Definition of diagnosis Gout is a term used for a group of at least nine metabolic disorders characterized by an elevation in the serum

uric acid concentration (hyperuricemia). Gout may be primary or secondary. Primary gout is the direct result of the bodys overproduction of or decreased secretion of uric acid. Secondary gout occurs when the overproduction or decreased secretion of uric acid is secondary to another disease process or medication. The problem develops when the crystals of monosodium urate monohydrate form in the joints and surrounding tissues. These needlelike crystals are responsible for the acute inflammatory reaction that develops, resulting in the severe pain commonly associated with an acute gouty attack. These crystal deposits can lead to extensive joint and soft-tissue damage if left untreated. (Anderson, Sylvia et.al (1992).pathophysiology clinical concepts of disease processes 4th edition. Mosby-yearbook, Inc.11830 st.louis) Gout is actually a group of diseases known as the gout syndrome. It includes acute gouty arthritis with recurrent attacks of severe articular and periarticular inflammation; tophi or the accumulation of crystalline deposits in articular surfaces, bones, soft tissues, and cartilages; gouty nephropathy or renal impairement; and uric acid kidney stones. The term primary gout is used to designate cases in which the cause of the disorder is unknown or an inborn error in metabolism and is characterized primarily by hyperuricemia and gout. Primary gout is predominantly a disease of men, with a peak incidence in the fourth to sixth decade. In secondary gout, the cause of the hyperuricemia is known but the gout is not the main disorder. Asymptomatic hyperuricemia is a laboratory finding and not a disease. (porth) NAKALIMOT QG KUHA SA BIBLIO ANI HEHE..BASTA PORTH NI) Gout is a heterogenous group of conditions related to a genetic defect of purine metabolism that results in hyperuricemia. Oversecretion of uric acid or a renal defect resulting in decreased excretion of uric acid, or a combination of both, occurs. In primary hyperuricemia, elevated serum urate levels or manifestations of urate deposition appear to be consequences of faulty uric acid metabolism. In secondary hyperuricemia, gout is a clinical feature secondary to any number of genetic or acquired processes, including conditions in which there is an increase

in cell turnover and an increase in cell breakdown. Altered renal tubular function, either as a major action or as an unintended side effect of certain pharmacological agent, low-dose salicylates or ethanol, can contribute to uric acid undersecretion. (Brunner and Suddarths textbook of medical surgical nursing. 11th edition. Lippincot Williams and wilkins, Philadelphia.) Gouty arthritis is a type of arthritis characterized by swelling in the joints, extreme tenderness in the joint area, and a sudden onset of intense joint pain, among other things. It can occur when uric acid, which is normally dissolved in the blood and passed through the kidneys into the urine, builds up in the blood. Diabetes, HIV infection, and pseudogout are among the conditions that can share similar symptoms with this type of arthritis. While there is no cure, the disease can be controlled with drugs and certain lifestyle changes. The term arthritis refers to more than 100 different rheumatic diseases that affect the joints, muscles, and bones, as well as other tissues and structures. Gouty arthritis accounts for approximately 5 percent of all cases of arthritis. (http://arthritis.emedtv.com/gout/gouty-arthritis.html) Gout is a complex form of arthritis characterized by sudden, severe attacks of pain, redness and tenderness in joints, often the joint at the base of the big toe. Gout can affect anyone. Men are more likely to get gout, but women become increasingly susceptible to gout after menopause. An acute attack of gout can wake you up in the middle of the night feeling like your big toe is on fire. The affected joint is hot, swollen and so tender that even the weight of the sheet on it seems intolerable.

(http://www.mayoclinic.com/health/gout/DS00090) *note: jinky nalibug gud ko kng unsa ba jud..primary gout or secondary gout..kay ang precipitating factors bah..lahi2 mn gud..basta ang predisposing factors ngadescribe xa sa mga predisposing factors na mkalead sa gout..ang precipitating kay secondary..ai basta..hehe (^^)/

Predisposing and precipitating factors Predisposing factors Heredity Present Absent Justification Primary gout is caused by inherited defect of purine metabolism leading to a decreased or increased renal excretion. Age

* *

The initial attack of gout occurs in the third or fourth decade of life.

Sex

Primary gout is predominantly a disease of men. Men account for almost 95% of the cases. The serum urate level in men normally begins to increase after puberty. The urate level does not increase In women after menopause, since estrogens increase the renal excretion of uric acid.

Race/Ethnicity

Gout is slightly more prevalent in blacks than in whites.

Precipitating factors Diet

Present

Absent

Justification A diet high in purines can trigger a gouty attack in a person with one of inborn errors of purine metabolism that causes an overproduction of uric acid.

Hematopoietic

Secondary gout is an acquired condition following hematopoietic (multiple myeloma, polycythemia vera, and leukemia) where in there is an increase cell turnover and uric acid production.

Renal disorder

* *

Renal

disorder

decreases

the

excretion of uric acid that leads to hyperuricemia or gout.

Hypertension

This condition promotes increased serum levels of uric acid that predispose to gout. Although no evidence has shown that gout or hyperuricemia causes this disorder, elevated urate levels have been shown to correlate with blood pressure in adolescents, and, among middle-aged men

Alcohol intoxication

*
Di ko sure kng alcoholic xa or dii.

Ingestion of alcohol can bring on a gouty attack because alcohol increases uric production. Blood lactate levels increase as a byproduct of normal alcohol metabolism. Lactic acid blocks the renal excretion of uric acid with a concomitant rise in serum level.

Cardiovascular disorder

Gout is found in higher rates in people with high blood pressure, coronary artery disease, and heart failure. Hyperuricemia, in fact, has been associated with a higher risk of death from heart conditions. According to some studies,

hyperuricemia may be associated with heart disease, but there is not enough data to confirm such an association. Obesity

Weight

may

precipitate

gout

because of the destruction of cells which releases uric acid.

Starvation

Serum urate level is increased by starvation because it may inhibit the excretion of urate as a result of lactic acidosis and ketosis.

Prolonged diuretics

use

of

Prolonged decreases

use the

of renal

diuretics tubular

excretion of urate.

Lead exposure

Chronic occupational exposure to lead is associated with build-up of uric acid and a high incidence of gout.

Organ transplant

Kidney transplantation poses a high risk for renal insufficiency and gout. In addition, other transplantation procedures, such as heart and liver, increase the risk of gout. The procedure itself poses a risk of gout, as rejection does the of the medication (cyclosporine) used to prevent transplanted organ. Cyclosporine also interacts with indomethacin, a common gout treatment.

Symptomatology Signs and symptoms Increased serum urate level Actual Rationale Attacks of gouty arthritis develop with increased serum urate concentrations. It occurs with sudden or sustained increase s of hyperuricemia that can trigger the attack. Pain (Dolor)

The primary symptom is severe pain. The pain felt is due to the inflammatory process where in there is a synthesis of prostaglandin by the mast cells which help increase vascular permeability, chemical chemotaxis and induces pain.

Swelling (Tumor)

In the process of inflammation, there is a momentary vasoconstriction, followed by a vasodilation which increases blood flow to the site of injury. Arteriolar dilation increases pressure in the microcirculation, which may increase exudation of plasma and blood cells into the tissues causing edema or swelling.

Warmth/Heat (Calor)

Heat is caused by the congestion of blood cells in the site of injury due to the vasodilation which increases blood flow and pressure into the tissues.

Redness (Rubor)

Redness is caused by the congestion of blood cells in the site of injury due to the vasodilation which increases blood flow into the tissues.

Loss of function (Functiolaesa)

It is a nuerological reflex in response to pain due to the congestion of blood cells in the tissues, resulting to compressed nerve endings which may cause a loss in functioning.

Fever

A local inflammatory response is usually accompanied by systemic changes such as fever and increase in leukocyte count (leukocytosis).

Elevated white cell count

In the normal process of onflammation, leukocytes (white blood cells) migrate to vessel walls and proceeds to the affected tissues to facilitate phagocytosis of the formed urate crystals in the site of injury.

Local desquamation (tissue loss)

Tissue damage begins to occur when the neutrophils release the contents of their digestive vacuoles (lysosomes). Neutrophils lysosomes contain substances that not only damage tissues, but also perpetuate inflammation.

Presence of Tophi

Progressive inability to excrete uric acid expands the urate pool until urate crystal deposits (tophi) appear in the cartilage, synovial membranes

Renal disorders

i.apil nq ni?

Renal disorder results from the accumulated urate

Complication crystals in the kidney. Renal stones can form in the gud ni hehe.. collecting tubules, pelvis, or ureters, causing obstruction,
dilatation, and atrophy of the more proximals tubules and leading eventually to acute renal failure.

*note: jinky basaha jud ni please..as in basha jud kay mhadlok bia ko mgkamali..hehe Narrative Pathophysiology The pathophysiology of gout is closely linked to purine metabolism (or cellular metabolism of purines) and kidney function. Uric acid is a breakdown product of purine neuclotides. Some individuals with gout have an accelerated rate of purine synthesis accompanied by an over production of uric acid. Production of uric acid also can be the result of an increased turnover of cells at the other body sites. The increased turnover of nucleic acids leads to increased levels of uric acid (hyperuricemia) with a compensatory increase in urine synthesis. Kidney function is involved in the pathophysiology of gout because most uric acid is eliminated from the body through the kidneys. Urate (uric acid salts) is normally freely filtered at the glomerulus and undergoes both reabsorption and excretion within the renal tubules. In most individuals with primary gout, urate excretion by the kidneys is sluggish. The sluggish excretion may be the result of a decrease in glomerular filtration of urate or acceleration in the urate reabsorption causing in an increase serum uric acid level (stage I: Asymptomatic Hyperuricemia). The exact process by which crystals of monosodium urate are deposited in the joints and induce gouty arthritis is unknown, but several mechanisms have been proposed (1) monosodium urate precipitates at the periphery of the body, where lower body temperatures may reduce the solubility of monosodium urate; (2) decreases in albumin or glycosaminoglycan levels decreases urate solubility; (3) changes in ion concentration and decreases in pH enhance urate deposition; and (4) trauma promotes urate crystal precipitation. The monosodium urate crystals may form in the synovial fluid or in the synovial membrane, cartilage, or other connective tissues in the joints and elsewhere, such as heart, earlobes,a nd kidneys. Mechanical or metabolic changes probably cause release of the crystals from connective tissues into the synovial fluid. Monosodium urate crystals are capable of both stimulating and perpetuating inflammatory response (stage II: acute gout attack). The presence of crystal triggers the acute inflammatory response, during which neutrophils are attracted out of the circulation. During the inflammatory process, the arterioles near the site of injury constrict briefly. Vasoconstriction is

followed by vasodilation, (hyperemic response) which increases blood flow to the inflamed site. Arteriolar dilation increases pressure in the microcirculation, which may increase the exudation of plasma and blood cells into the tissue. Exudation causes edema and swelling. As plasma moves outward, blood remaining in the microcirculation flows more viscous. Leukocytes migrate and adhere (margination) in the vessel walls at the same time biochemical mediators stimulate the endothelial cells that line capillaries and venules to retract, creating spaces at the junctions between the cells. The leukocytes, which otherwise could not penetrate vessel walls, are able to squeeze out through the spaces created by endothelial retraction (immigration). This state of vascular permeability continues throughout acute inflammation, permitting blood cells and plasma proteins to exude continuously into inflamed tissues (chemotaxis). Neutrophils are the first phagocytic leukocytes to arrive at the inflamed site to phagocyte the urate crystals (phagocytosis). Tissue damage begins to occur when the neutrophils release the contents of their digestive vacuoles. Lysosomal contents are released through one of the different mechanism: (1) dissolution of neutrophils that have died of old age (neutrophil life span: 2days) (2) leakage from neutrophils that have been injured by biochemical reactions with ingested urate crystals, or (3) rupture of neutrophils during attempts to ingest exceptionally large urate crystals. The neutrophils lysosomes contain substances that not only damage tissues, but also perpetuate inflammation. Most tissue damage in gouty arthritis is caused by powerful lysosomal enzymes. Other lysosomal substances include the undigested urate crystals and biochemicals that attract more neutrophils to the site and trigger acute inflammation anew. Attacks of gouty arthritis occur abruptly, usually in a peripheral joint. The primary symptom is severe pain and is usually noticed at night. Approximately 50% of all attacks occur in the metatarsophalangeal joint of the great toe. The othe 50% includes the heel, the ankle, instep of the foot, knee wrist or elbow. Severe attacks may persist for several days or weeks. On recovery, the pain, swelling and other symptoms resolves completely. The intervals between acute attacks of gouty arthritis are called intercritical period (Stage III) or the asymptomatic stage. Some individuals never have a second attack. Others experience subsequent attacks 510 years after the first. The fourth and chronic stage of the disease is called the Tophaceous Gout. It can begin as early as 3 years or as late as 40 years after the initial attack of gouty arthritis. Progressive inability to excrete uric acid expands the pool until urate crystal deposits (tophi) appear in the cartilage, synovial membrane, tendons, and soft tissue. The helix of the ear is the most common

site of tophi, which is the characteristic diagnostic lesion of chronic gout. Each tophus consists of a deposit of urate crystals, surrounded by a granuloma made up of mononuclear phagocytes that have developed into epithelial and giant cells. Chronic inflammation is characterized by a dense filtration of lymphocytes and macrophages. If macrophages are unable to protect the host from tissue damage, the body attempts to wall off and isolate the infected site, thus forming a granuloma. Granuloma formation begins when some of the macrophages differentiate into large epitheloid cells; cells that are incapable of phagocytosis but capable of taking up debris and other small particles. Other macrophages fuse into multinucleated giant cells, which are active phagocytes and can engulf particles too large to be engulf by single macrophage. Tophaceous deposits produce irregular swellings of the fingers, hands, knees and feet. Tophi commonly form lumps along the ulnar surface of the forearm, the tibial surface of the leg, Achilles tendon, and olecranon bursae. Tophi may produce marked limitation of joint movement and eventually cause grotesque deformities of the hands and feet. Although the tophi themselves are painless, they often cause progressive stiffness and persistent aching of the affected joint. Renal stones are 1000 times more prevalent in individuals with primary gout that in the general population. The stones can be the size of a grain of sand or a piece of gravel, or can accumulate in massive deposits called staghorn calculi. They range in color from pale yellow to brown to reddish black depending on their composition. Some stones consist of pure monosodium urate; others consist of calcium oxalate or calcium phosphate. Renal stones can form in the collecting tubules, renal pelvis pelvis, or ureters, causing obstruction, dilatation, and atrophy of the more proximal tubules leading to a decrease in renal blood flow which causes tubular cell damage and obstruction with cellular debris, eventually leading to acute renal failure. Stones deposited directly in the renal interstitial tissue initiate an inflammatory reaction that leads to chronic renal disease, later to progressive renal failure and eventually death. *note: jinky taas na kaau kung i.insert nq ang exact patho sa renal failure..mura qg ngpatho ug renal failure ug gout. Hehe..ayaw nlng..sabotable n bitaw na na ma2tay pg d maagapan ang renal failure hehe.. giapilan pa bia nq na ug granuloma formation dra kay k2 mn dw mglead ug tophi formation hehe..char na kaau..abi nqg gamai lng ni..taas mn d.i.

Schematic Diagram
Precipitating factors (PRIMARY CAUSE) Diet Obesity Starvation Hematopoietic Renal Disorder Hypertension Alcohol Intoxication Prolonged use of Diuretics Cardiovascular Disorder Organ Transplant Lead exposure Predisposing factors: (SECONDARY GOUT) Heredity Age Sex Race/Ethnicity

Purine synthesis

Kidney Function Free Filtration of urate (serum uric acid) at the glomerulus Accelerated rate of purine synthesis into purine nucleotides

Cellular function turn over of nucleic acids

Over production of uric acid Accelerated urate reabsorption Accelerated rate of purine synthesis into purine nucleotides

Over production of Uric Acid

Under excretion of uric acid Hyperuricemia

--------------------------------

SUA: 0.41

Production of monosodium urate crystals Formation of monosodium urate crystals in the synovial fluid, synovial membrane or cartilages Stimulation of inflammatory process Momentary constriction of small vessels Vasodilation (Hyperemic Response) Capillary permeability Fluid Shifting Rubor , Calor Margination
y Low purine diet, OFI to urinary output

--------

Tumor, Dolor, Functiolaesa

----------------WBC Fever

Congestion
NSAIDS, Colchicine, and other inflammatory drugs

Immigration

Phagocytosis of urate crystals

Release of lysosomal contents from neutrophils Lysosomal enzymes Urate crystals Biochemicals that trigger inflammation Biochemicals that attract more neutrophils

Continued Inflammation

Intercritical stage

Progressive inability to excrete uric acid

Chronic inflammation

Macrophage differentiate into large epitheloid cells

Multinucleated giant cells

y y

5 cardinal signs of inflammatio n Lyphm angitis Fever WBC

Sustained Uric acid concentrations

--------

Chronic Gouty Arthritis

Accumulation of monosodium urate in the kidney Staghorn Calculi

TOPHI deposits

Granuloma Formation -------------y NSAIDS, Colchicine, and other inflammatory drugs

Inflammatory reaction of stone deposits in the renal interstitial

Acute Renal Failure

Obstruction, dilatation and atrophy of more proximal tubules

Chronic renal disease

Continued inflammation

Progressive renal failure

DEATH