2. 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
3. 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
4. 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
5. 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
6. !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
7. 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
13. Atherosclerosis: Macroscopic Features
Common Locations
● Abdominal aorta
● Coronary arteries
● Popliteal arteries
● Internal carotid arteries
● Circle of Willis
● At any ostia and branching points
14. 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!
16. 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
17. 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
19. 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.
21. 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!
22. Hypertension: Macroscopic Features of benign hypertension
http://www.sclerodermasociety.co.uk/Theheartandscleroderma1.php
● nephrosclerosis
● “cobblestone” kidney
23. 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
24. 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
26. 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
27. 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
28. 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
29. 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!
30. 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
31. Vasculitis
● Definition and Aetiology
● Organising Vasculitides
● Pathogenesis
● Clinical Features
● Overview
32. 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
38. PAN
l Necrosis of blood vessels leads to formation of
characteristic nodules in the blood vessels of the kidney
39. 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)
40. 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
41. 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?
42. 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?
43. 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
44. 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
45. 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