Lecture 28: Pathology of Hypertension Flashcards Preview

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Flashcards in Lecture 28: Pathology of Hypertension Deck (68):
1

What are the key points of the pathology of HTN?

1. Systemic arterial hypertension is a functional state that may produce structural changes in vessels
i. atherosclerosis in large/medium size arteries
ii. fibroelastic intimal hyperplasia of small arteries
iii. hyaline and hyperplastic arteriolitis in arterioles
iv. microaneurysms of cerebral arteries
2. The structural changes in vessels may produce 2NDary effects in organs:
i. LV hypertrophy
ii. nephrosclerosis in vessels
iii. morbidity/mortality due to CHF or MI
iv. renal failure
v. stroke
vi. ischemic infarcts
3. Dissecting hematoma of aorta and major arteries occurs in structurally abnormal vessels (medial degeneration), a process accelerated by HTN or Marfan’s syndrome
-produces protean and lethal manifestations
-leads to death from exsanguination or cardiac tamponade

2

What are the characteristics of benign HTN?

95%
Diastolic > 90 and syst > 140
Silent until late in course (silent killer)

3

What are the characteristics of malignant hypertension?

5% and follows benign
Diastolic > 120 and systolic >210
Clinically SYMPTOMATIC
LETHAL if not treated rapidly/adequately

4

What are the key characteristics of secondary HTN?

5-10%
Due to underlying disease, most often from renal or adrenal

5

What are the key characteristics of primary hypertension?

No identified single cause
Multigene controlled + environmental factors (stress, salt, diet)

6

What are the vascular changes of HTN?

1. acceleration of other vascular diseases like atherosclerosis
2. changes unique to hypertension
a. adaptive (vasoconstriction, fibroelastic intimal hyperplasia)
b. destructive (fibrinoid necrosis, hyperplastic arteriolitis)
-seen with malignant HTN only

7

What are the adaptive changes of benign HTN?

1. vasoconstriction
2. Fibroelastic intimal hyperplasia (small arteries in the kidneys)
3. medial hypertrophy of large and medium arteries

8

What causes particularly bad nephroarteriosclerosis?

HTN + Diabetes!
Remember diabetes leads to nephropathy as well

9

What are the characteristics of fibrinoid necrosis?

A type of destructive change in malignant HTN
Characterized by deposition of fibrin in arterioles
Associated with necrosis in endothelial and SMCs

10

What are the characteristics of hyperplastic arteriolitis?

Concentric proliferation of SMCs
Interstitial proteoglycan deposition in small arteries (onion skinning)
Driven by growth factors such as PDGF

11

What are the characterisitcs of microangiopathic hemolytic anemia?

Shearing off of red cell fragments
Results in shistocytes with bites taken out
Occurs due to passage through fibrin mesh at increased pressures

12

What characterizes the early lesion of atherosclerosis?

Fatty streaks (the yellow in the descending aorta)

13

What are the histological features of hyaline atherosclerosis?

Adaptive change of HTN
Thick pink layer around the lumen of the arteriole

14

What are the histological features of
Intimal fibroelastic hyperplasia?

Presence of brown squiggly lines in the
Tunica intima
Narrowing of the lumen of a small renal artery

15

Whats the difference between a functional and a structural change?

The former is reversible
The latter is irreversible

16

What an example of a functional (and sometimes structural) change?

Vasoconstriction
Medial hypertrophy

17

What are examples of irreversible structural changes?

1. hyaline arteriolosclerosis
2. arterial fibroelastic intimal hyperplasia
What are the histologic features of normal small artery?

18

What are the histological features of fibrinoid necrosis?

Destructive changes in malignant HTN
Loss of nuclei
Presence of fibrin

19

What are the histological features of hyperplastic intimal arteriolitis?

Destructive change in malignant HTN
Concentric proliferation of SMCs
ONION SKINNING!

20

What are the histologic features of microangiopathic hemolytic anemia?

Destructive adaptation to malignant HTN
Presence of shistocytes (RBCs that look like bites were taken off them
Caused by force of going through fibrin strands at high pressure

21

What is the clinical manifestation of benign HTN?

1. CHF
2. MI
3. Stroke
4. Chronic renal failure
5. Subsequent malignant HTN

22

What are the effects of benign HTN on cardiac tissue?

i. atheroscelerosis
ii. LV hypertrophy
Can result in angina when demand outstrips supply
Less efficient function of myofibrils
Fibrosis that leads to decreased LV compliance
Impaired diastolic filling and systolic contractility

23

What are the effects of HTN on renal tissue?

1. nephroarteriolosclerosis
i. bilateral symmetrical decrease in renal cortical thickness
ii. granular surface
iii. arteriolar changes (eg intimal hyperplasia)
iv. fibrous replacememnt of glomeruli
2. chronic renal failure

24

What are the effects of HTN on cerebral tissue?

1. microaneurysms (Charcot-Bouchard)
2. ischemic infarction
3. rupture of Berry aneurysm

25

What are the gross features of LV hypertrophy?

Concentric due to increased workload

26

What are the histologic characteristics of hyaline arteriolosclerosis with glomerular sclerosis and tubular atrophy due to HTN?

Loss of nuclei in glomeruli
Atrophic tubules
Hyaline arteriosclerosis present

27

What are the key characteristics of nephroarteriolosclerosis?

It is a microvascular disease with glomerular scarring and tubular atrophy
-leads to chronic renal failure
Aggravates HTN by
i. decreased GFR and increased Na excretion
ii. activation of RAAS
iii. loss of urodilatin

28

What is urodilatin?

A hormone that cause diuresis by increasing renal blood flow

29

What are the ophthalmic complications due to HTN?

Microaneurysms

30

How is intracerebral hemorrhage related to HTN?

Hemorrhage may occur as a result of HTN

31

What are the epidemiologic features of malignant hypertension?

75% 5 year survival if adequately treated
Seen most in African Americans age 35-50
Preceded by benign HTN

32

What are the clinical manifestations of malignant HTN?

1. visual defects
2. papilledema
3. retinal hemorrhage
4. exudates
5. headache and hematuria
6. labs will show azotemia with proteinuria and hematuria, activation of RAA

33

What are the organ effects of malignant HTN?

1. Kidney = destructive vascular changes = acute cortical necrosis
2. Adrenal = cortical hyperplasia
3. Cerebral = increased intracranial pressure, edema

34

What is the gross ophthalmic presentation of malignant HTN?

Papilladema and hemorrhage

35

What is the gross renal presentation of malignant HTN?

Hemorrhage and acute cortical necrosis

36

What are causes of death in malignant HTN?

1. Acute renal failure
2. Stroke
3. Acute congestive heart failure

37

What are the causes of death from HTN overall?

1. CHF = 26%
2. Renal failure = 20
3. CVA (cardio vascular accident)
4. CAD

38

What is cardiovascular accident?

A stroke

39

What are types of secondary HTN?

1. renal
2. chronic renal disease
3. renal artery sclerosis
4. adrenocortical hyperfunction (Cushing and primary aldosteronism)
5. Pheochromocytoma
6. Prengnacy-induced
7. Increased intracranial pressure

40

How does the kidney lead to 2ndary HTN?

Increase RAAS
Decrased Na excretion and decreased GFR
Loss or urodilatin production

41

How does adrenal dysfunction lead to 2ndary HTN?

Increased aldosterone (Conn’s syndrome), glucocorticoids (Cushing’s) and catecholamines (Pheochromocytoma) all increase BP

42

How does pregnancy lead to HTN?

Overproduction in placenta of anti-angiogenic compounds that inhibit VEGF which then leads to renal abnormalities

43

What produces renin?

Juxtaglomerular cells

44

What stimulated JG cells to produce renin?

Decrease in vascular tone
Macula densa feedback
Sympathetic stimulation

45

What are the types of adrenocortical hyperfunction?

Adrenal cortical adenoma
Adrenal cortical hyperplasia (due to either ectopic ACTH production or excessive anterior pituitary production of ACTH)

46

What are patients with renal atherosclerotic changes at risk for?

Renal artery stenosis

47

What are the characteristics of renal artery stenosis?

Caused by atheroscler in old patients
-proximal and eccentric narrowing unilaterally
Caused by fibromuscular dysplasia in young patients
-often in women
-concentric narrowing
-rare

48

What is an aneurysm?

Localized dilation of a blood vessel, usually an artery

49

What are the different types of aneurysms?

1. Saccular vs. fusiform
2. True aneurysms (Berry, atherosclerotic, syphilitic)
3. Dissecting hematoma

50

What are the characteristics of saccular aneurysms?

Eccentric
Spherical
Lumen is out of mainstream of blood flow

51

What are the characteristics of fusiform aneurysm?

Circumferential
Lumen traversed by mainstream flow

52

Where is the berry aneurysm located? Characteristics?

At junction of internal carotid and middle cerebral arteries
Saccular
Releated to congenital waeakness in arterial wall

53

What is the disease process of abdominal Aortic aneurysm?

Atherosclerosis
Due to weakening of arterial wall by destruction of internal elastics/media
Most frequent cause of aortic aneursysms
Can be fusiform or saccular

54

How do aneursyms cause symptoms?

1. mass effect (when its size impinges on other structures)
2. distal embolization from contained thrombus
3. Rupture (due to LaPlace)

55

What happens when you stretch a vessel?

Thinning a vessel
Increase in wall stress (increase in radius and decrease in wall thickness = increased wall tension)

56

What are the characteristics of dissecting hematoma?

Occur in aortic media and usually involves thoracic, abdominal or branches of aorta
Can be caused by
i. underlying medial necrosis
ii. role of hypertension
iii. marfan’s syndrome (hereditary fibrillin defect)
iv. TGF-beta receptor protein
v. type III collagen

57

What is a dissection?

When a false lumen has formed
Blood from false lumen can come from vasa vasorum (which may have been ruptured upstream to this picture)

58

What causes dissecting hematomas?

1. Initiated by rupture of vasa vasorum within the weakened media
-variable extension in either direction
2. exit site usually present, most often above aortic valve
-possible reentry site distally
3. Possible hemorrhage outside wall into soft tissue or body cavity, with possible exsanguination
4. Abnormally weak arterial media fails to provide good support for delicate vasa vasorum entering media from adventitia
5. shear forces in aortic wall from LV contractions rupture vas vasorum which dissects along the plane of least resistance after intramural hemorrhage occurs
Can spread retrograde or anterograde from lesion

59


What is medial degeneration?

Degeneration of elastic fibers and
muscle in aortic media
Leads to dissecting aneurysm

60

What is the pathological characterization of dissecting aneurysms?

Focal destruction of elastic and accumulation of mucopolysacchardie in cystic spaces
Weakening of arterial media that leads to
i. Dilation (ectasia) of arteries
ii. Disruption of vasa vasorum that allows for hemorrhage in the media

61

How do patients with Marfan’s syndrome get dissecting aneurysms?

Normal fibrillin = downregulation of TGF-beta activity
However, in Marfan, abnormal fibrillin (defective elastic fibers) = overactivity of TGF-Beta, leading to defects you seen in Marfan’s including weakened arterial walls

62

What is ectasia?

Dilatin or distention of a tubular structure

63

What is the medical therapy for dissecting aneurysm?

1. lower BP and decrease flow (beta blockers0
2. Losartan to antagonize TGF-beta
Losartan = angio II receptor blockeer

64

Can dissection occur without an intimal tear?

Yes
But often there is an exit tear (intimal tear) located in the aorta above the aortic valve
Once there is an intimal tear, LV contraction promote further spread of dissecton

65

What happens if there is a second tear downstream?

Allows for reentry of dissection
Leads to double barrel aorta
Helps limit further spread of dissection

66

What are the symptoms of dissecting hematoma?

1. pain (tearing, migratory)
2. blocking aortic branches
3. rupture, cardiac tamponade

67

What are the types of dissection?

Type A involves the aorta
Type B does not involve the ascending aorta

68

When there is a dissecting hematoma associated with the peridcardium, what type of dissection is this?

Type A, the middle one in the picture