Pa Tho Physiology Cardio&Renal

8/9/2019 Pa Tho Physiology Cardio&Renal

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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 factorsA. Alterable:- Diet- Smoking

- Hypertension- Stress- Sedentary Living- Diabetes Mellitus- AlcoholB. Unalterable- Age- Sex- Race- Genetic Heritage

Alterable Risk FactorsA. 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


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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 FactorsA. 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)


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- 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 collateralcirculation- 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 pressureor 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 systolicpressures

Determinants of Blood Pressure:

Pumping Action of the HeartWhen the pumping action of the heart is weak, less blood is pumped

into arteries (lower cardiac output), and the blood pressure decreases. Whenthe hearts pumping action is strong and the volume of blood pumped intocirculation increases (higher cardiac output), the blood pressure increases.

Peripheral Vascular ResistancePeripheral resistance can increase blood pressure. The diastolic

pressure especially is affected. Some factors that create resistance in the


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arterial system are the capacity of the arterioles and capillaries, thecompliance of the arteries, and the viscosity of the blood.

The internal diameter or capacity of the arterioles and the capillariesdetermines 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 vasoconstrictionraises the blood pressure, whereas decreased vasoconstriction lowers theblood pressure.

Blood VolumeWhen the blood volume decreases (for example, as a result of

hemorrhage or dehydration), the blood pressure decreases because ofdecreased fluid in the arteries. Conversely, when the volume increases (forexample, as a result of a rapid intravenous infusion), the blood pressureincreases because of the greater fluid within the circulatory system.

Blood ViscosityBlood 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 isreferred to as the hematocrit. The viscosity increases markedly when thehematocrit 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 Hypertensiono Advancing Age

o Gender (more common in men than women before age 55 years, more

common in womeno after age 55)

o Black Race

o High Dietary Sodium Intake


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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 complicatedinteraction of genetics and the environment mediated by a host ofneurohumoral effects. Multiple pathophysiologic mechanisms mediate theseeffects, including the sympathetic nervous system (SNS), the rennin-angiotensin-aldosterone (RAA) system, and natriuretic peptides.Inflammation, endothelial dysfunction, and insulin resistance also contributeto 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. Thismeans that for a given blood pressure, individuals with hypertension tend tosecrete less salt in their urine.

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

The sympathetic nervous system has been implicated in both thedevelopment and the maintenance of elevated blood pressure and plays a

SNS SNS

RAA (especially

aldosterone)

RAA (especiallyaldosterone)

Endothelial

dysfunction

Endothelial

dysfunction

Dysfunction of the

natriuretic

hormones

Dysfunction of the

natriuretic

hormonesRenal glomerular

and tubular

inflammation

Renal glomerular

and tubular

inflammation

ObesityObesity

Insulin resistanceInsulin resistance

Increased dietary

sodium intake

Increased dietarysodium intake

Decreased dietary

potassium,

magnesium and

calcium

Decreased dietary

potassium,

magnesium and

calcium

GeneticsGenetics

Decreased renal

salt excretion (shift

in pressure

natriuresis

relationship)

Decreased renal

salt excretion (shift

in pressure

natriuresis

relationship)


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role in hypertensive end-organ damage. Increased SNS activity causesincreased heart rate and systemic vasoconstriction, thus raising the bloodpressure. Additional mechanisms of SNS-induced hypertension includestructural changes in blood vessels (vascular remodeling), renal sodiumretention (shift in natriuresis curve), insulin resistance, increased renin and

angiotensin levels, and procoagulant effects.The rennin-angiotensin-aldosterone system plays an important role inblood pressure regulation by moderating vascular tone and influencing saltand water retention by the kidneys. Further, angiotensin II mediatesarteriolar remodeling, which is structural change in the vessel wall thatresults in permanent increases in peripheral resistance. Angiotensin II isassociated with end-organ effects of hypertension, including atherosclerosis,renal disease and cardiac hypertrophy. Finally, aldosterone not onlycontributes to sodium retention by the kidney but also has other deleteriouseffects 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 canbe affected by excessive sodium intake; inadequate dietary intake ofpotassium, magnesium and calcium; and obesity. Dysfunctions of thesehormones, along with alterations in the RAA system and the SNS, cause anincrease in vascular tone and a shift in the pressure-natriuresis relationship.Salt retention leads to water retention and increased blood volume, whichcontributes to an increase in blood pressure. Subtle renal injury results, withrenal vasoconstriction and tissue ischemia. Tissue ischemia causesinflammation of the kidneys and contributes to dysfunction of the glomeruliand 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 vasoactiveinflammatory 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 musclecontraction. Endothelial injury and dysfunction in primary hypertension isfurther characterized by a decreased production of vasodilators, such asnitric oxide, and increased production of vasoconstrictors, such asendothelin.

Obesity causes changes in systematic hemodynamics that maycontribute to hypertension. It is also associated with increased activity of the

sympathetic nervous system (perhaps because of high levels of leptin), andRAA system. Obesity is linked to endothelial dysfunction (increasedendogenous vasoconstrictors and insulin resistance).

Finally, insulin resistance is common in hypertension, even inindividuals without clinical diabetes. Insulin resistance is associated withdecreased endothelial release of nitric oxide and other vasodilators. It alsoaffects renal function and causes renal salt and water retention. Insulinresistance is associated wit over activity of the sympathetic nervous system


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and renin-angiotensin-aldosterone system. It is interesting to note that inmany individuals with diabetes treated with drugs that increase insulinsensitivity, blood pressure often declines, even in the absence ofantihypertensive drugs.

It is likely that primary hypertension is an interaction between many of

these factors leading to sustained increases in blood volume and peripheralresistance.

Figure: Pathophysiology of Hypertension

Secondary HypertensionSecondary 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, adrenocorticaltumors, adrenomedullary tumors (peochromocytoma), and drugs (oralcontraceptives, corticosteroids, antihistamines). If the cause is identified andremoved before permanent structural changes occur, blood pressure returnsto normal.

Isolated Systolic HypertensionIsolated 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 orderthan 65 years and is strongly associated with cardiovascular andcerebrovascular events.

An increased pulse pressure (PP) indicates reduced vascularcompliance of large arteries. PP is always increased in isolated systolic

Genetic +

Environment

Insulin

resistance

Dysfunction of the SNS, RAA,

adducin, and natriuretic hormones Inflammation

Vasoconstrictio

n

Renal salt and water

retention

Increased peripheral

resistance

Increased blood

volume

Sustained Hypertension


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hypertension. Mechanisms of aortic stiffening include gradual vascularcalcification, changes in elastic fibers, and increases of a rigid componentlike collagen.

Complicated Hypertension

Cardiovascular complications of sustained hypertension include leftventricular hypertrophy, angina pectoris, congestive heart failure (left heartfailure), coronary artery disease, myocardial infarction, and sudden death.Myocardial hypertrophy in response to hypertension is mediated by severalneurohumoral substances, including catecholamines from the SNS andangiotensin II. This results in changes in the myocyte proteins, apoptosis ofmyocytes, and deposition of collagen in heart muscle. In addition, theincreased size of the heart muscle increases demand for oxygen deliveryover time, contractility of the heart is impaired and the individual is atincreased 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 areparenchymal damage, nephrosclerosis, renal arteriosclerosis, and renalinsufficiency or failure. Microalbiminuria (small amounts of protein in theurine) occurs in 10% to 25% of individual with essential hypertension and isnow recognized as an early sign of impending renal dysfunction andsignificantly increased risk for cardiovascular events, especially in those whoalso have diabetes.

Changes in the vascular beds can be estimated by viewing thearterioles of the retina. Complications specific to the retina include retinalvascular sclerosis, exudation, and hemorrhage. Cerebrovascularcomplications are similar to those of other arterial beds and include transient

ischemia, stroke, cerebral thrombosis, aneurysm, and hemorrhage. Chronichypertension also has been linked to competitive decline in the elderly.

Malignant hypertension (rapidly progressive hypertension in whichdiastolic pressure is usually above 140 mm Hg) can cause encephalopathy, aprofound cerebral edema that disrupts cerebral function and causes loss ofconsciousness. High arterial pressure renders the cerebral arteriolesincapable of regulating blood flow to the cerebral capillary beds. Highhydrostatic pressures in the capillaries cause vascular fluid to exude in theinterstitial space. If blood pressure is not reduced, cerebral edema andcerebral dysfunction increase until death occurs. Organ damage resultingfrom 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


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HEART

Myocardium Increased workloadcombined with diminished

blood flow throughcoronary arteries

Left ventricularhypertrophy, myocardial

ischemia, left heart failure

Coronary Arteries Accelerated atherosclerosis

(coronary artery disease)

Myocardial ischemia,

myocardial infarction,

sudden death

KIDNEYS

Renin and aldosterone

secretion stimulated byreduced blood flow

Reduced oxygen supply

High pressures in renalarterioles

Retention of sodium and

water, leading to increasedblood volume and

perpetuation of

hypertensionTissue damage that

compromises filtrationNephrosclerosis leading torenal failure

BRAIN Reduced blood flow andoxygen supply; weakened

vessel walls, accelerated

atherosclerosis

Transient ischemic attacks,cerebral thrombosis,

aneurysm, hemorrhage,

acute brain infarction

EYES (RETINAS) Reduced blood flow

High arteriolar pressure

Retinal vascular sclerosis

Exudation, hemorrhage

AORTA Weakened vessel wall Dissecting aneurysm

ARTERIES OF LOWEREXTREMITIES

Reduced blood flow andhigh pressures in arterioles,

accelerated atherosclerosis

Intermittent claudication,gangrene

ACUTE/CHRONIC ARTERIAL INSUFFICIENCY

Orthostatic (Postural) HypotensionThe term orthostatic (postural) hypotension refers to a decrease in

both systolic and diastolic arterial blood pressure on standing. Normallywhen an individual stands up, the gravitational changes on the circulationare compensated for by such mechanisms as reflex arteriolar and venous

constriction, increased heart rate, and mechanical factors, such as theclosure of valves in the venous system, pumping of the leg muscles, and adecrease in intrathoracic pressure. The normally increased sympatheticactivity during upright posture is mediated through a stretch receptor(baroreceptor) reflex that responds to shifts in volume caused by posturalchanges. This reflex promptly increases heart rate and constricts thesystemic arterioles. Thus, arterial blood pressure is maintained.


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Orthostatic hypotension is often accompanied by dizziness, blurring orloss of vision, and syncope or fainting caused by insufficient vasomotorcompensation and reduction of blood flow through the brain. This occursbecause the normal or compensatory vasoconstrictor response to standing isabsent 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. Acuteorthostatic hypotension is caused when the normal regulatory mechanismsare sluggish as a result of 910 altered body chemistry, (2) drug action (e.g.,antihypertensive, antidepressants), (3) prolonged immobility caused byillness, (4) starvation, (5) physical exhaustion, (6) any condition thatproduces volume depletion (e.g., dehydration, diuresis, potassium or sodiumdepletion), or (7) venous pooling (e.g., pregnancy, extensive varicosities ofthe lower extremities). Elderly persons are particularly susceptible to thistype of orthostatic hypotension.

Chronic orthostatic hypotension may be (1) secondary to a specific

disease or (2) idiopathic or primary. The disease that cause secondaryorthostatic hypotension are endocrine disorders (e.g., adrenal insufficiency,diabetes mellitus), metallic disorders (e.g., porphyria), or diseases of thecentral or peripheral nervous systems (e.g., intracranial tumors, cerebralinfarcts, Wernicke encephalopathy, peripheral neuropathies).

The term idiopathic or primary, orthostatic hypotension implies noknown initial cause. Some define the disorder as a separate entity, whereasothers suggest it is a part of a generalized degenerative central nervoussystem disease. It affects men more often than women and usually occursbetween the ages of 40 and 70 years. One third to half of the elderlypopulation may be affected by primary orthostatic hypotension, and it is a

significant risk factor for falls and associated injury. In addition tocardiovascular symptoms, associated impotence and bowel and bladderdysfunction are common.

Although no curative treatment is available for idiopathic orthostatichypotension, often it can be managed adequately with a combination ofnondrug and drug therapies. For both acute and secondary forms,hypotension resolves when the underlying disorder is corrected.

Raynauds 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

Raynauds disease. This effect is because of the vasospasm that reducesblood flow in other parts of the body, such as fingers and toes and onrare occasions the nose, ears, nipples and lips.

Overview :Cause

- Usually unknown, it is called primary Raynauds or idiopathic .


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- When it is cause by other factors it is called as Raynauds phenomenonor secondary Raynauds. This is much rarer and much dangerous thanprimary Raynauds. this usually occurs in people who has predisposingfactors such as collagen vascular diseases. Ex.

Polymyositis An inflammation of many muscles.

Pulmonary hypertension A severe form of high blood pressure caused bydiseased arteries in the lung.Rheumatoid arthritis Chronic, autoimmune disease marked byinflammation of the membranes surrounding joints.Scleroderma A relatively rare autoimmune disease affecting blood vesselsand connective tissue that makes skin appear thickened.Systemic lupus erythematosus A chronic inflammatory disease that affectsmany tissues and parts of the body including the skin.

- When one has either both, cold temperature and stressful emotions cansuddenly occur. It is known as Raynauds attacks . During attacks onlylittle or no blood flow is happening.

- When attack stops normal blood flow returns but not instantly. May benoticeable by the change of pallor finger tips to the preferred color ofthe 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 tissuedamage . A severe Raynaud however is characterized by thedevelopment of gangrene or skin sores from repeated attacks.

- So far no cure is available for this disease , as such, advice is given toavoid triggering factors, these factors are age and smoking for malewhile marital status and alcohol intake with women.

- A cold stimulation test is sometimes provided for the proper diagnosingof Raynauds disease.

- Raynauds is in need of advance control to prevent drastic measuressuch as amputation. Or with Sympathectomy , surgical procedurethat destroys nerves in the sympathetic nervous system. Is done toincrease blood flow and decrease long-term pain in certain diseasesthat cause narrowed blood vessels. It can also be used to decreaseexcessive sweating. This surgical procedure cuts or destroys thesympathetic ganglia, collections of nerve cell bodies in clusters alongthe 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 ofthe clot can break off and travel (embolism) to the heart or lungswhere 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.


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- Genetic abnormalities are more likely a factor of thrombosisSymptoms =

o Pain in affected area

o Tenderness in affected area

o Swelling in affected area

o Increased warmth in affected areao Altered skin color in affected area

Possible Cause = Virchows Triad

- It is the three group factors that may help develop any blood clotformation.

a. Venous stasisb. Venous endothelial damagec. 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 isthen observe through X-ray for any obstruction of the vessel.Treatment = medications such as Blood anticoagulant

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

SHOCK

is a medical emergency in which the organs and tissues of the bodyare not receiving an adequate flow of blood. This deprives the organs andtissues of oxygen (carried in the blood) and allows the buildup of wasteproducts. 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). Asdescribed previously, each of these share similar effects on tissues and cellsbut can vary in their clinical manifestations and severity.

NEUROGENIC SHOCKSometimes called as Vasogenic shock, is the result of widespread andmassive vasodilation that results from parasympathetic overstimulation andsympathetic understimulation.This type of shock can be caused by any factor that stimulatesparasympathetic or inhibits sympathetic stimulation of vascular smoothmuscle. Trauma to the spinal cord or medulla and conditions that interrupt


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the supply of oxygen or glucose to the medulla can cause neurogenic shockby interrupting sympathetic activity. Depressive drugs, anesthetic agents,and severe emotional stress and pain are other causes. The loss of vasculartone results in relative hypovolemia. Blood volume has not changed, butthe amount of space containing the blood has increased, so that SVR

decreases drastically, meaning that pressure in the vessels is inadequate todrive nutrients across capillary membranes to the cells. In addition,bradycardia can occur with a decrease in cardiac output that furthercontributes to hypotension and underperfusion of tissues. As with othertypes of shock, this leads to impaired cellular metabolism. Managementincludes 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 inmassive 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 SVRManagement:

Goal is to treat or remove cause, prevent cardiovascular instability andpromote tissue

perfusion.


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Treat hypovolemia with fluids carefully to prevent overload.Vasopressors may be used.

Warming blankets to regulate temperature.

ABCs 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, providecomfort and emotional support. Autonomic hyper-reflexia

Autonomic hyper-reflexia (AKA dysreflexia) is a sympatheticoverresponse. 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 SHOCKIs defined as decreased cardiac output and evidence of tissue hypoxia inthe presence of adequate intravascular volume. Most cases of cardiogenicshock follow myocardial infarction, but shock also can follow left heartfailure, arrhythmias, acute valvular dysfunction, ventricular or septal rupture,

myocardial or pericardial infections, and heart failure resulting from drugtoxicity. Cardiogenic shock is often unresponsive to treatment, with amortality of more than 70% reported. Mortality improves with the use ofpercutaneous coronary angioplasty and thrombolytic/aspirin therapy.

The clinical manifestations of cardiogenic shock are caused by widespreadimpairment of cellular metabolism. They include impaired mentation,elevated preload in the systemic and pulmonary vasculature, systemic andpulmonary edema, dusky skin color, marked hypotension, oliguria, ileus, anddyspnea. Management of cardiogenic shock includes careful fluid andpressor 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 nitricoxide synthetase inhibitors.

PATHOPHYSIOLOGY


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RENAL FAILURE

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

When a person suffers from renal failure, their kidneys are notfunctioning properly or no longer work at all. Renal failure can bea progressive disease or a temporary one depending on thecause and available treatment options.

o The kidneys are glands that are located in the abdominal regionjust above the pelvis on either side of the body. Whenfunctioning normally, the kidneys separate and filter excesswater and waste from the blood stream. The kidneys areresponsible for producing urine, which is used to flush away thetoxins. The kidneys also maintain a healthy balance of fluidsand electrolytes, or salt compounds, in the body.

In renal failure the kidneys undergo cellular death and are unable tofilter wastes, produce urine and maintain fluid balances. This dysfunctioncauses a build up of toxins in the body which can affect the blood, brain andheart, as well as other complications. Renal failure is very serious and evendeadly if left untreated.

TYPES OF RENAL FAILURE:

ACUTE RENAL FAILURE (ARF)

- Acute renal failure occurs suddenly and is usually initiated byunderlying causes, for example dehydration, infection, serious injuryto the kidney or the chronic use of over the counter painmedications 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 inglomerular 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 urineoutput may be normal or increased. Fluid is still filtered at the glomerulus

but there is an alteration in tubular secretion or reabsorption. Most types ofacute renal failure are reversible if diagnosed and treated early. Acute renalfailure can be classified as prerenal, intrarenal, or psotrenal (obstructive).

Prerenalas an adaptive response to severe volume depletion andhypotension, with structurally intact nephrons

Intrarenalin response to cytotoxic, ischemic, or inflammatory insultsto the kidney, with structural and functional damage
http://www.wisegeek.com/what-is-an-electrolyte.htmhttp://www.wisegeek.com/what-is-acute-renal-failure.htmhttp://www.wisegeek.com/what-is-ibuprofen.htmhttp://www.wisegeek.com/what-is-acute-renal-failure.htmhttp://www.wisegeek.com/what-is-ibuprofen.htmhttp://www.wisegeek.com/what-is-an-electrolyte.htm


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Postrenalfrom 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 lossfrom GI, renal, cutaneous (eg, burns), and internal or externalhemorrhage can result in this syndrome. Prerenal AKI can also resultfrom 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 safelytolerated 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 prerenalARF, because functional renal failure develops from diffusevasoconstriction 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 orcytotoxic. Frank necrosis is not prominent in most human cases of ATNand tends to be patchy. Less obvious injury includes loss of brushborders, flattening of the epithelium, detachment of cells, formation ofintratubular casts, and dilatation of the lumen. Although these changesare observed predominantly in proximal tubules, injury to the distalnephron can also be demonstrated. In addition, the distal nephron maybecome obstructed by desquamated cells and cellular debris.

POSTRENAL

Mechanical obstruction of the urinary collecting system, including therenal pelvis, ureters, bladder, or urethra, results in obstructiveuropathy or postrenal ARF.
http://emedicine.medscape.com/article/178208-overviewhttp://emedicine.medscape.com/article/178208-overview


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If the site of obstruction is unilateral, then a rise in the serumcreatinine level may not be apparent due to contralateral renalfunction. Although the serum creatinine level may remain low withunilateral obstruction, a significant loss of GFR occurs, and patientswith partial obstruction may develop progressive loss of GFR if the

obstruction is not relieved. Causes of obstruction include stonedisease; stricture; and intraluminal, extraluminal, or intramural tumors.

Bilateral obstruction is usually a result of prostate enlargement ortumors in men and urologic or gynecologic tumors in women.

Patients who develop anuria typically have obstruction at the level ofthe bladder or downstream to it.

CAUSES

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

Prerenal ARFo 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 overdoseo Afferent arteriolar vasoconstriction

Hypercalcemia Drugs (NSAIDs, amphotericin B, calcineurin inhibitors,

norepinephrine, radiocontrast agents) Hepatorenal syndrome

o Efferent arteriolar vasodilation ACEIs or ARBs


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Intrarenal ARFo 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 Antiglomerular basement membrane (GBM) disease

(Goodpasture syndrome) Antineutrophil cytoplasmic antibody-associated

glomerulonephritis (ANCA-associated GN) (Wegener

granulomatosis, Churg-Strauss syndrome, microscopicpolyangiitis)

Immune complex GN (lupus, postinfectious,cryoglobulinemia, primary membranoproliferativeglomerulonephritis)

o Tubular Ischemic Cytotoxic

Heme pigment (rhabdomyolysis, intravascularhemolysis)

Crystals (tumor lysis syndrome, seizures, ethylene

glycol poisoning, megadose vitamin C, acyclovir,indinavir, methotrexate)

Drugs (aminoglycosides, lithium, amphotericin B,pentamidine, cisplatin, ifosfamide, radiocontrastagents)

o Interstitial Drugs (penicillins, cephalosporins, NSAIDs, proton-pump

inhibitors, allopurinol, rifampin, indinavir, mesalamine,sulfonamides)

Infection (pyelonephritis, viral nephritides) Systemic disease (Sj gren syndrome, sarcoid, lupus,

lymphoma, leukemia, tubulonephritis, uveitis) Postrenal ARF

o Ureteric obstruction (stone disease, tumor, fibrosis, ligationduring pelvic surgery)

o Bladder neck obstruction (benign prostatic hypertrophy [BPH],cancer of the prostate [CA prostate or prostatic CA], neurogenicbladder, tricyclic antidepressants, ganglion blockers, bladdertumor, stone disease, hemorrhage/clot)


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o Urethral obstruction (strictures, tumor, phimosis)

TREATMENT

Medical Care

The mortality rate for patients in the intensive care unit (ICU) is higher inthose who have ARF, especially when ARF is severe enough to requiredialysis treatment. In addition, evidence suggests that the relative risk ofdeath is 4.9 in patients in the ICU who have renal failure that is not severeenough to require dialysis. This reflects that the high mortality rate inpatients with ARF who require dialysis may not be related to the dialysisprocedure or accompanying comorbidities and that AKI alone may be anindependent indicator of mortality.

Aggressive treatment should begin at the earliest indication of renal

dysfunction. A large proportion of the renal mass is damaged beforeany biochemical evidence of renal dysfunction is appreciated becausethe relationship between the GFR and the serum creatinine level isexponential, not linear. The rise of serum creatinine may not beevident before 50% of the GFR is lost.

At this point, recognizing the presence of AKI and promptly initiatingtherapy aimed at minimizing the damage to the remaining functionalrenal mass are important considerations. This may also aid in reversingthe renal damage that has already occurred. Reversing renal damagecan be accomplished only by identifying the underlying cause anddirecting the appropriate therapy.

Maintenance of volume homeostasis and correction of biochemicalabnormalities remain the primary goals of treatment. Furosemide canbe used to correct volume overload when the patients are stillresponsive to it. Furosemide plays no role in converting an oliguric AKIto a nonoliguric ARF or to increase urine output when a patient is nothypervolemic. However, the response to furosemide can be taken as agood prognostic sign. At this stage, the kidneys remain vulnerable tothe toxic effects of various chemicals. All nephrotoxic agents (eg,radiocontrast agents, antibiotics with nephrotoxic potential, heavymetal preparations, cancer chemotherapeutic agents, NSAIDs) areeither avoided or used with extreme caution. Similarly, all medications

cleared by renal excretion should be avoided or their doses should beadjusted appropriately.

Correcting acidosis with bicarbonate administration is important. Itcannot be overstated that the current treatment of AKI is mainlysupportive in nature and no therapeutic modalities to date have shownefficacy in treating the condition. Therapeutic agents, such asdopamine, fenoldopam, and mannitol, are not indicated in themanagement of AKI and may be harmful for the patient.


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Hyperkalemia, which can be life-threatening, should be treated bydecreasing the intake of potassium, delaying the absorption ofpotassium, exchanging potassium across the gut lumen usingpotassium-binding resins, controlling intracellular shifts, and institutingdialysis.

Correcting hematologic abnormalities (eg, anemia, plateletdysfunction) warrants appropriate measures, including transfusionsand 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 oneof the clinical hallmarks of renal failure and has been used as a criterion fordiagnosing and staging acute renal failure. At onset, oliguria is frequentlyacute. It is often the earliest sign of impaired renal function and poses a

diagnostic and management challenge to the clinician. All cases of acuterenal failure are not characterized by oliguria. For example, subjects withacute renal failure due to nephrotoxins, interstitial nephritis, or neonatalasphyxia are typically nonoliguric. In addition, the degree of oliguria dependson hydration and concomitant use of diuretics.

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

Pathophysiology of Pyelonephritis

AbstractEscherichia coli is the most frequent cause of pyelonephritis. Its

possible virulence factors include the ability to adhere and colonize theurinary tract, an important initiating factor in all urinary tract infections(UTIs). The importance of P fimbriae in this adhesion is stressed and theevidence for its importance in pyelonephritis is presented in epidemiologicstudies of patients, as well as in animal studies. It appears that both hostreceptor density and the nonsecretor state is responsible for susceptibility to

urinary tract infection. Vesicoureteral reflux can be responsible for ascendingupper tract infection, but infection with P-fimbriated E coli may lead toascending pyelonephritis without reflux because of the paralytic effect oflipid A on ureteral peristaltic activity. Renal ischemia leads to renal damagefollowing infection by reperfusion damage due to the release of superoxide.Experimentally, this ischemic damage can be prevented by allopurinol, axanthine oxidase inhibitor. The acute inflammatory response can producerenal damage because of the respiratory burst of phagocytosis, which while
http://emedicine.medscape.com/article/982811-overviewhttp://emedicine.medscape.com/article/982811-overview


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killing phagocytosed bacteria also damages renal tubules. An amelioration ofthe inflammatory response by treatment with superoxide dismutase orcorticosteroids has been shown to modulate renal damage. Vaccination withP fimbriae has been shown experimentally to prevent the initiation of thedisease. However, since vaccines are not clinically available, the clinical and

animal studies on therapy of acute disease are stressed. Acutepyelonephritis during the first 3 years of life more often produced the renaldamage that could lead to end-stage renal disease.

Acute Pyelonephritis

Acute uncomplicated pyelonephritis most often develops as a result ofan ascending UTI. In these cases, symptoms of cystitis often precede acutepyelonephritis, particularly in patients with uncomplicated infections.Alternatively, pathogenesis may involve haematogenous seeding of thekidneys in patients with bacteraemia. Typically in women who develop acutepyelonephritis, pathogens first colonise the distal urethra and vaginal

introitus and then ascend via the bladder and ureters to the kidney. Womenwith 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 urethralobstruction leading to bacteriuria and consequently often pyelonephritis.Dilation and obstruction of the ureter cause inflammation of the kidneyparenchyma, which is seen on histopathological examination as purulentexudates in the renal tubules. View imageView imageView imageView imageAdditionally, obstruction as a result of any cause (e.g., calculi, tumor, foreignbody, BPH, or neurogenic bladder) often leads to treatment failure andeventual renal abscess as continued blockage may lead to re-infection.

Chronically ill patients and those receiving immunosuppressive therapy areat highest risk. [2] Seeding in the kidney from bone or skin may occur frommetastatic staphylococcal or fungal infections as well.

Uropathogenic E coli are a common cause of infection in patients withnormal urinary tract anatomy. The enhanced virulence potential ofuropathogenic E coli is thought to derive mainly from factors that enhancethe ability of these strains to adhere to and colonise the urinary tract. Thesefactors include flagella, which increase motility, haemolysins that breakdown RBCs, and iron-scavenging molecules that pick up the iron releasedfrom red cell lysis to use for cell growth and adhesions on the bacterial

fimbriae that help the organisms stick to the uroepithelial surface. Theproteins requied for P-fimbrial biogenesis, a mannose-resistant adhesin ofuropathogenic Escherchia coli (UPEC), are encoded by the pap gene clustercodons. P fimbriae appear to play some role in mediating adherence touroepithelial cells in vivo and establishing an inflammatory response duringrenal colonization, thus contributing to kidney damage during acutepyelonephritis. [13] Other properties assist the bacteria in avoiding orsubverting host defenses, injuring or invading host cells and tissues and


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stimulating a noxious inflammatory response. [14] Virulence ofuropathogenic E coli has been linked to the presence of pathogenicityislands, unstable large regions of the bacterial genome encoding for thesevirulence factors, which are present in approximately 80% of E coli strainsidentified in the blood and urine of patients with acute pyelonephritis. [15]

More than 30 bacterial species carrying pathogenicity islands have beendescribed.

Chronic PyelonephritisChronic pyelonephritis is renal injury induced by recurrent or persistent

renal infection. It occurs almost exclusively in patients with major anatomicanomalies, including urinary tract obstruction, struvite calculi, renaldysplasia, or, most commonly, vesicoureteral reflux (VUR) in young children.Sometimes, this diagnosis is established based on radiologic evidenceobtained during an evaluation for recurrent urinary tract infection (UTI) inyoung children. VUR is a congenital defect that results in incompetence ofthe ureterovesical valve due to a short intramural segment. The condition is

present in 30-40% of young children with symptomatic UTIs and in almost allchildren with renal scars. VUR may also be acquired by patients with aflaccid 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, refluxnephropathy. Intrarenal reflux of infected urine is suggested to induce renal

injury, which heals with scar formation. In some cases, scars may form inutero in patients with renal dysplasia with perfusion defects. Infectionwithout reflux is less likely to produce injury. Dysplasia may also be acquiredfrom obstruction. Scars of high-pressure reflux can occur in persons of anyage. In some cases, normal growth may lead to spontaneous cessation ofreflux by age 6 years.

Factors that may affect the pathogenesis of chronic pyelonephritis areas 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 renalfunction; (3) genetic factors; (4) bacterial virulence factors; and (5)

neurogenic bladder dysfunction. In cases with obstruction, the kidney maybecome 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


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glomerulosclerosis, and (6) xanthogranulomatous pyelonephritis (XPN). XPNoccurs in 8.2% of patients and in 25% of patients with pyonephrosis.Race:

Chronic pyelonephritis is 3 times more common in white children thanin 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 ApplicationHistory:Many cases of VUR are suggested based on prenatal sonography findings.Patients with chronic pyelonephritis may report the following:FeverLethargy

Nausea and vomitingFlank pain or dysuriaSome children may present with failure to thrive.Physical:The following may be noted:HypertensionFailure to thrive in young childrenFlank tendernessCauses:Chronic pyelonephritis is renal injury induced by recurrent or persistent renalinfection.

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