Hypertensive Cardiovascular Disease

Hypertension Formation

Regulation of Blood Pressure (BP) (CO = cardiac output; TPR = Total Peripheral Resistance ANG II = Angiotensin II)

Blood Volume: Na⁺, Mineralocorticoids, Atriopeptin

Hormonal Factors (HF):

Constrictors = Ang II, Catecholamines, Thromboxane, Leukotrienes, Endothelin
Dilators = Prostaglandins, Kinins, NO/EDRF

Local Factors: Autoregulation, Ionic (pH, hypoxia)

Cardiac Factors: Heart Rate (HR), contractility

Neural Factors(NF):

Constrictors = a -adrenergic;

Dilators = b₂-adrenergic

Role of the Kidneys in Blood Pressure Regulation

the kidneys influence both TPR and sodium homeostasis by controlling the output of the renin-angiotensin system

renin secreted by the juxtaglomerular (JG) cells of the kidney converts plasma angiotensinogen to angiotensin I (Ang I) which is converted to angiotensin II (Ang II) by angiotensinogen converting enzyme (ACE)

Ang II then Ý TPR by causing vasoconstriction and Ý blood volume by stimulation of aldosterone secretion

Diseases which cause HTN – 90% of HTN is idiopathic and apparently primary (essential HTN); and 10% is secondary

Malignant or Accelerated HTN: term used to describe rapid rise in BP which if untreated leads to death (5% of HTN)

Secondary Hypertension

(1) Renal Diseases

Parenchymal (60%) – disease involving the renal parenchyma may cause HTN; more important ones are:

Glomerulonephritis (acute or chronic)
Chronic Pyelonephritis
Diabetic glomerulosclerosis (Kimmelstiel-Wilson Syndrome)
Any collagen disease
Congenital Polycystic kidneys
Gout
Nephrocalcinosis
Renal amyloidosis
Obstructive Uropathy
Radiation nephritis

Vascular (30%)

Stenosing atherosclerosis (main renal artery or branch thereof)
Fibromuscular hyperplasia of main renal artery
A-V fistula
Embolism with segmental infarction

(2) Endocrine Diseases (10%)

Adrenal

Cortex (hyperplasia, adenoma or carcinoma) – primary aldosteronism, Cushings Syndrome, adrenogenital syndrome
Medulla – pheochromacytoma or related tumor (may occur in sites other than adrenal)

Thyroid – HTN associated with hyperthyroidism is usually systolic only
Pituitary – hypersecretion of ACTH with Cushing’s Disease
Parathyroid – Nephrocalcinosis secondary to hyperparathyroidism

(3) Diseases or the Aorta

Coarctation
Inelasticity due to marked arteriosclerosis (systolic only)
Atherosclerotic stenosis of ostium of main renal artery or involvement of renal artery by aneurysm

(4) Toxemia of pregnancy

(5) Neurogenic

Anxiety states

Ý intracranial pressure (ICP)

(6) Miscellaneous –disorders causing Ý CO can cause systolic HTN; ex. anemia, arteriovenous fistula and beriberi

Pathology of Uncomplicated Established Essential HTN

Hypertrophy of heart walls (initially only left ventricle (LV) and then right ventricle (RV))

Coronary Artery Disease (CAD) – HTN accelerates atherosclerosis

Pleural effusions

Hepatosplenomegaly

Adrenal Hyperplasia – Ý aldosterone secretion due to loss of electrolytes by kidneys

Kidney – constriction of arterioles causing Ý TPR

Enhanced Atherosclerotic Process – often aorta

Cerebral Blood Supply – atherosclerotic changes Þ potential thrombosis and stroke: 30-70 % of patients with HTN have cerebral involvement

(1) Pathology of the Heart with Uncomplicated HTN CO = HR X TPR

Resistance: Ý TPR Þ Ý afterload (Ý force that the left ventricle (LV) must produce to maintain the CO.)

Peripheral Resistance (TPR) is determined by the equation TPR = LV/r⁴. (L = length of the system; V= viscosity of the blood; r = radius of the blood vessels. The arterioles are the primary site of resistance.

Early Effects: Ý TPR Þ Ý in LV pumping force to maintain CO; transient Ý in BP Þ physiologic stretching of myocardial fibers (Starling’s Law); if persists Þ hypertrophy

Intermediate Effects: Maintained Ý work of heart due to persistent HTN produces concentric hypertrophy of LV. LV wall exhibits Ý width (normal = 1.2 cm) without enlargement of ventricular chamber (so heart size looks normal on CXR)

Heart weight reflects the degree of LV hypertrophy. In normal individuals, heart is about 350-375 g in women and 375-400 g in men (.40-.45% of total body weight, somewhat lower in obese individuals and women). Severe HTN can cause heart to become 500-1000 g; if weight exceeds 700-800 g, it is labeled cor bovinum (cow heart)

Late Effects: The LV dilates during LV failure and produces eccentric hypertrophy. The heart is now enlarged on chest X-ray. As the LV continues to dilate the myocardial fibers cannot continue to hypertrophy and the stretched actin and myosin fibers are now stretched so they do not overlap to the same extent. They are now on the downward portion of Starling’s curve.

New blood vessels do not form in the hypertrophied heart and the heart muscle becomes limited by the available blood supply. It becomes vulnerable to ischemic injury.

Histology: large "box car" nuclei found in myocytes; nuclei are enlarged, centrally located and have nucleolar changes

(2) Pathology of the Kidneys with Uncomplicated HTN (culminates in benign nephrosclerosis)

Early Effects: - kidneys remain normal

Late Effects: Arteriolar sclerosis of afferent arterioles, which is characterized by hypertrophy of the media and smooth eosinophilic hyaline thickening of the subintimal tissue. Over time the hyalinization may involved the entire thickness of the arteriolar wall leading to stenosis and finally obliteration of the artery lumen. Larger arteries are frequently involved in artherosclerosis and may also show elastic hyperplasia or elastics. In general, the amount of elastic tissue in the wall of an artery reflects the blood pressure within it.

Artery Obliteration: Effects of artery obliteration are determined by the size of the artery occluded.

Smaller renal arteries:

basement membrane thickening followed by generalized thickening of the of the capillary walls
shrinkage/fibrosis of glomerulus
conversion of glomerulus into a contracted fibrotic sphere

Larger arterial vessels:

Atrophy of groups of glomeruli and tubules

Replacement of atrophied glomeruli with fibrous tissue that contains lymphocytic inflammatory infiltrate causing scaring and retraction

Non-fibrotic tubules enlarge and dilate (probably to compensate for the ß number of working nephrons.)

all of this leads to benign nephrosclerosis

Area of atrophy is wedge-shaped and involves the full thickness of the renal cortex; apex of the wedge points to the obstructed artery and the base of the wedge is no the sub capsular surface of the kidney.

Gross Appearance: Slightly reduced in size; subcapsular surface is finely granular due to the nodules of dilated tubules intervening the retracted scars. Þ benign nephrosclerosis

(3) Pathology of the Systemic Arterioles with Uncomplicated HTN

Early effects: Arteriolar sclerosis with medial hypertrophy with or without hyalinization and intimal fibrous proliferation. With low grade HTN, initial fibrosis is relatively acellular; more intimal cellularity if more severe HTN

Late Effects: Fibrous proliferation is cellular.

Major Complications of Hypertensive Cardiovascular Disease

(1) Malignant Hypertension (MHTN) – accelerated phase of hypertension; usually fatal if not treated

usually the onset is superimposed on a background of pre-existing high BP

Effects on Systemic Arterioles: cellular or proliferative hyperplasia and arteriolar necrosis is the pathologic hallmark of MHTN; occurring systemically, but the kidneys are most severely affected (malignant nephrosclerosis)

Subintimal fibroblastic proliferation and hypertrophy of the media; the lumens are narrowed or obliterated, producing an onion skin appearance

Necrotizing arteriolitis occurs and is characterized by loss of structural detail and bright eosinophilic staining of the walls of the vessel (fibrinoid necrosis) with neutrophilic infiltration
Necrotic capillaries and arterioles may form aneurysmal dilations or rupture with small hemorrhages

Effects on Kidneys (culminates in malignant nephrosclerosis): no gross changes seen if there was no previous renal atrophy; if previous atrophy was present, petechial hemorrhages will be seen in cortex ("flea bitten kidney")

Arteriolar and glomerular necrosis of tubules show variable degrees of ischemic degeneration and contain proteinaceous material or blood; patients can die due to uremia

Benign nephrosclerosis is usually also present

(2) Congestive Heart Failure (CHF) – severe complication of HTN

Definition: heart is unable to pump the blood returned to it via the great veins

CO usually low, but may be high if failure is due severe anemia, thyrotoxicosis, arteriovenous fistula or beriberi

Forward Heart Failure: insufficient blood flow to various organs

Backward Heart Failure: accumulation of an excess of blood in various organs due to insufficient drainage

Edema Formation: kidneys retain Na⁺⁺ Þ retain H₂O; excess fluid leaves bloodstream and enters tissues

CHF due to HTN: - begins as LV failure Þ Ý LVEDP (LV end diastolic pressure) Þ Ý LA pressure Þ Ý pressure in pulmonary vasculature (pulm. edema) Þ Ý pressure in RV (most common cause of RV failure is LV failure)

failure of RV causes passive hyperemia of viscera, pleural effusions (hydrothorax), ascites, peripheral edema

Signs and Symptoms of CHF:

Dyspnea on exertion
Orthopnea
Paroxysmal dyspnea, paroxysmal nocturnal dyspnea or cardiac asthma
Cough
Hemoptysis
Weight loss
Anorexia, nausea and vomiting
Hepatomegaly and abdominal pain
Cerebral symptoms
Anxiety

Complications of CHF:

Renal failure due to arteriolar nephrosclerosis, benign or malignant

Intracerebral hemorrhage and cerebral thrombosis or embolism

Dissecting aneurysm of aorta

Acceleration of atherosclerosis

Predisposition to rupture of infarct of myocardium

Retinal changes

Sudden death