomplex deposition => GN (can be severe) ○ infarctions
  • References histological slides: wheater’s histology pathogenesis of atherosclerosis: http://quizlet.com/7447571/hypotheses-for-atherosclerosis-flash-cards/ microscopic features of atherosclerosis: http://www.drugdevelopment-technology.com/projects/prasugrel/prasugrel2.html PAN contrast X-ray: picture from http://www.learningradiology.com/notes/chestnotes/polyarteritisnodosapage.htm also see: http://www.dr-cee.net/?page_id=1438