Pathophysiology 1 Exam 2

What is the total blood volume for male and female?

Total blood volume

o 75.5 mL/kg in men

o 66.5 mL/kg in women

7% to 8% of body weight

5 to 6 L

Blood cells make up ~ 40-45% of blood volume

RBCs

Most numerous

4.2 to 6.2 x 109 cells/mL

Transport oxygen to tissues

Remove carbon dioxide from the tissues

Buffer blood pH

oContain carbonic anhydrase

Plasma makes up what percent of blood volume?

Plasma ~55-60% of blood volume

Plasma is composed of what?

Composed of 92% water, 7% plasma proteins

True or False: Red blood cells have a nucleus

False

No nucleus or cytoplasmic organelle

What is erythropoietin?

Hormone from kidney that stimulates erythrocyte production

RBCs are produced through Hematopoiesis

Two-stage process involving:

o Mitotic division (proliferation)

o Maturation (differentiation)

Erythropoiesis is controlled by a system sensitive to the concentration of hemoglobin in the blood

Per one hemoglobin molecule, how many oxygen molecules can it bind to?

Hemoglobin carrying oxygen: oxyhemoglobin; each Hb molecule can bind 4 oxygen molecules

What do hemoglobin carry?

Hemoglobin: oxygen-carrying protein in mature RBCs

Where does the production of hemoglobin take place?

Immature RBCs: factory for hemoglobin

90% of RBC dry weight

What is required for hemoglobin synthesis?

67% of total body iron is bound to heme and 30% is stored bound to ferritin. Remaining 3%

is lost in daily urine. IRON

What nutritional requirements are needed for normal RBC development?

Protein and Vitamins (B12, Folate, B6, Riboflavin, Niacin, Vit E and C)

RBC Development

Large nucleated cells change to small reticulocytes that have no nucleus

Reticulocyte leaves the marrow and enters the blood stream

Matures into erythrocyte (RBC) in 24-48 hrs.

Mitochondria and ribosomes disappear

Mature RBC can no longer make hemoglobin

RBC lifespan: ~120 days in adults

Red Blood cells + bone marrow precursors=

Erythron

A decrease in hemoglobin decreases what in kidneys?

A decrease in Hb level decreases the tissue oxygen tension in the kidney

In response to this hypoxia, the kidney secretes the hormone, erythropoietin (EPO) that stimulates stem cells in the marrow to differentiate to make RBC

What do RBCs need energy for?

to survive ~120 days

Oxygen transport and exchange processes are passive (don’t need energy)

RBC need energy for operate membrane pumps for maintaining

o High intracellular potassium ion [K+]

o Low intracellular sodium ion [Na+]

o Very low intracellular calcium ion [Ca++]

RBC rely on glycolysis to produce the energy, because they don’t have mitochondria, nuclei and other subcellular organelles

Where do RBC get digested by macrophages?

80-90% of RBC get digested by macrophages in spleen and liver. 10-20% inside blood vessels

Red Cell Destruction

As RBCs age, enzyme activities decrease

Amount of membrane lipids decrease

Cell loses ability to deform and becomes fragile

Hb A levels increase

Heme is reduced to bilirubin

Globin and iron portions are conserved and reused

Bilirubin is then degraded to urobilinogen and excreted primarily in the feces and in the urine.

Increased levels of bilirubin give the skin a yellowish tone (jaundice).

True or False: The 3% that is dissolved in plasma is measured as PO2

TRUE

What does the oxygen-hemoglobin dissociation curve describe?

Describes the relationship between PO2 (pressure) and SO2 (saturation)

Gas Transport and Acid-Base Balance

Oxygen Transport

97% of oxygen transported in blood is bound to Hb within the RBC

PaO2 = PO2 in arterial blood = 80-100 mmHg

PvO2 = PO2 in venous blood = 35-40 mmHg

What three forms is CO2 transported as?

Transported in 3 forms

1. As dissolved gas (5%)

2. As bicarbonate ion (HCO3- ,75%)

3. In association with hemoglobin forming carbaminohemoglobin (20%)

In body tissues, CO2 inside the cells diffuses into the blood and attaches to hemoglobin as oxygen is released to the tissues

RBC contain the enzyme carbonic anhydrase which greatly increases the conversion of water and CO2 into HCO3- and H+

True or False: Carbaminohemoglobin release CO2 in the lungs which we exhale out

TRUE

What are the RBC disorders?

Alterations of Oxygen transport

Decreased oxygen reaching the tissues results in secretion of erythropoietin (EPO) and increase in the production of RBCs.

Factors that decrease hemoglobin mass (anemia) or decrease arterial saturation (hypoxia) lead to increased release of erythropoietin.

Red blood cell disorders

Anemia: Deficit of RBC

o Patient has tissue hypoxia due to low-oxygen-carrying capacity of blood

General Effects of Anemia

Reduction in oxygen-carrying capacity- Tissue hypoxia (low oxygen)

Compensatory mechanism to restore tissue oxygenation

• Increased heart rate

• Increased cardiac output,

• Preferential increased flow to vital organs

• Increase in erythropoietin activity

Mild anemia

• Usually, no clinical symptoms

• Elderly with cardiovascular, pulmonary disease may have symptoms

Mild to moderate anemia

• Fatigue,

• generalized weakness

• loss of stamina, followed by tachycardia and exertional dyspnea

Moderate to severe anemia

o Decrease in blood pressure: orthostatic (after standing) and generalized hypotension

o Vasoconstriction

o pallor

o Tachypnea (rapid breathing), dyspnea (labored breathing)

o Tachycardia (rapid heart rate), transient murmurs, angina pectoris, heart failure

o Intermittent claudication, night cramps in muscles

o Headache, lightheadedness and faintness

o Tinnitus, roaring in the ears

Polycythemia: Excess of RBC

o Patient has increased blood viscosity and volume due to the increase in RBC numbers

What is the pathogenesis of aplastic anemia?

Etiology and Pathogenesis

o Stem cell disorder characterized by reduction of hematopoietic tissue, fatty marrow replacement

o Caused by toxic, radiant, or immunologic injury to the bone marrow stem cells

Laboratory features

o Pancytopenia (low RBC, WBC and platelets)

o Low WBC is important for prognosis (low leukocytes = susceptibility to infections)

o Diagnosed with bone marrow biopsy

Clinical Manifestation

• Insidious onset of symptoms

• Late symptoms include weakness, fatigue, lethargy, pallor, dyspnea, palpitations, transient murmurs and tachycardia related to low RBCs.

• Thrombocytopenia (low platelets; prone to bleeding)

• Neutropenia (low WBC; prone to infections)

• Disease of the young (15 to 25) or old (>60)

Treatment

• Determine efficacy of bone marrow transplantation.

• Administer immunosuppressive therapy or stimulate hematopoiesis and bone marrow regeneration.

Prognosis

• Fatal unless bone marrow transplant successful

• Bone Marrow transplantation is highly successful and curative for 80-85% of un-transfused patient and 55-60% of patients with multiple previous transfusions

What does anemia chronic renal failure cause?

Etiology and Pathogenesis

o Primarily from failure of the renal endocrine function, which causes impaired erythropoietin (EPO) production

o Secondarily from failure of renal excretory function

o Leads to hemolysis, bone marrow cell depression and blood loss

Laboratory features and clinical manifestations

o Low RBC count

o Low hematocrit

o Low hemoglobin

o Some grossly deformed RBC

o General signs and symptoms of anemia usually manifest when hematocrit decreases to < 20%

Treatment

Dialysis

Administration of erythropoietin

o Erythropoietin is only used until Hgb is 12 g/dL.

Replacement of iron, folate, and B12 due to dietary restrictions and anorexia

Prognosis

o 95% respond to erythropoietin therapy.

Anemia in relation to vitamin B12 or Folate deficiency causes a disruption in what?

Etiology and Pathogenesis

Disruption in DNA synthesis of blast cells produces megaloblasts (macrocytic)

Pernicious anemia is caused by lack of intrinsic factor leading to vitamin B12 deficiency. Problem is with B12 absorption rather than “deficiency”.

Folate deficiencies from dietary deficiencies, alcoholism, cirrhosis, pregnancy, or infancy

• Low folate levels associated with neural tube deficits

Laboratory Features

o Low RBC, WBC, and platelet counts; megaloblastic dysplasia

o Macrocytic and hyper-segmented neutrophils

Clinical Manifestation

o Clinical features of vitamin B12 deficiency:

o Paranoia, dementia, cognitive dysfunction, delusions, hallucinations

o Peripheral nerve degeneration and memory impairment

o Clinical features of both B12 and folate deficiency:

o Edema in the feet/ Tachypnea/ Weight loss

Treatment

o Administer B12 and folate parenterally or orally

Prognosis

o Majority respond well to treatment.

o Reversibility of the neurologic damage is slow

What is the most common cause of anemia?

Iron Deficiency Anemia

Etiology and Pathogenesis

o Most common cause anemia (iron deficiency is the most common nutritional deficiency in the world)

o Results in the unavailability of iron for hemoglobin synthesis

Possible causes

o Low iron intake

o Diminished absorption

o Increased requirement (e.g. pregnancy)

o Excessive iron loss (e.g. hemorrhage)

o Renal failure

o Hemodialysis

o GI bleeding

o Menorrhagia

Laboratory features

o Smaller and paler RBC

o Low red cell indices

o Decreased serum ferritin

Treatment and Prognosis

o Oral administration of ferrous sulfate or intravenous ferric gluconate (only in severe cases); continue for 4 to 6 months

o Treat underlying cause

o Prognosis: Usually very good

True or False: Thalassemia has increased RBC destruction referred to as hemolysis

TRUE
Thalassemia

Etiology and pathogenesis

o Increased RBC destruction (hemolysis) resulting in decreased RBC survival rates

o Associated with mutant genes that suppress the rate of globin chain synthesis

o Classified by the polypeptide chain(s) with deficient synthesis

• α-thalassemia or β-thalassemia

o Most clinically severe form: thalassemia major (homozygous);

Thalassemia minor (heterozygous) is less severe

Laboratory Features

o Hypochromic, microcytic RBCs

o RBC indices are low

o Erythroblastic hyperplasia (bone marrow)

INHERITED

For hemolytic newborns, what is clinically relevant?

Anemia related to extrinsic red cell destruction or loss

Hemolytic disease of the newborn

Etiology and pathogenesis

o Fetal RBCs cross placenta, stimulate production of maternal antibodies against antigen on fetal

RBC not inherited from mother.

o Maternal antibodies cross into the fetal circulation causing destruction of fetal cells in subsequent pregnancies.

Laboratory features

o Elevated serum bilirubin due to hemolysis

o Bilirubin in amniotic fluid is an indicator

Clinical manifestation

o Jaundice

o Hepatomegaly

o Splenomegaly

o Diffuse intravascular coagulation

Treatment and prognosis

o Standard dose of anti-Rh immune globulin (RhoGAM) is given to the mother before or after delivery.

o Severe cases, in utero blood transfusion and early delivery

o Prognosis: Death, possible retardation, or barely perceptible hemolytic process

Polycythemia can be defined as?

Excess RBC results in increased blood viscosity, leading to clinical symptoms such as hypertension.

Types of polycythemia are categorized by the cause.

1. Polycythemia Vera

o Neoplastic transformation of bone marrow stem cells

2. Secondary Polycythemia

o Caused by chronic hypoxemia with resultant increase in erythropoietin

production

3. Relative Polycythemia

o Caused by dehydration with spurious increase in RBC production

What are the three types of polycythemia?

Polycythemia Vera

Absolute increase in RBC mass, leukocytosis, thrombocytosis; increased uric acid because of excess proliferation; oxygen saturation normal.

Signs and symptoms from increased viscosity

o Hypertension

o Thrombosis

o Congested spleen and liver

Treatment

o Reducing increased blood volume, viscosity, RBC mass, and platelet count with phlebotomy,

radioactive phosphorus, and chemotherapeutic agents

Prognosis

o Poor unless properly managed

o No cure

Secondary Polycythemia

Increased RBC production without increase in WBCs or platelets

Treatment: Identify and manage underlying cause of hypoxemia; phlebotomy may be used to decrease cardiovascular workload

Prognosis: depends on underlying condition

Relative Polycythemia

Elevated hematocrit, hemoglobin, and RBC count

Two groups

o Disturbed fluid balance

o Stress polycythemia (long-standing state of low plasma volume)

Treatment

• Recognize and manage underlying cause

• Fluid administration with management of long-term conditions

Prognosis: Excellent if managed properly

Chapter 15: Alterations in Blood Flow:

What does the circulatory circuit do?

Absorption and delivery of nutrients

Oxygen uptake and delivery

Removal of waste products

Lymphatic circulation

o Specialized system of channels and tissues (nodes)

o Collect the excess fluid (2-4 liters/day) that leaks from vascular network into the interstitium and returns it to the general circulation.

How long does it take to move 5 liters of blood through the entire circuit?

The complete process moving ~5 liters of blood through the entire circuit takes only ~1 minute

What do arteries contain in comparison to veins?

Three microscopically distinct layers (tunicae)

o Intima: endothelial cells in direct contact with the blood as it flows through the vessel

• Periodically, the intima layer protrudes into the lumen, creating valves that prevent the backflow of blood

o Media: smooth muscle tissue (thickest section in arteries)

o Adventitia: collagenous connective tissue (thickest section in veins)

Arteries only contain elastic tissue, veins only have elastic tissue in large veins

What does the intima layer function in?

endothelial cells in direct contact with the blood as it flows through the vessel

• Periodically, the intima layer protrudes into the lumen, creating valves that prevent the backflow

True or False: Blood flow is measured as a given number of liters or milliliters per

second, minute, or hour

TRUE
Includes the concepts of

• Pressure

• Resistance

• Velocity

• Turbulent flow

• Wall tension

Describe how pressure works

Blood flow—movement along a pressure gradient within the vascular bed

Pressure—blood moves from areas of higher pressure (arteries) to an area of lower pressure (veins); the greater the pressure difference, the greater the blood flow

Resistance—opposing forces that deter blood flow; as resistance increases, blood flow decreases

Physical laws govern the flow of blood though vessels

Important Laws:

• Flow = Pressure/Resistance

• Blood pressure = flow (cardiac output) x Resistance

• Resistance = Pressure/Flow

What are the determinants of vascular resistance?

Determinants of Vascular Resistance

1. Vessel length

2. Vessel radius

3. Blood viscosity

also includes elastic flexibility of tube

At a constant pressure gradient:

The longer the blood vessel, the higher the resistance and the lower the flow

The narrower the blood vessel, the higher the resistance, the lower the flow

True or False: the longer the blood vessels, the higher the resistance and lower the flow

TRUE

Turbulent flow is generated where?

Turbulent flow generated at a vessel bifurcation

Velocity and Laminar and Turbulent Flow

• Laminar flow: Fastest blood flow in the center of stream

• Turbulent flow is an interruption in the forward current of blood flow by crosswise flow.

Turbulent flow may manifest as

• Bruit (audible vascular sound)

• Thrill (vibratory sensation on the skin over a turbulent flow)

• Thrombus formation (blood clot affecting flow)

• Example of pathologic cause of turbulence

What is clinically important in capillaries?

Dynamics in the Microcirculation (Capillaries)

Essence of the entire circulatory system

Exchange of nutrients and gases takes place

Clinically, The capillary fluid pressure and plasma colloid osmotic pressure are most important

Capillary fluid pressure is the blood pressure inside the capillary (force that pushes fluid out of

vessel)

Pathologic conditions resulting in increases in BP or resistance to flow, can alter this force, increasing it and propelling more fluid into the interstitial space, resulting in the formation of edema

What are the controls of blood flow?

By Extrinsic mechanisms (Central control)

All blood vessels except small venules and capillaries contain smooth muscle cells.

Arteries have much more smooth muscle than veins

Smooth muscle cells are innervated by nerve fibers from the sympathetic nervous system (SNS)

Smooth muscle cells have α1 adrenergic receptors that respond to the SNS neurotransmitter, noradrenaline resulting in vasoconstriction

Skeletal muscle blood vessels contain β2 adrenergic receptors which respond to epinephrine (adrenaline) resulting in vasodilation

By intrinsic mechanisms (Local control)

Autoregulation is ability of blood vessels within organs to maintain a relatively constant blood flow regardless of changes in arterial pressure

oWhen vascular smooth muscle is stretched, it contracts in response causing vasoconstriction

oEndothelial cells also play an important role in vessel dilation and constriction

• Produce nitric oxide (NO) gas which causes dilation by relaxing neighboring smooth muscle cells

What happens when systemic vascular resistance is increased?

It causes the heart to work harder to meet metabolic demands of the body

Thrombosis is initiated by alterations in what?

Thrombus is a stationary blood clot formed within a vessel or a chamber of the heart

• Clot is composed of aggregated platelets, clotting factors and fibrin that adhere to the vessel wall

Etiology: Thrombosis is Initiated by alterations in one or more of the following:

• Blood flow: slow or turbulent flow

• Blood vessel wall: damage or inflammation to the intimal wall of vessel

• Blood coagulability: emergence of a hypercoagulable state

Can occur in arteries (arterial thrombosis) and veins (venous thrombosis)

Oral contraceptives may increase tendency for thrombosis

Arterial thrombosis is classified as?

Arterial thrombosis

• Clot within an artery reduces flow and increases turbulence which enhances thrombus enlargement and formation of more thrombi

• Decreased distal flow can cause ischemia which can cause

Arterial occlusion

Myocardial infarction (heart attack)

Stroke

True or False: Venous thrombosis symptoms may be absent or maybe life- threatening secondary to pulmonary embolism

TRUE

Venous thrombosis

• Clot in a vein alters venous return impairing the removal of metabolic waste and producing swelling

• Inflammation that occurs in a vein is called phlebitis and when it is accompanied with a clot, it is called thrombophlebitis

What is the major reason for arterial disease?

Athclerosis

Means hardening of the arteries

Pathologic origin for the vast majority of arterial disease

Ultimately the leading cause of death in U.S and western Europe

Develops mostly in large and medium size arteries

o Coronary (associated with most mortality; coronary artery disease [CAD])

o Cerebral

o Carotid

o Femoral

o Aorta

o Other organs

Modifiable Risk Factors

• Smoking

• Elevated blood pressure

• Glucose intolerance (e.g. diabetes)

• Elevated cholesterol

• Decreased physical activity

• Ineffective stress management

• Depression

Nonmodifiable Risk Factors

• Age

• Gender

• Heredity (Family history)

What is atherosclerosis an underlying condition of?

hypertension , renal disease, cardiac disease, and peripheral arterial disease

Where are aneurysms mostly found?

Localized arterial dilations, bulge outward

Classified as true or false aneurysms

True aneurysms include

• Saccular: one-sided balloon

• Fusiform: both sides balloon out

• Berry: balloon has a stem/neck

Frequently found in cerebral circulation and thoracic and abdominal aorta

Alterations in venous flow can be accompanied with?

Incompetent valves (e.g. in obesity, pregnancy, right heart failure, prolonged standing) producing

o Varicose veins- Superficial veins affected

o Chronic venous insufficiency- Deep veins affected

o Deep vein thrombosis- Could lead to life-threatening pulmonary emboli

Accompanied by edema, venous stasis, inflammation, ulcers, and pain

True or False: Lymphedema is most common in the U.S because of lymph node removal,

and radiation

TRUE

Alterations in Lymphatic Flow

Lymphedema

Occurs when normal flow is obstructed or altered in some fashion

Primary lymphedema results from congenital anomaly or dysfunction of the lymphatic system.

Secondary lymphedema associated with a disease process or iatrogenic

oMost common in United States because of lymph node removal, radiation

Chapter 16: Alterations of Blood Pressure

Systemic arterial blood pressure is the result of what?

Provides momentum for the flow of blood around the body

Arterial blood pressure is produced by the force of the left ventricle contraction overcoming the resistance of the aorta to open the aortic valve

• Pressure is maintained in the arterial system throughout the cardiac cycle

It is the pressure difference between the left and right sides of the heart that produces the gradient allowing this systemic movement of blood

The systemic arterial blood pressure is the physiologic result of:

cardiac output and resistance to the ejection of blood from the heart

The resistance to ejection into arterial circulation is known as the systemic vascular resistance (SVR) and is determined by:

• Radius of arteries

• Degree of vessel compliance

• SVR is also known as cardiac afterload

SVR can be altered by constricting or relaxing (dilating) arterial smooth muscle

What is the difference between systolic and diastolic pressure?

Cardiac Function

Cardiac output (CO)

• Blood ejected by a ventricle in 1 minute

• CO = SV (Stroke volume) x HR (heart rate)

Stroke volume (SV)

• Volume of blood pumped out of ventricle with each contraction

Blood Pressure

Systolic pressure: exerted when blood is ejected from ventricles (high)

Diastolic pressure: sustained pressure when ventricles relax (lower)

BP is directly proportional to blood volume and is controlled by hormones

What is used clinically as part of cardiovascular assessment?

Mean Arterial Pressure Map (MAP) is the calculated average pressure within the circulatory system

(2 x Diastolic P) + Systolic P] / 3

Pulse Pressure = Systolic - Diastolic

Out of the Korokthoff sounds, which is classified as the systolic and diastolic pressure

I. Initiation of a clear Tapping Sound (Systolic P)

II. Murmuring or swishing sounds

III. Increase in intensity and crispness of sound

IV. Muffling of sound

V. Disappearance of sound (Diastolic P)

According to American Heart Association, what are the guidelines for hypertension

grade 1 and 2 for both pressures?

What is the short term regulation mechanism mediated by?

Short Term Regulation Mechanisms

Rapid adjustments in response to

• Position changes

• Exercise

• Emotional changes (e.g. fear/anxiety)

• Physiologic changes (e.g. volume depletion)

Mediated by the sympathetic branch of the autonomic nervous system

Long Term Regulation Mechanisms

o Week after week and month after month

o Interplay of neural, hormonal, and renal interactions

• Intimately connected with the body’s fluid volume

What activates the vasomotor center directly and indirectly?

Short-Term Regulation of Blood Pressure

Regulated by the vasomotor center (located in medulla of brainstem)

Vasomotor center directly activated by various stimuli or indirectly via pressure-sensitive baroreceptors ( which monitor arterial pressure (MAP) variations)

Stimulation of SNS results in the release of neurotransmitters noradrenaline and adrenaline

Activates α1 receptors on smooth muscle of arterioles, causing vasoconstriction (↑ Systemic

vascular resistance, [SVR])

• Activates β1 receptors of the heart (↑ heart rate)

• Receptor responsiveness decline with age (age-related arterial stiffening)

Chemoreceptors stimulate the medullary vasomotor center to increase SNS activity.

• Located in carotid and aortic arterials

• Activated only when BP extremely low

Beta receptors of the heart increase or decrease heart rate?

Increase

When the kidney is stimulated by low arterial pressure, what happens?

Long-Term Regulation of Blood Pressure: The Renin –Angiotensin- Aldosterone System (RAAS)

Juxtaglomerular cells (in the kidney when stimulated by low arterial pressure release renin activates angiotensinogen to angiotensin I.

Angiotensin I when in contact with ACE is converted to angiotensin II, a potent vasoconstrictor and stimulates release of aldosterone by the adrenal cortex.

Aldosterone, a hormone, causes reabsorption of sodium and water passively follows.

What is the function of the aldosterone?

Aldosterone, a hormone, causes reabsorption of sodium and water passively follows.

What is the most common primary diagnosis in the U.S?

Hypertension (High Blood Pressure)

Most common primary diagnosis in the U.S

Most common risk factor for cardiovascular disease worldwide

Increases morbidity and mortality associated with heart disease, kidney disease, peripheral vascular disease, and stroke

> 40% of adults 25 years or older are diagnosed

Responsible for an annual worldwide death rate of 7.6 million

Areas most frequently damaged by hypertension

• Kidneys

• Heart

• Brain

• Retina

Predisposing factors

• Incidence increases with age

• Men affected more frequently and more severely

• Incidence in women increases after middle age

• Genetic factors

• Sodium intake, excessive alcohol intake, obesity, smoking, prolonged or recurrent stress

Describe hypertensive crisis?

Hypertensive crisis: Systolic over 180 and/or diastolic over 120, with patients needing prompt changes in medication if there are no other indications of problems, or immediate hospitalization if there are signs of organ damage.

True or False: Primary essential hypertension, majority of the cases are caused unknown

TRUE

Essential hypertension – idiopathic (Majority of cases: 90 -95% of hypertensive patients)

• Blood pressure consistently above 130/90 mm Hg

Also called essential hypertension

Rare prior to the age of 10

Incidence in children is escalating

Systolic BP: major risk factor for cardiovascular disease

Isolated systolic hypertension: systolic BP is ≥130 mm Hg while diastolic pressure remains <90 mm Hg

Isolated diastolic hypertension: diastolic pressure is ≥90 mm Hg with a systolic pressure of <130 mm Hg

Combined systolic and diastolic hypertension: both systolic and diastolic exceed prehypertension levels

Nonmodifiable

o Family history

o Age

o Ethnicity/Genetics

Modifiable

o Dietary factors

o Sedentary lifestyle

o Obesity/weight gain

o Metabolic syndrome

• Elevated circulating insulin and lipid levels

o Elevated blood glucose levels/diabetes

o Elevated total cholesterol

o Alcohol and smoking

What does the silent killer refer to?

Primary Hypertension: Outcomes

Sometimes called the “silent killer” as damage has already occurred to organs before diagnosis is made

o End-organ damage: a function of stage and duration of hypertension

• Renal failure, stroke, heart disease

• Damage to arterial system and acceleration of atherosclerosis lead to cardiovascular disease

• Increased myocardial work results in heart failure.

• Glomerular damage results in kidney failure.

• Affects microcirculation of the eyes

• Increased pressure in cerebral vasculature can result in hemorrhage (stroke, Brain

What constitutes a hypertensive emergency?

Hypertensive emergency: sudden increase in either or both systolic or diastolic blood pressure with evidence of end-organ damage

o Rapid but controlled reduction of blood pressure using parenteral antihypertensive agents under close monitoring (typically in ICU setting)

o Responsible for 25% of emergency visits

Hypertensive urgency: similar blood pressure elevation without evidence of end-organ damage

o Oral medications to bring blood pressure under control over 24 to 48 hours

Chapter 17: Cardiac Function

63. Describe the Circulatory System

Left sided heart chambers produce the force to propel blood through the vessels of the systemic (body) circulation

The left atrium receives oxygenated blood from the lungs by the way of pulmonary veins and delivers it to the left ventricle

The oxygenated blood is pumped by the left ventricle into the aorta which supplies the arteries of the systemic circulation

Venous blood is collected from the capillary networks of the body and is returned to the right atrium by the way of vena cava

Blood from the head returns via the inferior vena cava

The blood supplied to the heart muscle is provided by?

The Coronary Arteries

The blood supply of the heart muscle is provided by the coronary arteries

1. Right coronary artery

2. Left circumflex artery

3. Left anterior descending

Describe the cardiac cycle

Each heartbeat is composed of a period of ventricular contraction (systole) followed

a period of relaxation diastole.

What does blood flow equal to?

Blood flow = Pressure/Resistance

What are the two determinants of coronary vascular resistance?

Coronary vascular resistance has 2 major determinants

1. Artery diameter

2. Varying degrees of external compression by myocardial contraction and relaxation

Coronary artery diameter is continuously adjusted to maintain blood flow at a level adequate for myocardial demands

Vessel dilation (vasodilation) occurs in response to increased tissue metabolism

Vessel constriction (vasoconstriction) in response to decreased metabolic activity

A disruption in cardiac blood flow (ischemia) generally results in some degree of pump failure and damage to cardiac tissues.

 Reduction in coronary blood flow

 Increased myocardial demand for oxygen

What are the two general cardiac myocytes?

Two general type

1. Working cells (mechanical pumping functions)

2. Electrical cells (transmit electrical impulses)

Both types are excitable and unable to proliferate

How do the heart cells store excess ATP?

Like other tissues, the heart utilizes from ATP generated by glycolysis and oxidative reactions

Under conditions of ATP excess, heart cells are able to store the excess ATP as creatine phosphate (CP) by the enzyme creatine kinase (CK)

The enzyme CK is useful in the diagnosis of myocardial infarction (heart attack) because it leaks into the blood stream

Both cardiac contraction and relaxation require energy

True or False: Both cardiac contraction and relaxation require energy

TRUE

Describe the determinants of stroke volume

Volume of blood in the heart (preload)

• Resistance to ejection from the ventricle (afterload)

Chapter 18: Alterations of Heart Function

72. What is cardiac output(CO)?

Cardiac Output (CO) = Stroke Volume (SV) x heart rate (HR)

CO depends on:

Determinants of heart rate

• Under the control of sympathetic and parasympathetic nervous system

Determinants of Stroke Volume

• Volume of blood in the heart (preload)

• Resistance to ejection from the ventricle (afterload)

What is stroke volume(SV)?

The amount of blood ejected from the ventricle with each contraction

What are the determinants of stroke volume?

Determinants of Stroke Volume

• Volume of blood in the heart (preload)

• Resistance to ejection from the ventricle (afterload)

Preload, contractility, afterload

True or False: Coronary Heart Disease (CHD) is responsible for approx 50% of deaths by

CVD

TRUE

What is CHD characterized by?

Also called ischemic heart disease or coronary artery disease (CAD)

Accounts for 31% of all deaths

Coronary Hearty Disease (CHD) is responsible for ~50% of deaths by CVD

Stroke, high blood pressure, heart failure and others claim the remainder

16 million in the US have history of CHD

Men and women equally represented

• Characterized by insufficient delivery of oxygenated blood to the myocardium caused by

atherosclerotic coronary arteries

• Sequelae of CHD includes:

• Angina pectoris

• Myocardial infarction

• Dysrhythmias

• Heart failure

• Sudden cardiac death

Lipid Processing Basics

Chylomicrons from dietary fat absorption are taken up by the liver and resynthesized into

• VLDL

• LDL

• HDL

HDL (“good cholesterol”) circulates to the tissues and takes up excess free cholesterol and takes it back to the liver

Triglycerides are removed from VLDL for tissue use

More triglyceride removal leads to formation of LDL

LDL (“bad cholesterol”) is absorbed by the tissues and 70% returns to the liver

What are the known risk factors for CHD?

Known risk factors:

• Atherosclerosis: the source of nearly all CHD

• Possible microcirculation abnormalities

Atherosclerosis causes narrowing of the arterial lumen that can lead to cardiac ischemia through

• thrombus formation.

• coronary vasospasm.

• endothelial cell dysfunction.

Risk factors of CHD

Nonmodifiable

o Age: >45yrs in men; >55 yrs for women

o Family history: MI or sudden cardiac death in male first degree relative (< 55 yrs old; female < 65)

o Gender: male (earlier onset)

Lipid Risk factors

o Total cholesterol (>200 mg/dL)

o LDL cholesterol (>130 mg/dL)

o Triglycerides (>150 mg/dL)

o HDL cholesterol (< 40 mg/dL)

Nonlipid Risk factors

o Hypertension

o Cigarette smoking

o Thrombogenic state

o Diabetes

o Obesity

o Physical inactivity

o Poor diet

Probable (emerging) Risk factors

o Chronic inflammation

What is defined as good and bad cholesterol?

HDL (“good cholesterol”) circulates to the tissues and takes up excess free cholesterol and takes it back to the liver

LDL (“bad cholesterol”) is absorbed by the tissues and 70% returns to the liver

What are lipids transported via?

Mechanisms of CHD

Lipids are transported via apoproteins.

o Lipid + protein = Lipoprotein

Lipoproteins associated with a greater risk of atherosclerosis

High-density lipoproteins (HDL) transport cholesterol from peripheral tissue back to the liver, clearing atheromatous plaque.

LDL = “Bad cholesterol”

HDL = “Good cholesterol

What does HDL do?

HDL circulates to the tissues and takes up excess free cholesterol and takes it back to the liver

What does LDL do?

LDL is absorbed by tissues and 70% is returned to the liver

What is atherosclerotic plaque formation initiated by?

Atherosclerotic plaque formation initiated by injury to coronary artery endothelium

Endothelium becomes dysfunctional, permeable and recruits leukocytes

LDL leakage into the vessel wall occurs with oxidation by endothelial cells and macrophages.

Oxidized lipids are damaging to endothelial and smooth muscle cells and stimulate recruitment of macrophages into the vessel.

Macrophages (and smooth muscle cells) engulf the lipids becoming foam cells (lipid-filled macrophages) which will release inflammatory mediators and growth factors, attracting more

leukocytes and stimulating smooth muscle proliferation.

Excess lipid and debris accumulate within vessel wall and coalesce into lipid core.

Vulnerable plaques may rupture or become eroded, which stimulates clot formation on the plaque.

What are the differences between vulnerable and stable plaques?

Pathogenesis of Coronary Atherosclerosis

Vulnerable plaques have

• large lipid core.

• thin cap.

• high shear stress.

• Inflammation within

Stable plaques have

• more collagen and fibrin.

• stable cap

Plaques increase in size overtime

Often all three coronary arteries are Simultaneously affected

What can ischemia result in?

It can result in chronic or acute coronary syndromes.

Ischemia results from oxygen supply insufficient to meet metabolic demands

Chronic Occlusion of a coronary vessel is associated with clinical syndrome of stable angina

Acute occlusion is associated with plaque disruption (rupture) and thrombus (clot) formation and results in acute coronary syndrome (unstable angina or MI)

Ischemia can also be caused by vasospasm

• Usually occur in areas of atherosclerotic plaque

• In response to some drugs (e.g. cocaine)

• Inflammation

True or False: Ischemia results in oxygen supply insufficient to meet metabolic demands.

TRUE

The rate of coronary perfusion can be altered by?

1. Large, stable atherosclerotic 2. Acute platelet aggregation and thrombosis 3.

Vasospasm 4. Failure of autoregulation by microcirculation 5. Poor perfusion

pressure

Describe the pathophysiology of chronic and acute ischemia

Chronic occlusion of a coronary vessel is associated with clinical syndrome of stable

angina. Acute occlusion is associated with plaque disruption (rupture) and

thrombus (clot) formation and results in acute coronary syndrome (unstable angina

or MI)

Acute Coronary Syndromes

Associated with acute changes in plaque morphology and thrombosis (clot formation) leading to sudden obstruction of coronary artery

Unstable Angina

Myocardial Infarction (MI)

Sudden cardiac arrest

Abrupt onset and life-threatening consequences

Any of the coronary heart syndromes (chronic or acute) may precipitate Sudden Cardiac Arrest and associated Dysrhythmias!

True or False: Acute Coronary Syndrome is associated with acute changes in plaque

morphology and thrombosis (clot formation), which causes a sudden obstruction of

coronary artery.

TRUE

True or False: Chronic or acute coronary heart syndromes may precipitate sudden cardiac

arrest and associated dysrhythmias.

TRUE

True or False: Stable angina cannot be relieved by rest.

FALSE
Stable angina (Classic or Typical Angina)

• Most common (also called typical or classic angina)

• Narrow atherosclerotic coronary vessels

• Coronary perfusion is inadequate during physical exertion

• Onset of pain is predictable and relieved by rest

What factors of stable angina may upset the balance?

Factors that decrease coronary supply OR increase myocardial oxygen demand can

upset the balance and lead to ischemia and anginal pain

True or False: MI occlusion is complete and the thrombus lasts long enough to cause

irreversible damage.

TRUE

Acute Coronary Syndrome

Unstable Angina and MI are difficult to distinguish on the basis of clinical manifestation and are lumped together as ACS

Chest pain usually more severe and lasts longer than typical angina

In both cases plaque rupture with acute thrombus development

Unstable angina: occlusion is partial, or the clot is dissolved before myocardial tissue damage

MI: occlusion is complete, and thrombus lasts long enough to causes irreversible damage

o Necrosis of myocardial cells

ECG and biomarkers used for diagnosis

What is an accurate diagnosis of ACS?

Accurate Diagnosis of ACS: Serum Biomarkers

The appearance of certain proteins in the blood after myocardial cell death is a sensitive and reliable indicator of MI

Elevated levels indicate suggest leakage from fatally damaged heart cells

• Myoglobin

• Troponins I and T (Test of choice)

• Lactate dehydrogenase

• Creatine kinase (CK-MB; specific for heart muscle necrosis)

1.Signs and symptoms

2.ECG changes

3.Biomarkers

MI is a result of prolonged or total disruption of blood flow

• More than 125,000 deaths/year in U.S.)

Acute occlusion causes a range of cellular events, depending on

• availability and adequacy of collateral blood flow.

• relative workload.

• length of time that flow is interrupted.

Ultimate size of the infarcted tissue depends on the extent, duration, and severity of ischemia.

Nearly all (>97%) infarcts are located in the left ventricular walls

7-day old Infarction

After 18 to 24 hours: area of infarction becomes paler than surrounding tissues

5 to 7 days: turns yellowish and soft with a rim of red vascular connective tissue

At 1 to 2 weeks: necrotic tissue progressively degraded and cleared away; infarcted myocardium weakened and susceptible to rupture

By 6 weeks: necrotic tissue replaced by tough fibrous scar tissue

What does chronic ischemic cardiomyopathy refer to?

Refers to a disorder in which heart failure develops insidiously (slowly) because of progressive ischemic myocardial damage.

Patients typically have history of angina or MI

Appears to be a consequence of slow, progressive apoptotic death of myocytes from chronic ischemia

oScattered throughout the myocardium

More common in older adults

Mitral valve is between which atrium and ventricle?

Mitral valve (valve between the left atrium and left ventricle)

Disorders of the Heart Valves

Heart valves may be damaged by

• inflammation and scarring.

• calcification.

• congenital malformations.

Murmurs are common with valvular disorders

Mitral Valve Stenosis and Regurgitation

Stenosis

Blood flow from left atrium to left ventricle impaired during ventricular diastole

Increased pressure of the left atrium leads to atrial chamber enlargement and hypertrophy.

Can lead to chronic pulmonary hypertension, right ventricular hypertrophy, and right-sided heart failure

Low-pitched, rumbling diastolic murmur; open snap; atrial dysrhythmias, atrial clots; exertional dyspnea

Regurgitation

Backflow of blood from the left ventricle to the left atrium during ventricular systole

Left atrium and ventricle dilate and hypertrophy cause by extra volume

May lead to left-sided heart failure

High-pitched, pansystolic, blowing murmur; giant V waves; chronic weakness and fatigue

What is the function of the aortic valve?

Aortic valve (valve allowing outflow from left ventricle to the aorta)

Aortic Valve Stenosis and Regurgitation

Stenosis

Results in obstruction of aortic outflow from the left ventricle into the aorta during systole

Predominant cause is age-related calcium deposits on the aortic cusps.

Left ventricle hypertrophy may result in ischemia and left-sided heart failure.

Regurgitation

Incompetent aortic valve allows blood to leak back from the aorta into the left ventricle during diastole.

Causes: abnormal aortic valve or aortic root dilation

Leads to left ventricle hypertrophy and dilation with eventual left-sided heart failure

High-pitched blowing murmur during ventricular diastole; high systolic blood pressure; diastolic blood pressure usually low; palpitations

What is Stenosis?

Stenosis: failure of the valve to open completely results in extra pressure work for the heart

What is regurgitation?

Regurgitation (insufficiency): inability of a valve to close completely results in extra volume work for the heart

What defines rheumatic heart disease?

Diseases of the Endocardium

• Acute inflammatory disease that follows infection with group A β- hemolytic streptococci

• Damage is caused by immune attack on the individual’s own tissues.

• Antibodies against the streptococcal antigens damage connective tissue in joints, heart, skin.

o Cause valve swelling and damage

• Occurs mainly in children

• Fever; sore throat; joint inflammation; involuntary movements (Sydenham chorea); and a distinctive truncal rash

What defines infective endocarditis?

Diseases of the Endocardium

• Invasion and colonization of endocardial structures by microorganisms with resulting inflammation—vegetations

• Most common bacteria

o Streptococcus

o Staphylococcus

• Acute infective endocarditis

o Prognosis poor

o Intravenous drug users susceptible

• Subacute infective endocarditis

o Onset is insidious

o Risk factor for acute endocarditis