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

ToxinsTurbulence

InflammationInjury Macrophage

infiltrationLipid

Insudation*

Foam cells ┼lipid release

T-cell infiltration

aneurysmdissection

Sm.m. hyperplasiaFibrous tissue

Platelet adhesionremodelling

vascularisation

weakening of vessel wall**

stenosisrupture, embolisation

clotting, thrombusocclusion

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 >85mmHgAbove 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, embolisationclotting, thrombus

occlusion5% 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 blocker3: ACE-i/ARB* and Ca2+-channel blocker and

thiazide diuretic4: 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

CaseA 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?

Case ctnd.

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

Referenceshistological 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