ARTERIOSCLEROSIS Flashcards
Explain intimal thickening?
As mentioned previously, intimal thickening is a stereotypic vascular (particularly arterial) response to injury. The normal intima is a thin layer, consisting of an endothelial layer, a basal lamina, and a tiny amount of subendothelial connective tissue in which is usually elastic fibers that create the internal elastic membrane. Note in the images to the left, the totality of the normal intima is almost not even discernable. As pathology develops, the injured intima will undergo thickening (extracellular matrix material or plasma proteins usually) and/or infiltration by cells (often by inflammatory cells or mediaderived smooth muscle cells), depending upon the type, duration, severity, etc. of the pathology process
What is ARTERIOSCLEROSIS? what are the types?
First things first: Don’t confuse arteriosclerosis (as a general organizing concept) with arteriolosclerosis (as a specific process affecting the specific structures we know as arterioles). Arteriosclerosis, as a word, means ‘thickening/hardening of the arteries,’ and so applied as a general paradigm, refers to the process of pathologic thickening of, or material accumulation within the walls of, any artery/arteriole structure. Functionally, as an arterial wall thickens, it is much less able to engage in elastic change, creating obvious pressure and flow issues. In human pathobiology, the primary forms of arteriosclerosis are the following: 1) arteriolosclerosis – usually HTN-induced, can be diabetes-induced, as its name implies affects arterioles and small arteries, discussed next section 2) atherosclerosis – a lipid and inflammatory process, affects medium-large arteries, discussed later 3) Monckeberg calcific medial sclerosis – an extremely common aging phenomenon due to unknown reasons. Calcium can collect in the wall, typically involving the internal elastic membrane, but doesn’t usually affect wall function or luminal diameter to any significant degree – current thinking is that this process is relatively clinically insignificant.
In HTN what will show pathology?
Recall that blood pressure is a function of cardiac output and peripheral resistance. The arterioles are the critical pressure regulators and are most responsible for peripheral vascular resistance. When dysfunction occurs in systemic pressure regulation (eg. hypertension, HTN), it logically follows that arterioles may be part of that disease’s etiology or pathogenesis. In HTN, at some point, arterioles will show pathology.
Explain the pathophysiology in arteriolosclerosis (really begnin HTN)?
Most arteriolosclerosis seen in humans is HTN-related (although diabetes can also cause it, particularly in the kidneys), and the vast majority (up to 95%) is idiopathic, meaning the etiology is not known well. Elements of essential/’benign’ HTN pathogenesis are somewhat known, and include the following: • genes – several polymorphisms across several genes probably confer an increased risk, such as those that regulate sodium reabsorption or renin secretion • reduced renal sodium excretion – a predictable event in the natural history of HTN, causing increased intravascular sodium and fluid in a new homeostatic state • vessel constriction – several factors (humoral substances causing vasoconstriction, material causing wall thickening, etc.) lead to a loss of vascular pliability • environmental factors – high salt diets, smoking, obesity, physical inactivity, etc.
What happens to the arterioles in begnin HTN? Pathology?
In benign HTN (see below clinical features, slow onset disease over decades), a stereotypic reaction occurs within the walls of the arterioles, causing an alteration in their structure and function. Increased intraluminal pressures will injure endothelial cells making their cell-cell junctions less intact, and allowing for plasma proteins to leak into the smooth muscle wall. These plasma proteins will aggregate and begin to thicken the intimal layer. Eventually, smooth muscle cells begin to reorganize themselves, some undergo likely pressure-induced apoptosis, and the wall begins to appear smooth, homogenous, and somewhat non-cellular – i.e., the walls will appear hyalinized. This process can appear with other types of endothelial injury (such as hyperglycemia-induced injury in diabetes), but HTN is so prevalent (and so “arteriolar-centric”) Pathology: Hyaline arteriolosclerosis involving an arteriole. Kimmelstein-Wilson nodules present in the glomerulus, causing nodular glomerulosclerosis
When protein collects what do we see on H and E prep?
When protein collects we see hyaline appearance/hyalonosis on H&E
In malignant HTN what do we see?
In “malignant” HTN, the relatively rapid onset of symptoms (over several months to 1-2 years) leads to the following: • severe HTN (>200 mm Hg systolic, >120 mm Hg diastolic) • retinal hemorrhages or retinal exudates (white-yellow retinal deposits usually made of lipid residues) • renal failure In this case, a different type of vascular process occurs. With high pressure injury, the intima undergoes thickening due to increased basement membrane material produced by activated smooth muscle cells. Keep in mind that smooth muscle cells of vessel walls can be activated, undergo hyperplasia, and be induced to produce different types of proteins. In malignant HTN they begin to lay down new basement membrane proteins in a laminated (line-like) fashion. This new protein material will cause luminal narrowing, and with enough injury, fibrinoid necrosis of the wall may be seen as a late change. we see Hyperplastic arteriolosclerosis in the pathology as severe HTN injury continues, the wall can undergo fibrinoid necrosis.
When does arteriolosclerosis become evident?
If we restrict the discussion of arteriolosclerosis to that induced by HTN (which is the majority of time), a certain clinical paradigm becomes evident with benign HTN (which is the vast majority of HTN) HTN arteriolosclerosis doesn’t present until very late in its natural history. Said another, often no clinical symptoms are seen until terminal events/irreparable damage occur.
Effects of arteriolosclerosis on the heart?
arteriolar pathology leads to increased afterload, leading to myocardial hypertrophy, leading potentially to abrupt myocardial infarction, arrhythmia, and/or congestive heart failure
Effects of arteriolosclerosis on the eyes?
the retina undergoes arteriole thickening (PE findings ‘copper wire’ and ‘silver wire’ arterioles), arteriovenular remodeling (‘AV nicking’), and ischemic (‘cotton wool spots’) and hemorrhagic (‘flame hemorrhages’) changes; the totality of these changes are blurred vision and visual acuity loss, often in an emergent way when they declare themselves clinically.
Effects of arteriolosclerosis on the kidneys?
thickened arteriolar walls and decreased lumens lead to renal parenchymal ischemia, which can lead to chronic glomerulosclerosis and chronic tubulointerstitial disease, all resulting in loss of renal cortical tissue by atrophy, causing the kidney to shrink in size and have a granular or pebbly surface; clinically this process can be tolerated until very late in disease, manifesting as chronic or end-stage kidney disease.
Effects of arteriolosclerosis on the Brain?
increased blood pressure will increase the likelihood of rupture in a Berry aneurysm, causing subarachnoid hemorrhage around the brain proper. HTN-induced arteriolosclerosis will also severely impact the small vessels of the brain, particularly the very small penetrating arterioles, which can undergo aneurysmal dilation (so-called Charcot-Bouchard microaneurysms) and hemorrhage, causing intraparenchymal/hemorrhagic stroke, particularly in susceptible regions, such as the putamen, basal ganglia, pons, medulla, thalamus, and cerebellum. Thickening and occlusion of arterioles can also cause less severe, more localized lesions, so-called lacunar infarcts and slit hemorrhages.
What is Atherosclerosis? Risk factors?
The decades-long acquisition of fibrofatty (lipid + fibrous tissue) plaques in the walls of medium-large sized arteries has many important risk factors. Some major ones: • Abnormal circulating cholesterol levels – can be due to hereditary or environment • Obesity and/or unhealthy diets • Family history – can contribute to many known or unknown factors • Diabetes • Smoking • Hypertension – very important concept; HTN can exacerbate atherosclerotic plaque development, most likely through mechanisms of endothelial injury • Inflammation – may or may not be clinically known or apparent
Explain the pathophysiology of atherosclerosis?
This complex process begins as an endothelial injury for any reason, which will stimulate cytokine release that promotes aggregation and inflammatory cell activation, particularly of macrophages and platelets. Macrophages will collect in the subendothelial space of the intima, causing intimal thickening. Lipid particles also begin to invade the subendothelial space and become oxidized. Macrophages will ingest the oxidized, predominately LDL-derived lipids causing their ‘foam cell’ appearance with abundant lipid accumulation. As this pathophysiology continues over years, slowly smooth muscle cells from the media will be drawn into the intimal action, where they begin to proliferate; they also begin to change their phenotype and function, allowing for their ingestion of lipids and their ability to begin to produce new collagen. Now all the elements are in place for the atheroma (AKA: atherosclerotic plaque) to continue to grow and evolve, producing larger and more complex fibrofatty plaques, including those with variable calcification.
Explain the names for various degrees of atherosclerosis?
Different names and different features (both pathologic and clinical) can be used to stratify the degree/severity of atherosclerotic plaque development. The names used can vary somewhat from resource to resource, but the important concept of plaque progression is the same. Lesions to be discussed below in increasing severity: • Fatty streak • Atheroma • Fibroatheroma/fibrous cap lesion/stable plaque • Complicated/unstable plaque
Compare and contrast Atherosclerosis vs. arteriosclerosis on the vessels affected? Wall infiltrated by? Clinical presentation? Clinical progression? and if they potentiate the other?
