Coronary Artery Disease: Ischemic Heart disease

- Leading cause of death and disability in the United States

- One of every three men
- One of every two women
- Application of cpr
- Better medical control of emergencies
- Control of hypertension
- Lower cholesterol diets
- Coronary artery disease (CAD)
- Men have higher incidence
- Almost totally caused by atherosclerosis

Risk factors
A. Alterable:
- Diet
- Smoking
- Hypertension
- Stress
- Sedentary Living
- Diabetes Mellitus
- Alcohol
B. Unalterable
- Age
- Sex
- Race
- Genetic Heritage

Alterable Risk Factors

A. Diet

- Main factor in development of CAD

- High serum plasma cholesterol
- Foods high in saturated fat content
- Low-density lipoprotein (LDL)
- High-density lipoprotein (HDL)
- Exercise; age (children and premenopausal women); diet
- Hyperlipidemia

B. Cigarette Smoking
- Most preventable
- Risk of cerebrovascular accident is also decreased
- Decreased fibrinogen levels
- Decreased HDL
- Increases LDL cholesterol
- Alters O2 transport in myocardium
 C. Hypertension
- Can be decreased with antihypertensive drugs, diet and exercise
- Elevation of the systolic pressure

D. Stress/Behavioral Factors
- Type A Behavioral Pattern
- Stressful life events
- Job problems
- Limited social support
- Lifestyle changes
- May be associated with diet and smoking

E. Sedentary Living
- Regular, moderate or vigorous physical activity

F. Diabetes Mellitus
- Alteration in carbohydrate and fat metabolism
- Body weight
- Blood sugar levels

G. Alcohol
- Correlated with high blood pressure
- Increased smoking behavior, alcoholism, obesity, systemic problems
- Increased serum HDL levels

Unalterable Risk Factors

A. Age
- more common

B. Sex differences
- Increased incidence in men
- Female hormones are protective

C. Racial Differences
- Little conclusive evidence
- Blacks have an equal incidence of CAD; higher incidence of
hypertension
- Asians have lower incidence

D. Genetic Heritage
- Strong factor

Pathogenesis of coronary Artery Disease

- Fatty streak
- Fibrous plaque or atheroma
- Atheromatous plaque (white)
 - Occludes the lumen of artery
- Core of plaque becomes necrotic
- Hemorrhage and calcification
- Thrombosis
- Lesions = 75% occluding
- Total occlusion does not cause ischemia because of collateral
circulation
- Channels dilate
- Bifurcations, curvatures, tapering of arteries
- Resistance to blood flow increases
- Compromised myocardial muscle blood supply
- Decreased O2 uptake
- Myocardial ischemia, angina pectoris results
- Necrosis

SYSTEMIC HYPERTENSION

-consistent elevation of systemic arterial blood pressure

-sustained systolic blood pressure of 140 mm Hg or greater systolic pressure
or a diastolic
pressure of 90 mm Hg or greater

Two Blood Pressure Measures:

Systolic – pressure of the blood as a result of contraction of the ventricles,

that is, the
pressure of the height of the blood wave
Diastolic – pressure when the ventricles are at rest, the lower pressure,
present at all
times within the arteries

 Pulse Pressure – difference between the diastolic and systolic

pressures

Determinants of Blood Pressure:

Pumping Action of the Heart

When the pumping action of the heart is weak, less blood is pumped
into arteries (lower cardiac output), and the blood pressure decreases. When
the heart’s pumping action is strong and the volume of blood pumped into
circulation increases (higher cardiac output), the blood pressure increases.

Peripheral Vascular Resistance

Peripheral resistance can increase blood pressure. The diastolic
pressure especially is affected. Some factors that create resistance in the
arterial system are the capacity of the arterioles and capillaries, the
compliance of the arteries, and the viscosity of the blood.
The internal diameter or capacity of the arterioles and the capillaries
determines in great part the peripheral resistance to the blood in the body.
The smaller the space within a vessel, the greater the resistance. Normally,
the arterioles are in a state of partial constriction. Increased vasoconstriction
raises the blood pressure, whereas decreased vasoconstriction lowers the
blood pressure.

Blood Volume
When the blood volume decreases (for example, as a result of
hemorrhage or dehydration), the blood pressure decreases because of
decreased fluid in the arteries. Conversely, when the volume increases (for
example, as a result of a rapid intravenous infusion), the blood pressure
increases because of the greater fluid within the circulatory system.

Blood Viscosity
Blood pressure is higher when the blood is highly viscous (thick), that
is, when the portion of red blood cells to the plasma is high. This portion is
referred to as the hematocrit. The viscosity increases markedly when the
hematocrit is more than 60% to 65%.

Classification of Blood Pressure for Adults Age 18 Years or Older

Systolic (mm Hg) Diastolic Category (mm

Hg)

Normal < 120 < 80

Prehypertension 120-139 80-89

Stage 1 hypertension 140-159 90-99

Stage 2 hypertension ≥ 160 ≥ 100

Factors Associated with Primary Hypertension:

o Family History of Hypertension

o Advancing Age
o Gender (more common in men than women before age 55 years, more
common in women
o after age 55)
o Black Race
o High Dietary Sodium Intake
 o Glucose Intolerance (Diabetes Mellitus)
o Cigarette Smoking
o Obesity
o Heavy Alcohol Consumption
o Low Dietary Intake of Potassium, Calcium, and Magnesium

Primary Hypertension

Primary Hypertension is the result of an extremely complicated

interaction of genetics and the environment mediated by a host of
neurohumoral effects. Multiple pathophysiologic mechanisms mediate these
effects, including the sympathetic nervous system (SNS), the rennin-
angiotensin-aldosterone (RAA) system, and natriuretic peptides.
Inflammation, endothelial dysfunction, and insulin resistance also contribute
to both increased peripheral resistance and increased blood volume.
Increased vascular volume is related to a decrease in renal excretion of salt,
often referred to as a shift in the pressure-natriuresis relationship. This
means that for a given blood pressure, individuals with hypertension tend to
secrete less salt in their urine.

Decreased dietary
Genetics Decreased dietary
Genetics potassium,
potassium,
magnesium and
↑ SNS magnesium and
↑ SNS calcium
calcium

↑ RAA (especially Increased dietary

↑ RAA (especially Decreased renal Increased dietary
aldosterone) Decreased renal sodium intake
aldosterone) salt excretion (shift sodium intake
salt excretion (shift
in pressure
in pressure
natriuresis
natriuresis
relationship)
relationship)
Endothelial
Endothelial Insulin resistance
dysfunction Insulin resistance
dysfunction

Dysfunction of the
Dysfunction of the
natriuretic Renal glomerular Obesity
natriuretic Renal glomerular Obesity
hormones and tubular
hormones and tubular
inflammation
inflammation

Figure: Factors that Cause a Shift in the Pressure-Natriuresis

Relationship

The sympathetic nervous system has been implicated in both the

development and the maintenance of elevated blood pressure and plays a
role in hypertensive end-organ damage. Increased SNS activity causes
increased heart rate and systemic vasoconstriction, thus raising the blood
pressure. Additional mechanisms of SNS-induced hypertension include
structural changes in blood vessels (vascular remodeling), renal sodium
retention (shift in natriuresis curve), insulin resistance, increased renin and
angiotensin levels, and procoagulant effects.
The rennin-angiotensin-aldosterone system plays an important role in
blood pressure regulation by moderating vascular tone and influencing salt
and water retention by the kidneys. Further, angiotensin II mediates
arteriolar remodeling, which is structural change in the vessel wall that
results in permanent increases in peripheral resistance. Angiotensin II is
associated with end-organ effects of hypertension, including atherosclerosis,
renal disease and cardiac hypertrophy. Finally, aldosterone not only
contributes to sodium retention by the kidney but also has other deleterious
effects on the cardiovascular system.
Natriuretic hormones modulate renal sodium (Na+) excretion and
include atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), C-
type natriuretic peptide, and urodilatin. The functions of these hormones can
be affected by excessive sodium intake; inadequate dietary intake of
potassium, magnesium and calcium; and obesity. Dysfunctions of these
hormones, along with alterations in the RAA system and the SNS, cause an
increase in vascular tone and a shift in the pressure-natriuresis relationship.
Salt retention leads to water retention and increased blood volume, which
contributes to an increase in blood pressure. Subtle renal injury results, with
renal vasoconstriction and tissue ischemia. Tissue ischemia causes
inflammation of the kidneys and contributes to dysfunction of the glomeruli
and tubules and promotes additional sodium retention.
Inflammation plays a role in the pathogenesis of hypertension.
Endothelial injury and tissue ischemia result in the release of vasoactive
inflammatory cytokines. Although many of these cytokines (e.g., histamine,
prostaglandins) have vasodilatory actions in acute inflammatory injury,
chronic inflammation contributes to vascular remodeling and smooth muscle
contraction. Endothelial injury and dysfunction in primary hypertension is
further characterized by a decreased production of vasodilators, such as
nitric oxide, and increased production of vasoconstrictors, such as
endothelin.
Obesity causes changes in systematic hemodynamics that may
contribute to hypertension. It is also associated with increased activity of the
sympathetic nervous system (perhaps because of high levels of leptin), and
RAA system. Obesity is linked to endothelial dysfunction (increased
endogenous vasoconstrictors and insulin resistance).
Finally, insulin resistance is common in hypertension, even in
individuals without clinical diabetes. Insulin resistance is associated with
decreased endothelial release of nitric oxide and other vasodilators. It also
affects renal function and causes renal salt and water retention. Insulin
resistance is associated wit over activity of the sympathetic nervous system
and renin-angiotensin-aldosterone system. It is interesting to note that in
many individuals with diabetes treated with drugs that increase insulin
sensitivity, blood pressure often declines, even in the absence of
antihypertensive drugs.
It is likely that primary hypertension is an interaction between many of
these factors leading to sustained increases in blood volume and peripheral
resistance.

Genetic +
Environment

Dysfunction of the SNS, RAA,

Insulin
adducin, and natriuretic hormones Inflammation
resistance

Vasoconstrictio Renal salt and water

n retention

Increased peripheral Increased blood

resistance volume

Sustained Hypertension

Figure: Pathophysiology of Hypertension

Secondary Hypertension
Secondary hypertension is caused by an underlying disease process or
medication that raises peripheral vascular resistance or cardiac output.
Examples include renal vascular or parenchymal disease, adrenocortical
tumors, adrenomedullary tumors (peochromocytoma), and drugs (oral
contraceptives, corticosteroids, antihistamines). If the cause is identified and
removed before permanent structural changes occur, blood pressure returns
to normal.

Isolated Systolic Hypertension

Isolated systolic hypertension (ISH) is typically defined as a sustained
systolic BP that is ≥ 140 mm Hg and diastolic BP that is below 90 mm Hg.
ISH accounts for a substantial proportion of hypertension in individuals order
than 65 years and is strongly associated with cardiovascular and
cerebrovascular events.
An increased pulse pressure (PP) indicates reduced vascular
compliance of large arteries. PP is always increased in isolated systolic
hypertension. Mechanisms of aortic stiffening include gradual vascular
calcification, changes in elastic fibers, and increases of a rigid component
like collagen.

Complicated Hypertension
Cardiovascular complications of sustained hypertension include left
ventricular hypertrophy, angina pectoris, congestive heart failure (left heart
failure), coronary artery disease, myocardial infarction, and sudden death.
Myocardial hypertrophy in response to hypertension is mediated by several
neurohumoral substances, including catecholamines from the SNS and
angiotensin II. This results in changes in the myocyte proteins, apoptosis of
myocytes, and deposition of collagen in heart muscle. In addition, the
increased size of the heart muscle increases demand for oxygen delivery
over time, contractility of the heart is impaired and the individual is at
increased risk for heart failure. Vascular complications include the formation,
dissection, and rupture of aneurysms (outpouchings in vessel walls) and
atherosclerosis leading to vessel occlusion. Possible renal complications are
parenchymal damage, nephrosclerosis, renal arteriosclerosis, and renal
insufficiency or failure. Microalbiminuria (small amounts of protein in the
urine) occurs in 10% to 25% of individual with essential hypertension and is
now recognized as an early sign of impending renal dysfunction and
significantly increased risk for cardiovascular events, especially in those who
also have diabetes.
Changes in the vascular beds can be estimated by viewing the
arterioles of the retina. Complications specific to the retina include retinal
vascular sclerosis, exudation, and hemorrhage. Cerebrovascular
complications are similar to those of other arterial beds and include transient
ischemia, stroke, cerebral thrombosis, aneurysm, and hemorrhage. Chronic
hypertension also has been linked to competitive decline in the elderly.
Malignant hypertension (rapidly progressive hypertension in which
diastolic pressure is usually above 140 mm Hg) can cause encephalopathy, a
profound cerebral edema that disrupts cerebral function and causes loss of
consciousness. High arterial pressure renders the cerebral arterioles
incapable of regulating blood flow to the cerebral capillary beds. High
hydrostatic pressures in the capillaries cause vascular fluid to exude in the
interstitial space. If blood pressure is not reduced, cerebral edema and
cerebral dysfunction increase until death occurs. Organ damage resulting
from malignant hypertension is life threatening. Besides encephalopathy,
malignant hypertension can cause papilledema, cardiac failure, uremia,
retinopathy, and cerebrovascular accident.

Pathologic Effects of Sustained, Complicated Primary Hypertension

Site of Injury Mechanism of Injury Potential Pathologic Effect

HEART

Myocardium Increased workload Left ventricular

combined with diminished
blood flow through
coronary arteries
Coronary Arteries Accelerated atherosclerosis
(coronary artery disease)
Renin and aldosterone
KIDNEYS secretion stimulated by
reduced blood flow
Reduced oxygen supply
High pressures in renal
arterioles
hypertrophy, myocardial
ischemia, left heart failure
Myocardial ischemia,
myocardial infarction,
sudden death
Retention of sodium and
water, leading to increased
blood volume and
perpetuation of
hypertension
Tissue damage that
compromises filtration
Nephrosclerosis leading to
renal failure

BRAIN Reduced blood flow and Transient ischemic attacks,

oxygen supply; weakened
vessel walls, accelerated
atherosclerosis
EYES (RETINAS) Reduced blood flow
High arteriolar pressure
AORTA Weakened vessel wall
ARTERIES OF LOWER Reduced blood flow and
EXTREMITIES high pressures in arterioles,
accelerated atherosclerosis
cerebral thrombosis,
aneurysm, hemorrhage,
acute brain infarction
Retinal vascular sclerosis
Exudation, hemorrhage
Dissecting aneurysm
Intermittent claudication,
gangrene

ACUTE/CHRONIC ARTERIAL INSUFFICIENCY

Orthostatic (Postural) Hypotension

The term orthostatic (postural) hypotension refers to a decrease in
both systolic and diastolic arterial blood pressure on standing. Normally
when an individual stands up, the gravitational changes on the circulation
are compensated for by such mechanisms as reflex arteriolar and venous
constriction, increased heart rate, and mechanical factors, such as the
closure of valves in the venous system, pumping of the leg muscles, and a
decrease in intrathoracic pressure. The normally increased sympathetic
activity during upright posture is mediated through a stretch receptor
(baroreceptor) reflex that responds to shifts in volume caused by postural
changes. This reflex promptly increases heart rate and constricts the
systemic arterioles. Thus, arterial blood pressure is maintained.
 Orthostatic hypotension is often accompanied by dizziness, blurring or
loss of vision, and syncope or fainting caused by insufficient vasomotor
compensation and reduction of blood flow through the brain. This occurs
because the normal or compensatory vasoconstrictor response to standing is
absent so that there is blood pooling in the muscle vasculature, as well as in
the splanchic and renal beds.
Orthostatic hypotension may be acute and temporary or chronic. Acute
orthostatic hypotension is caused when the normal regulatory mechanisms
are sluggish as a result of 910 altered body chemistry, (2) drug action (e.g.,
antihypertensive, antidepressants), (3) prolonged immobility caused by
illness, (4) starvation, (5) physical exhaustion, (6) any condition that
produces volume depletion (e.g., dehydration, diuresis, potassium or sodium
depletion), or (7) venous pooling (e.g., pregnancy, extensive varicosities of
the lower extremities). Elderly persons are particularly susceptible to this
type of orthostatic hypotension.
Chronic orthostatic hypotension may be (1) secondary to a specific
disease or (2) idiopathic or primary. The disease that cause secondary
orthostatic hypotension are endocrine disorders (e.g., adrenal insufficiency,
diabetes mellitus), metallic disorders (e.g., porphyria), or diseases of the
central or peripheral nervous systems (e.g., intracranial tumors, cerebral
infarcts, Wernicke encephalopathy, peripheral neuropathies).
The term idiopathic or primary, orthostatic hypotension implies no
known initial cause. Some define the disorder as a separate entity, whereas
others suggest it is a part of a generalized degenerative central nervous
system disease. It affects men more often than women and usually occurs
between the ages of 40 and 70 years. One third to half of the elderly
population may be affected by primary orthostatic hypotension, and it is a
significant risk factor for falls and associated injury. In addition to
cardiovascular symptoms, associated impotence and bowel and bladder
dysfunction are common.
Although no curative treatment is available for idiopathic orthostatic
hypotension, often it can be managed adequately with a combination of
nondrug and drug therapies. For both acute and secondary forms,
hypotension resolves when the underlying disorder is corrected.

Raynaud’s Disease
- A rare disorder that affects the arteries
- A marking of this disease is the brief vasospasm which occurs in
different periods.
- This disorder also affects the fingers and toes of a client known to have
Raynaud’s disease. This effect is because of the vasospasm that reduces
blood flow in other parts of the body, such as fingers and toes and on
rare occasions the nose, ears, nipples and lips.
Overview :
Cause
- Usually unknown, it is called primary Raynaud’s or idiopathic .
 - When it is cause by other factors it is called as Raynaud’s phenomenon
or secondary Raynaud’s. This is much rarer and much dangerous than
primary Raynaud’s. this usually occurs in people who has predisposing
factors such as collagen vascular diseases. Ex.
Polymyositis — An inflammation of many muscles.
Pulmonary hypertension — A severe form of high blood pressure caused by
diseased arteries in the lung.
Rheumatoid arthritis — Chronic, autoimmune disease marked by
inflammation of the membranes surrounding joints.
Scleroderma — A relatively rare autoimmune disease affecting blood vessels
and connective tissue that makes skin appear thickened.
Systemic lupus erythematosus — A chronic inflammatory disease that affects
many tissues and parts of the body including the skin.
- When one has either both, cold temperature and stressful emotions can
suddenly occur. It is known as “Raynaud’s attacks” . During attacks only
little or no blood flow is happening.
- When attack stops normal blood flow returns but not instantly. May be
noticeable by the change of pallor finger tips to the preferred color of
the skin, or a tingle feeling or numbing.
- Both Raynaud cases may be triggered by sudden environment temp.
changes. But is more common on cold temperature.
- A person with Raynaud does not necessarily have any long term tissue
damage . A severe Raynaud however is characterized by the
development of gangrene or skin sores from repeated attacks.
- So far no cure is available for this disease , as such, advice is given to
avoid triggering factors, these factors are age and smoking for male
while marital status and alcohol intake with women.
- A cold stimulation test is sometimes provided for the proper diagnosing
of Raynaud’s disease.
- Raynaud’s is in need of advance control to prevent drastic measures
such as amputation. Or with Sympathectomy , surgical procedure
that destroys nerves in the sympathetic nervous system. Is done to
increase blood flow and decrease long-term pain in certain diseases
that cause narrowed blood vessels. It can also be used to decrease
excessive sweating. This surgical procedure cuts or destroys the
sympathetic ganglia, collections of nerve cell bodies in clusters along
the thoracic or lumbar spinal cord.

Venous Thrombosis
- Formation of a blood clot in a vein. The clot can form in superficial
veins and cause few if any symptoms or it can form in the deeper,
larger leg veins which can be life-threatening in serious cases. A part of
the clot can break off and travel (embolism) to the heart or lungs
where it can cause serious problems.
- It is believe to be as one of the unknown cause of stroke.
- Deep venous thrombosis occurs on lower extremity.
 - Genetic abnormalities are more likely a factor of thrombosis
Symptoms =
o Pain in affected area
o Tenderness in affected area
o Swelling in affected area
o Increased warmth in affected area
o Altered skin color in affected area

Possible Cause = Virchow’s Triad

- It is the three group factors that may help develop any blood clot
formation.
a. Venous stasis
b. Venous endothelial damage
c. Hypercoagulable states.

Diagnosing
- Before a solid diagnosis is given a intravenous venography is done.
- Intravenous Venography is when an injected contrast to the vessel and is
then observe through X-ray for any obstruction of the vessel.

Treatment = medications such as Blood anticoagulant

Vitamin E may be use to prevent Thrombosis
Thrombotic therapy , Inferior vena cava filter

SHOCK
is a medical emergency in which the organs and tissues of the body
are not receiving an adequate flow of blood. This deprives the organs and
tissues of oxygen (carried in the blood) and allows the buildup of waste
products. Shock can result in serious damage or even death.

is classified by cause as cardiogenic (caused by heart failure),

hypovolemic (caused by insufficient intravascular fluid volume), neurogenic
(caused by neural alterations of vascular smooth muscle tone), anaphylactic
(caused by immunologic processes), or septic (caused by infection). As
described previously, each of these share similar effects on tissues and cells
but can vary in their clinical manifestations and severity.

NEUROGENIC SHOCK
Sometimes called as Vasogenic shock, is the result of widespread and
massive vasodilation that results from parasympathetic overstimulation and
sympathetic understimulation.
This type of shock can be caused by any factor that stimulates
parasympathetic or inhibits sympathetic stimulation of vascular smooth
muscle. Trauma to the spinal cord or medulla and conditions that interrupt
the supply of oxygen or glucose to the medulla can cause neurogenic shock
by interrupting sympathetic activity. Depressive drugs, anesthetic agents,
and severe emotional stress and pain are other causes. The loss of vascular
tone results in “relative hypovolemia”. Blood volume has not changed, but
the amount of space containing the blood has increased, so that SVR
decreases drastically, meaning that pressure in the vessels is inadequate to
drive nutrients across capillary membranes to the cells. In addition,
bradycardia can occur with a decrease in cardiac output that further
contributes to hypotension and underperfusion of tissues. As with other
types of shock, this leads to impaired cellular metabolism. Management
includes the careful use of fluids and pressors until blood pressure stabilizes.
Causation:
Other causes
• Spinal anesthesia
• Drugs
• Emotional stress
• Pain
• CNS dysfunction

Pathophysiology:
• Loss of sympathetic tone (parasympathetic response) results in
massive vasodilitation,
inhibition of the baro-receptor response, and impaired thermo-regulation.
• Arterial vasodilitation = drop in BP
• Decrease in BP & drop in CO = impaired tissue perfusion.
• Inhibition of baro-receptors = no reflex tachycardia, further
compromising tissue perfusion

Assessment:
• Usually pt. will present with:
• Hypotension
• Bradycardia
• Hypothermia
• Warm/dry skin (lost the ability to sweat)

Hemodynamics:
• Decreased CO & CI
• Decrease in pre-load
• Decrease in RAP & PAWP
• Decrease in after-load =low SVR
Management:
• Goal is to treat or remove cause, prevent cardiovascular instability and
promote tissue
perfusion.
 • Treat hypovolemia with fluids carefully to prevent overload.
Vasopressors may be used.
• Warming blankets to regulate temperature.
• ABC’s are addressed and interventions as necessary.
• Cardiac dysrhythmia seen is bradycardia, treat with atropine.

Nursing Management:
• Prevention by assessment of at risk patients
• Treat hypovolemia, maintain normothermia, prevent hypoxia, provide
comfort and emotional support. Autonomic hyper-reflexia
• Autonomic hyper-reflexia (AKA dysreflexia) is a sympathetic
overresponse. Seen in spinal cord injury above T6
• S/S: H/A, blurred vision, nausea, sweating below level of injury.
• Severe hypertension with SBP >300.
• Risk for stroke!!
Causation:
• Most common cause is a full bladder
• Assess for kinked foley
• Intestinal obstruction caused by fecal impaction
• Monitor bowel movements and use laxatives as necessary

CARDIOGENIC SHOCK
Is defined as “decreased cardiac output and evidence of tissue hypoxia in
the presence of adequate intravascular volume”. Most cases of cardiogenic
shock follow myocardial infarction, but shock also can follow left heart
failure, arrhythmias, acute valvular dysfunction, ventricular or septal rupture,
myocardial or pericardial infections, and heart failure resulting from drug
toxicity. Cardiogenic shock is often unresponsive to treatment, with a
mortality of more than 70% reported. Mortality improves with the use of
percutaneous coronary angioplasty and thrombolytic/aspirin therapy.

The clinical manifestations of cardiogenic shock are caused by widespread

impairment of cellular metabolism. They include impaired mentation,
elevated preload in the systemic and pulmonary vasculature, systemic and
pulmonary edema, dusky skin color, marked hypotension, oliguria, ileus, and
dyspnea. Management of cardiogenic shock includes careful fluid and
pressor administration followed by early angiography, intra-aortic balloon
pump counterpulsation, and early revascularization (PCI or bypass surgery).
New therapies being explored include anti-inflammatory drugs and nitric
oxide synthetase inhibitors.

PATHOPHYSIOLOGY
 • RENAL FAILURE

o Renal failure is a serious medical condition affecting the kidneys.

When a person suffers from renal failure, their kidneys are not
functioning properly or no longer work at all. Renal failure can be
a progressive disease or a temporary one depending on the
cause and available treatment options.
o The kidneys are glands that are located in the abdominal region
just above the pelvis on either side of the body. When
functioning normally, the kidneys separate and filter excess
water and waste from the blood stream. The kidneys are
responsible for producing urine, which is used to flush away the
toxins. The kidneys also maintain a healthy balance of fluids
and electrolytes, or salt compounds, in the body.

In renal failure the kidneys undergo cellular death and are unable to
filter wastes, produce urine and maintain fluid balances. This dysfunction
causes a build up of toxins in the body which can affect the blood, brain and
heart, as well as other complications. Renal failure is very serious and even
deadly if left untreated.

• TYPES OF RENAL FAILURE:

ACUTE RENAL FAILURE (ARF)

- Acute renal failure occurs suddenly and is usually initiated by

underlying causes, for example dehydration, infection, serious injury
to the kidney or the chronic use of over the counter pain
medications like Tylenol (acetaminophen) or Advil (ibuprofen).
Acute renal failure is often reversible with no lasting damage.

It occurs rapidly over a period of days or weeks with a reduction in

glomerular flitration rate (GFR) and elevation of blood urea nitrogen (BUN),
plasma creatinine and cystatin C levels. It is usually associated with oliguria
(urine output of less than 30 ml/hr or less than 400 ml/day), although urine
output may be normal or increased. Fluid is still filtered at the glomerulus
but there is an alteration in tubular secretion or reabsorption. Most types of
acute renal failure are reversible if diagnosed and treated early. Acute renal
failure can be classified as prerenal, intrarenal, or psotrenal (obstructive).

• Prerenal—as an adaptive response to severe volume depletion and

hypotension, with structurally intact nephrons
• Intrarenal—in response to cytotoxic, ischemic, or inflammatory insults
to the kidney, with structural and functional damage
 • Postrenal—from obstruction to the passage of urine.

PRERENAL

• Prerenal ARF represents the most common form of kidney injury and
often leads to intrinsic AKI if it is not promptly corrected. Volume loss
from GI, renal, cutaneous (eg, burns), and internal or external
hemorrhage can result in this syndrome. Prerenal AKI can also result
from decreased renal perfusion in patients with heart failure or shock
(eg, sepsis, anaphylaxis).

Special classes of medications that can induce prerenal ARF in volume-

depleted states are angiotensin-converting enzyme inhibitors (ACEIs)
and angiotensin receptor blockers (ARBs), which are otherwise safely
tolerated and beneficial in most patients with chronic kidney disease.
Arteriolar vasoconstriction leading to prerenal ARF can occur in
hypercalcemic states, with the use of radiocontrast agents,
nonsteroidal anti-inflammatory drugs (NSAIDs), amphotericin,
calcineurin inhibitors, norepinephrine, and other pressor agents.

The hepatorenal syndrome can also be considered a form of prerenal

ARF, because functional renal failure develops from diffuse
vasoconstriction in vessels supplying the kidney.

INTRARENAL

• Structural injury in the kidney is the hallmark of intrarenal ARF, and the
most common form is acute tubular injury (ATN), either ischemic or
cytotoxic. Frank necrosis is not prominent in most human cases of ATN
and tends to be patchy. Less obvious injury includes loss of brush
borders, flattening of the epithelium, detachment of cells, formation of
intratubular casts, and dilatation of the lumen. Although these changes
are observed predominantly in proximal tubules, injury to the distal
nephron can also be demonstrated. In addition, the distal nephron may
become obstructed by desquamated cells and cellular debris.

POSTRENAL

• Mechanical obstruction of the urinary collecting system, including the

renal pelvis, ureters, bladder, or urethra, results in obstructive
uropathy or postrenal ARF.
 • If the site of obstruction is unilateral, then a rise in the serum
creatinine level may not be apparent due to contralateral renal
function. Although the serum creatinine level may remain low with
unilateral obstruction, a significant loss of GFR occurs, and patients
with partial obstruction may develop progressive loss of GFR if the
obstruction is not relieved. Causes of obstruction include stone
disease; stricture; and intraluminal, extraluminal, or intramural tumors.

• Bilateral obstruction is usually a result of prostate enlargement or

tumors in men and urologic or gynecologic tumors in women.

• Patients who develop anuria typically have obstruction at the level of

the bladder or downstream to it.

CAUSES
The causes of ARF traditionally are divided into 3 main categories: prerenal,
intrarenal, and postrenal.

• Prerenal ARF
o Volume depletion
 Renal losses (diuretics, polyuria)
 GI losses (vomiting, diarrhea)
 Cutaneous losses (burns, Stevens-Johnson syndrome)
 Hemorrhage
 Pancreatitis
o Decreased cardiac output
 Heart failure
 Pulmonary embolus
 Acute myocardial infarction
 Severe valvular disease
 Abdominal compartment syndrome (tense ascites)
o Systemic vasodilation
 Sepsis
 Anaphylaxis
 Anesthetics
 Drug overdose
o Afferent arteriolar vasoconstriction
 Hypercalcemia
 Drugs (NSAIDs, amphotericin B, calcineurin inhibitors,
norepinephrine, radiocontrast agents)
 Hepatorenal syndrome
o Efferent arteriolar vasodilation – ACEIs or ARBs
• Intrarenal ARF
o Vascular (large and small vessel)
 Renal artery obstruction (thrombosis, emboli, dissection,
vasculitis)
 Renal vein obstruction (thrombosis)
 Microangiopathy (TTP, hemolytic uremic syndrome [HUS],
DIC, preeclampsia)
 Malignant hypertension
 Scleroderma renal crisis
 Transplant rejection
 Atheroembolic disease
o Glomerular
 Anti–glomerular basement membrane (GBM) disease
(Goodpasture syndrome)
 Anti–neutrophil cytoplasmic antibody-associated
glomerulonephritis (ANCA-associated GN) (Wegener
granulomatosis, Churg-Strauss syndrome, microscopic
polyangiitis)
 Immune complex GN (lupus, postinfectious,
cryoglobulinemia, primary membranoproliferative
glomerulonephritis)
o Tubular
 Ischemic
 Cytotoxic
 Heme pigment (rhabdomyolysis, intravascular
hemolysis)
 Crystals (tumor lysis syndrome, seizures, ethylene
glycol poisoning, megadose vitamin C, acyclovir,
indinavir, methotrexate)
 Drugs (aminoglycosides, lithium, amphotericin B,
pentamidine, cisplatin, ifosfamide, radiocontrast
agents)
o Interstitial
 Drugs (penicillins, cephalosporins, NSAIDs, proton-pump
inhibitors, allopurinol, rifampin, indinavir, mesalamine,
sulfonamides)
 Infection (pyelonephritis, viral nephritides)
 Systemic disease (Sj ö gren syndrome, sarcoid, lupus,
lymphoma, leukemia, tubulonephritis, uveitis)
• Postrenal ARF
o Ureteric obstruction (stone disease, tumor, fibrosis, ligation
during pelvic surgery)
o Bladder neck obstruction (benign prostatic hypertrophy [BPH],
cancer of the prostate [CA prostate or prostatic CA], neurogenic
bladder, tricyclic antidepressants, ganglion blockers, bladder
tumor, stone disease, hemorrhage/clot)
 o Urethral obstruction (strictures, tumor, phimosis)

TREATMENT

• Medical Care
The mortality rate for patients in the intensive care unit (ICU) is higher in
those who have ARF, especially when ARF is severe enough to require
dialysis treatment. In addition, evidence suggests that the relative risk of
death is 4.9 in patients in the ICU who have renal failure that is not severe
enough to require dialysis. This reflects that the high mortality rate in
patients with ARF who require dialysis may not be related to the dialysis
procedure or accompanying comorbidities and that AKI alone may be an
independent indicator of mortality.

• Aggressive treatment should begin at the earliest indication of renal

dysfunction. A large proportion of the renal mass is damaged before
any biochemical evidence of renal dysfunction is appreciated because
the relationship between the GFR and the serum creatinine level is
exponential, not linear. The rise of serum creatinine may not be
evident before 50% of the GFR is lost.
• At this point, recognizing the presence of AKI and promptly initiating
therapy aimed at minimizing the damage to the remaining functional
renal mass are important considerations. This may also aid in reversing
the renal damage that has already occurred. Reversing renal damage
can be accomplished only by identifying the underlying cause and
directing the appropriate therapy.
• Maintenance of volume homeostasis and correction of biochemical
abnormalities remain the primary goals of treatment. Furosemide can
be used to correct volume overload when the patients are still
responsive to it. Furosemide plays no role in converting an oliguric AKI
to a nonoliguric ARF or to increase urine output when a patient is not
hypervolemic. However, the response to furosemide can be taken as a
good prognostic sign. At this stage, the kidneys remain vulnerable to
the toxic effects of various chemicals. All nephrotoxic agents (eg,
radiocontrast agents, antibiotics with nephrotoxic potential, heavy
metal preparations, cancer chemotherapeutic agents, NSAIDs) are
either avoided or used with extreme caution. Similarly, all medications
cleared by renal excretion should be avoided or their doses should be
adjusted appropriately.
• Correcting acidosis with bicarbonate administration is important. It
cannot be overstated that the current treatment of AKI is mainly
supportive in nature and no therapeutic modalities to date have shown
efficacy in treating the condition. Therapeutic agents, such as
dopamine, fenoldopam, and mannitol, are not indicated in the
management of AKI and may be harmful for the patient.
 • Hyperkalemia, which can be life-threatening, should be treated by
decreasing the intake of potassium, delaying the absorption of
potassium, exchanging potassium across the gut lumen using
potassium-binding resins, controlling intracellular shifts, and instituting
dialysis.
• Correcting hematologic abnormalities (eg, anemia, platelet
dysfunction) warrants appropriate measures, including transfusions
and administration of desmopressin or estrogens.

OLIGURIA

Oliguria is defined as a urine output that is less than 1 mL/kg/h in infants,

less than 0.5 mL/kg/h in children, and less than 400 mL/d in adults. It is one
of the clinical hallmarks of renal failure and has been used as a criterion for
diagnosing and staging acute renal failure. At onset, oliguria is frequently
acute. It is often the earliest sign of impaired renal function and poses a
diagnostic and management challenge to the clinician. All cases of acute
renal failure are not characterized by oliguria. For example, subjects with
acute renal failure due to nephrotoxins, interstitial nephritis, or neonatal
asphyxia are typically nonoliguric. In addition, the degree of oliguria depends
on hydration and concomitant use of diuretics.

In most clinical situations, acute oliguria is reversible and does not result in
intrinsic renal failure. However, identification and timely treatment of
reversible causes is crucial because the therapeutic window may be small.

Pathophysiology of Pyelonephritis

Abstract
Escherichia coli is the most frequent cause of pyelonephritis. Its
possible virulence factors include the ability to adhere and colonize the
urinary tract, an important initiating factor in all urinary tract infections
(UTIs). The importance of P fimbriae in this adhesion is stressed and the
evidence for its importance in pyelonephritis is presented in epidemiologic
studies of patients, as well as in animal studies. It appears that both host
receptor density and the nonsecretor state is responsible for susceptibility to
urinary tract infection. Vesicoureteral reflux can be responsible for ascending
upper tract infection, but infection with P-fimbriated E coli may lead to
ascending pyelonephritis without reflux because of the paralytic effect of
lipid A on ureteral peristaltic activity. Renal ischemia leads to renal damage
following infection by reperfusion damage due to the release of superoxide.
Experimentally, this ischemic damage can be prevented by allopurinol, a
xanthine oxidase inhibitor. The acute inflammatory response can produce
renal damage because of the respiratory burst of phagocytosis, which while
killing phagocytosed bacteria also damages renal tubules. An amelioration of
the inflammatory response by treatment with superoxide dismutase or
corticosteroids has been shown to modulate renal damage. Vaccination with
P fimbriae has been shown experimentally to prevent the initiation of the
disease. However, since vaccines are not clinically available, the clinical and
animal studies on therapy of acute disease are stressed. Acute
pyelonephritis during the first 3 years of life more often produced the renal
damage that could lead to end-stage renal disease.
Acute Pyelonephritis
Acute uncomplicated pyelonephritis most often develops as a result of
an ascending UTI. In these cases, symptoms of cystitis often precede acute
pyelonephritis, particularly in patients with uncomplicated infections.
Alternatively, pathogenesis may involve haematogenous seeding of the
kidneys in patients with bacteraemia. Typically in women who develop acute
pyelonephritis, pathogens first colonise the distal urethra and vaginal
introitus and then ascend via the bladder and ureters to the kidney. Women
with cystitis-like symptoms (e.g., burning on urinating, urgency) commonly
(30%) have asymptomatic pyelonephritis, rarely causing kidney damage.
Men are more prone to prostatitis and BPH, which cause a urethral
obstruction leading to bacteriuria and consequently often pyelonephritis.
Dilation and obstruction of the ureter cause inflammation of the kidney
parenchyma, which is seen on histopathological examination as purulent
exudates in the renal tubules. View imageView imageView imageView image
Additionally, obstruction as a result of any cause (e.g., calculi, tumor, foreign
body, BPH, or neurogenic bladder) often leads to treatment failure and
eventual renal abscess as continued blockage may lead to re-infection.
Chronically ill patients and those receiving immunosuppressive therapy are
at highest risk. [2] Seeding in the kidney from bone or skin may occur from
metastatic staphylococcal or fungal infections as well.
Uropathogenic E coli are a common cause of infection in patients with
normal urinary tract anatomy. The enhanced virulence potential of
uropathogenic E coli is thought to derive mainly from factors that enhance
the ability of these strains to adhere to and colonise the urinary tract. These
factors include flagella, which increase motility, haemolysins that break
down RBCs, and iron-scavenging molecules that pick up the iron released
from red cell lysis to use for cell growth and adhesions on the bacterial
fimbriae that help the organisms stick to the uroepithelial surface. The
proteins requied for P-fimbrial biogenesis, a mannose-resistant adhesin of
uropathogenic Escherchia coli (UPEC), are encoded by the pap gene cluster
codons. P fimbriae appear to play some role in mediating adherence to
uroepithelial cells in vivo and establishing an inflammatory response during
renal colonization, thus contributing to kidney damage during acute
pyelonephritis. [13] Other properties assist the bacteria in avoiding or
subverting host defenses, injuring or invading host cells and tissues and
stimulating a noxious inflammatory response. [14] Virulence of
uropathogenic E coli has been linked to the presence of pathogenicity
islands, unstable large regions of the bacterial genome encoding for these
virulence factors, which are present in approximately 80% of E coli strains
identified in the blood and urine of patients with acute pyelonephritis. [15]
More than 30 bacterial species carrying pathogenicity islands have been
described.
Chronic Pyelonephritis
Chronic pyelonephritis is renal injury induced by recurrent or persistent
renal infection. It occurs almost exclusively in patients with major anatomic
anomalies, including urinary tract obstruction, struvite calculi, renal
dysplasia, or, most commonly, vesicoureteral reflux (VUR) in young children.
Sometimes, this diagnosis is established based on radiologic evidence
obtained during an evaluation for recurrent urinary tract infection (UTI) in
young children. VUR is a congenital defect that results in incompetence of
the ureterovesical valve due to a short intramural segment. The condition is
present in 30-40% of young children with symptomatic UTIs and in almost all
children with renal scars. VUR may also be acquired by patients with a
flaccid bladder due to spinal cord injury. VUR is classified into 5 grades (I-V),
according to the increasing degree of reflux.

Pathophysiology:
Chronic pyelonephritis is associated with progressive renal scarring,
which can lead to end-stage renal disease (ESRD), for example, reflux
nephropathy. Intrarenal reflux of infected urine is suggested to induce renal
injury, which heals with scar formation. In some cases, scars may form in
utero in patients with renal dysplasia with perfusion defects. Infection
without reflux is less likely to produce injury. Dysplasia may also be acquired
from obstruction. Scars of high-pressure reflux can occur in persons of any
age. In some cases, normal growth may lead to spontaneous cessation of
reflux by age 6 years.

Factors that may affect the pathogenesis of chronic pyelonephritis are

as follows: (1) the sex of the patient and his or her sexual activity; (2)
pregnancy, which may lead to progression of renal injury with loss of renal
function; (3) genetic factors; (4) bacterial virulence factors; and (5)
neurogenic bladder dysfunction. In cases with obstruction, the kidney may
become filled with abscess cavities

Mortality/Morbidity:
Conditions associated with mortality and morbidity related to chronic
pyelonephritis include the following: (1) progressive renal scarring, (2)
proteinuria, (3) hypertension, (4) end-stage renal disease, (5) focal
glomerulosclerosis, and (6) xanthogranulomatous pyelonephritis (XPN). XPN
occurs in 8.2% of patients and in 25% of patients with pyonephrosis.
Race:
Chronic pyelonephritis is 3 times more common in white children than
in African American children.
Sex:
Chronic pyelonephritis is 2 times more common in females than in males.
Age:
Chronic pyelonephritis occurs more often in infants and young children
(younger than 2 y) than in older children and adults.
Clinical Application
History:
Many cases of VUR are suggested based on prenatal sonography findings.
Patients with chronic pyelonephritis may report the following:
Fever
Lethargy
Nausea and vomiting
Flank pain or dysuria
Some children may present with failure to thrive.
Physical:
The following may be noted:
Hypertension
Failure to thrive in young children
Flank tenderness
Causes:
Chronic pyelonephritis is renal injury induced by recurrent or persistent renal
infection.