Cerebral autoregulation is the ability of the blood vessels in the brain to maintain a constant blood flow.

It has been shown that people who suffer from chronic hypertension can tolerate higher arterial pressure before their autoregulation system is disrupted and that they have an increased cerebrovascular resistance which makes them more at risk of developing cerebral ischemia if the blood flow decreases into normotensive ranges. On the other hand, sudden or rapid rises in blood pressure may cause hyperperfusion and increased cerebral blood flow, causing increased intracranial pressure and cerebral edema. In patients without hypertension, flow is kept constant over a mean pressure of 60-120 mm Hg. In patients with hypertension, flow is constant over a mean pressure of 110-180 mm Hg because of arteriolar thickening. When blood pressure is raised above the upper limit of autoregulation, arterioles dilate. This results in hyperperfusion and cerebral edema, which cause the clinical manifestations of hypertensive encephalopathy.Hypertensive encephalopathy is one of the clinical manifestations of cerebral edema and microhemorrhages seen with dysfunction of cerebral autoregulation and is characterized by hypertension, altered mentation, and papilledema. It describes cerebral conditions, typically reversible, caused by sudden and sustained severe elevation of blood pressure. Symptoms of hypertensive encephalopathy include headache, restlessness, nausea, disturbances of consciousness, seizures, retinalhemorrhage and papilledema. In what concerns heart damage, this seems to be caused by an increased arterial stiffness, increased systolic blood pressure, and widened pulse pressures, all of these as results of chronic hypertension.Arterial stiffness occurs as a consequence of age and arteriosclerosis. Age related stiffness occurs when the elastic fibres within the arterial wall (elastin) begin to fray due to mechanical stress. Normally, arteries are compliant and are readily able to expand due to pressure, but they also possess the ability to recoil.. stiffened arteries require a greater amount of force to cause them to expand and take up the blood ejected from the heart. This increased force requirement is provided by the heart, which begins to contract harder to accommodate the artery. Over time, this increased load placed on the heart causes left ventricular hypertrophy and eventually left ventricular failure. Causing further damage is the increased time required for systole and the reduction of diastole. This reduction in both time and pressure during diastole decreases the amount of perfusion for cardiac tissue. Thus the heart, which is becoming hypertrophic (and with therefore a greater oxygen demand) is starved of oxygen and nutrition, adding to cardiac damage. Chronic hypertension has a great impact on the renal vasculature as well as it may cause pathologic changes to the small arteries of the kidney. The arteries develop endothelial dysfunction and impaired vasodilation, which alter renal autoregulation. When the renal autoregulatory system is disrupted, the intraglomerular pressure starts to vary directly with the systemic arterial pressure, thus offering no protection to the kidney during blood pressure fluctuations. During a hypertensive crisis, this can lead to acute renal ischemia. Hypertensive nephropathy (or "hypertensive nephrosclerosis", or "Hypertensive renal disease") is a medical condition referring to damage to the kidneydue to chronic high blood pressure. In the kidneys, as a result of benign arterial hypertension, hyaline (pink, amorphous, homogeneous material) accumulates in the wall of small arteries and arterioles, producing the thickening of their walls and the narrowing of the lumina hyaline arteriolosclerosis. Consequent ischemia will produce tubular atrophy, interstitial fibrosis, glomerular alterations (smaller glomeruli with different degrees of hyalinization - from mild to sclerosis of glomeruli) and periglomerular fibrosisglomerular damage resulting in proteinuria and hematuria. Hyaline arteriolosclerosis is a major morphologic characteristic of benign nephrosclerosis, in which the arteriolar narrowing causes diffuse impairment of renal blood supply, with loss of nephrons. The narrowing of the lumen can decrease renal blood flow and hence glomerular filtration rate leading to increased renin secretion and a perpetuating cycle with increasing blood pressure and decreasing kidney function. The atherosclerotic, hypertension-related vascular lesions in the kidney primarily affect the preglomerular arterioles, resulting in ischemic changes in the glomeruli and postglomerular structures. Glomerular injury may also be a consequence of direct damage to the glomerular capillaries due to glomerular hyperperfusion. Glomerular pathology progresses to glomerulosclerosis, and eventually the renal
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tubules may also become ischemic and gradually atrophic. The renal lesion associated with malignant hypertension consists of brinoid necrosis of the afferent arterioles, sometimes extending into the glomerulus, and may result in focal necrosis of the glomerular tuft. Clinically, macroalbuminuria (a random urine albumin/creatinine ratio > 300 mg/g) or microalbuminuria (a random urine albumin/ creatinine ratio 30300 mg/g) are early markers of renal injury. Endothelial injury occurs due to severe elevations of blood pressure and fibrinoid necrosis of the arterioles follow. The vascular injury leads to deposition of platelets and fibrin, and a breakdown of the normal autoregulatory function. Ischemia occurs as a result which prompts further release of vasoactive substances. This process completes the vicious cycle.
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With severe mechanical injury from hypertension, autoregulation fails, resulting in focal vasodilation and transmission of high BP to the endothelium. Endothelial damage leads to enhanced vascular permeability with leakage and deposition of plasma proteins and fibrinogen in vessel walls and activation of mediators of coagulation and cell proliferation. RAAS may be activated primary or secondary to renal ischemia produced by arteriolar occlusion. Increased angiotensin II production leads to further renal vasoconstriction and ischemia. Volume depletion due to pressure natriuresis stimulates further renin release and worsens malignant hypertension. Local intravascular activation of the clotting cascade and plateletes, in the setting of microangiopathic hemolytic anemia, produces a vicious cycle of fibrin deposition and tissue ischemia leading to fibrinoid necrosis. Increased total production of cytokines and growth factors stimulates proliferation of medial smooth muscle cells. (1) initiating mechanism specific to underlying etiology Atherosclerotic, hypertensive-related vascular lesions affecting preglomular arterioles ischemic changes in glomeruli and post-glomeruli structure

(2) progressive mechanisms of hyperfiltration and hypertrophy of remaining nephrons Increasing pressure and flow predisposes to sclerosis and dropout of remaining nephrons

Fibrinoid necrosis of the afferent arterioles, sometimes extending into the glomerulus and may result in focal necrosis of the glomerular tuft highly associated with Malignant Hypertension anemia insufficient production of EPO by the diseased kidneys

Stage A: Patients are at high risk for heart failure but there is no evidence of structural damage to the heart. Risk factors include high blood pressure, heart diseases, diabetes, previous use of medications toxic to the heart (such in some chemotherapies), history of rheumatic fever, family history of cardiomyopathy. Stage B: Patients have a structural heart abnormality but no symptoms of heart failure. Such abnormalities include left ventricular hypertrophy or dilatation, asymptomatic valvular heart disease, a previous heart attack. Stage C: Patients have a structural abnormality and have present or previous symptoms of heart failure, including shortness of breath or fatigue related to the heart problem. Stage D: Patients have end-stage symptoms that do not respond to standard treatment

Silent Ischemia Inadequate supply of blood and oxygen to a portion of the myocardium Asymptomatic; detected during ECG monitoring Most common cause: atherosclerotic disease of an epicardial coronary artery/ies

Chronic elevation of blood glucose level leads to damage of blood vessels (angiopathy). The endothelial cells lining the blood vessels take in more glucose than normal, since they do not depend on insulin. They then form more surface glycoproteins than normal, and cause the basement membrane to grow thicker and weaker. In diabetes, the resulting problems are grouped under "microvascular disease" (due to damage to small blood vessels) and "macrovascular disease" (due to damage to the arteries).

myocardial supply and demand! ECGinversion of T waves) , displacement of ST segments (ST segment depression subendocardial ischemia; ST segment elevation more severe transmural ischemia Type 1 DM the result of complete or near total insulin deficiency Type 2 DM is a heterogenous group of disorders characterized by variable degrees of insulin resistance, impaired insulin secretion and increased glucose production
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Diabetic nephropathy (nephropatia diabetica), also known as Kimmelstiel-Wilson syndrome, or nodular diabetic glomerulosclerosis andintercapillary glomerulonephritis, is a progressive kidney disease caused by angiopathy of capillaries in the kidney glomeruli. It is characterized bynephrotic syndrome and diffuse glomerulosclerosis. It is due to longstanding diabetes mellitus, As diabetic nephropathy progresses, increasing numbers of glomeruli are destroyed by progressive nodular glomerulosclerosis

GET TABLE CRITERIA AND DIG IN + INSULIM RESISTANCE An early major contributor to the development of insulin resistance is an overabundance of circulating fatty acids. A polymorphism in the human IRS-1, G972R, is associated with insulin resistance and increased risk of type 2 DM; this polymorphic IRS-1 appears to act as an inhibitor of the insulin-receptor tyrosine kinase.

Virtually all forms of DM are caused by a decrease in the circulating concentration of insulin (insulin deficiency) and a decrease in the response of peripheral tissues to insulin (insulin resistance) leading to alterations in the metabolism of carbohydrates, lipids, ketones, and amino acids; the central feature is hyperglycemia. In a patient with insulin deficiency or insulin resistance and hyperglucagonemia, there is an increase in hepatic glucose production, a decrease in peripheral glucose uptake, and a decrease in the conversion of glucose to glycogen in the liver.

metabolic syndrome= pathophysio Hypertension and dyslipidemia frequently occur together and in association with resistance to insulin-stimulated glucose uptake. The constellation of insulin resistance, hypertension, and dyslipidemia has been designated as the metabolic syndrome.