Practice Essentials Upper respiratory tract infection (URI) represents the most common acute illness evaluated in the outpatient setting. URIs range from the common cold —typically a mild, self-limited, catarrhal syndrome of the nasopharyn—to lifethreatening illnesses such as epiglottitis (see the image !elo").
#ateral nec$ radiograph demonstrates epiglottitis. %ourtesy of &arilyn 'os$e, &, %leveland %linic oundation. *ie" &edia 'allery +igns and symptoms etails of the patients history aid in differentiating a common cold from conditions that reuire targeted therapy, such as group streptococcal pharyngitis pharyngitis,, !acterialsinusitis, !acterialsinusitis, and and lo"er respiratory tract infections. %linical manifestations of these conditions, as "ell as allergy, sho" significant overlap. Viral nasopharyng nasopharyngitis itis
Patients "ith the common cold may have a paucity of clinical findings despite nota!le su!/ective discomfort. indings may include the follo"ing0 1asal mucosal erythema and edema are common 1asal discharge0 Profuse discharge is more characteristic of viral infections than !acterial infections2 initially clear secretions typically !ecome cloudy "hite, yello", or green over several days, even in viral infections • •
oul !reath ever0 #ess common in adults !ut may !e present in children "ith rhinoviral infections Group A streptococcal pharyngitis 3he follo"ing physical findings suggest a high ris$ for group gr oup streptococcal disease 456 0 Erythema, s"elling, or eudates of the tonsils or pharyn 3emperature of 78.79% (5::.;9) or higher 3ender anterior cervical nodes (orsening course (ne" or "orse nasal discharge, cough, fever) after initial improvement • •
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+evere onset (fever of 5:=9 or greater "ith nasal discharge) for at least 7 consecutive days In older children and adults, symptoms (eg, pain, pressure) tend to locali?e to the affected sinus. Epiglottitis
3his condition is more often found in children aged 5-@ years, "ho present "ith a sudden onset of the follo"ing symptoms0 +ore throat rooling, difficulty or pain during s"allo"ing, glo!us sensation of a lump in the throat &uffled dysphonia or loss of voice • •
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ry cough or no cough, dyspnea ever, fatigue or malaise (may !e seen "ith any URI) 3ripod or sniffing posture
Laryngotracheitis Laryngotrach eitis and laryngotrach laryngotracheobronchitis eobronchitis
1asopharyngitis often precedes laryngitis and tracheitis !y several days +"allo"ing may !e difficult or painful Patients may eperience a glo!us sensation of a lump in the throat Aoarseness or loss of voice is a $ey manifestation of laryngeal involvement eatures of "hooping cough (pertussis) are as follo"s0 • • • •
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3he classic sound !et"een is an inspiratory gasping suea$ that rises in pitch, typically"hoop interspersed hac$ing coughs
3he "hoop is more common in children %oughing often comes in paroysms of a do?en coughs or more at a time and is often "orst at night 3he 7 classic phases of "hooping cough are as follo"s0 %atarrhal (C-5: days) "ith predominantly URI symptoms Paroysmal (5-D "ee$s) "ith episodic cough %onvalescent (C-5: days) of gradual recovery 4@6 +ee %linical Presentation for Presentation for more detail. • •
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iagnosis 3ests of nasopharyngeal nasophar yngeal specimens for specific pathogens are helpful he lpful "hen targeted therapy depends on the results (eg, group streptococcal infection, gonococcus, pertussis). +pecific !acterial or viral testing is also "arranted in other selected situations, such as "hen patients are immunocompromised, during certain out!rea$s, or to provide specific therapy to contacts. iagnosis of specific disorders is !ased on the follo"ing0 'roup streptococcal infection0 %linical findings or a history of eposure to a case, supported !y results of rapid-detection assays and cultures (positive rapid antigen detection tests do not necessitate a !ac$up culture) cute !acterial rhinosinusitis0 #a!oratory studies are generally not indicated2 %omputed tomography (%3) scanning or other sinus imaging may !e appropriate if symptoms persist despite therapy or if complications (eg, etension of disease into surrounding tissue) are suspected Influen?a0 Rapid tests have over C: sensitivity and more than ;: specificity &ononucleosis0 Aeterophile anti!ody testing (eg, &onospot) Aerpes simple virus infection0 %ell culture or polymerase chain reaction (P%R) assay Pertussis0 Rapid tests2 culture of a nasopharyngeal aspirate (criterion standard) Epiglottitis0 irect visuali?ation !y laryngoscopy, l aryngoscopy, performed !y an otorhinolaryngologist 'onococcal pharyngitis0 3hroat culture for Neisseria gonorrhoeae Flood cultures are typically appropriate only in hospitali?ed patients "ith suspected systemic illness. Imaging studies are "arranted in patients "ith suspected mass lesions (eg, peritonsillar a!scess, intracranial suppurative •
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+ee >or$up >or$up for for more detail. &anagement +ymptom-!asedtherapy represents the mainstay of URI treatment in immunocompetent adults. ntimicro!ial or antiviral therapy is appropriate in selected patients. Epiglottitis • •
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Immediately admit the patient to the nearest hospital void instrumentation2 insertion of tongue depressors or other instruments may provo$e air"ay spasm and precipitate respiratory compromise &onitor for respiratory fatigue, visually and "ith continuous pulse oimetry dminister oygen according to pulse oimetry results Aave euipment and personnel availa!le for immediate intu!ation if necessary +tart intravenous (I*) anti!iotics after collecting culture specimens Empiric coverage for Haemophilus influenzae is appropriate2 common choices include ceftriaone or other third-generation cephalosporins, cefuroime, and cefamandole %orrect volume deficits "ith I* fluids2 avoid sedatives
Laryngotracheitis •
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Aospitali?ation may !e necessary, especially in infants and young children "ho have hypoemia, volume depletion, a ris$ of air"ay compromise, or respiratory fatigue &ild cases of croup (ie, laryngotracheo!ronchitis) may !e managed at home "ith moist air inhalation Aospitali?ed patients reuire monitoring for respiratory fatigue, visually and "ith continuous pulse oimetry Epertise for immediate intu!ation and access to the necessary euipment are reuired if respiratory failure is a possi!ility dminister humidified oygen to all hypoemic patients. In patients "ho do not reuire oygen therapy, a cool-mist humidifier may !e used I* or oral glucocorticoids are commonly used to reduce symptoms and shorten hospitali?ation in patients "ith moderate to severe croup Inhaled racemic epinephrine may temporarily dilate the air"ays
Rhinosinusitis •
&ost cases of acute rhinosinusitis, including mild and moderate !acterial sinusitis, resolve "ithout anti!iotics 4D6
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%onsider anti!iotic treatment if symptoms persist "ithout improving for 5: or more days, or if symptoms are severe or "orsening during a period of 7-B days or longer 4C6 'ive first-line anti!iotics for @-C days in most adults2 for 5:-5B days in children Fegin treatment "ith an agent that most narro"ly covers li$ely pathogens, including Streptococcus pneumoniae, nontypea!le H influenzae, andora!ella catarrhalis Initial first-line options include amoicillinGclavulanate lternatives in penicillin-allergic patients are doycycline and respiratory fluorouinolones (eg, levofloacin, moifloacin) In patients "ho "orsen or do not improve after 7-@ days of empirical therapy, consider resistant pathogens, structural a!normality, or noninfectious etiology d/unctive therapy for adults includes nasal saline irrigation and intranasal steroids
GroupHral A streptococcal disease penicillin or amoicillin for 5: days for patients "ithout an allergy to •
penicillin If compliance is a concern, consider a single I& in/ection of !en?athine penicillin ' first-generation cephalosporin may !e used in patients "ith nonanaphylactic penicillin allergy Hptions for penicillin-allergic patients include clindamycin or clarithromycin for 5: days or a?ithromycin for @ days 4=6 +ee 3reatment 3reatment and and &edication &edication for for more detail. •
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Fac$ground Upper respiratory tract infection (URI) represents the most common acute illness evaluated in the outpatient setting. URIs range from the common cold —typically a mild, self-limited, catarrhal syndrome of the nasopharyn—to lifethreatening illnesses such as epiglottitis. *iruses account for most URIs (see Etiology). ppropriate management in these cases may consist of reassurance, education, and instructions for symptomatic home treatment. iagnostic tests for specific agents are helpful "hen targeted URI therapy depends on the results (see >or$up). Facterial primary infection or superinfection may reuire targeted therapy (see 3reatment). 3he upper respiratory tract includes the sinuses, nasal passages, pharyn, and laryn, "hich serve as gate"ays to the trachea, !ronchi, and pulmonary
alveolar spaces. Rhinitis, pharyngitis, sinusitis, epiglottitis, laryngitis, and tracheitis are specific manifestations of URIs. urther information can !e found in the &edscape Reference articles cute articles cute #aryngitis, #aryngitis, cute +inusitis,, llergic Rhinitis, +inusitis Rhinitis, Facterial 3racheitis, 3racheitis, %roup %roup,, Epiglottitis Epiglottitis,, Pharyngitis Pharyngitis,, and *iral Pharyngitis. Pharyngitis. %ommon URI terms are defined as follo"s0 • •
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Rhinitis0 Inflammation of the nasal mucosa Rhinosinusitis or sinusitis0 Inflammation of the nares and paranasal sinuses, including frontal, ethmoid, maillary, and sphenoid 1asopharyngitis (rhinopharyngitis or the common cold)0 Inflammation of the nares, pharyn, hypopharyn, uvula, and tonsils Pharyngitis0 Inflammation of the pharyn, hypopharyn, uvula, and tonsils Epiglottitis (supraglottitis)0 Inflammation of the superior portion of the laryn and supraglottic area #aryngitis0 Inflammation of the laryn
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#aryngotracheitis0 Inflammation of the laryn, trachea, and su!glottic area 3racheitis0 Inflammation of the trachea and su!glottic area
Pathophysiology URIs involve direct invasion of the mucosa lining the upper air"ay. Inoculation of !acteria or viruses occurs "hen a persons hand comes in contact "ith pathogens and the person then touches the nose or mouth or "hen a person directly inhales respiratory droplets from an infected person "ho is coughing or snee?ing. fter inoculation, viruses and !acteria encounter several !arriers, including physical, mechanical, humoral, and cellular immune defenses. Physical and mechanical !arriers include the follo"ing0 Aair lining the nose filters and traps some pathogens &ucus coats much of the upper respiratory tract, trapping potential invaders 3he angle resulting from the /unction of the posterior nose to the pharyn causes large particles to impinge on the !ac$ of the throat %iliated cells lo"er in the respiratory tract trap and transport pathogens up to the pharyn2 from there they are s"allo"ed into the stomach denoids and tonsils contain immune cells that respond to pathogens. Aumoral immunity (immunoglo!ulin ) and cellular immunity act to reduce infections throughout the entire respiratory tract. Resident and recruited • •
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macrophages, monocytes, neutrophils, and eosinophils coordinate to engulf and destroy invaders. host of inflammatory cyto$ines mediates the immune response to invading pathogens. 1ormal nasopharyngeal flora, including various staphylococcal and streptococcal species, help to defend against potential pathogens. Patients "ith su!optimal humoral and phagocytic immune function are at increased ris$ for contracting a URI, and they are at increased ris$ for a severe or prolonged course of disease. Inflammation (chronic or acute) from allergy predisposes to URI. %hildren "ith allergy are particularly su!/ect to freuent URIs. "nfection
Person-to-person spread of viruses accounts for most URIs. Aousehold and child care settings can serve as reservoirs for infection. Facterial infections may develop de novo or as a superinfection of a viral URI. *iral agents occurring in URIs include a vast num!er of serotypes, "hich undergo freuent changes in antigenicity, posing challenges to immune defense. Pathogens resist destruction !y a variety of mechanisms, including the production ofof toins, proteases, andphagocytosis. !acterial adherence factors, as "ell as the formation capsules that resist Incu!ation times !efore the appearance of symptoms vary among pathogens. Rhinoviruses and group streptococci may incu!ate for 5-@ days, influen?a and parainfluen?a may incu!ate for 5-B days, and respiratory syncytial virus (R+*) may incu!ate for a "ee$. Pertussis typically incu!ates for C-5: days, or even as long as =5 days, !efore causing symptoms. iphtheria incu!ates for 5-5: days. 3he incu!ation period of Epstein-Farr virus (EF*) is B-D "ee$s. &ost symptoms of URIs—including local s"elling, erythema, edema, secretions, and fever—result from the inflammatory response of the immune system to invading pathogens and from toins produced !y pathogens. n initial nasopharyngeal infection may spread to ad/acent structures, resulting in the follo"ing0 +inusitis Htitis media Epiglottitis #aryngitis 3racheo!ronchitis Pneumonia Inflammatory narro"ing at the level of the epiglottis and laryn may result in a dangerous compromise of airflo", especially in children, in "hom a small reduction in the luminal diameter of the su!glottic laryn and trachea may !e • • • • • •
critical. Feyond childhood, laryngotracheal inflammation may also pose serious threats to individuals "ith congenital or acuired su!glottic stenosis. Susceptibility
'enetic suscepti!ility is involved in determining "hich patients have more severe disease courses than others. 3here are some recogni?ed candidate gene polymorphisms "ith $no"n functional changes in genes that may lead to immunosuppression. 4 4886 It has also !een sho"n that host immunogenetic variation plays a role in the immune response to A515 and A@15 viruses, there!y influencing disease severity and outcome in influen?a caused !y 5:66 these viruses. 4;, 5:
Etiology &ost URIs are viral in origin. 3ypical viral agents that cause URIs include the follo"ing0 Rhinoviruses %oronaviruses denoviruses %osac$ieviruses or the most part, similar agents cause URI in adults and children2 ho"ever,ora!ella catarrhalis and !ocavirus cause URIs more commonly in children than in adults. • • • •
1asopharyngitis Hf the more than =:: viruses $no"n to cause the symptoms of the common cold, the principal ones are as follo"s0 Rhinoviruses0 3hese cause approimately 7:-@: of colds in adults2 they gro" optimally at temperatures near 7=.89% (;59), "hich is the temperature inside the human nares %oronaviruses0 >hile they are a significant cause of colds, eact case num!ers are difficult to determine !ecause, unli$e rhinoviruses, coronaviruses are difficult to culture in the la!oratory Enteroviruses, including cosac$ieviruses, echoviruses, and others Hther viruses that account for many URIs include the follo"ing0 denoviruses Hrthomyoviruses (including influen?a and F viruses) Paramyoviruses (eg, parainfluen?a virus 4PI*6) R+* EF* Auman metapneumovirus (h&P*) •
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Focavirus0 %ommonly associated "ith nasopharyngeal symptoms in 5566 children 455 Unidentified, !ut presuma!ly viral, pathogens account for more than 7: of common colds in adults. In addition, varicella, ru!ella, and ru!eola infections may manifest as nasopharyngitis !efore other classic signs and symptoms develop. •
Pharyngitis 3his is most often viral in origin. Recognition Recogn ition of group streptococcal pharyngitis is vital !ecause serious complications may follo" untreated disease. *iral causes of pharyngitis include the follo"ing0 denovirus0 &ay also cause laryngitis and con/unctivitis Influen?a viruses %osac$ievirus Aerpes simple virus (A+*) EF* (infectious mononucleosis) %ytomegalovirus (%&*) Facterial causes of pharyngitis include the follo"ing0 'roup streptococci (approimately @-5@ of all cases of pharyngitis phar yngitis in 4=6 adults2 =:-7: in children) 'roup % and ' streptococci • • • • • •
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Neisseria gonorrhoeae Arcanobacterium Arcanobacteriu m ( #orynebacterium) hemolyticum #orynebacterium diphtheriae typical !acteria (eg, ycoplasma pneumoniae and #hlamydia pneumoniae2 a!sent lo"er respiratory tract disease, the clinical
significance of these pathogens is uncertain) naero!ic !acteria
Rhinosinusitis Rhinosinusitis in an immunocompetent person is typically related to an uncomplicated viral URI. *iral causes are similar to those of viral nasopharyngitis and include the follo"ing0 Rhinovirus Enterovirus %oronavirus Influen?a and F virus PI* • • • • •
R+* denovirus Facterial causes are similar to those seen in otitis media. Facterial pathogens isolated from maillary sinus aspirates of patients "ith acute !acterial rhinosinusitis include the follo"ing 4 4CC6 0 Streptococcus Streptococcu s pneumoniae0 78 in adults, =5-77 in children Haemophilus influenzae0 7D in adults, 75-7= in children ora!ella catarrhalis0 5D in adults2 8-55 in children Staphylococcus Staphylococcu s aureus0 57 in adults, 5 in children Hther pathogens include includ e group streptococci streptococci and other streptococcal species. Uncommon causes include # pneumoniae, Neisseria species, anaero!es, and gram-negative rods. 1osocomial sinusitis often involves pathogens that coloni?e the upper respiratory tract and migrate into the sinuses. Prolonged endotracheal intu!ation places patients at increased ris$ for nosocomial sinusitis. ðicillin-resistant S aureus(&R+) is less common than sensitive • •
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coli,$seudomonas nas staphylococci. aeruginosa) are 'ram-negative other causes. !acilli (eg,Escherichia coli,$seudomo Aspergillus species are the leading causes of noninvasive fungal sinusitis. lthough fungi are part of the normal flora of the upper air"ays, they may cause acute sinusitis in patients "ith immunocompromise or dia!etes mellitus.
Epiglottitis 3his is a !acterial infection. In the vast ma/ority of children, H influenzae type ! (Ai!) is isolated from !lood or epiglottal cultures. +ince the routine use of the Ai! con/ugate vaccine !egan in 5;;:, case rates in children younger than @ years have declined !y more than ;@. 3he prevalence of invasive Ai! 5=66 disease is approimately 5.7 cases per 5::,::: children. 45= Rates in adults have remained lo" and sta!le2 las$an 1atives have the highest rates of disease. Hther !acteria, found more commonly in adults than in children, include group streptococci, S pneumoniae, and catarrhalis. In adults, cultures are most li$ely to !e negative. #aryngotracheitis %roup, or laryngotracheo!ronchitis, is typically caused !y PI* type 5, =, or 7. PI*s account for up to 8: of croup cases. PI* type 5 is the leading cause of 5766 croup in children. 457 Hther viruses include influen?a viruses and R+* R+*.. Uncommon causes include h&P* h&P*,, adenovirus, rhinovirus, enterovirus
(including cosac$ievirus and enteric cytopathic human orphan 4E%AH6 viruses), and measles virus. pproimately ;@ of all cases of "hooping cough are caused !y the gramnegative rod %ordetella pertussis. 3he remaining cases result from % parapertussis. Hther forms of laryngitis and laryngotracheitis are typically caused !y viruses similar to those that cause nasopharyngitis, including rhinovirus, coronavirus, adenovirus, influen?a virus, parainfluen?a virus, and a nd R+*. #andida species may cause laryngitis in immunocompromised hosts. 5B66 Facterial laryngitis is far less common than viral laryngitis. 45B Facterial causes include the follo"ing0'roup streptococci #orynebacterium diphtheriae, an aero!ic gram-positive rod that may infect only the laryn or may represent an etension of nasopharyngeal infection •
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#hlamydia pneumoniae ycoplasma pneumoniae ora!ella catarrhalis H influenzae S aureus ycobacterium tuberculosis0 3u!erculosis has !een reported in renal
transplant recipients transplant recipients and human immuno immunodefici deficiency ency virus (AI*) infect infected ed patients Ris$ factors for URIs Ris$ factors for contracting a URI include the follo"ing0 %ontact0 %lose contact "ith small children "ho freuent group settings, such as school or daycare, increases the ris$ of URI, as does the presence of URI in the household or family Inflammation0 Inflammation and o!struction from allergic rhinitis or asthma can predispose to infections 3ravel0 3he incidence of contracting a URI is increased !ecause of eposure to large num!ers of individuals in closed settings +mo$ing and eposure to second-hand smo$e0 3hese may alter mucosal resistance to URI Immunocompromise that affects cellular or humoral immunity0 >ea$ened immune function may result from splenectomy, AI* infection, use of corticosteroids, immunosuppressive treatment after stem cell or organ transplantation, multiple medical pro!lems, or common stress2 cilia •
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dys$inesia syndrome and cystic fi!rosis also predispose individuals to URIs
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natomic changes due to facial dysmorphisms, previous upper air"ay trauma, and nasal polyposis %arrier state0 lthough some people are ar e chronic carriers of group streptococci, repeated URIs in such patients may !e viral in origin 4=6
Epidemiology URIs are thecause mostof common illness in the general population are the leading missed infectious days at "or$ or school. 3hey represent theand most 5@66 freuent acute diagnosis in the office setting. 45@ 1asopharyngitis 3he incidence of the common cold varies !y age. Rates are highest in children younger than @ years. %hildren "ho attend school or day care are a large reservoir for URIs, and they transfer infection to the adults "ho care for them. In the first year after starting at a ne" school or day care, children eperience more infections, as do their family mem!ers. %hildren have a!out 7-8 viral respiratory illnesses per year, adolescents and adults have approimately =-B colds annually, and people older than D: years have fe"er than 5 cold per year. Pharyngitis 5@66 cute pharyngitis accounts for 5 of all am!ulatory office visits. visits. 45@ 3he incidence of viral and !acterial pharyngitis pea$s in children aged B-C years.
Rhinosinusitis +inusitis is common in persons "ith viral URIs. 3ransient changes in the paranasal sinuses are noted on computed tomography (%3) scans in more 5D66 than 8: of patients "ith uncomplicated viral URIs. 4 45D Ao"ever, !acterial rhinosinusitis occurs as a complication in only a!out = of persons "ith viral 5C66 URIs. 45C Epiglottitis
3he occurrence of epiglottitis has decreased dramatically in the United +tates and other developed nations since the introduction of Ai! vaccine. +"edish study documented that the Ai! vaccination program "as associated "ith a decrease in the overall annual incidence of acute epiglottitis from B.@ cases to :.;8 cases per 5::,::: population2 the incidence decreased in children and adults. Ao"ever, the annual incidence of pneumococcal epiglottitis in adults increased from :.5 to :.=8 cases per 5::,::: population over the same 5866 period. 458 #aryngitis and laryngotracheitis
%roup, or laryngotracheo!ronchitis, may affect people of any age !ut usually occurs in children aged D months to D years. 3he pea$ incidence is in the second year of life. 3hereafter, the enlarging cali!er of the air"ay reduces the severity of the manifestations of su!glottic inflammation. *accination *a ccination has dramatically dramaticall y reduced rates of pertussis. Ao"ever, the incidence of "hooping cough in the United +tates has increased steadily since =::C, reaching approimately ; cases per 5::,::: population in =:5:. Rates of pertussis are highest in infants !elo" age 5 year2 adolescents and adults accounted for approimately BB of the =C,@@: cases of pertussis 5;66 reported in the United +tates in =:5:. 4 45; >orld"ide, pertussis has an estimated incidence of B8.@ million cases and causes nearly =;@,::: deaths per year. In lo"-income countries, the case=:66 fatality rate among infants may !e as high as B. 4=: lthough pertussis is a nationally notifia!le disease in the United +tates, many cases li$ely go undiagnosed and unreported. Hn the other hand, challenges in la!oratory diagnosis and overreliance on polymerase chain reaction (P%R) assays have resulted in reports of respiratory illness out!rea$s mista$enly 4=5 =566
attri!uted to pertussis. Hccurrence rate of selected pathogens 'roup streptococcal !acteria cause approimately app roimately @-5@ of all a ll pharyngitis 4=6 infections, accounting for several million cases of streptococcal pharyngitis each year. 3his infection is rarely diagnosed in children younger than = years. Influen?a affects approimately @-=: of the U+ population during each flu ==66 season.4== Early presentations include symptoms of URI. EF* infection affects as many as ;@ of merican adults !y age 7@-B: years. %hildhood EF* infection is indistinguisha!le from other transient childhood infections. pproimately 7@-@: of adolescents and young adults "ho =766 contract EF* infection have mononucleosis. 4 4=7 iphtheria rates fell dramatically in the United +tates after the advent of diphtheria vaccine. +ince 5;8:, the prevalence of diphtheria has !een approimately :.::5 case per 5::,::: population. confirmed case of the =B66 disease has not !een reported in the United +tates since =::7. 4=B Ao"ever, diphtheria remains endemic in developing countries. +easonality lthough URIs may occur year round, in the United +tates most colds occur during fall and "inter. Feginning Feginning in late ugust or early +eptem!er, rates of colds increase over several "ee$s and remain elevated until &arch or =@66 pril. 4=@ Epidemics and mini-epidemics are most common during cold months, "ith a pea$ incidence from late "inter to early spring.
%old "eather results in more time spent indoors (eg, at "or$, home, school) and close eposure to others "ho may !e infected. Aumidity may also affect the prevalence of colds, !ecause most viral URI agents thrive in the lo" humidity that is characteristic of "inter months. #o" indoor air moisture may increase fria!ility of the nasal mucosa, increasing a persons suscepti!ility to infection. #aryngotracheo!ronchitis, or croup, occurs in fall and "inter. +easonality does not affect rates of epiglottitis. 3he figure !elo" illustrates the pea$ incidences of various agents !y season. Rhinoviruses, "hich account for a su!stantial percentage of URIs, are most active in spring, summer, and early autumn. %oronaviral URIs manifest primarily in the "inter and early spring. Enteroviral URIs are most noticea!le in summer and early fall, "hen other URI pathogens are at a nadir. denoviral respiratory infections can occur throughout the year !ut are most common in the late "inter, spring, and early earl y summer.
variation of selected upper respiratory tract infection pathogens. PI* +easonal is parainfluen?a virus, R+* is respiratory syncytial virus, &P* is metapneumovirus, metapn eumovirus, and 'roup +trept is group streptococcal disease. *ie" &edia 'allery +easonal influen?a typically lasts from 1ovem!er until &arch. +ome PI*s have a !iennial pattern. 3he patterns for human PI* types 5-7 are as follo"s0 Auman PI* type 50 %urrently produces autumnal out!rea$s in the United +tates during odd-num!ered years2 the leading cause of croup in children Auman PI* type =0 &ay cause annual or !iennial fall out!rea$s •
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Aumanho"ever, PI* type the 70 Pea$ during the spring and 4576 months2 virusactivity may !eisisolated throughout theearly year.summer
Auman metapneumovirus (h&P*) infection may also occur year round, although the infection rates pea$ !et"een ecem!er and e!ruary. Race- and se-related demographics 1o nota!le racial difference is o!served "ith URIs. Ao"ever, las$an 1atives 5=66 have rates of Ai! disease higher than those of other groups. 45= +eual disparities among URIs are as follo"s0 Rhinitis0 Aormonal changes during the middle of the menstrual cycle and during pregnancy may produce hyperemia of the nasal and sinus mucosa and increase nasal secretions2 URI may !e superimposed over these !aseline changes and may increase the intensity of symptoms in some "omen 1asopharyngitis0 3he common cold occurs freuently in "omen, =@66 especially those aged =:-7: years 4=@ 2 this freuency may represent increased eposure to small children, "ho represent a large reservoir for URIs, !ut hormonal effects on the nasal mucosa may also play a role Epiglottitis0 male predominance is reported, "ith a male-to-female •
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ratio of approimately 70= #aryngotracheo!ronchitis, or croup0 &ore common in !oys than in girls, "ith a male-to-female ratio of approimately 70=
ge-related demographics 3he incidence of the common cold varies !y age. Rates are highest in children younger than @ years. %hildren have approimately 7-8 viral respiratory illnesses per year, "hile adolescents and adults have approimately =-B colds a year, and people older than D: years have fe"er than 5 cold per year. 3he age-related occurrence of other infections is as follo"s0 • •
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*iral and !acterial pharyngitis0 Pea$s in children aged B-C years. Epiglottitis0 3ypically occurs in children aged =-C years and has a pea$ incidence in those aged 7 years #aryngotracheo!ronchitis (croup)0 (croup) 0 s s previously stated, it may affect people of any age !ut usually occurs in children aged D months to D years2 the pea$ incidence is in the second year of life
Prognosis URIs cause people to spend time a"ay from their usual daily activities, !ut alone, these infections rarely cause permanent seuelae or death. URIs may, ho"ever, serve as a gate"ay to infection of ad/acent structures, resulting in the follo"ing infections (and others, as "ell)0 Htitis media •
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Fronchitis Fronchiolitis Pneumonia +epsis &eningitis
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Intracranial a!scess +erious complications may result in clinically significant mor!idity and rare deaths. 1asopharyngitis common cold may last up to 5B days, "ith symptoms averaging C-55 C-55 days in 5C66 duration. 4 45C ever, snee?ing, and sore throat typically typicall y resolve early, "hereas cough and nasal discharge are among the symptoms that last longest. ttendance at day care may affect the duration of symptoms symptoms in young children. In one study, the duration of viral URIs ranged from D.D days for children years in home care to 8.;indays children younger year "hoaged "ere5-= in day care. Joung children day for care "ere also morethan li$ely5 =D66 to have protracted respiratory symptoms lasting more than 5@ days. 4=D &ost patients "ith influen?a recover "ithin a "ee$, although cough, fatigue, and malaise may persist for up to = "ee$s. or ne"!orns, elderly persons, and patients "ith chronic medical conditions, the flu may !e life threatening. &ore than =::,::: people per year are hospitali?ed !ecause of complications of the flu, "ith :.7D deaths per 5::,::: patients occurring =C66 annually. 4=C Influen?a may !e follo"ed !y !acterial superinfection. Pharyngitis *iral pharyngitis typically resolves in 5-= "ee$s, !ut immunocompromised persons may have a more severe course. Untreated group streptococcal streptococcal pharyngitis can result in the follo"ing0 cute rheumatic fever cute glomerulonephritis Peritonsillar a!scess 3oic shoc$ syndrome Impetigo %ellulitis or a!scess Htitis +inusitis • • • • • • • • •
%on/unctivitis
Fronchitis &ortality from group streptococcal pharyngitis is rare, !ut serious mor!idity or death may result from one of its complications. +treptococcal pharyngitis "ithout complications rarely poses significant ris$ for mor!idity. Ao"ever, Ao"ever, retropharyngeal, intraor!ital, or intracranial a!scesses may cause serious seuelae. 3he ris$ of mortality is significant in patients "ho progress to streptococcal toic shoc$ syndrome, "hich is characteri?ed !y multiorgan failure and hypotension. In patients "ith penicillin-sensitive streptococcal pharyngitis, symptomatic improvement is epected "ithin =B-C= hours if anti!iotic treatment is started in the first =B hours after onset. 3reatment failures are common and are mainly attri!uted to poor adherence, anti!iotic resistance, and untreated close contacts, usually "ithin the household or family. chronic carrier state may develop "ith group streptococcal infection. Eradicating the pathogen is difficult in these cases2 ho"ever, carriers "ithout active symptoms are unli$ely unli$el y to spread group grou p streptococci, and they are at lo" ris$ for developing rheumatic fever. •
ononucleosis
>ith infectious mononucleosis from EF*, complete resolution of symptoms may ta$e up to = months. cute symptoms rarely last more than B months. EF* typically remains dormant throughout the patients life. Reactivation of the virus is not usually symptomatic. Rhinosinusitis 3he prognosis is generally favora!le for acute rhinosinusitis, and many cases appear to resolve reso lve even "ithout anti!iotic a nti!iotic therapy. s many as C: of immunocompetent adults "ith rhinosinusitis !egin to improve "ithin = "ee$s of presentation "ithout anti!iotics. >ith anti!iotics, up to 8@ have improvement "ee$s. resolution may ta$e "ee$s to months. +inusitis itselfat is =rarely life%omplete threatening, !ut it can lead to serious complications if the infection etends into surrounding deep tissue, including the follo"ing0 Hr!ital cellulitis +u!periosteal a!scess Hr!ital a!scess rontal and maillary osteomyelitis +u!dural a!scess &eningitis Frain a!scess • • • • • • •
Epiglottitis
Epiglottitis poses a ris$ of death due to sudden air"ay o!struction and other complications, including septic arthritis, meningitis, empyema, and mediastinitis. In adults, epiglottitis has a fatality rate of approimately 5. 3he prognosis is favora!le "ith appropriate air"ay management, and most patients noticea!ly improve "ithin =B-B8 hours after anti!iotics are started. Rarely, cases of epiglottitis may ma y recur. Recurrent symptoms raise concern a!out potential underlying disorders, such as rheumatic conditions, sarcoidosis, and occult malignancy. m alignancy. #aryngitis and laryngotracheitis >ith croup, laryngotracheo!ronchitis typically !egins to improve "ithin 7-B days. Recovery is usually complete. Ao"ever, patients may have a recurrence, including during the same season. Pertussis ("hooping cough) leads to hospitali?ation in more than half of infants younger than 5= months and particularly in infants younger than D months. Infants and young children are most suscepti!le to severe courses that include respiratory compromise. Hf infants "ho are hospitali?ed "ith approimately @::.7 havehave apnea, =: develop pneumonia, 5pertussis, have sei?ures, 5 die, and =866 encephalopathy. 4=8 Recovery from "hooping cough is typically complete. Ao"ever, paroysms of coughing may last for several "ee$s. %omplications &ost URIs are self-limited and a nd resolve completely. Ao"ever, a variety of conditions may complicate a URI. luid loss may occur in patients una!le to tolerate adeuate oral inta$e !ecause of upper air"ay inflammation or may result from fever. Htitis media may complicate @ of colds in children and up =;66 to = of colds in adults 4=; ir"ay hyperreactivity may increase after a URI, resulting in ne" or eacer!ated asthma. %ough asthma, "herein a cough is the predominant manifestation of reactive air"ays disease, may mimic ongoing infection. 3his may !e diagnosed "ith pulmonary function testing. postinfectious cough is defined as coughing that persists 7-8 "ee$s after the onset of a URI in the a!sence of other clearly defined causes. Eacer!ations of chronic o!structive pulmonary disease, including emphysema and chronic !ronchitis, may occur during and after a URI. Upper air"ays cough syndrome (post-nasal drip) may result from upper air"ay secretions dripping onto the pharyn. Epistais may also occur. #o"er respiratory tract disease and sepsis represent serious complications, especially in patients "ith immunocompromise. #o"er respiratory tract disease should !e considered "hen symptoms such as fever, cough, sputum,
and malaise "orsen progressively or after initial transient improvement. 3achypnea and dyspnea are also signs of lo"er respiratory involvement. *iral infection and resulting inflammation may ma$e an individual suscepti!le to concomitant or seuential infection "ith a !acterial agent. Streptococcus pneumoniae, Staphylococcu Staphylococcus s aureus, H influenzae, and Streptococcus pyogenesare common superinfecting agents. &eningococci may cause superinfection "ith influen?al infections. Inflammation of the laryn and trachea area may lead to air"ay compromise, especially in children and in patients "ith narro"ed air"ays due to congenital or acuired su!glottic stenosis. 3he "or$ of !reathing during epiglottitis or laryngotracheitis may lead to respiratory failure. +leep apnea may occur from hypertrophied tonsils. eep tissue infection may occur !y etension of the infection into the or!it, middle ear, cranium, or other areas. Peritonsillar a!scess (uinsy) may complicate !acterial pharyngitis, leading to difficulty s"allo"ing and pain radiating to the ear. Retropharyngeal a!scess may also complicate pharyngitis. #emierre syndrome is an etension of pharyngitis that leads to a suppurative throm!ophle!itis of the internal /ugular vein2 septic throm!oem!oli may then spread throughout the !ody. %omplications of sinusitis include the follo"ing0 Hr!ital cellulitis +u!periosteal a!scess Hr!ital a!scess &astoiditis rontal or maillary osteomyelitis +u!dural a!scess %avernous sinus throm!osis • • • • • • • •
Frain a!scess +uspect a deep tissue infection "hen a patient has or!ital or perior!ital s"elling, proptosis, impaired etraocular movements, or impaired vision. +igns of increased intracranial pressure (eg, papilledema, altered mental status, neurologic findings) may suggest intracranial involvement. Encephalitis, meningitis, or su!arachnoid hemorrhage may follo" a URI. Hsteomyelitis may complicate persistent or recurrent sinusitis. Hsteomyelitis may affect the or!ital plate, frontal !one, or sphenoid !one. &ucoceles are epanding cystic defects of the paranasal sinuses that may result from prolonged sinusitis. Epiglottic a!scess may result from epiglottitis. #ymphadenitis may follo" or accompany URI. 'uillain-FarrK syndrome may manifest as an ascending polyneuropathy a fe" days or "ee$s after a URI. In children or adolescents, the use of aspirin during a viral infection may rarely
cause Reye syndrome. spirin is contraindicated for the management of fevers in children or adolescents. URI, especially "ith fever, may increase the "or$ of the heart, adding strain to persons "ith su!optimal cardiovascular status, and can lead to cardiovascular decompensation. &yositis or pericarditis may result from viral infection. Ayperglycemia may occur during a URI in patients "ith dia!etes. Ri! fracture may !e seen follo"ing an episode of severe coughing, such as that associated "ith "hooping cough. Aernia may develop follo"ing an episode of severe coughing. %utaneous complications such as rash, cellulitis, and toic shoc$ syndrome may occur "ith group streptococcus. 3his pathogen can also !e associated "ith glomerulonephritis, glomeruloneph ritis, acute rheumatic fever, and P1+ P1+ syndrome (Pediatric utoimmune 1europsychiatric isorders ssociated "ith +treptococcal infections). Aemoptysis suggests the possi!ility possi!ilit y of tu!erculosis. tu!erculin s$in test, chest radiography, or !oth are appropriate in these patients. %omplications of specific conditions #omplications of group A streptococcal disease
'roup streptococcal pharyngitis is of special speci al concern !ecause its complications include streptococcal toic shoc$ syndrome, acute rheumatic fever (R), acute glomerulonephritis, and scarlet fever, as "ell as cutaneous infections. In addition, this pathogen is readily transmissi!le, especially in households, families, and other intimate groups. R affects approimately 7 of patients "ith strep throat, primarily occurring in persons aged D-=: years. 3he condition develops approimately =-B "ee$s after streptococcal pharyngitis occurs, and it may last several months. +igns of rheumatic fever include arthritis, fever, and valvular disease. Uncommon features include an epanding truncal eanthem (erythema marginata), su!cutaneous nodules, and chorea. Poststreptococcal glomerulonephritis can affect persons of any age group, !ut it is most common in children aged 7-C years. Foys are affected slightly more often than girls. Patients "ith glomerulonephritis may have loss of appetite, lethargy, dull !ac$ pain, and dar$ urine. Flood pressure may !e elevated, and edema may occur. +carlet fever is a self-limited eanthem that spreads from the chest and a!domen to the entire !ody. 3iny red papules create a rough s$in teture similar to that of sandpaper. 3he rash is typically !lanching. lthough it commonly affects the face, circumoral pallor p allor is present. uring uring recovery, the s$in on the fingers and toes peels. +treptococcal toic shoc$ syndrome may also occur, affecting s$in and mucosa.
P1+ is a rare syndrome in children and adolescents, "ho eperience sudden onset or "orsening of o!sessive-compulsive disorder follo"ing streptococcal infection. ssociated manifestations include tics and a variety of 7:66 neuropsychiatric symptoms. 47: #omplications of mononucleo mononucleosis sis
%omplications can include the follo"ing0 +plenic rupture Aepatitis 'uillain-FarrK syndrome Encephalitis Aemolytic anemia granulocytosis &yocarditis Fur$itt lymphoma 1asopharyngeal carcinoma Rash ("ith concomitant use of ampicillin) • • • • • • • • • •
#omplications of diphtheria
%omplications may include air"ay o!struction, myocarditis, polyneuritis, throm!ocytopenia, and proteinuria. mong patients "ho survive diphtheria, as 5766 many as =: have permanent hearing loss or other long-term seuelae. 457 #omplications from pertussis
&ore than half of infants younger than 5= months "ho contract pertussis reuire hospitali?ation, especially those "ho are younger than D months. =866 %omplications of pertussis in hospitali?ed infants include the follo"ing 4=8 0 pnea (@:) Pneumonia (=:) +ei?ures (5) Encephalopathy (:.7) eath (5) In addition, severe cough may result in ri! fractures, hernia, incontinence, or su!con/unctival hemorrhages. • • • • •
#omplications of influenza
3hese include the follo"ing0 Facterial superinfection Pneumonia *olume *o lume depletion dep letion &yositis • • • •
•
Pericarditis
• • • • •
Rha!domyolysis Encephalitis &eningitis &yelitis Renal failure
isseminated intravascular coagulation s "ith any systemic infection, the flu flu poses a ris$ of "orsening underlying medical conditions, such as heart failure, asthma, or dia!etes. fter influen?al infection, children may eperience sinus pro!lems or otitis media. •
Patient Education ddress the patients epectations a!out anti!iotic therapy. *a *alidate lidate the patients symptoms and their severity, listen to the concerns epressed, and educate the patient a!out possi!le conseuences of inappropriate anti!iotic use, including conseuences affecting himGher and the community. &any people hold misperceptions a!out the duration and intensity of symptoms associated "ith URI and a!out the !enefits and ris$s of anti!iotic therapy. +ome are una"are that cold symptoms may last as long as 5B days. +ome !elieve that anti!iotics "ill help them to avoid serious disease and recover more uic$ly than "ithout treatment. Patients may epect to receive anti!iotics solely !ased on the severity of their symptoms, and they may not appreciate the negative conseuences of using anti!iotics in viral disease. 1egative results on a rapid strep test may provide reassurance a!out the appropriateness of supportive care. ctively promote self-care, and outline a realistic time course for the resolution of symptoms. Reassure the patient a!out access to clinical care and follo"-up in the event that symptoms progress. Friefly eplore factors that may have contri!uted to the current infection, and address prevention for the future. Patient satisfaction is less lin$ed tointeraction. anti!iotic prescriptions and more lin$ed to the uality of the physician-patient Reflecting understanding of the details of the patients situation, epressing concern for the patients "ell!eing, eplaining ho" recommendations are appropriately tailored to the individuals current condition, and providing reassurance are important to patient satisfaction. Patients should !e counseled on hand"ashing and proper methods of covering coughs and snee?es. Patients "ho smo$e should receive smo$ing cessation encouragement and materials. >hen anti!iotics are prescri!ed, patients should !e instructed to complete the full course of anti!iotic therapy. Patients should !e instructed to follo" up "hen indicated or if symptoms "orsen. inally, patients "ith infectious mononucleosis should !e instructed to avoid contact sports for D "ee$s !ecause of the possi!ility of splenic rupture.
or patient education information, see the Aeadache and &igraine %enter , as "ell as +inus Infection and Infection and +ore 3hroat. 3hroat.
Practice Essentials Aypertension affects approimately 8D million adults (hitehall II cohort, "ith 7 years follo"-up of an occupational cohort in previously healthy patients, investigators reported 5@.; of the patient sample developed hypertension in
response to la!oratory-induced mental stressors and found an association =:66 !et"een cortisol stress reactivity and incident hypertension. 4=:
Etiology Aypertension may !e primary, "hich may develop as a result of environmental or genetic causes, or secondary, "hich has multiple etiologies, including renal, vascular, and causes. or essential accounts for ;:-;@ of endocrine adult cases, and a Primary small percentage of hypertension patients (=-5:) have a secondary cause. Aypertensive emergencies are most often precipitated !y inadeuate medication or poor compliance. Environmental and geneticGepigenetic causes Aypertension develops secondary to environmental factors, as "ell as 5=,, =5 =566 multiple genes, "hose inheritance appears to !e comple. 4 45= urthermore, o!esity, dia!etes, and heart disease also have genetic components and contri!ute to hypertension. Epidemiological studies using t"in data and data from ramingham Aeart +tudy families reveal that FP has a su!stantial ==,, =7 =7,, =B =B66 herita!le component, ranging from 77-@C. 4 4== In an attempt to elucidate the genetic components of hypertension, multiple genome "ide association studies ('>+) have !een conducted, revealing multiple gene loci in $no"n path"ays of hypertension as "ell as some novel =@66 genes "ith no $no"n lin$ to hypertension as of yet. 4=@ urther research into these novel genes, some of "hich are immune-related, "ill li$ely increase the understanding of hypertensions pathophysiology, allo"ing for increased ris$ stratification and individuali?ed treatment. Epigenetic phenomena, such as 1 methylation and histone modification, have also !een implicated in the pathogenesis of hypertension. or eample, a high-salt diet appears to unmas$ nephron development caused !y methylation. &aternal "ater deprivation and protein restriction during pregnancy increase renin-angiotensin epression in the fetus. &ental stress induces a 1 methylase, "hich enhances autonomic responsiveness. 3he pattern of serine protease inhi!itor gene methylation predicts preeclampsia in =D66 pregnant "omen. 4=D espite these genetic findings, targeted genetic therapy seems to have little impact on hypertension. In the general population, not only does it appear that individual and /oint genetic mutations have very small effects on FP levels, !ut it has not !een sho"n that any of these genetic a!normalities are responsi!le for any applica!le percentage of cases of hypertension in the general =C66 population. 4=C +econdary causes of hypertension related to single genes are very rare. 3hey include #iddle syndrome, glucocorticoid-remedia!le hyperaldosteronism, 55
!eta-hydroylase and 5C alpha-hydroylase deficiencies, the syndrome of apparent mineralocorticoid ecess, and pseudohypoaldosteronism type II. 4 4==6 %auses of secondary hypertension Renal causes (=.@-D) of hypertension include the renal parenchymal diseases and renal vascular diseases, as follo"s0 Polycystic $idney disease %hronic $idney disease Urinary tract o!struction Renin-producing tumor #iddle syndrome Renovascular hypertension (R*A3) causes :.=-B of cases. +ince the =866 seminal eperiment in 5;7B !y 'old!latt et al, 4=8 R*A3 has !ecome increasingly recogni?ed as an important cause of clinically atypical hypertension and chronic $idney disease—the latter !y virtue of renal ischemia. 3he coeistence of renal arterial vascular (ie, renovascular) disease • • • • •
and hypertension defines this type of"hen nonessential hypertension. &ore specific diagnosesroughly are made retrospectively hypertension is improved after intravascular intervention. *ascular *a scular causes include the follo"ing0 %oarctation of aorta *asculitis %ollagen vascular disease Endocrine causes account for 5-= and include eogenous or endogenous hormonal im!alances. Eogenous causes include administration of steroids. 3he most common form of secondary hypertension is a renal cause (although the true prevalence of hyperaldosteronism is not clear). • • •
nother common endocrine cause is oral contraceptive use. ctivation of the ctivation renin-angiotensin-aldosterone system (R+) is the li$ely mechanism, !ecause hepatic synthesis of angiotensinogen is induced !y the estrogen component of oral contraceptives. pproimately @ of "omen ta$ing oral contraceptives may develop hypertension, "hich a!ates "ithin D months after discontinuation. 3he ris$ factors for oral contraceptiveOassociated hypertension include mild renal disease, familial history of essential hypertension, age older than 7@ years, and o!esity. It "ould !e !etter to group oral contraceptives and steroids "ith drug-induced hypertension (see 3a!le 5, !elo"). Eogenous administration of the other steroids used for therapeutic purposes also increases !lood pressure (FP), especially in suscepti!le individuals, mainly !y volume epansion. 1onsteroidal anti-inflammatory drugs (1+Is)
may also have adverse a dverse effects on FP. 1+Is !loc$ !oth cyclooygenase-5 (%H-5) and %H-= en?ymes. 3he inhi!ition of %H-= can inhi!it its natriuretic effect, "hich, in turn, increases sodium retention. 1+Is also inhi!it the vasodilating effects of prostaglandins and the production of vasoconstricting factors—namely, endothelin-5. 3hese effects can contri!ute to the induction of hypertension in a normotensive or controlled hypertensive patient. Endogenous hormonal causes include the follo"ing0 Primary hyperaldosteronism %ushing syndrome Pheochromocytoma %ongenital adrenal hyperplasia 1eurogenic causes include the follo"ing0 Frain tumor utonomic dysfunction +leep apnea • • • •
• • •
Intracranial hypertension rugs and toins that cause hypertension include the follo"ing0 lcohol %ocaine %yclosporine, tacrolimus 1+Is Erythropoietin drenergic medications econgestants containing ephedrine Aer!al remedies containing licorice (including licorice root) or ephedrine •
• • • • • • • •
(and ephedra) 1icotine Hther causes include the follo"ing0 Ayperthyroidism and hypothyroidism Aypercalcemia Ayperparathyroidism cromegaly H!structive sleep apnea Pregnancy-induced hypertension H!structive sleep apnea (H+) is a common !ut freuently undiagnosed sleep-related !reathing disorder defined as an average of at least 5: apneic and hypopenic episodes per sleep hour, "hich leads to ecessive daytime •
• • • • • •
sleepiness. &ultiple studies have sho"n H+ to !e an independent ris$ factor for the development of essential hypertension, even after ad/usting for age, gender, and degree of o!esity. o !esity. pproimately half of individuals "ith hypertension have H+, and approimately half "ith H+ have hypertension. m!ulatory FP monitoring normally reveals a QdipQ in FP of at least 5: during sleep. Ao"ever, if a patient is a Qnondipper,Q the chances that the patient has H+ is increased. 1ondipping is thought to !e caused !y freuent apneicGhypopneic episodes that end "ith arousals associated "ith mar$ed spi$es in FP that last for several seconds. pneic episodes are associated "ith stri$ing increases in sympathetic nerve activity and enormous elevations of FP. FP. Individuals "ith sleep apnea have increased cardiovascular mortality, in part li$ely related to the high incidence of hypertension. lthough treatment of sleep apnea "ith continuous air"ay positive pressure (%PP) (%P P) "ould logically seem to improve %* outcomes and hypertension, h ypertension, studies evaluating this mode of therapy have !een disappointing. =:5D revie" of several studies indicated that %PP either had no effect or a modest mo dest =;66 FP-lo"ering effect. 4=; indings from +*E study sho"ed no effect of %PP 7:66 the +*E therapy on FP a!ove usual care. 4 47: It is li$ely that patients "ith sleep apnea have other etiologies of hypertension, including o!esity, hyperaldosteronism, increased sympathetic drive, and activation of the reninGangiotensin system that contri!ute to their hypertension. lthough %PP remains an effective therapy for other aspects of sleep apnea, it should not !e epected to normali?e FP in the ma/ority of patients.
%auses of hypertensive emergencies 3he most common hypertensive emergency is a rapid uneplained rise in FP in patients "ith chronic essential hypertension. &ost patients "ho develop 475 75,, 7= 7=66 hypertensive emergencies have a history of inadeuate hypertensive treatment or an a!rupt discontinuation of their medications. Hther causes of hypertensive emergencies include the use of recreational drugs, a!rupt clonidine "ithdra"al, post pheochromocytoma removal, and systemic sclerosis, as "ell as the follo"ing0 Renal parenchymal disease0 chronic pyelonephritis, primary glomerulonephritis, tu!ulointerstitial nephritis (accounts for 8: of all secondary causes) +ystemic disorders "ith renal involvement0 systemic lupus erythematosus, systemic sclerosis, vasculitides Renovascular disease0 atherosclerotic disease, fi!romuscular dysplasia, •
•
•
polyarteritis nodosa
•
•
•
•
• • •
Endocrine disease0 pheochromocytoma, %ushing syndrome, primary hyperaldosteronism 7766 rugs0 cocaine, 477 amphetamines, cyclosporine, clonidine ("ithdra"al), phencyclidine, diet pills, oral contraceptive pills rug interactions0 monoamine oidase inhi!itors "ith tricyclic antidepressants, tyramine-containing %entral nervousantihistamines, system factors0or%1+ trauma or spinal food cord disorders, such as 'uillain-FarrK syndrome %oarctation of the aorta PreeclampsiaGeclampsia Postoperative hypertension
Epidemiology Aypertension is a "orld"ide epidemic2 accordingly, its epidemiology has !een "ell studied. ata from 1ational Aealth and 1utrition Eamination +urvey (1A1E+) spanning =:55-=:5B in the United +tates found that in the population aged =: years or older, an estimated 8D million adults had hypertension, "ith a prevalence of 7B.456 Aypertension affects U+ men and "omen nearly eually, affecting an estimated B:.8 million men and BB.; million "omen. 456 'lo!ally, an estimated =D of the "orlds population (;C= million people) has hypertension, and the prevalence is epected to increase to =; !y =:=@, 7B66 driven largely !y increases in economically developing nations. 47B 3he high prevelance of hypertension eacts a tremendous pu!lic health !urden. s a primary contri!utor to heart disease and stro$e, the first and third leading causes of death "orld"ide, respectively, high !lood pressure "as the top modifia!le ris$ factor for disa!ility ad/usted life-years lost "orld"ide in 7@,, 7D 7D66 =:57. 47@ Fet"een =::D and =:55, there "as a =@ increase in the num!er of people visiting U+ emergency rooms for essential hypertension, according to an analysis of data from the 1ation"ide Emergency epartment +ample in 7C66 =:5B. 47C 3he reason for the increase, ho"ever, remained uncertain. 3he rate of emergency department visits also increased significantly, according to the study, rising from 5;:.5 visits per 5::,::: population in =::D to =78.@ visits per 5::,::: population in =:55. Hver the same period, ho"ever, admission 7C66 rates decreased, from 5:.BC in =::D to 8.8@ in =:55. 47C Emergency department visits for hypertension "ith complications and secondary hypertension also rose, from C5.= per 5::,::: population in =::D to 8B.C per 5::,::: population in =:55, "hile again, admission rates fell, dropping from CC.C; in =::D to D8.C@ in =:55. 3he in-hospital mortality
rate for admitted patients dropped as "ell, from 5.;@ in =::D to 5.=@ in 7C66 =:55. 47C Aypertension and se- and age-related statistics Until age B@ years, a higher percentage of men than "omen have hypertension2 from age B@ to DB years, the percentages are nearly eual !et"een men and "omen. Feyond age DB years, a higher percentage of 7866 "omen have hypertension than men. 4 478 Aypertension in !lac$ adults 'lo!ally, !lac$ adults have among the highest rates of hypertension, "ith an increasing prevalence. lthough "hite adults also have an increasing incidence of high FP, they develop this condition later in life than !lac$ adults and have much lo"er average FPs. In fact, compared to hypertensive "hite persons, hypertensive !lac$ individuals have a 5.7-fold higher rate of nonfatal stro$e, a 5.8-fold higher rate of fatal stro$e, a 5.@-fold higher mortality rate due to heart disease, and a B.=-fold higher rate of end-stage renal disease 478 7866
(E+R). 3a!le 5, !elo", !e lo", summari?es summari?es age-ad/usted prevalence estimates from the 1ational Aealth Intervie" +urvey (1AI+) and the 1ational %enter for Aealth +tatistics (1%A+) according to racialGethnic groups and diagnosed conditions in individuals 58 years of age and older. 3a!le 5. 1AI+G1%A+ ge-d/usted ge-d/usted Prevalence Estimates in Individuals ged 58 Jears Jears and Hlder in =:5@. (Hpen =:5@. (Hpen 3a!le 3a!le in a ne" "indo") RaceGEthnic 'roup
Aave Aypertension,
Aave Aeart isease,
Aave %oronary Aeart isease,
Aave Aad a +tro$e,
>hite only
=7.8
55.7
@.D
=.B
Flac$Gfrican merican
7B.B
;.@
@.B
7.C
AispanicG#atino
=7.:
8.=
@.5
=.B
sian
=:.D
C.5
7.C
5.B
merican IndianGlas$a IndianGlas$a 1ative
=8.B
57.C
;.7
=.= (this num!er is considered unrelia!le)
+ource0 +ummary health statistics0 1a 1ational tional Aealth Intervie" +urvey +urvey,, =:5@. vaila!le https0GGftp.cdc.govGpu!GAealth+tatisticsG1%A+G1AI+G+ alth+tatisticsG1%A+G1AI+G+A+G=:5@+A+3 A+G=:5@+A+3a!le-5.pd a!le-5.pdf f . ccessed0 at0 at0https0GGftp.cdc.govGpu!GAe 1ovem!er 5B, =:5D.
1%A+ S 1ational %enter for Aealth +tatistics2 1AI+ S 1ational Aealth Intervie" +urvey.
Prognosis &ost individuals diagnosed "ith hypertension "ill have increasing !lood pressure (FP) as they age. Untreated hypertension is notorious for increasing the ris$ of mortality and is often descri!ed as a silent $iller. &ild to moderate hypertension, if left untreated, may !e associated "ith a ris$ of atherosclerotic disease in 7: of people and organ damage in @: of people "ithin 8-5: years after onset. eath from ischemic heart disease or stro$e increases progressively as FP increases. or every =: mm Ag systolic or 5: mm Ag diastolic increase in FP a!ove 55@GC@ mm Ag, the mortality rate for !oth ischemic heart disease and stro$e dou!les. 4 4==6 Aypertensive retinopathy "as associated "ith an increased long-term ris$ of stro$e, even in patients p atients "ith "ell-controlled FP, in a report of =;:C adults ad ults "ith hypertension participating in the therosclerosis Ris$ in %ommunities (RI%) 7;,, B: B:66 study.47; Increasing severity of hypertensive retinopathy "as associated "ith an increased ris$ of stro$e2 the stro$e ris$ "as 5.7@ in the mild retinopathy group and =.7C in the moderateGsevere group. In a meta-analysis of pooled data from 5; prospective cohort studies involving CD=,7;7 patients, Auang et al reported that, after ad/ustment for multiple cardiovascular ris$ factors, prehypertension "as associated "ith a DD increased ris$ for stro$e, compared "ith an optimal !lood pressure (M5=:G8: B5,, B= B=66 mm Ag). 4B5 Patients in the high range of prehypertension (57:-57;G8@-8; mm Ag) had a ;@ increased ris$ of stro$e, compared "ith a BB increased ris$ for those in the lo" range of prehypertension (5=:-5=;G8:-8B mm 4B5 4 B5,, B= B=66
Ag). 3he mor!idity and mortality of hypertensive emergencies depend on the etent of end-organ dysfunction on presentation and the degree to "hich FP is controlled su!seuently. >ith FP control and medication compliance, the B766 5:-year survival rate of patients "ith hypertensive crises approaches C:. 4B7 In the ramingham Aeart +tudy, the age-ad/usted ris$ of congestive heart failure "as =.7 times higher in men and 7 times higher in "omen "hen the BB66 highest FP "as compared to the lo"est FP. 4BB &ultiple Ris$ actor Intervention 3rial (&RI3) data sho"ed that the relative ris$ for coronary artery disease mortality "as =.7 to D.; times higher for persons "ith mild to B@66 severe hypertension than it "as for persons "ith normal FP. 4B@ 3he relative ris$ for stro$e ranged from 7.D to 5;.=. 3he population-attri!uta!le ris$
percentage for coronary artery disease varied from =.7 to
[email protected], "hereas the population-attri!uta!le ris$ for stro$e ranged from D.8-B:. 3he ramingham Aeart +tudy found a C= increase in the ris$ of all-cause death and a @C increase in the ris$ of any cardiovascular event in patients BD66 "ith hypertension "ho "ere also diagnosed "ith dia!etes mellitus. 4BD 1ephrosclerosis is one of the possi!le complications of long-standing hypertension. 3he ris$ of hypertension-induced end-stage renal disease is higher in !lac$ patients, even "hen !lood pressure is under good control. urthermore, patients "ith dia!etic nephropathy "ho are hypertensive are also at high ris$ for developing end-stage renal disease. %omparative data from the 1A1E+ I and III sho"ed a decrease in mortality over time in hypertensive adults, !ut the mortality gap !et"een hypertensive BC66 and normotensive adults remained high. 4BC %linical trials have demonstrated the follo"ing !enefits "ith antihypertensive therapy 4=6 0 verage 7@-B: reduction in stro$e incidence verage =:-=@ reduction in myocardial infarction verage N@: reduction in heart failure &oreover, it is estimated that 5 death is prevented per 55 patients treated for stage 5 hypertension and other cardiovascular ris$ factors "hen a sustained reduction of 5= mm Ag in systolic FP over 5: years is achieved. 4=6 Ao"ever, for the same reduction is systolic FP reduction, it is estimated that 5 death is prevented per ; patients treated "hen cardiovascular disease or end-organ damage is present. 4=6 • • •
Patient Education Aypertension is a lifelong disorder. or optimal control, a long-term commitment to lifestyle modifications and pharmacologic therapy is reuired. 3herefore, repeated in-depth patient education and counseling not only improve compliance "ith medical therapy !ut also reduce cardiovascular ris$ factors. *arious strategies to decrease cardiovascular disease ris$ include the follo"ing0 Prevention and treatment of o!esity0 an increase in !ody mass inde (F&I) and "aist circumference is associated "ith an increased ris$ of developing conditions "ith high cardiovascular ris$, such as hypertension, dia!etes mellitus, impaired fasting glucose, and left B866 ventricular hypertrophy h ypertrophy 4#*A6 4#*A6 4B8 ppropriate amounts of aero!ic physical activity iets lo" in salt, total fat, and cholesterol deuate dietary inta$e of potassium, calcium, and magnesium •
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#imited alcohol consumption voidance of cigarette smo$ing voidance of the use of illicit drugs, such as cocaine %linicians may also "ish to refer patients to the follo"ing short video, "hich provides a simplified !ut clear and concise overvie" a!out "hat hypertension • • •
is, as "ell as its different stages, causes, and types.
Practice Essentials 3ype = dia!etes mellitus consists of an array of dysfunctions characteri?ed !y hyperglycemia and resulting from the com!ination of resistance to insulin action, inadeuate insulin secretion, and ecessive or inappropriate glucagon secretion. +ee the image !elo".
+implified scheme for the pathophysiology of type = dia!etes mellitus. *ie" &edia 'allery +ee %linical indings in ia!etes &ellitus, &ellitus, a %ritical Images slidesho", to help identify various cutaneous, ophthalmologic, vascular, and neurologic manifestations of &. +igns and symptoms &any patients "ith type = dia!etes are asymptomatic. %linical manifestations include the follo"ing0 %lassic symptoms0 Polyuria, polydipsia, polyphagia, and "eight loss •
Flurred vision #o"er-etremity paresthesias Jeast infections (eg, !alanitis in men) +ee Presentation Presentation for for more detail. • • •
iagnosis iagnostic criteria !y the merican ia!etes ssociation () include the follo"ing 4 4556 0 fasting plasma glucose (P') level of 5=D mgGd# (C.: mmolG#) or higher, or =-hour plasma glucose level of =:: mgGd# (55.5 (55.5 mmolG#) or higher during a C@-g oral glucose tolerance test (H'33), or random plasma glucose of =:: mgGd# (55.5 (55.5 mmolG#) or higher in a patient "ith classic symptoms of hyperglycemia or hyperglycemic crisis >hether a hemoglo!in 5c (A!5c) level of D.@ or higher should !e a primary diagnostic criterion or an optional criterion remains a point of •
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controversy. Indications for dia!etes screening in asymptomatic adults includes the follo"ing 4 4==,76 0 +ustained !lood pressure N57@G8: mm Ag Hver"eight and 5 or more other ris$ factors for dia!etes (eg, firstdegree relative "ith dia!etes, FP N5B:G;: mm Ag, and A# M 7@ mgGd# andGor triglyceride level N=@: mgGd#) recommends screening at age B@ years in the a!sence of the a!ove criteria +ee >or$up >or$up for for more detail. • •
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&anagement 'oals of treatment are as follo"s0 &icrovascular (ie, eye and $idney disease) ris$ reduction through control of glycemia and !lood pressure &acrovascular (ie, coronary, coronar y, cere!rovascular, peripheral vascular) ris$ reduction through control of lipids and hypertension, smo$ing cessation &eta!olic and neurologic ris$ reduction through control of glycemia Recommendations for the treatment of type = dia!etes mellitus from the European ssociation for the +tudy of ia!etes (E+) and the merican ia!etes ssociation () place the patients condition, desires, a!ilities, and tolerances at the center of the decision-ma$ing process. 4B, @, D6 •
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3he E+G position statement contains C $ey points0 5. Indi Individu viduali ali?ed ?ed glyc glycemi emic c target targets s and and glucose glucose-lo" -lo"erin ering g therap therapies ies
=.
iet, eer iet, eercis cise, e, and and educa educatio tion n as the foun foundat dation ion of the the trea treatmen tmentt program 7. Use of of metfor metformin min as as the opt optima imall firstfirst-line line dru drug g unless unless con contrai traindi ndicat cated ed B. ft fter er metfo metformi rmin, n, the the use use of 5 or = addit addition ional al oral oral or in/ in/ect ecta!le a!le agen agents, ts, "ith a goal of minimi?ing adverse effects if possi!le @. Ult Ultima imately tely,, insul insulin in therap therapy y alone alone or or "ith "ith other other agen agents ts ifif needed needed to to maintain !lood glucose control D. >he >here re possi! possi!le, le, all all treat treatment ment deci decision sions s should should invol involve ve the pati patient ent,, "ith "ith a focus on patient preferences, needs, and values C. ma/o ma/orr focus focus on comp comprehe rehensi nsive ve cardi cardiova ovascu scular lar ris ris$ $ reduc reductio tion n 3he =:57 guidelines for +&F' freuency freu ency focus on an individuals specific situation rather than uantifying the num!er of tests that should !e done. 3he recommendations include the follo"ing 4C, 86 0 Patients on intensive insulin regimens O Perform +&F' at least !efore meals and snac$s, as "ell as occasionally after meals2 at !edtime2 !efore eercise and !efore critical tas$s (eg, driving)2 "hen hypoglycemia is suspected2 and after treating hypoglycemia until normoglycemia is achieved. Patients using less freuent insulin in/ections or noninsulin therapies O Use +&F' results to ad/ust to food inta$e, activity, or medications to reach specific treatment goals2 clinicians must not only educate these individuals on ho" to interpret their +&F' data, !ut they should also reevaluate the ongoing need for and freuency of +&F' at each routine visit. pproaches to prevention of dia!etic complications include the follo"ing0 A!5c every 7-D months Jearly dilated eye eaminations nnual microal!umin chec$s oot eaminations at each visit Flood pressure M 57:G8: mm Ag, lo"er in dia!etic nephropathy +tatin therapy to reduce lo"-density lipoprotein cholesterol +ee 3reatment 3reatment and and &edication &edication for for more detail. •
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Fac$ground 3ype = dia!etes mellitus consists of an array of dysfunctions characteri?ed !y hyperglycemia and resulting from the com!ination of resistance to insulin action, inadeuate insulin secretion, and ecessive or inappropriate glucagon secretion. Poorly controlled type = dia!etes is associated "ith an array of microvascular, macrovascular, macrovascular, and neuropathic neurop athic complications. &icrovascular complications of dia!etes include retinal, renal, and possi!ly neuropathic disease. &acrovascular complications include coronary artery
and peripheral vascular disease. ia!etic neuropathy affects autonomic and peripheral nerves. (+ee Pathophysiology and Presentation.) Unli$e patients "ith type 5 dia!etes mellitus, mellitus, patients "ith type = are not a!solutely dependent on insulin for life. 3his distinction "as the !asis for the older terms for types 5 and =, insulin dependent and nonOinsulin dependent dia!etes. Ao"ever, many patients "ith type = dia!etes are ultimately treated "ith insulin. Fecause they retain the a!ility to secrete some endogenous insulin, they are considered to reuire insulin !ut not to depend on insulin. 1evertheless, given the potential for confusion due to classification !ased on treatment rather than etiology, the older terms have !een a!andoned. 4 4;;6 nother older term for type = dia!etes mellitus "as adult-onset dia!etes. %urrently, !ecause of the epidemic of o!esity and inactivity in children, type = dia!etes mellitus is occurring at younger and younger ages. lthough type = dia!etes mellitus typically affects individuals older than B: years, it has !een diagnosed in children as young as = years of age "ho have a family history of dia!etes. In many communities, type = dia!etes no" outnum!ers type 5 among children "ith ne"ly diagnosed dia!etes. (+ee Epidemiology.) ia!etes mellitus is a chronic disease that reuires long-term medical attention to limit the development of its devastating complications and to manage them "hen they do occur. It is a disproportionately epensive disease2 in the United +tates in =::C, the direct medical costs of dia!etes "ere T55D !illion, and the total costs "ere T5CB !illion2 people "ith dia!etes had average medical ependitures =.7 times those of people "ithout dia!etes. 3he emergency department utili?ation rate !y people "ith dia!etes is t"ice 5:,, 55 5566 that of the unaffected population. 4 45: 3his article focuses on the diagnosis and treatment of type = dia!etes and its acute and chronic other than those directly "ith hypoglycemia and complications, severe meta!olic distur!ances, such asassociated hyperosmolar hyperglycemic state (AA+) and dia!etic $etoacidosis (). or more information on those topics, seeAyperosmolar see Ayperosmolar Ayperglycemic +tate and +tate and ia!etic etoacidosis. etoacidosis.
Pathophysiology 3ype = dia!etes is characteri?ed !y a com!ination of peripheral insulin resistance and inadeuate insulin secretion !y pancreatic !eta cells. Insulin resistance, "hich has !een attri!uted to elevated levels of free fatty acids and proinflammatory cyto$ines in plasma, leads to decreased glucose transport into muscle cells, elevated hepatic glucose production, and increased !rea$do"n of fat.
role for ecess glucagon cannot !e underestimated2 indeed, type = dia!etes is an islet paracrinopathy in "hich the reciprocal relationship !et"een the glucagon-secreting alpha cell and the insulin-secreting !eta cell is lost, 5:66 leading to hyperglucagonemia and hence the conseuent hyperglycemia. 4 45: or type = dia!etes mellitus to occur, !oth insulin resistance and inadeuate insulin secretion must eist. or eample, all over"eight individuals have insulin resistance, !ut dia!etes develops only in those "ho cannot increase insulin secretion sufficiently to compensate for their insulin resistance. 3heir insulin concentrations may !e high, yet inappropriately lo" for the level of glycemia. simplified scheme for the pathophysiology of a!normal glucose meta!olism in type = dia!etes mellitus is depicted in the image !elo".
+implified scheme for the pathophysiology of type = dia!etes mellitus. *ie" &edia 'allery >ith prolonged dia!etes, atrophy of the pancreas may occur. study !y Philippe et al used computed tomography (%3) scan findings, glucagon stimulation test results, and fecal elastase-5 measurements to confirm reduced pancreatic volume in individuals "ith a median 5@-year history of dia!etes mellitus (range, @-=D years). 45=63his may also eplain the associated eocrine deficiency seen in prolonged dia!etes. Feta-cell dysfunction Feta-cell dysfunction is a ma/or factor across the spectrum of predia!etes to dia!etes. study of o!ese adolescents a dolescents !y Facha et al confirms "hat is
increasingly !eing stressed in adults as "ell0 Feta-cell dysfunction develops early in the pathologic process and does not necessarily follo" the stage of 5766 insulin resistance.457 +ingular focus on insulin resistance as the Q!e all and end allQ is gradually shifting, and hopefully !etter treatment options that address the !eta-cell pathology "ill emerge for early therapy. Insulin resistance In the progression from normal to a!normal glucose tolerance, postprandial !lood glucose levels increase first. Eventually, fasting hyperglycemia develops as suppression of hepatic gluconeogenesis fails. uring the induction of insulin resistance (such as occurs "ith a high-calorie diet, steroid administration, or physical inactivity), increased glucagon levels and increased glucose-dependent insulinotropic polypeptide ('IP) levels accompanyglucose accompany glucose intolerance. intolerance. Ao"ever, the postprandial glucagonli$e 5B6 peptide-5 ('#P-5) response is unaltered. 4 45B 'enomic factors 'enome-"ide association studies of single-nucleotide polymorphisms (+1Ps) have identified a num!er of genetic variants that are associated "ith !eta-cell function and insulin resistance. +ome of these +1Ps appear to increase the ris$ for type = dia!etes. Hver B: independent loci demonstrating an 5@66 association "ith an increased ris$ for type = dia!etes have !een sho"n. 45@ 45D 5D66 su!set of the most potent are shared !elo" 0 ecreased !eta-cell responsiveness, leading to impaired insulin processing and decreased insulin secretion ( &#'(L)* #o"ered early glucose-stimulated insulin release ( &NR+%, 'AS+, G-%,G#- ) ltered meta!olism of unsaturated fatty acids ( 'SAS+) •
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ysregulation of fat meta!olism ( $$ARG) 5C66 Inhi!ition of serum glucose release ( -#N.++) 45C 58,, 5; 5;66 Increased adiposity and insulin resistance ( '&/ and "G')%$) ) 458 %ontrol of the development of pancreatic structures, including !eta-islet =:66 cells (HHE0 ) 4=: 3ransport of ?inc into the !eta-islet cells, "hich influences the =:66 production and secretion of insulin ( SL#12A3 ) 4=: =566 +urvival and function of !eta-islet cells ( 4'S+) 4=5 +uscepti!ility to type = dia!etes may also !e affected !y genetic variants involving incretin hormones, "hich are released from endocrine cells in the • • • •
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gut and stimulate insulin secretion in response to digestion of food. or
eample, reduced !eta-cell function has !een associated "ith a variant in the ==66 gene that codes for the receptor of gastric inhi!itory polypeptide (G"$R ). ). 4== 3he high mo!ility group 5 (A&'5) protein is a $ey regulator of the insulin =766 receptor gene ("NSR ). ). 4=7 unctional variants of the HGA+ gene are associated "ith an increased ris$ of dia!etes. mino acid meta!olism mino acid meta!olism may play a $ey role early in the development of type = dia!etes. >ang et al reported that the ris$ of future dia!etes "as at least Bfold higher in normoglycemic individuals "ith high fasting plasma concentrations of 7 amino acids (isoleucine, phenylalanine, and tyrosine). %oncentrations of these amino acids "ere elevated up to 5= years prior to the =B66 onset of dia!etes. 4 4=B In this study, amino acids, amines, and other polar meta!olites "ere profiled using liuid chromatography tandem mass spectrometry. ia!etes complications lthough the pathophysiology of the disease differs !et"een the types of dia!etes, most of the complications, including microvascular, macrovascular, and neuropathic, are similar regardless of the type of dia!etes. Ayperglycemia appears to !e the determinant of microvascular and meta!olic complications. &acrovascular disease may !e less related to glycemia. 3elomere attrition may !e a mar$er associated "ith presence and the num!er of dia!etic complications. >hether it is a cause or a conseuence of dia!etes =@66 remains to !e seen. 4 4=@ #ardio5ascular ris6
%ardiovascular ris$ in people "ith dia!etes is related in part to insulin resistance, "ith the follo"ing concomitant lipid a!normalities0 •
Elevated levels of small, dense lo"-density lipoprotein (##) cholesterol particles #o" levels of high-density lipoprotein (A#) cholesterol Elevated levels of triglyceride-rich remnant lipoproteins 3hrom!otic a!normalities (ie, elevated type-5 plasminogen activator inhi!itor 4PI-56, elevated fi!rinogen) and hypertension are also involved. Hther conventional atherosclerotic ris$ factors (eg, family history, smo$ing, elevated ## cholesterol) also affect cardiovascular ris$. Insulin resistance is associated "ith increased lipid accumulation in liver and smooth muscle, !ut not "ith increased myocardial lipid =D66 accumulation. 4=D Persistent lipid a!normalities remain in patients "ith dia!etes • •
despite the use of lipid-modifying drugs, although evidence supports the
!enefits of these drugs. +tatin dose up-titration and the addition of other lipid=C66 modifying agents are needed. 4=C Increased cardiovascular ris$ appears to !egin prior to the development of fran$ hyperglycemia, presuma!ly !ecause of the effects of insulin resistance. =866 =;66 +tern in 5;;D 4=8 and Aaffner and gostino in 5;;; 4=; developed the Qtic$ing cloc$Q hypothesis of complications, asserting that the cloc$ starts tic$ing for microvascular ris$ at the onset of hyperglycemia, "hile the cloc$ starts tic$ing for macrovascular ris$ at some antecedent point, presuma!ly "ith the onset of insulin resistance. 3he uestion of "hen dia!etes !ecomes a cardiovascular ris$ euivalent has not yet !een settled. e!ate has moved !eyond automatically considering dia!etes a cardiovascular ris$ euivalent. Perhaps it "ould !e prudent to assume the euivalency "ith dia!etes that is more than @-5: years in duration. #ogniti5e decline
In a cross-sectional study of 7@: patients aged @@ years and older "ith type = dia!etes and 7D7 control participants aged D: years and older "ithout dia!etes, dia!etic individuals "ere more li$ely to have !rain atrophy than cere!rovascular lesions, "ith patterns resem!ling those of preclinical 7:,, 75 7566 l?heimer disease. 47: 3ype = dia!etes "as associated "ith hippocampal atrophy2 temporal, frontal, and lim!ic gray-matter atrophy2 and, to a lesser etent, frontal and temporal "hite-matter atrophy. 3ype = dia!etes "as also lin$ed "ith poorer performance on certain cognitive tests. 3he strength of these associations dropped !y almost @: "hen ad/usted for hippocampal and total gray-matter volumes !ut "as unchanged "hen ad/usted for cere!rovascular lesions or "hite-matter 7:,, 75 7566 volume. 47: Patients "ith type = dia!etes "ere more li$ely to have graymatter atrophy in several !ilateral regions of the cortices, especially in the left hemisphere, similar 47: to6 the distri!ution of cortical atrophy descri!ed in early 7:6 l?heimer disease. In a B:-month study of =;CC middle-aged and older adults "ith long-standing type = dia!etes, depression at !aseline "as associated "ith accelerated 7=,, 77 7766 cognitive decline. 4 47= 3he @75 su!/ects "ith scores of 5: or higher on the Patient Aealth Vuestionnaire epression +cale at !aseline had significantly lo"er scores on o n the igit +ym!ol +u!stitution 3est 3est (++3), the Rey Re y uditory *er!al #earning 3est (R*#3), and the modified +troop test. d/ustment for other ris$ factors did not affect the association. +econdary dia!etes *arious other types of dia!etes, previously called secondary dia!etes, are caused !y other illnesses or medications. epending on the primary process
involved (eg, destruction of pancreatic !eta cells or development of peripheral insulin resistance), these types of dia!etes !ehave similarly to type 5 or type = dia!etes. 3he most common causes of secondary dia!etes are as follo"s0 iseases of the pancreas that destroy the pancreatic !eta cells (eg, hemochromatosis, pancreatitis, cystic fi!rosis, fi!rosis, pancreatic cancer ) Aormonal syndromes that interfere "ith insulin secretion (eg, pheochromocytoma) Aormonal syndromes that cause peripheral insulin resistance (eg, acromegaly, %ushing syndrome, pheochromocytoma) rugs (eg, phenytoin, glucocorticoids, estrogens) •
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'estational dia!etes 'estational dia!etes mellitus is defined as any degree of glucose intolerance "ith onset or first recognition during pregnancy (see ia!etes &ellitus and Pregnancy). Pregnancy ). 'estational dia!etes mellitus is a complication of approimately B of all pregnancies pre the Unitedis+tates. steady decline in insulin sensitivity asgnancies gestationinprogresses a normal feature of pregnancy2 gestational dia!etes mellitus results "hen maternal insulin secretion cannot increase sufficiently to counteract the decrease in insulin sensitivity.
Etiology 3he etiology of type = dia!etes mellitus appears to involve comple interactions !et"een environmental and genetic factors. Presuma!ly, the disease develops "hen a dia!etogenic lifestyle (ie, ecessive caloric inta$e, inadeuate caloric ependiture, o!esity) is superimposed on a suscepti!le genotype. 3he !ody mass inde (F&I) at "hich ecess "eight increases ris$ for dia!etes varies "ithancestry, different racial groups. orancestry eample,are compared "ith persons European persons of sian sian at increased ris$ for of dia!etes at lo"er levels of over"eight. 47B6 Aypertension and prehypertension are associated "ith a greater ris$ of developing dia!etes in "hites than in 7@66 frican mericans. mericans. 4 47@ In addition, an in utero environment resulting in lo" !irth "eight may 7D,, 7C 7C,, 78 7866 predispose some individuals to develop type = dia!etes mellitus. 47D Infant "eight velocity has a small, indirect effect on adult insulin resistance, and this 7;66 is primarily mediated through its effect on F&I and "aist circumference. 47; !out ;: of patients "ho develop type = dia!etes mellitus are o!ese. Ao"ever, a large, population-!ased, prospective study has sho"n that an energy-dense diet may !e a ris$ factor for the development of dia!etes that is B:66 independent of !aseline o!esity. 4 4B:
+ome studies suggest that environmental pollutants may play a role in the B566 development and progression of type = dia!etes mellitus. 4 4B5 structured and planned platform is needed to fully eplore the dia!etes-inducing potential of environmental pollutants. +econdary dia!etes may occur in patients ta$ing glucocorticoids or "hen patients have conditions that antagoni?e the actions of insulin (eg, %ushing syndrome, acromegaly, pheochromocytoma). &a/or ris$ factors 3he ma/or ris$ factors for type = dia!etes mellitus are the follo"ing0 ge greater than B@ years (though, as noted a!ove, type = dia!etes mellitus is occurring "ith increasing freuency in young individuals) >eight greater than 5=: of desira!le !ody "eight amily history of type = dia!etes in a first-degree relative (eg, parent or si!ling) Aispanic, 1ative merican, frican frican merican, sian merican, or Pacific •
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Islander Aistory descent of previous impaired glucose tolerance (I'3) or impaired fasting glucose (I') Aypertension (N5B:G;: mm Ag) or dyslipidemia (A# cholesterol level M B: mgGd# or triglyceride level N5@: mgGd#) Aistory of gestational dia!etes mellitus or of delivering a !a!y "ith a !irth "eight of over ; l! Polycystic ovarian syndrome ("hich results in insulin resistance)
'enetic influences 3he genetics of type = dia!etes are comple and not completely understood. Evidence the involvement of multiple genes in pancreatic !eta-cell failure andsupports insulin resistance. 'enome-"ide association studies have identified do?ens of common genetic 5D66 variants associated "ith increased ris$ for type = dia!etes. 45D Hf the variants thus far discovered, the one "ith the strongest effect on suscepti!ility is the transcription factor COli$e = ( &#'(L) ) gene. (or more information, see 3ype = ia!etes and 3%C#=.) 3%C#=.) Identified genetic variants account for only a!out 5: of the herita!le component of most type = dia!etes. 45D6 n international research consortium found that use of a B:-+1P genetic ris$ score improves the a!ility to ma$e an approimate 8-year ris$ prediction for dia!etes !eyond that "hich is achieva!le "hen only common clinical dia!etes ris$ factors are used. &oreover, the predictive a!ility is !etter in younger persons (in "hom early
preventive strategies could delay dia!etes onset) than in those older than @: B=66 years. 4B= +ome forms of dia!etes have a clear association "ith genetic defects. 3he syndrome historically $no"n as maturity onset dia!etes of youth (&HJ), "hich is no" understood to !e a variety of defects in !eta-cell function, accounts for =-@ of individuals "ith type = dia!etes "ho present at a young age and have mild disease. 3he trait is autosomal dominant and can !e screened for through commercial la!oratories. 3o date, 55 &HJ su!types have !een identified, involving mutations in the B7,, BB BB66 follo"ing genes 4B7 0 A1-B-alpha 'luco$inase gene A1-5-alpha IP-5 A1-5-!eta 1EURH5 • • • • • •
4B@ B@66
#55 BD66 %E# 4BD BC66 PB 4BC I1+ B866 F# 4B8 &ost of the &HJ su!types are associated "ith dia!etes only2 ho"ever, B;66 &HJ type @ is $no"n to !e associated "ith renal cysts, 4B; and &HJ type 8 4BD 4 BD66 is associated "ith eocrine pancreatic dysfunction. num!er of variants in mitochondrial deoyri!onucleic acid (1) have !een proposed as an etiologic factor for a small percentage of patients "ith type = dia!etes. 3"o specific point mutations and some deletions and duplications in the mitochondrial genome can cause type = dia!etes and sensorineural @:66 hearing loss.4@: ia!etes can also !e a finding in more severe mitochondrial disorders such as earns-+ayre syndrome and mitochondrial encephalomyopathy, lactic acidosis, and stro$eli$e episode (&E#+). &itochondrial forms of dia!etes mellitus should !e considered "hen dia!etes occurs in con/unction "ith hearing loss, myopathy, m yopathy, sei?ure disorder, stro$eli$e episodes, retinitis pigmentosa, eternal ophthalmoplegia, or cataracts. 3hese findings are of particular significance if there is evidence of maternal inheritance. meta-analysis of t"o studies indicated that a genetically associated lo" !irth "eight increases an individuals ris$ for developing type = dia!etes. 3he report • • • • •
found that for each one-point increase in an individuals genetic ris$ score for @5,, @= @=6 6 lo" !irth "eight, the type = dia!etes ris$ rose !y D. 4 4@5
epression ccumulating evidence suggests that depression is a significant ris$ factor for developing type = dia!etes. Pan et al found that the relative ris$ "as 5.5C in "omen "ith depressed mood and 5.=@ in "omen using @766 antidepressants. 4@7 ntidepressant use may !e a mar$er of more severe, chronic, or recurrent depression, or antidepressant use itself may increase dia!etes ris$, possi!ly !y altering glucose homeostasis or promoting "eight gain. In turn, type = dia!etes has !een identified as a ris$ factor for the development of depression. epressive symptoms and ma/or depressive disorder are t"ice as prevalent in patients "ith type = dia!etes as in the @B66 general population. 4@B +chi?ophrenia +chi?ophrenia has !een lin$ed to the ris$ for type = dia!etes. ysfunctional signaling involving protein $inase F ($t) is a possi!le mechanism for schi?ophrenia2 moreover, $t defects associated "ith impaired impaire regulation of !lood glucoseacuired and dia!etes, "hichare is overrepresented in first-d @@66 episode, medication-naive patients "ith schi?ophrenia. 4 4@@ In addition, secondgeneration antipsychotics are associated "ith greater ris$ for type-= dia!etes. Preeclampsia and gestational hypertension population-!ased, retrospective cohort study of 5,:5:,:D8 pregnant "omen eamined the association !et"een preeclampsia and gestational hypertension during pregnancy and the ris$ of developing dia!etes post partum. Results sho"ed the incidence rate of dia!etes per 5::: person-years "as D.BC for "omen "ith preeclampsia and @.=D for those "ith gestational hypertension, compared "ith =.85 in "omen "ith neither condition. Ris$ "as further elevated in "omen "ith preeclampsia or gesntational hypertension comor!id @D66 "ith gestational dia!etes. 4 4@D
Epidemiology Hccurrence in the United +tates =:55 %enters for isease %ontrol and Prevention (%%) report estimated 5566 that nearly =D million mericans have dia!etes. 455 dditionally, an estimated C; million mericans have predia!etes. ia!etes affects 8.7 of mericans of all ages, 55.7 of adults aged =: years and older, and =@ of persons age D@ and older, according to the 1ational 5566 ia!etes act +heet for =:55 =:55.. 4 455 !out =C of those "ith dia!etes—C million mericans—do not $no" that they have the disease. !out !out =5@,::: people
younger than =: years had dia!etes (type 5 or type =) in the United +tates in 5566 =:5:. 455 In =:5B, the %% reported that a!out B: of U+ adults "ill develop dia!etes, primarily type =, in their lifetime, and more than @: of ethnic minorities "ill !e affected. 3his is su!stantially higher than previous estimates. 3he central @C,, @8 @866 reason for the increase is o!esity. 4@C Predia!etes affects 7@ of adults aged =: years and older. Predia!etes, as defined !y the merican ia!etes ssociation, is that state in "hich !lood glucose levels are higher than normal !ut not high enough to !e diagnosed as dia!etes. It is presumed that most persons "ith predia!etes "ill su!seuently progress to dia!etes. 3he %% estimated that in =:5:, C; million mericans aged =: years or older had predia!etes—7@ of U+ adults aged =: years or older and @: of those aged D@ years or older. study !y #ud"ig et al found that neigh!orhoods "ith high levels of poverty are associated "ith increases in the incidence of etreme o!esity and dia!etes. lthough the mechanisms !ehind this association is unclear, further @;66 investigation is "arranted. 4@; International occurrence 3ype = dia!etes mellitus is less common in non->estern countries "here the diet contains fe"er calories and daily caloric ependiture is higher. Ao"ever, as people in these countries adopt >estern lifestyles, "eight gain and type = dia!etes mellitus are !ecoming virtually epidemic. Rates of dia!etes are increasing "orld"ide. 3he International ia!etes ederation predicts that the num!er of people living "ith dia!etes "ill to rise D:66 from 7DD million in =:55 to @@= million !y =:7:. 4D: In the United +tates, the prevalence of diagnosed dia!etes has more than dou!led in the last 7 decades, largely !ecause of the increase in o!esity. 3he topthe 5:United countries in num!er of people "ith dia!etesRussia, are currently %hina, +tates, Indonesia, Lapan, Pa$istan, Fra?il, India, Italy, and Fangladesh. 3he greatest percentage increase in rates of dia!etes "ill occur in frica over the net =: years. Unfortunately, at least 8: of people in frica "ith dia!etes are undiagnosed, and many in their 7:s to D:s "ill die from dia!etes there. Race-related demographics 3he prevalence of type = dia!etes mellitus varies "idely among various racial and ethnic groups. 3he image !elo" sho"s data for various populations. 3ype = dia!etes mellitus is more prevalent among Aispanics, 1ative mericans, frican mericans, mericans, and siansGPacific siansGPacific Islanders than in non-Aispanic "hites. Indeed, the disease is !ecoming virtually pandemic in some groups of 1ative
mericans and Aispanic people. 3he ris$ of retinopathy and nephropathy appears to !e greater in !lac$s, 1ative mericans, and Aispanics.
Prevalence of type = dia!etes mellitus in various racial and ethnic groups in the United +tates (=::C-=::; data). *ie" &edia 'allery In a study !y +elvin et al, differences !et"een !lac$s and "hites "ere noted in many glycemic mar$ers and not /ust the hemoglo!in 5c (A!5c) 4D5 4 D56
level. 3hisglycation suggestsprocess real differences in glycemia, rather than in the and hemoglo!in or erythrocyte turnover, !et"een !lac$s "hites. ge-related demographics 3ype = dia!etes mellitus occurs most commonly in adults aged B: years or older, and the prevalence of the disease increases "ith advancing age. Indeed, the aging of the population is one reason that type = dia!etes mellitus is !ecoming increasingly common. *irtually all cases of dia!etes mellitus in older individuals are type =. In addition, ho"ever, the incidence of type = dia!etes is increasing more rapidly in adolescents and young adults than in other age groups. 3he disease is !eing recogni?ed increasingly in younger persons, particularly in highly suscepti!le racial and ethnic groups and the o!ese. In some areas, more type = than type 5 dia!etes mellitus is !eing diagnosed in prepu!ertal children, teenagers, and young adults. 3he prevalence of dia!etes mellitus !y age is sho"n in the image !elo".
Prevalence of dia!etes mellitus type = !y age in the United +tates (=::C estimates). *ie" &edia 'allery
Prognosis 3he prognosis in patients "ith dia!etes mellitus is strongly influenced !y the degree of control of their disease. %hronic hyperglycemia is associated "ith an increased ris$ of microvascular complications, as sho"n in the ia!etes %ontrol and %omplications 3rial (%%3) in individuals "ith type 5 D=,, D76 dia!etes 4D= and the United ingdom Prospective ia!etes +tudy (UP+) DB66 in people "ith type = dia!etes. 4 4DB Reversion to normal glucose regulation during attempts to prevent progression of pre-dia!etes to fran$ dia!etes is a good indicator of slo"ing D@66 disease progression, and it is associated "ith a !etter prognosis. 4 4D@ Prognosis in intensive therapy In the UP+, more than @::: patients "ith type = dia!etes "ere follo"ed up for up to 5@ years. 3hose in the intensely treated group had a significantly lo"er rate of progression of microvascular complications than did patients receiving standard care. Rates of macrovascular disease "ere not altered ecept in the metformin-monotherapy arm in o!ese individuals, in "hich the ris$ of myocardial infarction "as significantly decreased. In the 5:-year follo"-up to the UP+, patients in the previously intensively treated group demonstrated a continued reduction in microvascular and allcause mortality, as "ell as in cardiovascular events, despite early loss of differences in glycated hemoglo!in levels !et"een the intensive-therapy and DD66 conventional-therapy groups.4DD 3he total follo"-up "as =: years, half "hile in the study and half after the study ended. Hther, shorter studies, such as ction in ia!etes and *a *ascular scular isease0 Pretera and iamicron &odified Release %ontrolled %on trolled Evaluation (*1%E) (*1%E) and the *e *eterans terans ffairs ia!etes 3rial (*3), (*3), sho"ed no improvement in
cardiovascular disease and death "ith tight control (lo"er targets than in the DC,, D8 D8,, D; D;66 UP+). 4DC In the ction to %ontrol %ardiovascular Ris$ in ia!etes (%%HR) study, increased mortality "as noted among the poorly-controlled patients in the intensive glycemic arm2 indeed there "as a DD increase in mortality for each 5 increase in A!5c2 the !est outcome occurred among patients "ho achieved the target of an A!5c of less than D. 3he ecess mortality !et"een the intensive and conventional glycemic arms occurred for 5c a!ove C. ifferences !et"een the patient populations in these studies and the UP+ may account for some of the differences in outcome. 3he patients in these 7 studies had esta!lished dia!etes and had a prior cardiovascular disease event or "ere at high ris$ for a cardiovascular disease event, "hereas patients in the UP+ study "ere younger, "ith ne"-onset dia!etes and lo" rates of cardiovascular disease. Early, intensive, multifactorial (!lood pressure, cholesterol) management in patients "ith type = dia!etes mellitus "as associated "ith a small, nonsignificant reduction in the incidence 4of cardiovascular disease events and C:66 C: death in a multinational European study. 3he 7:@C patients in this study had dia!etes detected !y screening and "ere randomi?ed to receive either standard dia!etes care or intensive management of hyperglycemia (target A!5c M C.:), !lood pressure, and cholesterol levels. 3he !enefits of intensive intervention "ere demonstrated in the +teno-= study in enmar$, "hich included 5D: patients "ith type = dia!etes and persistent microal!uminuria2 the mean treatment period "as C.8 years, follo"ed !y an o!servational period for a mean of @.@ years. Intensive therapy "as associated "ith a lo"er ris$ of cardiovascular events, death from cardiovascular causes, progression to end-stage renal disease, and need for 4C5 C566
retinal photocoagulation. Fritish study indicated that the A!5c level achieved 7 months after the initial diagnosis of type = dia!etes mellitus predicts su!seuent mortality. In other "ords, according to the report, aggressive lo"ering of glucose after diagnosis !odes "ell for long-term survival. (Intensified dia!etes control must C=66 !e introduced gradually in ne"ly diagnosed patients.) 4C= nother study, a revie" of randomi?ed clinical trials, sho"ed that intensive glycemic control reduces the ris$ of microvascular complications, !ut at the epense of increased ris$ of hypoglycemia. ll-cause mortality and cardiovascular mortality in the study did not differ significantly "ith intensive versus conventional glycemic control2 ho"ever, trials conducted in usual-care 4C7 C766
settings sho"ed a reduction in the ris$ of nonfatal myocardial infarction.
Hverall, these studies suggest that tight glycemic control (A!5c M C or lo"er) is valua!le for microvascular and macrovascular disease ris$ reduction in patients "ith recent-onset disease, no $no"n cardiovascular diseases, and a longer life epectancy. In patients "ith $no"n cardiovascular disease, a longer duration of dia!etes (5@ or more years), and a shorter life epectancy, ho"ever, tighter glycemic control is not as !eneficial, particularly "ith regard to cardiovascular disease ris$. Episodes of severe hypoglycemia may !e particularly harmful in older individuals "ith poorer glycemic control and eisting cardiovascular disease. *ascular *a scular disease considerations Hne prospective study "ith a long follo"-up challenges the concept of coronary disease ris$ euivalency !et"een nondia!etic patients "ith a first myocardial infarction and patients "ith type = dia!etes !ut "ithout any cardiovascular disease. 3he study found that patients "ith type = dia!etes had lo"er long-term cardiovascular ris$ compared "ith patients "ith first myocardial infarction. Hther studies have similarly uestioned this ris$ CB66 euivalency. 4CB Patients "ith dia!etes have a lifelong challenge to achieve and maintain !lood glucose levels as close to the reference range as possi!le. >ith appropriate glycemic control, the ris$ of microvascular and neuropathic complications is decreased mar$edly. In addition, if hypertension and hyperlipidemia are treated aggressively, the ris$ of macrovascular complications decreases as "ell. 3hese !enefits are "eighed against the ris$ of hypoglycemia and the shortterm costs of providing high-uality preventive care. +tudies have sho"n cost savings due to a reduction in acute dia!etes-related complications "ithin 5-7 years after starting effective preventive care. +ome studies suggest that !road-!ased on treatment glycemia, eercise, hypertension,focus smo$ing cessation)(eg, is much morenutrition, li$ely to reduce thelipids, !urden of ecess microvascular and macrovascular events. Jamasa$i et al found that a!normal results on single-photon %3 myocardial perfusion imaging in asymptomatic patients "ith type = dia!etes indicated a higher ris$ for cardiovascular events (57), including cardiac death. +mo$ing and lo" glomerular filtration rate "ere significant contri!uting C@66 factors. 4C@ Ao"ever, an earlier study uestioned the merit of routine screening "ith adenosine-stress radionuclide myocardial perfusion imaging (&PI) in other"ise asymptomatic type = dia!etic patients (the etection of Ischemia in CD66 symptomatic ia!etics 4I6 study). 4CD In !othindependent dia!etic and predictor nondia!etic patients, coronaryInvasodilator dysfunction is a strong of cardiac mortality. dia!etic patients "ithout
coronary artery disease, those "ith impaired coronary flo" reserve have event rates similar to those "ith prior coronary artery disease, "hile patients "ith preserved coronary flo" reserve have event rates similar to nondia!etic CC66 patients.4CC ia!etes-associated mortality and mor!idity In =::;, dia!etes mellitus "as the seventh leading cause of death in the C866 United +tates. 4C8 In addition, dia!etes is a contri!uting cause of death in many cases, and it is pro!a!ly underreported as a cause of death. Hverall, the death rate among people "ith dia!etes is a!out t"ice that of people of similar 5566 age !ut "ithout dia!etes. 455 ia!etes mellitus causes mor!idity and mortality !ecause of its role in the development of cardiovascular, renal, neuropathic, and retinal disease. 3hese complications, particularly cardiovascular disease (approimately @:-C@ of medical ependitures), are the ma/or sources of epenses for patients "ith dia!etes mellitus. 3he merican ia!etes ssociation ssociation estimated that in =::C, direct medical costs due to dia!etes in the United +tates "ere T55D !illion, "ith another T@8 !illion in indirect in direct costs (eg, disa!ility, "or$ loss, premature mortality). pproimately 5 in @ health care dollars in the United +tates "as spent caring for someone "ith diagnosed dia!etes, "hile 5 in 5: health care dollars "as C;66 attri!uted to dia!etes. 4C; iabetic retinopath retinopathy y
ia!etes mellitus is the ma/or cause of !lindness in adults aged =:-CB years in the United +tates2 dia!etic retinopathy accounts for 5=,:::-=B,::: ne"ly 8:66 !lind persons every year. 48: 3he 1ational Eye Institute estimates that laser surgery and appropriate follo"-up care can reduce the ris$ of !lindness from 8:66 dia!etic retinopathy !y ;:. 4 48: End7stage renal disease
ia!etes mellitus, and particularly type = dia!etes mellitus, is the leading contri!utor to end-stage renal disease (E+R) in the United 8:66 +tates. 48: ccording to the %enters for isease %ontrol and Prevention, 5566 dia!etes accounts for BB of ne" cases of E+R. 4 455 In =::8, B8,7CB people "ith dia!etes in the United +tates and Puerto Rico !egan renal replacement therapy, and =:=,=;: people "ith dia!etes "ere on dialysis or had received a 8:66 $idney transplant. 48: Neuropathy and 5asculopathy
ia!etes mellitus is the leading cause of nontraumatic lo"er lim! amputations in the United +tates, "ith a 5@- to B:-fold increase in ris$ over that of the 8:66 nondia!etic In =::D, a!out nontraumatic lo"er lim! 48: amputationspopulation. "ere performed related to D@,C:: neuropathy and vasculopathy.
#ardio5ascular disease
3he ris$ for coronary heart disease (%A) is =-B times greater in patients "ith dia!etes than in individuals "ithout dia!etes. %ardiovascular disease is the ma/or source of mortality in patients "ith type = dia!etes mellitus. pproimately t"o thirds of people "ith dia!etes die of heart disease or stro$e. &en "ith dia!etes face a =-fold increased ris$ for %A, and "omen have a 7- to B-fold increased ris$. lthough type = dia!etes mellitus, !oth early onset (M D: y) and late onset (ND: y), is associated "ith an increased ris$ of ma/or %A and mortality, only 8566 the early onset type (duration N5: y) appears to !e a %A ris$ euivalent. 485 In patients "ith type = dia!etes mellitus, a fasting glucose level of more than 5:: mgGd# significantly contri!utes to the ris$ of cardiovascular disease and 8=66 death, independent of other $no"n ris$ factors. 4 48= 3his is !ased on a revie" of ;C prospective studies involving 8=:,;:: patients. ata from a large population-!ased study affirms that "orsening glycemic 8766 control appears to increase the ris$ of heart failure. 487 dolescents "ith o!esity and o!esity-related type = dia!etes mellitus 8B66 demonstrate a decrease in diastolic dysfunction. 48B 3his suggests that they may !e at increased ris$ of progressing to early heart failure compared "ith adolescents "ho are either lean or o!ese !ut do not have type = dia!etes mellitus. #ancer
=:5: %onsensus Report from a panel of eperts chosen /ointly !y the merican ia!etes ssociation ssociation and the merican merican %ancer +ociety suggested that people "ith type = dia!etes are at an increased ris$ for many types of 8@66 cancer. 4 48@ Patients "ith dia!etes have a higher ris$ for !ladder cancer, 8D,, 8C 8C66 particularly those patients "ho use pioglita?one. 4 48D ge, male gender, neuropathy, and urinary tract infections "ere associated "ith this ris$. In a meta-analysis of =: pu!lications comprising 57,::8 cancer patients "ith concurrent type = dia!etes, researchers found that patients treated "ith metformin had !etter overall and cancer-specific survival than those treated 88,, 8; 8;66 "ith other types of glucose-lo"ering agents. 4 488 3hese improvements "ere o!served across cancer su!types and geographic locations. Ris$ reduction "as significant among patients "ith prostate, pancreatic, !reast, colorectal and other cancers, !ut not for those "ith lung cancer. Ao"ever, it remains unclear "hether metformin can modulate clinical outcomes in cancer patients "ith dia!etes. Pregnancy outcome Untreated gestational dia!etesand mellitus can lead to fetal hypoglycemia, hypocalcemia, hyper!iliru!inemia. In macrosomia, addition, mothers
"ith gestational dia!etes mellitus have increased rates of cesarean delivery and chronic hypertension. espite advanced age, ag e, multiparity, o!esity, o!esity, and social disadvantage, patients patie nts "ith type = dia!etes "ere found to have !etter glycemic control, fe"er largefor-gestational-age infants, fe"er preterm deliveries, and fe"er neonatal care admissions compared "ith patients "ith type 5 dia!etes. 3his suggests that !etter tools are needed to improve glycemic control in patients "ith type 5 ;:66 dia!etes. 4;: (or more information, see ia!etes &ellitus and Pregnancy.) Pregnancy.)
Patient Education 1o longer is it satisfactory to provide patients "ho have dia!etes "ith !rief instructions and a fe" pamphlets and epect them to manage their disease adeuately. Instead, education of these patients should !e an active and concerted effort involving the physician, nutritionist, dia!etes educator, and other health professionals. &oreover, dia!etes education needs to !e a lifetime eercise2 !elieving that it can !e accomplished in 5 or = encounters is misguided. randomi?ed, controlled trial found that for patients "ith poorly controlled dia!etes, individual attention and education is superior to group ;566 education. 4;5 +imilarly, a dia!etes education and self-management group program in the U for ne"ly diagnosed patients failed to yield significant !enefits. 4;=6 1onphysician health professionals are usually much more proficient at dia!etes education and have much more time for this very important activity activity.. systematic revie" suggested that patients "ith type = dia!etes "ho have a !aseline A!5c of greater than 8 may achieve !etter glycemic control "hen given individual education rather than usual care. Hutside that su!group, ho"ever, the report found no significant difference !et"een usual care and individual education. In addition, comparison of individual education "ith ;766 group education sho"ed eual impact on A!5c at 5=-58 months. 4 4;7 Patient education is an immensely comple topic, ho"ever. 3he clinical impression of most eperts in the field is that there is merit in the provision of careful dia!etes education at all stages of the disease. Fac$ground
ccording to the =:55 U+ Renal ata +ystem (U+R+) +ystem (U+R+) data, in the year =::;, hypertensive nephrosclerosis (A1) accounted for =8 of patients reaching end-stage renal disease ( disease (E+R E+R). ). 3he rate of E+R attri!uted to hypertension has gro"n 8.C since the year =:::. 456 Aypertensive nephrosclerosis is reportedly the second most common cause of E+R in
"hite people (=7) and is the leading cause of E+R in !lac$ people (BD). 3he histologic effects of nephrosclerosis are demonstrated in the images !elo".
1ephrosclerosis. 3he glomerular tuft is shrun$en, "ith "rin$ling of the capillary "alls (asteris$), glo!al glomerular sclerosis (arro"), and complete o!literation of the capillary loops and glomerular ischemia (periodic acid-+chiff stain at =@: magnification). *ie" &edia 'allery
1ephrosclerosis. 'lomerulus "ith "rin$ling of glomerular !asement mem!ranes accompanied !y reduction of capillary lumen diameter (silver stain at B:: magnification). *ie" &edia 'allery
1ephrosclerosis. Ayaline arteriosclerosis "ith hyaline deposits (arro"s) (trichrome stain at =@: magnification). *ie" &edia 'allery
1ephrosclerosis. i!rointimal proliferation of the arcuate artery (periodic acid-+chiff stain at 5@: magnification). *ie" &edia 'allery 3he term hypertensive nephrosclerosis has traditionally !een used to descri!e a clinical syndrome characteri?ed !y long-term essential hypertension hypertension,, hypertensiveretinopathy hypertensive retinopathy,, left ventricular hypertrophy, hypertrophy, minimal proteinuria proteinuria,, and progressive renal insufficiency. &ost cases are diagnosed !ased solely on clinical findings. In fact, most of the literature that dedicated to hypertensive nephrosclerosis is !ased on the assumption progressive renal failure in a
patient "ith long-standing hypertension, moderate proteinuria proteinuria,, and no evidence suggesting an alternative diagnosis characteri?es hypertensive nephrosclerosis. 3he lac$ of firm criteria on "hich to !ase a histologic diagnosis and the lac$ of a clear demonstration that hypertension hypertension initiates initiates the development of renal failure li$ely indicate that the true prevalence of hypertensive nephrosclerosis has !een overestimated. 3he paradoical results of increasing incidence of renal failure despite "ider antihypertensive drug therapy and reduction in hypertensive target events, such as stro$e and cardiovascular disease, raises uestions a!out the causal role of hypertension in this disorder. s reported !y WuccalX and Wucchelli (5;;D), part of the confusion in the classification of hypertensive nephrosclerosis stems from the use of the "ord nephrosclerosis. 4=6 %oined almost a century ago !y 3heodor ahr, nephrosclerosis literally means Qhardening of the $idney.Q In the United +tates and Europe, the terms hypertensive nephrosclerosis, !enign nephrosclerosis, and nephroangiosclerosis are commonly used to descri!e the same clinical condition. 3hese terms refer more to the renal pathologic changes attri!uted to the effects of hypertension than hypertension than to the clinical disorder in uestion. 476 Unfortunately, the pathologic changes are not specific to hypertensive renal in/ury2 they are also o!served in $idney !iopsy specimens of patients "ho are normotensive, particularly those of advanced age or "ith dia!etes. Unli$e mor!idity and mortality of stro$e and coronary disease, incident cases of E+R attri!uted to hypertension hypertension continue continue to increase. +ome authors suggest that many of these cases are more li$ely related to other factors, including small vessel in/ury related to aging, dia!etes dia!etes,, or o!esity o!esity -related -related $idney in/ury. couple of important points have !een made in different studies. irst, among an unselected sample of community-!ased participants in the ramingham Aeart +tudy, the the com!ination of hypertension hypertension and and a mild reduction in the glomerular filtration rate ('R) "as found to !e an important ris$ factor for the development of ne"-onset $idney disease. Hther factors noted "ere dia!etes, o!esity, smo$ing, and a lo" high-density lipoprotein cholesterol level. +econd,
systolic !lood pressure (FP) is a strong, independent predictor of a decline in $idney function among older persons "ith isolated systolic hypertension. 3his is a significant finding !ecause most cases of uncontrolled hypertension hypertension in in the United +tates are due to systolic hypertension hypertension among among older adults. &ost patients reaching E+R from any cause are hypertensive hypertensive,, "ith nephrosclerosis !eing the classic finding in end-stage $idneys. Regardless of the etiology, once hypertension hypertension develops, develops, a cycle of renal in/ury, in /ury, nephrosclerosis, "orsening of hypertension, and further renal in/ury is esta!lished. s a result, in a patient presenting "ith E+R, determining "hether nephrosclerosis is the cause or the conseuence of chronic renal in/ury may !e difficult. Pathophysiology
3"o pathophysiologic mechanisms have !een proposed for the development of hypertensive nephrosclerosis. Hne mechanism suggests that glomerular ischemia causes hypertensive nephrosclerosis. 3his occurs as a conseuence of chronic hypertension resulting in narro"ing of preglomerular arteries and arterioles, "ith a conseuent conse uent reduction in glomerular !lood flo". lternatively lternatively,, glomerulosclerosis occurs !ecause of glomerular hypertension and glomerular hyperfiltration. ccording to this theory, hypertension hypertension causes some glomeruli to !ecome sclerotic. s an attempt to compensate for the loss of renal function, the remaining nephrons undergo vasodilation of the preglomerular arterioles and eperience an increase in renal !lood flo" and glomerular filtration. 3heglomerular result is glomerular glomerular hyperfiltration, and progressive sclerosis. hypertension, 3hese mechanisms are not mutually eclusive, and they may operate simultaneously in the $idney. urthermore, 3racy and Ishii (=:::) postulate that nephrosclerosis may not !e a single disease entity in the sense of responding to a single etiology, such as hypertension or aging. 4 4BB6 Rather, nephrosclerosis appears to !e multifactorial. It may !e, in part, a conseuence of fi!roplasias in microscopic arteries causing ischemic damage to some nephrons2 ho"ever, it also may !e the end product of a miture of converging separate pathologic conditions, ie, Qsecond hits,Q of "hich only some are $no"n.
'enetically mediated animal models of hypertension, including the ahl rat and the spontaneous hypertensive rat (+AR), have !een used to investigate the role of hypertension in the development of nephrosclerosis. undamental differences eist among the strains and !et"een rat and human hypertension. 3he +AR most closely resem!les human essential hypertension. 3he +AR !ecomes hypertensive "ithout eposure to salt. &icropuncture studies in hypertensive rats demonstrate an increased preglomerular vasoconstriction that is effective in preventing the development of intraglomerular hypertension. In fact, the +AR develops little renal damage, unless uninephrectomi?ed. In these animals, rigorous FP control does not prevent the development of proteinuria and the pathologic changes of hypertensive nephrosclerosis. 3he ahl salt-sensitive rat develops proteinuria !efore hypertension and !efore a high-sodium diet is administered. In patients "ith primary hypertension, hemodynamic studies freuently sho" a reduction in renal !lood flo". 3he increased preglomerular vasoconstriction of the afferent arteriole and interlo!ular artery is thought, at least initially, to eert a protective effect in the glomerulus. >ith time, sclerosis of the preglomerular vessels causes further reduction in renal !lood flo". 3he 'R is maintained !ecause of increased intraglomerular pressure secondary to efferent arteriolar vasoconstriction and systemic hypertension. hypertension . Eventually, glomerular ischemia and tu!ular ischemia develop. %onsidered together, these data suggest that hypertension precedes and accelerates arteriolar changes in the renal vessels. >ang et al investigated "hether podocyte in/ury is an important factor in the pathogenesis of hypertensive nephrosclerosis. In a study involving B5 patients "ith !iopsy-proven hypertensive nephrosclerosis, 5: cadaveric $idney donors, and ; healthy su!/ects, the authors found that compared "ith controls, intrarenal messenger ri!onucleic acid (mR1) epression "as lo"er, and urinary mR1 epression "as higher, for the podocyte-associated molecules molecu les nephrin, podocin, and synaptopodin in patients "ith hypertensive nephrosclerosis. &oreover, patients "ith nephrosclerosis had a significantly lo"er density of glomerular podocytes than did $idney donors (@B@ YG- =7C vs CC7 YG- =;D per glomeruli, respectively2 $ M M .:=).4@, D6 'enetics
genetic lin$ for hypertension and related renal failure is supported !y studies demonstrating familial clustering of hypertensive nephrosclerosis in !lac$ people and, to some etent, in "hite people. In the &ultiple Ris$ actor Intervention 3rial (&RI3), no changes in the reciprocal creatinine slope "ere o!served in "hite people, !ut a significant loss in $idney function "as o!served in !lac$ people despite similar levels of FP control. +imilarly, secondary analyses from the &odification of iet in Renal iseases (&R) study demonstrated that at euivalent mean arterial pressures greater than ;8 mm Ag, !lac$ patients had a reduction in their 'R at a rate of approimately 5 m#GminGy more than "hite patients. 3hese o!servations have led to investigations into genetic factors predisposing to renal damage. In =::8, = separate groups sho"ed strong association !et"een genomic variants "ithin &JA; (nonOmuscle myosin heavy chain ;) on == and nondia!etic E+R in frican mericans. 4C, 86 3he = other disease entities associated "ith &JA; included AI* nephropathy and focal segmental glomerulosclerosis (+'+) in frican mericans. mericans. In =:5:, = other groups sho"ed an even stronger association !et"een 5:66 the A$/L+gene and ris$ of E+R in frican mericans. mericans. 4;, 5: A$/L+, "hich encodes apolipoprotein #5, is also on == and is separated from the 8H9 gene !y only 5B::: nucleotides. 3"o variants of A$/L+ that have !een associated "ith increased ris$ of nephropathy include nonsynonymous coding variants termed '5 (glycine-7B= to methionine-78B) and in-frame D!p deletion termed '=. 3he po#5 protein protects against &rypanosoma infection. Ao"ever, the "ild-type po#5 protein can !e neutrali?ed !y &rypanosoma brucei rhodesiense: 3hese = gene variants restore immunity to &rypanosoma brucei rhodesiense: s a result, genomic evolution has led to positive selection for A$/L+ ris$ variant. &ore recent studies have further sho"n that nondia!etic carriers of = A$/L+variants have a 7-times higher rate of proteinuria and reduced renal function and carriers of 5 or = variants are significantly younger at the time of initiation of dialysis.
merican +tudy of idney 3he frican merican idne y disease (+) trial evaluated the role of intensive versus standard FP control on progression of $idney disease in 5:;B !lac$ patients "ith chronic $idney disease ('R =:-D@ 5566 m#GminG+). 455 3he study "as done in a trial phase follo"ed !y a cohort phase. Hverall, no difference "as noted in the rate of disease progression in the = groups. In the su!analysis, in "hich patients "ere stratified !ased on the degree of proteinuria, patients "ho had initial urinary protein-to-creatinine ratios of less than :.== did not !enefit from the intensive FP control, "hereas those "ith urinary protein-to-creatinine ratio of greater than :.== !enefited from the intensive therapy at the end of the cohort phase. A$/L+ and 8H9 nephropathy ris$ variants have !een associated 5=66 "ith $idney disease in the + participants. 4 45= 3his genetic predisposition may !e the reason "hy tighter control of FP in this !lac$ population does not slo" the progression of $idney disease. +ome authors argue that hypertension in this setting is secondary to underlying renal 5766 in/ury. 457 In different populations studied regarding polymorphism in the angiotensinconverting en?yme (%E) gene, the genotype is associated "ith a higher prevalence of progressive renal disease. 3his genotype is more common in the !lac$ population than the "hite population. Flac$ people "ith hypertension also have increased angiotensinogen mutations compared "ith "hite people "ith hypertension. Aomo?ygous polymorphism is associated "ith an enhanced pressor response to angiotensin I. In patients "ith immunoglo!ulin nephropathy, homo?ygous polymorphism appears to influence the rate of progression of renal rena l diseases and the response to %E inhi!itors2 thus, %E polymorphism could !e a modulator for the renal response to in/ury and the response to treatment in persons "ith hypertensive nephrosclerosis. >hether these data are also applica!le to the !lac$ population remains to !e determined. 1oting that hypertension-associated E+R displays familial aggregation in the !lac$ population, ung et al investigated possi!le lin$s !et"een genetic variations and 'R declines. In a study of @@B !lac$ patients, the investigators found evidence that such declines can !e predicted !y variations in the adrenergic !eta-5 (RF5) receptor at the +erB;'ly position. 3he
authors also found that 'R decline "as significantly smaller in patients "ho "ere 'ly(B;)G'ly(B;) (minor allele) homo?ygotes than in those "ho "ere 5B66 +er(B;) carriers. 4 45B Epidemiology reuency
United States
Hver the last = decades, E+R attri!uted to hypertensive nephrosclerosis has contri!uted significantly to the increase in ne" patients starting dialysis in the United +tates. ccording to the =:55 U+R+ data, the rate of E+R due to hypertension has gro"n 8.C since the year =:::, "hereas the rate of E+R due to glomerulonephritis has fallen =7 and rate of E+R secondary to dia!etes has remained relatively sta!le. >hen patients are separated according to race, hypertension is the leading cause of E+R in !lac$ people, accounting for 7B of patients initiating dialysis during this period. International
In Europe, according to the European ialysis and 3ransplant ssociation registry, ssociation registry, hypertensive nephrosclerosis is a less common cause of E+R, accounting for 5= of ne" patients starting renal replacement therapy. Ao"ever, the reported incidence varies among different countries, "ith rance and Italy reporting hypertensive nephrosclerosis as !eing responsi!le for E+R in =@ and 5C of patients starting dialysis, respectively. >hereas >hereas in United ingdom (all countries included), it accounts for D.5 of patients starting ne" on dialysis. In sia, hypertension appears to !e a relatively infreuent cause of E+R, "ith !oth Lapanese and %hinese registries reporting D and C, respectively. Esta!lishing Esta!lishing "hether these differences are real or reflect differences in accuracy of diagnosis or criteria for diagnosis in different countries is difficult. &ortalityG&or!idity
ccording to the =:55 U+R+, the annual mortality rate for patients on hemodialysis in the United +tates is =7.7. Aypertensive nephrosclerosis accounts for more than one third of patients on hemodialysis. Race
&ar$ed differences eist in the stated prevalence of hypertensive nephrosclerosis among patients of different ethnic !ac$grounds. lthough !lac$ people ma$e up 5= of the U+ population, they account for =8.7 of the patients on renal replacement therapy. >ith perhaps the eception of atherosclerotic renal disease, !lac$ people are at an increased ris$ of renal diseases from any cause, especially hypertensive nephrosclerosis. In !lac$ people, hypertensive nephrosclerosis occurs earlier, is more severe, and more often causes E+R (7D.8 in !lac$ patients vs =D in "hite patients). In persons of all age groups, E+R is more common in !lac$ people2 the rate of developing E+R is 7.@ times higher than the rate found among "hites. 3he increased suscepti!ility of !lac$ patients "ith hypertension to develop progressive renal failure cannot !e eplained solely !y the higher prevalence of hypertension, severity of hypertension, or socioeconomic factors !ecause the rate of ne" n e" E+R cases has remained sta!le in frican mericans, mericans, "hereas it has gro"n C.= among "hite, and, in addition, the rates of stro$e and cardiovascular mortality have decreased eually in !oth "hite and frican merican populations. Results from the &RI3 trial indicated that effective FP control "as associated "ith sta!le renal function in "hite people !ut not in !lac$ people. In the + trial, "hich specifically evaluated !lac$ populations, intensive control of FP in nonproteinuric patients did not decrease progression of $idney disease. +everal renal, hormonal, physiologic, and genetic factors have !een proposed as eplanations for the increased rate of hypertension and progression of chronic $idney disease in frican mericans. mericans. 3hese include increased FP sensitivity to high-salt diet, increased renal vascular resistance, decreased renal !lood flo", increased tortuosity and occlusion in the interlo!ular and arcuate arteries !ased on renal angiograms in frican mericans, and
decreased nephron mass secondary to lo" !irth "eight (more common in frican mericans). mericans). #astly, the increased variant in A$/L+ gene has !een proposed as the cause of the increased increase d rate of E+R in frican mericans. ge
3he diagnosis of hypertensive nephrosclerosis increases "ith advancing age. 3he pea$ age for the development of E+R in "hite patients is D@ years and older, "hile the pea$ age is B@-D@ years in !lac$ people. In most cases, the diagnosis of hypertensive nephrosclerosis in older patients is made clinically !ecause of the reluctance to perform a renal !iopsy in this elderly 5@66 population. 45@ Even "hen a renal !iopsy specimen is availa!le, distinguishing vascular lesions due to aging from those due to hypertension may !e difficult. In this respect, atheromatous renal vascular disease has !een increasingly recogni?ed as a common finding in patients older than @: years. Rimmer and 'ennari (5;;7) estimate that atheromatous renal vascular 5D66 disease accounts for @-5@ of all patients "ho develop E+R each year. 45D In addition, cholesterol em!olism resulting from atheromatous plaue disruption "ith su!seuent shedding of cholesterol crystals into the renal circulation is freuently diagnosed in this patient population. Foth renal artery stenosis and cholesterol em!olism are associated "ith renal microvascular lesions and "ith glomerular sclerosis. 1either of these findings should !e underestimated !ecause patients older than D@ years represent at least B@ of the total population of patients on dialysis in the United +tates. +imilarly, ppel et al (5;;@) found !ilateral renal r enal artery stenoses in 55 55 of 5C66 patients on hemodialysis "ho are older than @: years. 45C fter etrapolating their results to the total num!er of cases of E+R, multiplying !y the num!er of patients aged @: years or older, and multiplying !y the num!er of patients "ith ischemic renal disease, ppel et al concluded that more than 7@:: cases of ischemic renal disease remain undiagnosed each year in the United 5C66 +tates. 45C If these predictions are correct, ischemic renal disease is li$ely the fourth most common cause of E+R in patients older than @: years. Aansen et al (=::=) provided the first population-!ased estimate of the prevalence of renovascular disease among free-living elderly merican
5866 participants of the %ardiovascular Aealth +tudy (%A+). 4 458 3his is a multicenter, longitudinal cohort study of cardiovascular disease ris$ factors, mor!idity, and mortality among free-living adults older than D@ years. %A+ participants num!ered 8C:, and each under"ent renal duple sonography to assess for the presence or a!sence of renovascular disease, defined as greater than or eual to D: diameter-reducing renal artery stenosis or occlusion. 3he results of this study sho" that renovascular disease is present in D.8 of all individuals, regardless of race (D.; of "hite participants and D.C of !lac$ participants).
Fac$ground
Pott disease, also $no"n as tu!erculous spondylitis, is one of the oldest demonstrated diseases of human$ind, having !een documented in spinal remains from the Iron ge in Europe and in ancient mummies from Egypt and the Pacific coast of +outh merica. 4 455, =6 In 5CC;, Percivall Pott, for "hom the disease is named, presented the classic description of spinal tu!erculosis tu!erculosis.. (+ee the image !elo".) 476
&RI of a 75-year-old man "ith tu!erculosis of the spine. Images sho" the thoracic spine !efore and after an infusion of intravenous gadolinium contrast. 3he a!scess and su!seuent destruction of the 355-35= disc interspace is mar$ed "ith arro"heads.
*erte!ral !ody alignment is normal. %ourtesy of &ar$ %. iamond, &, and L. ntonio Fouffard, &, etroit, &ich. &ich. *ie" &edia 'allery +ince the advent antitu!erculous drugs and pu!lic health measures, spinal of tu!erculosis has !ecome rareimproved in industriali?ed countries, although it is still a significant cause of disease in developing nations. 3u!erculous involvement of the spine has the potential to cause serious mor!idity, including permanent neurologic deficits and severe deformities. &edical treatment or com!ined medical and surgical strategies can control the disease in most patients. 4 4BB, @6 Patient education
Patients "ith Pott disease should !e instructed on the importance of therapy compliance. or patient education information, see the Infections %enter , as "ell as3u!erculosis as3u!erculosis.. Pathophysiology
Pott disease is usually secondary to an etraspinal source of infection. Pott disease manifests as a com!ination of osteomyelitis and arthritis that usually involves more than 5 verte!ra. 3he anterior aspect of the verte!ral !ody ad/acent to the su!chondral plate is usually affected. 3u!erculosis may spread from that area to ad/acent interverte!ral dis$s. In adults, dis$ disease is secondary to the of infection the verte!ral In children, the 4D6 dis$, !ecause it isspread vasculari?ed, can from !e the primary site.!ody. Progressive !one destruction leads to verte!ral collapse and $yphosis. 3he spinal canal can !e narro"ed !y a!scesses, granulation tissue, or direct dural invasion, leading to spinal cord compression and neurologic deficits. 3he $yphotic deformity is caused !y collapse in the anterior spine. #esions in the thoracic spine are more li$ely to lead to $yphosis than those in the lum!ar spine. cold a!scess can occur if the infection etends to ad/acent ligaments and soft tissues. !scesses in the lum!ar region may descend do"n the
sheath of the psoas to the femoral trigone region and eventually erode into the s$in. Epidemiology Hccurrence in the United +tates
lthough the incidence of tu!erculosis increased in the late 5;8:s to early 5;;:s, the total num!er of cases has decreased in recent years. 3he freuency of etrapulmonary tu!erculosis has remained sta!le. Fone and soft-tissue tu!erculosis accounts for approimately 5:-5@ of etrapulmonary tu!erculosis cases and !et"een 5 and = of total cases. 3u!erculous spondylitis is the most common manifestation of musculos$eletal tu!erculosis, accounting for approimately B:-@: of cases. 3hese figures are roughly similar for 1orth merican and international series. 4 4CC, 86 International occurrence
pproimately 5-= of total tu!erculosis cases are attri!uta!le to Pott disease. In the 1etherlands, !et"een 5;;7 and =::5, tu!erculosis of the !one and /oints accounted for 7.@ of all tu!erculosis cases (:.=-5.5 in patients of European origin, and =.7-D.7 in patients of non-European origin). 4;6 Race-, se-, and age-related demographics
ata from #os ngeles and 1e" Jor$ Jor$ sho" that musculos$eletal tu!erculosis affects primarily frican mericans, Aispanic mericans, sian mericans, mericans, and foreign-!orn individuals. s "ith other forms of tu!erculosis, the freuency of Pott isease isease is related to socioeconomic factors and historical eposure to the infection. lthough some series have found that Pott disease does not have a seual predilection, the disease is more common in males (male-to-female ratio of 5.@-=05).
In the United +tates and other developed countries, Pott disease occurs primarily in adults. In countries "ith higher rates of Pott disease, involvement 5:,, 55 5566 in young adults and older children predominates. 45: Prognosis
%urrent treatment modalities are highly effective against Pott disease if the disorder is not complicated !y severe deformity or esta!lished neurologic deficit. eformity and motor deficit are the most serious conseuences of Pott disease and continue to !e a serious pro!lem "hen diagnosis is delayed or 5=66 presentation of the patient is in advanced stages of the disease. 45= 3herapy compliance and drug resistance are additional factors that significantly affect individual outcomes. Paraplegia resulting from cord compression caused !y the active disease usually responds "ell to chemotherapy. Ao"ever, Ao"ever, paraplegia can manifest man ifest or persist during healing !ecause of permanent spinal cord damage. Hperative decompression can greatly increase the recovery rate, offering a means of treatment "hen medical therapy does not !ring rapid improvement. %areful long-term follo" up is also recommended, since late-onset complications can still occur (disease reactivation, late insta!ility or 457 5766
deformity). &or!idity
Pott disease is the most dangerous form of musculos$eletal tu!erculosis !ecause it can cause !one destruction, deformity, and paraplegia. Pott disease most commonly involves the thoracic and lum!osacral spine. 5B,, 5@ 5@,, 5D 5D,, 5C 5C66 Ao"ever, pu!lished series have sho"n some variation. 45B 3he lo"er thoracic verte!rae ma$e up the most common area of involvement (B:-@:), follo"ed closely !y the lum!ar spine (7@-B@). In other series, proportions are
5866 similar !ut favor lum!ar spine involvement. 458 pproimately 5: of Pott disease cases involve the cervical spine.
Internal iation for ractures !ro$en !one must !e carefully sta!ili?ed and supported until it is strong enough to handle the !odys "eight and movement. Until the last century, physicians relied on casts and splints to support and sta!ili?e the !one from outside the !ody. 3he advent of sterile surgical procedures reduced the ris$ of infection, allo"ing doctors to internally set and sta!ili?e fractured !ones. uring a surgical procedure to set a fracture, the !one fragments are first repositioned (reduced) into their normal alignment. 3hey are held together "ith special implants, such as plates, scre"s, nails and "ires. Internal fiation allo"s shorter hospital stays, ena!les patients to return to function earlier, and reduces the incidence of nonunion (improper healing) and malunion (healing in improper position) of !ro$en !ones. 3he implants used for internal fiation are made from stainless steel and titanium, "hich are dura!le and strong. If a /oint is to !e replaced, rather than fied, these implants can also !e made of co!alt and chrome. Implants are compati!le "ith the !ody and rarely cause an allergic reaction.
Plates Plates are li$e internal splints that hold the !ro$en pieces of !one together. 3hey are attached to the !one "ith scre"s. Plates may !e left in place after healing is complete, or they may !e removed (in select cases). 3op of page
+cre"s +cre"s are used for internal fiation more often than any other type of implant. lthough the scre" is a simple device, there are different designs !ased on the type of fracture and ho" the scre" "ill !e used. +cre"s come in different si?es for use "ith !ones of different si?es. +cre"s can !e used alone to hold a fracture, as "ell as "ith plates, rods, or nails. fter the !one heals, scre"s may !e either left in place or removed. 3op of page
1ails or Rods In some fractures of the long !ones the !est "ay to hold the !one pieces together is !y inserting a rod or nail through the hollo" center of the !one that normally contains some marro". +cre"s at each end of the rod are used to $eep the fracture from shortening or rotating, and also hold the rod in place until the fracture has healed. Rods and scre"s may !e left in the !one after healing is complete. 3his is the method used to treat the ma/ority of fractures in the femur (thigh!one) and ti!ia (shin!one).
(Left) 3his -ray sho"s a healed thigh!one fracture treated "ith intramedullary nailing. (Right) In this -ray, the thigh!one fracture has !een treated "ith plates and scre"s. 3op of page
>iresGPins >ires are often used to pin the !ones !ac$ together. 3hey are often used to hold together pieces of !one that are too small to !e fied "ith scre"s. In many cases, they are used in con/unction "ith other forms of internal fiation, !ut they can !e used alone to treat fractures of small !ones, such as those found in the hand or foot. >ires are usually removed after a certain amount of time, !ut may !e left in permanently for some fractures. 3op of page
Eternal iators n eternal fiator acts as a sta!ili?ing frame to hold the !ro$en !ones in proper position. In an eternal fiator, metal pins or scre"s are placed into the !one through small incisions into the s$in and muscle. 3he pins and scre"s are attached to a !ar outside the s$in. Fecause pins are inserted into !one, eternal fiators differ from casts and splints "hich rely solely on eternal support. In many cases, eternal fiation is used as a temporary treatment for fractures. Fecause they are easily applied, eternal fiators are often put on "hen a patient has multiple in/uries and is not yet ready for a longer surgery to fi the fracture. n eternal fiator provides good, temporary sta!ility until the patient is healthy enough for the final surgery. Hther times, an eternal fiator can !e used as the device to sta!ili?e the !one until healing is complete. 3here may !e some inflammation inflamm ation or, less commonly, infection associated "ith the use of eternal fiators. 3his is typically managed "ith "ound care andGor oral anti!iotics.
Eternal fiation is often used to hold the !ones together temporarily "hen the s$in and muscles have !een in/ured. 3op of page
Hther %onsiderations +terile conditions and advances in surgical techniues reduce, !ut do not remove, the ris$ of infection "hen internal fiation is used. 3he severity of the fracture, its location, and the medical status of the patient must all !e considered. In addition, no techniue is foolproof. 3he fracture may not heal properly or the plate or rod may !rea$ or deform. lthough some media attention has focused on the possi!ility that cancer could develop near a long-term implant, there is little evidence documenting an actual cancer ris$ and much evidence against that possi!ility. Hrthopaedic surgeons are continuing their research to develop improved methods for treating fractures. 3op of page
t er nal Fi x at i on Ex Ex t er nal Fi x at i onofLowerLeg Eternal fiationof the lo"er leg is a surgical procedure to eternally immo!ilise and fi a !one follo"ing a fracture allo"ing the !one to heal effectively. Physiotherapy after eternal fiation surgery is essential to mo!ilise and return function in the lo"er leg. 3he !ones in the lo"er leg include the ti!ia (shin !one) and the fi!ula (smaller long !one). fracture of the lo"er leg can affect the shaft of one or !oth of the !ones in the lo"er leg. ractures of the ti!ia G fi!ula are mainly caused !y either a direct !lo" to the lo"er leg or !y
a t"isting force "hen the foot is fied. 3here are many different types and severity of fractures. 3he various severities of fractures to the lo"er leg include0 •
1on-displaced (!ones are still in position)
•
isplaced (out of position)
•
%losed fractures ("here the s$in is not !ro$en !y the fracture fragments)
•
Hpen fractures ("here the fracture fragments have !ro$en through the s$in)
3he s$in and tissues that cover the front of the ti!ia and fi!ula are very thin and as a result of this, a significant num!er of fractures to the lo"er leg are displaced, open fractures. 3he main symptoms that follo" a fracture to the lo"er leg include severe pain and reduced mo!ility as the leg "ill !e etremely painful and difficult to move. >ith fractures of the lo"er leg there "ill !e deformity at the site of the fracture, especially "ith open fractures. s a result of the large amount of tissue damage and loss of !lood at the fracture site, there "ill also !e a considera!le amount of s"elling and discolouration. 3reatment of lo"er leg fractures can vary depending on the severity of the fracture. If the !one is still in its correct alignment (non-displaced) then immo!ilisation "ith use of a splint or cast follo"ed !y physiotherapy is recommended. If the fracture is out of position (displaced) !ut the s$in is still intact (closed fracture) then HRI of the lo"er leg (open leg (open reduction internal fiation) is reuired. In severe cases, eternal fiation surgery is necessary. Eternal fiation surgery is a method of holding together the fragments of a fractured !one !y using transfiing metal pins through the fragments and a compression device attached to the pins outside the s$in surface. 3he main indications for the use of eternal fiation surgery are in cases "here there has !een a displaced, open fracture (the !one is out of position and has !ro$en through the s$in). lso eternal fiation is indicated "hen there is high ris$ of infection, considera!le !one loss at the fracture site, and "hen other methods such as HRI of the lo"er leg are leg are inappropriate. %ommon types of eternal fiation used in the treatment of a lo"er leg fracture include i and #li?arov. Eternal fiation is a procedure that sets and immo!ilises the fractured !one in its correct alignment so as to ena!le and facilitate adeuate healing of the lo"er leg. 3he method provides rigid fiation of the !ones outside the !ody (eternal) in cases "here other forms of immo!ili?ationare inappropriate. Eternal fiation is performed in an operating room, normally under general anaesthesia. uring eternal fiation small holes are drilled into
unin/ured areas of !ones around the fracture and special !olts or "ires are scre"ed into the holes. Hutside the !ody, a rod or a curved piece of metal "ith special !all-and-soc$et /oints /oins the !olts to ma$e ma$e a rigid rigid support. support. 3he fracture fracture can can !e set in the proper proper anatomical anatomical configuration !y ad/usting the !all-and-soc$et /oints. fter the rods are fied, regular cleaning "here the pins have !een insertedmust !e performed to prevent infection at the site of surgery.In most cases it may !e necessary for the eternal fiator to !e in place for many "ee$s or even months. &ost fractures of the lo"er leg heal from !et"een D and 5= "ee$s. fter this time the eternal fiators are removed using specialised "renches and can !e removed "ithout any anaesthesia. Hnce the eternal fiator has !een removed, it is imperative to undergo a comprehensive and prolonged course of physiotherapy to maimise the success of the procedure and to help ensure the return of full or near to full function in the lo"er leg post fracture.
Sy mpt mp omsaf t erEx t er nal Fi x at i onoft heLowerLeg uring the months you have eternal fiators inserted into your lo"er leg you "ill !e given el!o" crutches to provide protection, support and independence. Jou "ill eperience pain in the area of insertion along "ith a!normal sensations. Jou "ill !e given medication to control for pain, reduce s"elling and prevent infection. 3he Zpin sites can !e a source of infection therefore you "ill !e sho"n !y hospital staff ho" to carry out effective "ound care and you may have to return to the hospital for regular chec$ ups during s period. fter you you have had had the eternal eternal fiators fiators removed, removed, you "ill eperience eperience pain, pain, s"elling and stiffness in and around the fracture site. Jou "ill have decreased range of movement, strength and muscle control in your lo"er leg as a result of the surgery and prolonged immo!ilisation. Jou "ill !e non-"eight !earing initially "ith progression to full "eight !earing !eing encouraged as soon as possi!le. comprehensive physiotherapy programme "ith Physio.co.u$ should !e initiated as soon as possi!le after the eternal fiators have !een removed to regain mo!ility as "ell as full or near to full function in your lo"er leg. Jou "ill not !e a!le to drive until you have full and painless function in your affected leg.
Phy s i ot her apyaf t erEx t er nal Fi x at i onoft heLowerLeg Physiotherapy can !egin immediately after you have had eternal fiation of your lo"er leg to help reduce pain, s"elling and stiffness. It is encouraged to !egin physiotherapy as soon as possi!le as this "ill help you regain mo!ility and improve range of movement and strength in your affected leg. Physio.co.u$ offers a comprehensive physiotherapy course that "ill maimise the success of the surgery, prevent any pro!lems occurring and ensure the return of full or near to full function in your lo"er leg. Reha!ilitation can ta$e up to D months after you have had HRI surgery to your lo"er leg. 3he main goals of your reha!ilitation "ith Physio.co.u$ include0 •
3o restore a pain free lo"er leg
•
3o restore full range of motion (RH&)
•
3o restore full muscle strength
•
3o restore full muscle length and flei!ility
•
3o improve cardiovascular fitness and muscle endurance
•
3o re-esta!lish independence
04weeks 3he main goals of your physiotherapy programme in the first month after undergoing eternal fiation "ill !e to reduce pain and s"elling in your lo"er leg. Jour physiotherapy programme "ith Physio.co.u$ "ill aim to gradually introduce you !ac$ to gentle activity. Physio.co.u$ "ill focus on maintaining the range of movement and strength in your affected and unaffected leg. dditionally, your physiotherapy "ill include activities that aim to progress your a!ility to "eight !ear as soon as possi!le. Jour reha!ilitation "ill include0 •
Pain $illers (to control pain)
•
Elevation (to control s"elling)
•
%rutch training
•
1on "eight !earing activities progressed to partial "eight !earing activities
•
Passive (assisted) range of movement eercises for affected leg ($nee, an$le etc)
•
+trengthening and range of movement eercises for unaffected leg
•
Upper lim! activities
58weeks uring the second month of your reha!ilitation "ith Physio.co.u$ your physiotherapy "ill focus on the continuation and progression of activities from previous "ee$s. Jour physiotherapy programme "ith Physio.co.u$ "ill continue to focus on controlling pain and s"elling. Physio.co.u$ "ill also continue to focus on improving range of movement nd flei!ility along "ith increasing muscle strength and control. Jour physiotherapy "ill include0 •
%ontinuation of modalities for pain and s"elling
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Passive (assisted) and active (independent) range of movement eercises
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+trengthening eercises for muscles of affected leg (calf, hamstring, uadriceps etc)
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+tretching eercises for muscles of affected leg (calf, hamstring, uadricep etc)
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Range of movement, strengthening and stretching eercises for unaffected leg
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Progression of "eight !earing O full "eight !earing activities if possi!le
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'ait re-education training
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Proprioception and !alance training
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Aip and an$le eercises
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Aydrotherapy
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+tatic !icycle
912weeks fter = months months of physiothe physiotherapy rapy,, your your reha!ilitation reha!ilitation your your physiotherapy physiotherapy programme programme "ill continue to focus on the progression from previous "ee$s. 3he main goals of your physiotherapy programme "ith Physio.co.u$ "ill aim to minimise pain, improve range of movement and increase strength. Hnce your a!ility to "eight !ear has improved, your physiotherapy programme "ill no" focus on gait re-training ("al$ing) and improving proprioception (!alance) in your lo"er leg. t this stage, your physiotherapy "ill also !egin to include activities that "ill improve your cardiovascular fitness and muscle endurance. Jour physiotherapy "ill include0 •
Pain control
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'ait training ("al$ing)
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Proprioception training (!alance)
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Range of movement eercises
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lei!ility eercises
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+trengthening eercises for muscles in affected and unaffected leg (calf, hamstring, uadriceps, ti!ialis anterior etc)
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Aydrotherapy
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+tatic !icycle
36mo mont hs
ollo"ing three months of successful reha!ilitation "ith Physio.co.u$ you "ill have seen mar$ed improvements in the function of your lo"er leg and you "ill !e eperiencing minimal if no pain and s"elling. fter 5= "ee$s, the eternal pins "ill have !een surgically removed and you "ill no" !e fully "eight !earing. 3he main goals of your physiotherapy "ill continue to focus on the progression of eercises from previous "ee$s. Jour physiotherapy "ill concentrate on activities that help improve the strength in the muscles of your lo"er leg !y consistently !uilding up resistance in the strengthening eercises. Jou should have full range of movement and your physiotherapy "ill aim to maintain and improve flei!ility of !oth your lo"er lim!s. Jour reha!ilitation "ill continue "ith proprioception and gait training. %ardiovascular activities such as hydrotherapy, cycling and gentle /ogging can !e included in your programme. unctional activities that focus on specific tas$s related to your lifestyle, ho!!ies or /o! "ill also !e included in your physiotherapy programme. 3he success of your recovery after eternal fiation surgery "ill highly depend on you commitment to your physiotherapy programme as "ell as the condition of your leg prior to the surgery. Recovery "ill ta$e up to D months.
Summar y Eternal fiation of the lo"er leg is a surgical procedure that uses rods or plates to immo!ilise and fi a !one follo"ing a fracture to allo" the !one to heal in its correct position. ractures in the lo"er leg can occur along the shaft of the ti!ia (shin !one), along the shaft of the fi!ula (smaller long !one) or !oth. 3reatment of a fracture to lo"er leg can vary depending on the severity of the in/ury. In severe cases "here the !one is displaced and the fracture fragments have !ro$en the s$in (open fracture) eternal fiation is the most commonly utilised procedure. Eternal fiation is reuired to ena!le correct alignment as "ell as facilitating adeuate healing of the lo"er leg. Eternal fiation allo"s the return of function as "ell as preventing future complications and deformation of the lo"er leg. Physiotherapy "ith Physio.co.u$ after eternal fiation is crucial to ensure the success of the surgery, prevent the li$elihood of any future pro!lems and to help you achieve the return of full or near to full function "ithin your lo"er leg. %ommitment to a personal physiotherapy programme "ith Physio.co.u$ "ill allo" a more rapid return to everyday activities, "or$,
ho!!ies, and sport. Call Physio.co.uk now on 0330 088 7800 for more information or to book an appointment please contact us. us. Add:
External Fixation Deices ! Concept an" #se
PUBLISHED - BY DR ARUN PAL SINGH LAST SINGH LAST EDITED AUG 29, 2016 @ 4:01 PM External fixation is a useful tool in the management of fractures and certain difficult orthopedic problems such as limb length discrepancy. discrepancy. External fixation a useful tool in fracture management and in the case of pelvic fracture it may be a primary life saving device With external fixation, pins and/or wires are percutaneously inserted into the bone and held in place by an external frame. [Know more about other types of fixations] fixations] External fixation is most successful successful in superficial bones lie tibia than deeper bones bones lie femur or humerus ! here the chance of pin tract sepsis sepsis is is greater. External fixators consist of modular components which are assembled to form a stable construct between bone fragments and an ad"ustable beam system. #he beam system is "oined to the bone by means of a number of pins screwed into the bone. #echni$ue #e chni$ue of external fixation f ixation was populari%ed in the mid&'(th century by )offman.
*ndications of external +ixation •
imb length discrepancy surgeries
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-rthrodesis
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orrection of angulatory or rotator deformity
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one segment transportation to fill the bone gap
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#emporary fixation of open fractures
o
0aintains stability
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Eases dressing
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When definitive surgery is delayed for some reason
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1apid 2tabili%ation
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3elvic fixation to stop bleeding
o
1apid fixation of polytrauma patients
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4efinitive external fixation of fractures especially intraarticular fractures fractures
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igamentotaxis
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#o position limb in desired position as in nerve or tendon repair
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*nfected fractures
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urns
-dvantages of External +ixation •
3rovides rigid fixation when other forms of immobili%ation are not feasible. +or example, severe open fractures cannot be managed by plaster casts or internal fixation due to ris involved.
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-llows compression, neutrali%ation, or fixed distraction of the ffracture racture fragments.
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-llows surveillance of the limb and wound status.
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-llows other treatments lie dressing changes, sin grafting, bone grafting, and irrigation, is possible without disturbing the fracture alignment or fixation.
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proximal and and distal distal "oints #his aids in reduction of edema edema and -llows immediate motion of the proximal nutrition of articular surfaces and retards capsular fibrosis, "oint stiffening, muscle atrophy, and osteoporosis.
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-llows limb elevation by suspending frame from overhead frames
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-llows early patient ambulation
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an be done with the patient under local anesthesia, if necessary.
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External fixators cause less disruption of the soft tissues, osseus blood supply, and periosteum. #his maes externa fixation excellent choice in o
-cute trauma with sin contusions and open wounds o
*n chronic trauma where the extremity is covered in thin sin grafts and muscle flaps,
o
3atients with poor sin healing
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-bility to fix the bone avoid fixation at the site of fracture or lesion, and still obtained the rigid fixation
4isadvantages of external fixation •
3ins inserted in the bones are exposed to internal environment and ris of pin tract infection is always there
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+racture may occur through pin tracts after frame removal. Extended protection may be re$uired.
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imb, is cumbersome and needs meticulous care. )igh -ssembly of the fixator lies outside the llimb, degree of compliance and motivation is re$uired
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non&cooperative ative patients 5ot suitable for non&cooper
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*n fixators with pins near the "oint or fixators that span "oint, "oint stiffness can occur occur..
#ypes #y pes of External +ixators *n strictest sense there are two types of fixators ! unilateral and circular. - combination of two is called hybrid fixators.
6nilateral +ixator [0odular -7 #ype] #ype]
External Fixator TIbia
Xray of External Fixator In Tibia With Kwires In Heel #hey are called so because they are generally are distinguished from circular frames in that they are positioned on one side of the limb. 6nilateral frames allow the limb to remain functional, avoid complications, and provide bony stability #wo most common designs are the bulier
Monobody designs #he monobody frames have considerable intrinsic stability owing to their heavy and rigid design.
Pin-to-bar fixators. #hese are ind of fixators use combination of schan% screws, rods and clamps which are assembled to form a construct.
ircular +ixators
Ilizarov External Fixation Device in Tibia. Note the circular rins an! thin wires I"ae #re!it$ Wi%i&e!ia #re!it$ Wi%i&e!ia
#hese ind of external fixators use construct formed by circular rings, wires, connecting rods, and struts. #his is $uite versatile type of external fixator fixator.. - partial ring is commonly used around the proximal proximal and and around the shoulder and proximal proximalfemur femur where a full ring would not fit comfortably.
6nilateral or 0odular -7 External +ixation omponents of this fixator are given below. •
2chan% 2crews
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onnecting rods
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lamps
Each of the components can come in different dimensions to suit the scale of the bone to which they are to be applied and to permit variation in the shape and configuration of the final bone&external fixator construct.
2chan% screws 2chan% screws are partially threaded pins. #hese are available in different diameters and lengths of shaft and threaded part and with different tips. 2tandard screws have trocar&shaped tips. #hey re$uire predrilling. 2elf&drilling and self&cutting screws are available. 2chan% screws are available in steel and titanium. 2han% pins with hydroxyapatite hydroxyapatite coating are aso available. #his maes bone purchase better and allows easier osseointegration, osseointegration, preventing loosening. 3ins with hydroxyapatite hydroxyapatite coating may be preferred for long&term long&term application of external fixators, eg, bone transport or deformity correction.
1ods/tubes #he -7 fixators consist of systems in four si%es, depending on the si%e of the rod8 •
arge8 99 mm tubes/rods with 2chan% screws from : to ; mm<
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0edium8 = mm tubes/rods with 2chan% screws from > to ; mm<
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2mall8 : mm tubes/rods with 2chan% screws from 9.= to : mm<
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0ini8 ' mm system for fingers. *ncludes multipin clamps for K&wires and ' mm longitudinal rods.
-ll systems are compatible with each other.
#he large 99 mm system contains both steel tubes and carbon fiber rods. 3recurved contoured contoured and # shaped rods are also available. urrently the :.?mm short threaded 2chan% screw is used in cortical bone and the @.(mm long threaded screw in cancellous bone. +or hand and wrist application smaller si%es are used. onnecting rods rods are made made of stainless steel steel of carbon fibre. fibre. #he latter are are very strong strong and are also radiolucent which is helpful when assessing bone alignment on x&ray x&ray..
lamps #he clamps provide the connection between the tubes or rods and the pins. iewise, rods or tubes can be connected to each other using the appropriate clamps Atube&to&tubeB. Atube&to&tubeB. *f one clamp allows the connection of both tubes and rods, they are called combination clamps. oth single&pin and multipin clamps are available.
lamps are available in three si%es with identical clamp design and application techni$ue. - larger tube to tube clamp permits two fracture components components to be held together in relatively stable alignment irrespective of the position the 2chan% pins tae up in the bone.
2tability of 6nilateral or 0odular -7 External +ixator #he bending stiffness of unilateral fixators is dependent dependent on the plane of the half pins and the plane of loading with anteriorly mounted frames providing greater bending stiffness. When these frames were loaded out of plane, with varus!v varus!valgus algus and torsional forces, they had poor control of the bone fragments with significant motion at the fracture f racture site. 0ore stability would be obtained from a multiplanar system. #he stiffness of the frame depends upon the following factors8 •
loser the 2chan% screws to the fracture, stiffer the construct
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+arther the last 2chan% screw placed on the fragment on each side of fracture, stiffer the construct
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loser the he longitudinal connecting tube/bar to the bone. 2tiffer the construct
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#wo bars/tubes are stiffer than one<
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+rame configuration ! #he stiffness of construct depends on the assembly assembly.. 4ifferent constructions of tubular external fixator which will produce increasing levels of stability are
o
6nilateral uniplanar single&tube fixator.
o
6nilateral uniplanar single&tube modular fixator. fixator.
o
6nilateral uniplanar double tube fixator.
o
6nilateral biplanar frame Adelta&frame or triangular frameB.
o
ilateral frame with transfixing pins [)ardly used now].
ircular +ixator *li%arov fixator is a typical circular fixator. ircular fixators consist of series of rings or arches which are connected to each other by connecting rods and rings are fixed to the bones by means of tensioned wires. 0any modifications can be added and accordingly the implant used in particular fracture f racture is used according to the indication for use and goals of the surgery. *li%arov fixtor is very versatile fixator and most people now it because it is used for lengthening the bones. *li%arov external fixator is discussed in detail separately. separately. *n circular external fixators, frame f rame stability is greatly impacted by ring properties. 2maller diameter rings are more stable than larger rings of the same thicness but a ring should not put pressure on the tissues and the final si%e is dictated by limb girth. 4ifferent diameter rings may be used in the same frame to ad"ust to contours of the limb. entrali%ing the bone is preferred but eccentric positioning has been found to have no adverse effect. #he closer the rings are , better is the frame stability. #he stability of construct is increased by •
6se of greater number of rings
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2horter distances between rings
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*ncreasing the span of the rings across the bone controlling both near and far ends of each segment
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*ncreasing the number of connections between the rings
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*ncreasing number of points of fixation to the bone.
est 3ractice #ips for External +ixator 9.
3lacing pins with aseptic techni$ue
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3rotecting soft tissues so that no necrotic tissue is left to encourage infection
>.
4rilling a pilot hole to remove bone debris debris and to reduce frictional resistance and so heat production during pin insertion.
:.
-chieving a firm pin fit with radial distribution of forces ! the pin is (.'mm larger than the pilot hole and this induces compression compression on the bone termed radial pre&load.
omplications of External +ixation omplications may arise in the fixator itself or most commonly at the bone pin interface. -s with any fracture especially in severe in"ury complications complications may occur at the fracture as a direct result of the in"ury.
3in #ract infection #his this may be the most common common complication, occurring occurring in about >(C >(C of patients. #he infection varies from minor sin inflammation to osteomy osteomyelitis elitis re$uiring se$uestrectomy. se$uestrectomy. 3in site infection occurs more when •
3in is inserted at place with greater soft tissue
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2in tethering over the pin
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*nade$uate pin care
5eurovascular *n"ury #he radial nerve in the distal distal half half of the arm and proximal and proximal half half of the forearm, thedorsal the dorsal sensory sensory radial nerve "ust above the wrist, and the anterior tibial artery and deep peroneal nerve at the "unction of the third and fourth $uarters of the leg are the structures most often involved. #he pins are nown to penetrate vessels, cause thrombosis when they are ad"oining the vessel, cause late erosion of the vessel, vessel, arterioveno arteriovenous us fistulas, and the formation of aneurysms. aneurysms.
0uscle +ibrosis and #endon #endon 1upture 3ins inserted through tendons may restrain normal excursion and can lead to tendon rupture, or muscle fibrosis
+racture omplications 5on union and delayed union can be seen with any mode of fixation and can occur with external fixator also. 1efracture 1efractur e can occur after fixator removal and the fracture needs protection for extended period after fixator is removed removed..
Internal fixation is an operation operation in in orthopedics orthopedics that involves the surgical implementation
of implants implants for for the purpose of repairing a a !one !one,, a concept that dates to the mid-nineteenth century and "as made applica!le for routine treatment in the mid-t"entieth century. century.456 n internal fiator may !e made of stainless steel steel or titanium titanium..4=6 3ypes of internal fiators include0 •
Plate and scre"s
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irschner "ires
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Intramedullary nails
Open Reduction Internal Fixation (ORIF) 4edit edit66 3his section does not cite cite any any sources. Please help improve this section !y section !y add citations to relia!le sources. sources . Unsourced material may !e challenged and removed removed.. ;.une )2+
