B4M1C1: Cardiovascular System Flashcards
What are the layers of the artery?
IMA
Tunica Intima
Tunica Media
Tunica Adventitia/Externa
The innermost layer of the artery, tunica intima, is made up of:
- Endothelium
- Subendothelial layer
- Internal elastic membrane
What contains rodlike inclusion bodies which contain a procoagulant factor?
Weibel Palade bodies
Layer of flattened cells
Endothelium
Delicate fibroelastic tissue
Subendothelial layer
What marks the boundary between the Tunica intima and Tunica media?
Internal elastic membrane
What contains fenestrations?
Internal elastic membrane
Importance of fenestrations
Essential for the nutrition of the avascular Tunica Media
What is made up of smooth muscle and elastic fibers?
Tunica media
Fibroelastic tissue & has external elastic membrane
Tunica adventitia/externa
What marks the boundary between the Tunica media and Tunica adventitia?
External elastic membrane
What are the layers of the wall of the heart?
EME
Endocardium - innermost layer
Myocardium - middle & thickest
Epicardium - outermost
Endocardium composition:
- Endothelium
- Sub-endothelial layer
- Sub-endocardial layer
Layer of flattened cells which form a long tube
Endothelium
What contains nerves and blood vessels, fiboblasts, collagen, and elastic fibers?
Sub-endothelial layer
What is a main mass of the endocardium, fibroelastic tissue, contains nerves, blood vessels, and fat cells?
Sub-endocardial layer
What is the middle and thickest layer made up of cardiac muscles?
Myocardium
What is composed of mesothelium and areolar tissue?
Epicardium
Forms the visceral layer of the pericardium
Epicardium
● independent of nervous stimulation
● long & branching with end to end attachment (intercalated disc)
● one nucleus at main segment
● myofibrils in parallel bundles
● fainter & closer cross striations
Cardiac muscle
● specialized for conduction of impulses
● bigger but shorter, more sarcoplasm but fewer myofibrils
● cross striations are fainter
● nuclei fewer, larger & paler
Purkinje fiber
What is a serous membrane that covers the heart?
Pericardium
BP = CO x PR
What affects Cardiac Output?
Blood Volume SAM
1. Sodium
2. Mineralocorticoids
3. Atriopeptin (ANP - atrial natriuretic peptide)
Cardiac Factors HC
1. Heart rate
2. Contractility
BP = CO x PR
What affects Peripheral Resistance?
HUMORAL FACTORS
Constrictors CATLE
1. Catecholamines
2. Angiotensin II
3. Thromboxane
4. Leukotrienes
5. Endothelin
Dilators PKN
1. Prostaglandins
2. Kinins
3. NO/EDRF (nitric oxide-endothelium-derived relaxing factor)
NEURAL FACTORS
Constrictors
a-adrenergic
Dilators
B-adrenergic
LOCAL FACTORS
1. Autoregulation
2. Ionic (pH, hypoxia)
There is no dividing line between normal and higher blood pressure. Arbitrary levels have to be established to define persons who have an increased risk of developing a morbid cardiovascular event and / or will benefit from medical therapy.
● Should take into account:
level of diastolic pressure also systolic pressure, age, sex, race, and concomitant disease.
What is an elevated arterial pressure without a known cause?
Essential Hypertension (Primary or Idiopathic)
What is an elevated arterial pressure as a result of known or definable cause?
Secondary Hypertension
What has an evidence of left ventricular hypertrophy or left ventricular failure in the presence of sustained arterial systolic and diastolic hypertension?
Hypertensive Heart Disease
What has an arterial pressure that is sometimes within the hypertensive range?
Labile Hypertension (Borderline Hypertension)
What has a significant recent increase over previous hypertensive levels associated with evidence of vascular damage on funduscopic examination but without papilledema?
Accelerated Hypertension
What is extremely elevated systolic and diastolic arterial pressures, or hypertension associated with end-organ damage (papilledema, usually accompanied by retinal hemorrhage, encephalopathy, eclampsia, etc.) which must be lowered in one hour?
Malignant Hypertension
What is an uncontrolled hypertension which must be lowered in 24 hours and No end organ damage as mentioned in hypertensive emergencies?
Hypertensive crisis
falsely elevated BP seen in:
● Elderly patients with atherosclerotic brachial arteries
● White coat hypertension
● Mismatch in size of pressure cuff and
patient’s arm
Pseudohypertension
What are anxious patients who get elevated BP readings at the doctor’s clinic called?
Whitecoat Hypertension
PREVALENCE OF HYPERTENSION
INDUSTRIALIZED SOCIETIES
● Blood pressure increases steadily during the first two decades of life.
● Blood pressure is associated with growth and development in children and adolescents.
● During early adulthood, average systolic blood pressure is higher for men than for women.
● Individuals aged 60 and older, the systolic blood pressure is higher in women than in males.
Prevalence of HPN
UNITED STATES 🇺🇸
● 30% of adults have hypertension with blood pressure of ≥140/≥90
○ 33.5% in non — Hispanic blacks
○ 28.9% in non — Hispanic whites
○ 20.7% in Mexican Americans
Prevalence of HPN
PHILIPPINES 🇵🇭
● Filipino adults 20 years and above with hypertension
○ 2012 - 21%
○ 2008 - 21%
○ 2003 - 16%
Prevalence of Various Forms of HPN in General Population and in Specialized Referral Clinics
Go back to notes 📝
Systolic Hypertension with Wide Pulse Pressure
- Decreased vascular compliance (arteriosclerosis)
-
Increased cardiac output FAPATH
- Fever
- Aortic regurgitation
- Patent ductus arteriosus
- Arteriovenous fistula
- Thyrotoxicosis
- Hyperkinetic heart syndrome
Secondary Causes of Systolic and Diastolic Hypertension
Renal: Parenchymal diseases, renal cysts (polycystic kidney disease), renal tumors (renin-secretin tumors), obstructive uropathy
Renovascular: Arteriosclerotic, fibromuscular dysplasia
Adrenal: Primary aldosteronism, Cushing’s syndrome, 17a-hydroxylase deficiency, 11B-hydroxylase def, 11-hydroxysteroid dehydrogenase (licorice), pheochromocytoma
Aortic coarctation
Obstructive sleep apnea
Preeclampsia/eclampsia
Neurogenic: Psychogenic, diencephalic syndrome, familial dysautonomia, polyneuritis (acute porphyria, lead poisoning), acute increased intracranial pressure, acute spinal cord section
Miscellaneous endocrine: Hypothyroidism, hyperthyroidism, hypercalcemia, acromegaly
Medications: High-dose estrogens, adrenal steroids, decongestants, appetite suppressants, cyclosporine, tricyclic anti-depressants, monoamine oxidase inhibitors, EPO, NSAIDs, cocaine
JNC 7
SBP then DBP althroughout
N: <120 / <80
Prehypertension: 120-139 / 80-89
Stage 1: 140-159 / 90-99
Stage 2: >=160 / >=100
JNC 8/AHA
look at cmap B4M1C1
What is a heterogeneous disorder, variables other than the arterial pressure modify its course?
● The probability of developing a morbid cardiovascular event with a given arterial pressure may vary as much as 20-fold depending on whether associated risks factors are present
● Most untreated adults with hypertension will develop further increase in arterial pressure with time.
Essential hypertension
What is associated with a shortening of life by 10-20 years, usually related to an acceleration of the atherosclerotic process?
Untreated hypertension
Who has a high risk of developing significant complications?
● Individuals who have relatively mild disease — i.e. without evidence of end organ damage — that is left untreated for 7-10 years
○ Nearly 30% will exhibit ________
○ More than 50% will have _________ related to the hypertension itself, such as cardiomegaly, congestive heart failure, retinopathy, a cerebrovascular accident, and/or renal insufficiency.
○ Nearly 30 % will exhibit atherosclerotic complications.
○ More than 50% will have end organ damage related to the hypertension itself, such as cardiomegaly, congestive heart failure, retinopathy, a cerebrovascular accident, and/or renal insufficiency.
Pathogenesis of essential hypertension
Genetic influences + Environmental factors
Defects in Renal Sodium Hemostasis
1. Inadequate Na excretion
2. Na & water retention
3. Increase Plasma and ECF volume (can also increase Natriuretic hormone w/c can increase Vascular reactivity)
4. Increase Cardiac Output (autoregulation)
5. HYPERTENSION
Functional, Vasoconstriction
1. Increase Vascular reactivity
2. Increase Total peripheral resistance
3. HYPERTENSION
Defects in Vascular Smooth Muscle Growth and Structure
1. Increase Vascular wall thickness
2. Increase Total peripheral resistance
3. HYPERTENSION
What clearly plays a role in determining blood pressure levels, as evidenced by studies comparing blood pressure in monozygotic and dizygotic twins, studies of familial aggregation of hypertension comparing the blood pressure of biologic and adoptive siblings, and adoption studies?
Genetic factors
Most studies support the concept that inheritance is probably multifactorial or that a number of different genetic defects each have an elevated blood pressure as one of their phenotypic expressions.
These lead to an adaptive increase in secretion of aldosterone, increased salt and water resorption, plasma volume expansion, and ultimately hypertension.
Gene defects in enzymes involved in aldosterone metabolism (e.g. aldosterone synthase, Il B - hydroxylase, 17 a - hydroxylase)
○ Mutations in proteins that affect sodium reabsorption.
■ For example, mutations in an epithelial sodium channel protein lead to increased distal tubular reabsorption of sodium induced by aldosterone, resulting in a moderately severe form of salt-sensitive hypertension called:
Liddle syndrome
Genesis hypothesized to be involved in essential hypertension
Table 246-3
Role of Intermediate Phenotype in Genetic Analysis
Table 246-4
ENVIRONMENTAL FACTORS
● Salt intake, obesity, occupation, alcohol intake, family size and crowding have been implicated in the development of hypertension.
● These factors have all been assumed to be important in the increase of blood pressure with age in more affluent societies, in contrast to the decline in blood pressure with age in less affluent groups.
● Salt intake is the environmental factor that has received the greatest attention.
○ Even this factor illustrates the heterogeneous nature of the essential hypertensive population, in that the blood pressure in only approximately 60% of hypertensive is particularly responsive to the level of sodium intake.
○ The cause of this special sensitivity to salt varies, with primary aldosteronism, bilateral renal artery stenosis, renal parenchymal disease, and low-renin essential hypertension accounting for about half the patients.
● Other postulated contributing factors include chloride intake, calcium intake, a generalized cellular membrane defect, insulin resistance and “non modulation.”
What is an enzyme secreted by the juxtaglomerular cell of the kidney and linked with aldosterone in a negative feedback loop?
Renin
What is the primary factor that modifies its rate of secretion?
Volume status of the individual, particularly as related to changes in dietary sodium intake.
The end product of the action of renin on its substrate is the generation of what peptide?
Angiotensin II
The response of target tissues to the peptide is uniquely determined by the
Prior dietary electrolyte intake
The sodium intake normally modulated adrenal and renal vascular responses to what?
angiotensin Il
With sodium restriction, what happens to the adrenal and renal vascular response?
Adrenal responses: enhanced
Renal vascular response: reduced
With sodium loading, what happens to the adrenal and renal vascular response?
Opposite of restriction
The range of plasma renin activities observed in hypertensive subjects compared to normotensive individuals?
Hypertensive: broader
Some hypertensive patients have been defined as having
low renin
and others as having high-renin essential hypertension
Low-Renin Essential Hypertension
● Approximately 20% of patients who have essential hypertension have suppressed plasma renin activity.
● This is more common in individuals of African descent than in white patients. The patients have expanded extracellular fluid volumes.
Hypothesis for the low plasma renin activity:
○ Sodium retention and renin suppression are due to excessive production of an unidentified mineralocorticoid.
○ The adrenal cortex has an increased sensitivity to angiotensin Il — this could be the cause of hypertension
High-Renin Essential Hypertension
● Approximately 15% of patients with essential hypertension have plasma renin activity levels above the normal range.
● Has been suggested that plasma renin plays an important role in the pathogenesis of the elevated arterial pressure in these patients.
● Postulated that the elevated renin levels and blood pressure may both be secondary to an increase in adrenergic system activity.
HORMONAL FACTORS (INSULIN RESISTANCE)
● Substantial fraction of the hypertensive population has insulin resistance and hyperinsulinemia.
● Insulin resistance is common in patients with non-insulin-dependent diabetes mellitus (NIDDM) or obesity.
What are more common in hypertensive than in normotensive individuals?
Both obesity and NIDDM
What are present even in lean hypertensive patients without NIDDM?
Hyperinsulinemia and insulin resistance
Hyperinsulinemia can increase arterial pressure by one or more of four mechanisms:
○ Hyperinsulinemia produces renal sodium retention and increases sympathetic activity.
○ Vascular smooth muscle hypertrophy secondary to the mitogenic action of insulin.
○ Insulin modifies ion transport across the cell membrane, thereby potentially increasing the cytosolic calcium levels of insulin-sensitive vascular or renal tissue.
○ Insulin resistance may be a marker for another pathologic process, e.g. non modulation, which could be the primary mechanism increasing blood pressure.
Note: Some hypertensives are termed as ________________ because of the absence of the sodium-mediated modulation of target tissue responses to angiotensin Il. Have hypertension that is salt sensitive because of a defect in the kidney’s ability to excrete sodium appropriately.
Non-modulators
EFFECTS OF HYPERTENSION IN THE HEART 💜
● Concentric left ventricular hypertrophy characterized by an increase in wall thickness.
● Dilatation of left ventricular cavity
● Myocardial damage — ischemia or infarction
● P.E. findings:
○ Heart is enlarged
○ Prominent left ventricular impulse
○ Sound of aortic closure is accentuated, and there maybe a faint murmur of aortic regurgitation
○ Pre Systolic (atrial, fourth) heart sounds are frequent
○ Pre Diastolic (ventricular, third) heart sound or
summation gallop rhythm may be present
EFFECTS OF HYPERTENSION IN THE RETINA 👁
● Retinal changes
○ Focal spasm and progressive general narrowing arteriole
○ Papilledema or hemorrhages of the macular area producing scotomata, blurred vision, and even blindness.
EFFECTS OF HYPERTENSION IN THE CNS 🧠
● Cerebral infarction which is secondary to the increased atherosclerosis.
● Cerebral hemorrhage which is the result of both the elevated arterial pressure and the development of cerebral vascular microaneurysms.
● Prominent symptoms:
○ Occipital headache
○ Dizziness
○ Light-headedness
○ Vertigo
○ Tinnitus
○ Dimmed vision
○ Syncope
EFFECTS OF HYPERTENSION IN THE KIDNEY 👶🦵
● Arteriosclerotic lesions of the afferent and efferent arterioles and the glomerular capillary tufts
● Decreased glomerular filtration rate
● Tubular dysfunction
● Proteinuria and microscopic hematuria
● Renal failure
TWO FORMS OF SMALL BLOOD VESSEL DISEASE ASSOCIATED WITH HYPERTENSION
HYALINE ARTERIOSCLEROSIS
&
HYPERPLASTIC ARTERIOSCLEROSIS
● Encountered frequently in elderly patients, whether normotensive or hypertensive but is more generalized and more severe in patients with hypertension.
● Vascular lesion consists of a homogenous, pink, hyaline thickening of the walls of arterioles with loss of underlying structural detail and with narrowing of the lumen.
○ The lesions reflect leakage of plasma components across vascular endothelium and increasing extracellular matrix production by smooth muscle cells.
○ Presumably the chronic hemodynamic stress of hypertension or a metabolic stress in diabetes accentuates endothelial injury, thus resulting in leakage and hyaline deposition.
● The narrowing of the arteriolar lumens causes impairment of the blood supply to affected organs, particularly in kidneys.
● This is a major morphological characteristic of benign nephrosclerosis, in which the arteriolar narrowing causes diffuse renal ischemia and symmetric shrinking of the kidneys.
HYALINE ARTERIOSCLEROSIS
● Generally related to more acute or severe elevations of blood pressure and is therefore characteristic but not limited to malignant hypertension
● Characterized by onion-skin, concentric, laminated thickening of the walls of the arteriole with progressive narrowing of the lumens as seen light microscope
● With an electron microscope, the laminations consist of smooth muscle cells and thickened and reduplicated basement membrane.
● These hyperplastic changes are accompanied by deposits of fibrinoid and acute necrosis of the vessel wall, referred to as necrotizing arteriolitis. The arterioles in all tissues throughout the body may be affected but the favored site is the kidney
HYPERPLASTIC ARTERIOSCLEROSIS
What are the 3 objectives for the evaluation of patients with hypertension?
● To assess lifestyle and identify other cardiovascular risk factors or concomitant disorders that may affect prognosis and guide treatment
● To reveal identifiable causes of high BP
● To assess the presence or absence of target organ damage and cardiovascular disease
Major risk factors: cardiovascular
Components of the metabolic syndrome:
🫀 Hypertension
🫀 Obesity (BMI >/=30kg/m2)
🫀 Dyslipidemia
🫀 DM
🫀 cigarette smoking
🫀 physical inactivity
🫀 microalbuminuria or estimated GFR <60mL/min
🫀 age (>55 for men; 65 women)
🫀 fam hx of premature cardiovascular dse (men under age 55 or women under 65)
Target organ damage:
Heart
🫀 left ventricular hypertrophy
🫀 angina or prior myocardial infarction
🫀 prior coronary revascularization
🫀 heart failure
Brain
🧠 stroke or transient ischemic attack
Chronic kidney disease
Retinopathy
What are identifiable causes of hypertension?
Sleep apnea
Drug-induced or related causes
CKD
Primary aldosteronism
Renovascular disease
Chronic steroid therapy and Cushing’s syndrome
Pheochromocytoma
Coarctation of the aorta
Thyroid or parathyroid disease
Medical History
● Most patients with hypertension have no specific symptoms referable to their blood pressure elevation.
● Common complaints are:
○ Headaches localized to the occipital region and are present when the patient awakens in the morning but subside spontaneously after several hours.
○ Dizziness, palpitation, easy fatigability, and impotence which may be related to elevated blood pressure.
● Referable to vascular diseases include epistaxis, hematuria, blurring of vision owing to retinal changes, episodes of weakness or dizziness due to transient cerebral ischemia, angina pectoris, and dyspnea due to cardiac failure.
● A strong family history of hypertension favors the diagnosis of essential hypertension.
● A history of use of adrenal steroids or estrogen is of obvious significance.
● History of repeated urinary tract infection suggests chronic pyelonephritis; nocturia and polydipsia suggest renal or endocrine disease.
○ History of weight gain is compatible with Cushing’s syndrome and one of weight loss is compatible with pheochromocytoma.
● A number of aspects of the history aid in determining whether vascular disease has progressed to a dangerous stage. These include angina pectoris and symptoms of cerebrovascular insufficiency, congestive heart failure, and/or peripheral vascular insufficiency.
● Other risk factors that should be asked about include smoking, diabetes mellitus, lipid disorders, and a family history of early deaths due to cardiovascular disease.
● Aspects of the patient’s lifestyle that could contribute to hypertension or affect its treatment should be assessed including diet, physical activity, family status, work, and educational level.
PHYSICAL EXAMINATION
● General appearance - observe for facial expression and contours, and muscular development in the upper extremities.
● Appropriate measurement of BP, with verification in the contralateral arm.
● Examination of the optic fundi
● Calculation of body mass index (BMI)
○ Measurement of the waist circumference also may be useful
● Auscultation of carotid, abdominal, and femoral bruits
● Palpation of the thyroid gland
● Thorough examination of the heart and lungs
● Examination of the abdomen for enlarged kidney masses, and abnormal aortic pulsation.
● Palpation of the lower extremities for edema and pulses
● Neurological assessment
