Blood vessels Pathology (GOMEZ) Flashcards
Congential aneurysm (Berry aneursym)
seen in 2% of autopsies
most involve circle of Willis
saccular type aneurysm arising in an artery with a developmental wall abnormality – weak area of vessel wall
berry aneurysm -> presents with headaches or sudden death
arteriovenous fistulas
rare abnormal communications between arteries and veins
most congenital; some produced (rupture of an arterial aneurysm into adjacent vein, injuries that pierce walls of artery and vein, or inflammatory necrosis of adjacent vessels)
short-circuit blood and cause heart to pump additional volume (high-output cardiac failure can ensue)
Both can rupture, especially critical in brain
fibromuscular dysplasia
focal irregular medial and intimal
hyperplasia with thickening of walls of medium and large muscular
arteries which occurs more commonly in young women (more later)
HTN
systolic > 140 mm Hg
2014 Evidence Based Guidelines suggest > 150/90 mm Hg for those > 60 years.
diastolic > 90 mm Hg
Prehypertension
Systolic 120-139 mm Hg
diastolic 80-89 mm Hg
Systolic blood pressure is more important than diastolic blood pressure as a determinant of cardiovascular risk
systolic >220 mm Hg or diastolic >120 mm Hg with no evidence of target organ damage
hypertensive urgency
Hypertensive emergency
Accelerated hypertension- significant increase in B. P. associated with target organ damage (flame-shaped hemorrhages or exudates of fundus, renal failure, headache, angina, etc.)
Malignant hypertension- as above + papilledema (swelling of optic disc)
Secondary HTN?
Renal
glomerulopathies, CRD, polycystic, renal artery stenosis, renal vasculitis
Endocrine adrenocortical hyperfunction (Cushing's, primary aldosteronism, adrenal hyperplasia, licorice ingestion)
Cardiovascular
Neurologic -
endothelin
causes vasoconstriction
Liddle syndrome
beta or gamma subunit of ENaC
•Mutations in renal epithelial Na channel protein → leads to increased sodium reabsorption –> HTN
moderately severe salt sensitive hypertension due to
Increased distal tubular reabsorption of Na+ with aldosterone stimulation
11-Beta hydroxylase deficiency
(enzyme that influences aldosterone synthesis) leading to increased aldosterone production
leads to HTN
hardening of arteries
arteriosclerosis
in muscular arteries of >50 y. o. with no vessel lumen narrowing (can ossify). Hardening of the media. Blood still passes through
monckeberg medial calcific sclerosis
arterioLOsclerosis
Hyaline arteriolosclerosis –common Protein deposition (hyalinized) Seen in : aging diabetes mellitus benign nephrosclerosis (hypertension)
Hyperplastic arteriolosclerosis Cell death (onion-skinning) \+/-necrotizing arteriolitis Seen in : malignant hypertension
atherosclerotic plaques
Cause decreased flow (obstruction)
myocardial infarction, cerebral infarction, aortic aneurysms, peripheral vascular disease (gangrene), mesenteric occlusion, sudden cardiac death, chronic ischemic heart disease, and ischemic encephalopathy
Can disrupt and precipitate thrombi (obstruction)
Can shed emboli
Can encroach on media and weaken the vessel wall
aneurysms and ruptures
***Turbulent flow and low shear stress areas are prone to atherosclerosis
Laminar flow induces endothelial genes for products that protect against atherosclerosis (superoxide dismutase)
Turbulent flow causes endothelial trauma and dysfunction increased risk for developing atherosclerotic plaque
nonmodifiable risk factors for atherosclerosis
genetic abnormalities
family history
increasing age
male gender
modifiable risk factors for atherosclerosis
Hyperlipidemia HTN BP > 169/95, increased risk of IHD Cigarette smoking Diabetes Inflammation
2 risk factors lead to 4x risk
3 lead to 7x risk
metabolic syndrome
Obesity, dyslipidemia, hypertension, and insulin resistance (can also have hypercoagulability and inflammatory state)***
statins
inhibit HMG-CoA reductase
promote synthesis of LDL receptors
acyl-CoA (ACAT)
favors esterification and storage of excess cholesterol
estrogens effect on cholesterol
increase HDL and decrease LDL
replacement therapy does NOT decrease risk for heart attacks in post menopausal women
exercise and alcohol
increase HDL (good)
obesity and smoking
decrease HDL (among other things)
familial hypercholesterolemia
Mutations in the LDL receptor gene
Impair the intracellular transport and catabolism of LDL
Also impair the transport of IDL (plasma IDL is converted into LDL)
Causes elevated LDL cholesterol in the plasma
Oxidized LDL receptors take over (scavenger receptor pathway)
Amount catabolized by scavenger receptor pathway is directly related to the plasma cholesterol level
Monocytes, macrophages, smooth muscle and endothelial cells have receptors for chemically modified (e.g., acetylated or oxidized) LDLs
Cholesterol in macrophages contributes to atherosclerosis and xanthoma formation
Oxidized LDL is cytotoxic to endothelial and smooth muscle cells
most common LDL receptor mutation?
class II - problem with transport
receptor protein transport from the endoplasmic reticulum to the Golgi apparatus is impaired due to abnormal protein folding
autosomal dominant heterozygotes in familial hypercholesterolemia
Heterozygotes 2-3x elevation of plasma cholesterol levels- don’t see xanthoma
autosomal dominant homozygotes
5x elevation of plasma cholesterol levels
Develop severe atherosclerosis, mitral valve stenosis corneal arcus and xanthomas
Die from complications as children or young adults
elevated homocyteine
(low folate and/or vitamin B intake, homocystinuria) associated with premature vascular disease
If you lower homocysteine it doesn’t lower risk
risk factor for atherosclerosis
lipoprotein A
(apolipoprotein B-100 portion of LDL linked to apolipoprotein A) associated with a higher risk of coronary and cerebrovascular disease. Can’t decrease this abnormal lipoprotein – but can control cholesterol levels in diet
BP systolic, cholesterol, HDL, Diabetes, Cigarettes, LVH by ECG (by the time you have this it means you’ve most likely had HTN for a long time)
what are these
risk factors for atherosclerosis
elevated plasminogen activator inhibitor 1
strong predictor of RISK for major atherosclerotic events
CRP
Acute-phase reactant synthesized primarily by the liver
Has roles in opsonizing bacteria and activating complement
Atherosclerosis - involved in endothelial adhesion of WBCs and thrombosis
Strongly and independently predicts the risk of myocardial infarction, stroke, peripheral arterial disease, and sudden cardiac death
No evidence that lowering CRP reduces cardiovascular risk,
Smoking cessation, weight loss, statins and exercise all reduce CRP
what infections MAY contribute to atherosclerosis
Chlamydia pneumoniae, herpesvirus, and cytomegalovirus
aspirin ?
inhibits cox 1 at low doses–> anti-clot
Celebrex (Celecoxib)
Cox 2 inhibitor (NSAID)
believed to ↓ endothelium-derived prostacyclin without inhibiting platelet-derived thromboxane A2 → prothrombotic state
aneurysm
Localized abnormal dilation of a blood vessel or the wall of the heart
Most important causes of aortic aneurysms are
atherosclerosis (abdominal aorta) – weaken the wall
Worst atherosclerosis down in abdomen area
hypertension via medial cystic degeneration (thoracic aorta)
Other causes: Marfan syndrome, Loeys-Dietz syndrome, Ehlers-Danlos syndrome, scurvy, trauma (traumatic aneurysms or arteriovenous aneurysms), congenital defects (berry aneurysms), syphilis and vasculitides
mycotic aneurysm
infections!
from embolization of a septic embolus (infective endocarditis)
from extension of an adjacent suppurative process - appendicitis
from circulating organisms infecting the arterial wall
Mycotic abdominal aortic aneurysms - atherosclerotic AAAs that have become infected (particularly in Salmonella gastroenteritis)
true aneurysm
– bounded by arterial wall component or myocardium
Saccular aneurysm – appears rounded, bubble
Fusiform aneurysm – involves long segment of artery and is not rounded
false aneurysm
(pseudoaneurysm) = hematoma secondary to transmural rupture
