(BQ) Part 2 book Differential diagnosis mnemonics has contents: Nephrology, acid base, gastroenterology, rheumatology, neurology, clinical conditions or diagnoses, clinical symptoms and signs, general considerations.
mD N E P HROLOGY Genera l Considerations There a re two ways of approaching renal disease : 1 ) based on etiology, as outli ned in the MEDICINE DOC mnemonic, and ) based on pathology from a renal biopsy It is i m po rta nt to recog n ize that the sa m e disease process can cause different pathological processes in the kidney Ifor exa mple , systemic lupus erythematosus may cause a variety of renal lesions) Metabol ic-e g , amyloidosis, hyperuricemia E ndocrine - e g , hyperca lcemia, hyper and hypothyroidism, SIADH and diabetes insipidus Drugs/medicines - e g , chemotherapeutic agents, anti biotics, rad iocontrast dye I nfection - e g , H IV-related , tuberculosis, pyelonephritis Congenita l - polycystic kidney disease, Alport's syndrome, reflux nephropathy I m munologic- e g , Goodpasture's, Wegener's g ranulomatOSiS, SLE Neoplastic - e g , renal cell carci noma , transitional cell carcinoma, tumor lysis syndrome Exotic diseases -e g , sarcoidosis, ITP, cryog lobulinemia Degenerative - ag i ng, ?hypertension Occupational!environmental - trauma Card iovascu la r - e g , atherosclerOSiS, hypertensive nephropathy, choles terol emboli A multitude of metabolic disorders may cause renal d isease These include amyloidosis, hypercalcemia, and other diseases that lead to abnormal i ncreases in metabolic products in the blood stream Hyperlipidemia leading to atheroscle rosis a lso could be considered a metabolic disease leading to renal insufficiency Endocrine diseases may be made man ifest by renal insufficiency Aga i n , hypercalcemia, secondary t o hyperpa rathyroidism, c a n lead t o renal fa i l u re and/or nephrolithiasis Dia betes can cause proteinu ria or progressive renal in sufficiency and, ulti mately, renal fa ilure Other endocri ne syndromes i nvolVing the kidney i nclude SIADH and hypo- and hyperthyroidism In addition, renal cell carcinoma may have several associated para neoplastic syndromes Nephrology Drugs are a frequent cause of renal insufficiency, and virtual ly any drug can cause renal disease A common problem is renal insufficiency ind uced by anti hypertensive a gents, especi a l ly ACE-i n h i bitors Other forms of d rug-i nduced renal disease i nclude interstitial nephritis and forms secondary to chemothera peutic agents, intravenous radiocontrast, or i ntravenous d rug a buse Many types of infections ca use renal d isease H I V d i sease ca n lead to severe protei nuria and renal fa i l u re Tu berculosis may prima rily involve the kid neys and the u rinary tract Pyeloneph ritis is also a common i nfectious disease in volving the kidneys Congenital diseases can cause renal man ifestations Anomalies of the uri nary tract and chronic reflux nephropathy may lead to renal fa i l ure Polycystic kidney disease and medulla ry sponge kidney disease are fa milial causes of renal fai lure Other inherited metabolic diseases such as Fabry's d isease and various storage diseases can lead to renal insufficiency A va riety of congenital disor ders may cause renal stones, including cystinosis and Lesch-Nyhan syndrome Immunologic diseases often affect the kid neys, and renal d isease may be the first man ifestation of an i m m u nolog ic disease Virtua lly a l l of the collagen vascular d iseases (e.g , SLE) have renal man ifestations The vasculitides, includ ing Wegener's , Goodpasture's, and polya rteritis nodosa , may lead to rena l fa ilure Neoplastic disease may a rise primarily i n the kidneys or involve the kidneys secondari ly Renal cel l ca rcinoma can be widely metastatic and often has asso ciated para neoplastic syndromes Metastatic tumors or loca lly invasive tumors, often gynecolog ic, may cause com press ion of the u reters and renal fa i l u re Hyperca lcemia secondary to malig nant disease c a n lead to renal fa i l u re, a s can mu ltiple myeloma Numerous exotic diseases affect the kid neys, i ncluding sarcoidosis, fam i l ial Mediterranean fever, and ITP Some of these d iseases a re thoug ht to have an im mu nologic basis Perhaps the most i m portant aspect of degenerative disease to consider is the effect of aging on renal functio n The glomerular fi ltration rate decreases steadily with age, and a low serum creati n i ne may not reflect actual renal func tion in an elderly patient Occupational and environmenta l exposures may lead to renal dysfu nc tion Extrinsic trauma can cause kidney damage, hematuria , or fra nk bleed ing Hydrocarbon exposure may cause Goodpasture's syndrome Cardiovascular diseases may i nvolve the kidneys secondarily C hronic hy perte nsion can lead to renal i nsuffi ciency a n d , u lti mately, re nal fa i l u re Cholesterol emboli m a y occur with severe atherosclerotic disease after a rad i ogra phic dye procedu re Also, congestive heart fa ilure is a very com mon cause of pre-renal azotemia 132 • Nephrology b Clin ical Sym ptoms and Signs EDEMA T H E L E A K O F V E I N S o r VA L V E S V e n o u s d i s e a s e (o bstru c t i o n , i n s u ff i c i e n cy) A l b u m i n u ri a/a l b u m i n l o s s i n sto o l L y m p h a t i c obstruct i o n ( c o n g e n it a l , a cq u i re d ) V o l u m e ove r l o a d E l ectro l yte/n u t ri t i o n a l d e f i c i e n cy S e p s i s/ca p i l l a ry l e a k or Tumor H ea rt fa i l u re E n teropathy ( p rote i n- l o s i n g ) L ive r fa i l u re E n d o c r i n e ( hypothyro i d i s m , a l d o s t e ro n i s m , d i a betes) A I t i t u d e s i ck n e s s K i d n ey d i se a s e ( re n a l fa i l u re , n e p h ro t i c syn d ro m e ) O bstruct i o n o f l y m p h a t i c s F i lariasis V e n o u s th ro m bo s i s E c l a m p s i a/preg n a n cy I a t rog e n i c N u t r it i o n a l d ef i c i e n cy S e p s i s/ca p i l l a ry l e a k N ote "VALVES" refers to the loss of venous va lvu lar com petence with a g i n g , a common cause of edema Edema may result from venous disease (thrombosis, Nephrologv 133 extrinsic com pressi on, tra u m a , venous va lvu lar i nsuffi ciency) , loss of a l b u m i n Inephrosis, protein-losing enteropathy) , lymphatic obstruction Icongenita l , malig nant, filariasis) , volume overload ICHF, renal fa ilure, ci rrhosis), electrolyte/nutri tional deficiencies that cause a loss of venous integrity, and sepsis a nd other systemic conditions causing capillary leak H E M AT U R I A UA RBCS U ret h A rt i fa ctua l (e g , d a r k u r i n e , m e n s e s , m e d icat i o n s ) R e n a l (e g , t u ma , cys t s , pye l o n e p h r i t i s ) B ladder C o l l e ct i n g syste m S yste m i c d i s o rd e r (e g , vasc u l i t i s , coa g u l o pa t hy) N otes Hematuria is defined as the presence of g ross blood or RBCs I> -2 per h pf) i n the spun u ri na ry sed iment It is important i n itially to look at the sed i ment to rule out false hematu ria Certa i n med ications Irifa m p i n , phenazopyrid ine) and diseases Iporphyria) may alter u rine color Nso, both myog lobinuria and hemo globinu ria cause a pos itive d i pstick test with a n egative u ri na ry sed i ment Menstruation also be mistaken for hematuria Hematuria may origi nate at any site from glomerulus to the u rethra The pres ence of "crenated" RBCs, RBC casts, proteinuria , or elevated BUN and creatinine su pport a glomerular source Isolated hematuria IWithout casts or prote i n u ria) suggests bleed i n g from a site i n the col lecti ng syste m , bladder, or u reth Poss ibil ities i nclude neoplasms, TB, renal stones, tra u m a , pa p i l l a ry necros is, ana lgesic neopathy, prostatitis, cystitis, or u reth ritis I n itially, exclude UTI , coagu lation disorders, and TB The patient's age and presentation determine the d i rection of the work-u p For exa m ple, a you n g female with dysuria would most likely b e treated with a trial o f anti biotics, while a n older man with recent onset of g ross hematuria may be i nvestigated with renal i maging a nd/or cystoscopy In younger patients without evidence of i n fection, an IVP is often the first imaging test ordered 134 • Nephrology A common rena l disease that features hematuria is IgA neph ropathy IgA nephropathy is cha racterized by gross or microscopic hematuria without other sym ptoms The prognosis is va riable, but disease progression Iypica lly is slow, with approximately 50% of patients developing renal fa ilure within 23 years of diag nosis Self-l imited acute renal fa ilure may develop folloWing on upper respi ratory infection There is no known effective treatment for IgA neph ropathy, and the role of renal biopsy in this disorder is controversia l Some of- the more common causes of hematu ria are summarized by the fol lowing m nemon ic: I PEE RBCS I nfecti o n P s e u d o h e m a t u r i a ( m e n se s , d a r k u r i n e ) E xe rc i s e E xt e r n a l t u m a R e n a l d i se a s e ( g l o m e ru l a r s o u rce) B e n i g n p rostat i c h y p e rt r o p hy C a n cer S to n e s Here i s a more complete differential for hematuria: I ' D PASS H E MATU RIA I gA n e p h ro pathy o r u g s/da rk u ri n e ( p s e u d o h e m atu r i a ) _ P o lycysti c k i d n ey d i s e a s e A n a l g e s i c n e p h ro pathy S ickle cell Stones Nephrology 35 H e m og l o b i n u ri a , myog l o b i n u ri a , p o rp h y r i a E xe rc i s e M a l i g n a n cy A c ute g l o m e ru l o n e p h r i t i s T u m a U re t h r i t i s R e n a l i n fa rct i o n I n fect i o n A I po rt 's syn d ro m e a n d o t h e r i n h e ri t e d d i s ea s e s ( e g , s i ck l e ce l l , p o l ycys t i c k i d n ey d i s e a s e ) H YP E RTE N S I O N I C H ECK A BP I d i o pa t h i c ( e s s e n t i a l ) C N S d i s o r d e rs H i g h o u t p u t states E ndocri ne d iseases C oa rctat i o n K i d n ey d i s e a s e A cu t e stress B i rt h c o n t r o l p i l l s a n d other d ru g s P re g n a n cy N ote Essential hypertension accou nts for g reater than 90% of hypertension cases The primary causes of a n elevated blood pressure a re outli ned by " C H EC K A B P " 136 • Nephrology S E C O N DA RY H Y P E RT E N S I O N R E NALS Renal E ndocri ne N e u ro l og i c A o rt i c coarct a t i o n L i c o ri ce g l u ttony S c l e ro d e r m a N otes Hypertension is idiopathic, "essentia l , " or secondary to one of the causes outli ned by "RENALS " Renal diseases that cause hypertension incl ude many types of re nal parenchymal d isease as well as renovascu lar hypertension Endocrine causes of secondary hypertension are acromegaly, aldosteronism, j-G cel l tumor, Cushing's synd rome, pheochromocytoma, and hyperca lcemia Pheochromocytomas are characterized by pa roxysmal or sustai ned episodes of severe hypertension Headache, pal pitations, and/or profuse diaphoresis a re almost a lways associated with the hypertension The tumors may secrete epi neph rine, norepinephrine, serotoni n , or nothing The "ten percent rule" refers to the ob servation that 0% a re malignant, 0% are bi latera l , and 0% are extra-adrenal Extra-adrenal sites include sympathetic ganglia (organ of Zuckerkandel) and the bladder (m icturition-ossociated symptoms) A J-G cell tumor produces ren in leading to hypertension It may resemble Conn's syndrome (primary hyperaldosteron ism ) , except that renin levels are decreased in Conn's synd rome Ora l contraceptives could be considered an exogenous endocrine cause of secondary hypertension Estrogens sti mulate ang iotensinogen production by the liver, thereby increasing ang iotensin I I and aldosterone levels Steroid therapy also raises blood pressure Neurologic disorders caus ing hypertension include increased intracranial pressure, acute spinal cord injury, dysautonom ia, polyneuritis (acute porphyria, lead poisoning), and psychogenic factors Aortic coarctation may be diagnosed by a blood pressure and pulse differ ential between upper and lower extremities and characteristic rib-notching (from increased flow through intercosta l a rteries) seen on x-ray Licorice contains glycyrrhizic acid , which increases the m i neralocorticoid ef fects of endogenous cortisol Scleroderma renal crisis is a d ramatic and l ife-threatening manifestation of the disease ACE inhi bitors are the treatment of choice Nephrology 137 C linical Conditions or Diagnoses H Y P E R KA L E M I A A HI K A cidosis H ypoa l d oste ro n i s m I a trog e n i c/ I n a cc u rate m e a s u re m e n t ( LA B e rror, d r u g s , I V p ota s s i u m ) K i d n ey d i se a s e ( re n a l fa i l u re , r e n a l t u b u l a r d i s e a s e ) N otes The primary causes of a high seru m potassium a re summa rized by "A H I K " Acidosis causes potassi u m to sh ift out o f cells Hypoaldosteronism causes hy perkalemia because aldosterone normally promotes renal potassi u m excretion Iatrogen ic causes of hyperka lemia include drug therapy ( h epari n , potassi um sparing d i u retics) and IV solutions containing potassi u m I naccurate measure ments may be obtai ned when hemolysis of the speci men occurs or from poor blood d rawi ng tech nique (overi nflation of blood pressure cuff) Fi nally, kidney disease inh ibits normal potassium excretion and leads to hyperka lem ia True hyperkalemia occurs by one of three mechanisms: inadequate excretion ( renal d isease, hypovolemia, hypoaldosteronism, potassiu m-spa ring diuretics), potassium shift from tissues (tissue damage, d rugs, acidosis, hyperosmolality, i n sulin deficiency, hyperka lemic periodic paralysis), or excessive i ntake Pseudo hyperkalemia occurs with thrombocytosis, leukocytOSiS, or in vitro hemolysis Renal mecha nisms of hyperka lemia i nvolve a decrease in fi ltered blood or tubular d isease Acute renal fa ilure is more l i kely to cause severe hyperka lemia than chron ic renal insufficiency, un less oligu ria supervenes Hyporen inemic hy poaldosteronism may be seen in patients with moderate renal dysfunction Type IV renal tubular acidosis, freq uently seen in diabetics as well as other interstitial nephritides, is assoc iated with a hyperchloremic meta bo l i c acidosis Non steroidal anti-inflam matory d rugs, converting enzyme inhi bitors, and beta-block ers may induce hypoperinemic hypoaldosteron ism 138 • NephrologV • Drugs that may induce hyperkalemia incl ude hepa rin ( i n h i bits aldosterone secretion), potassiu m-spa ring diuretics, succinylcholine, d igita l is, and a rg i n ine, as well as NSAIDs, ACE inh ibitors, and beta-blockers Artifactual elevation'of potassi u m may occur if blood is drown after repeated clenching of the fist and tourniq uet application For this reason , a lways i m medi ately recheck on elevated potassium level Ma nagement should involve o n i mmediate E KG to look for hig h-peaked T waves, prolongation of the PR interval , or com plete heart block Progressive hy perka lemia leads to a "sinewave" E KG configuration, ventricular fibrillation, and standsti l l Acute interventions include administration of IV ca lcium (which is car dioprotective) as well as IV insul i n , glucose, bicarbonate, and possibly epi neph rine, a l l of which sh ift potass i u m i ntracellula rly Potass i u m-bi nding resins, diuretics, and/or dialysis may be i nd icated to remove potassium from the body Here is a more complete list of the causes of hyperka lem i a : A BAD K PLI G HT A I d ostero n e d e f i c i e ncy (Ad d i s o n 's co n g e n i t a l a d re n a l hype r p l a s i a , hypore n i n e m i a , h e p a r i n ) B l ood d i se a s e s (th ro m b ocytos i s , l e u kocytos i s , l e u ke m i a ) A cidosis D ru g s K i d n ey d i se a s e ( re n a l fa i l u re , re n a l tu b u l a r d i s e a s e ) P e r i o d i c p a r a l ys i s ( hype rka l e m ic) L a b o ratory e rror I n trave n o u s pota s s i u m a d m i n i st rat i o n , a nt i b i ot i c s G eo p h a g i a/excess ive i n ta ke H yp e r os m o l a l ity T i s s u e n ec ros i s Nephrology 139 H Y P E R N AT R E M I A AVP A l tered m e n t a l statu s/a b n o rm a l t h i rst/a c c e s s to wate r i m pa i re d V o l u m e l o s s ( re n a l , ext ra-re n a l ) P r i m a ry s od i u m g a i n ( r a r e , i a t rog e n i c ) N otes Arg i n i n e vasopressi n IAVP) is a lso cal led antidiuretic hormone, and its major action is to conserve water by concentrating the urine AVP release is primarily regulated by changes in concentration of plasma solutes As plasma osmolality rises, so the levels of AVP To a lesser extent, decreases in plasma vol ume also stimulate the release of AVP Water deprivation causes both hyperosmolality a nd vol ume depleti on, and thus is a potent sti m u l us to AVP release AVP then acts to maxi mally concentrate the urine, thus defending vol u me The loss of ef fective AVP leads to volume loss and hypernatremia Hypernatremia is defined as a serum sod i u m of g reater tha n 45 mM/L Si nce sodi u m and its accompanying anions are the major effective osmols of the extracellular fluid, hypernatremia is by defin ition a state of hyperosmolalily The three major mechan isms of hypernatremia are outlined by the AVP m nemon ic: 1 ) altered mental status or impaired access to free water; 12) volume loss; 13) pri mary sod i u m ga i n In the strictest sense, either free water is lost, which is the most common scenario, or, more rarely, tota l sod i u m is gai ned The appropriate re sponse to hypovolem ia and hypernatremia is i ncreasing water intake Isti mu lated by th irst) and excreting a maximally concentrated u rine Icontrolled by AVP release) Most cases o f hypernatrem i a a re secondary to a net l oss o f free water Altered mental status in acutely ill or post-operative patients, l i m ited access in i nfants, hand icapped patients and mecha nically ventilated patients, and abnor mal thi rst mechanism in patients with a hypothalamic in jury all cause a net loss of free water Hypothalamic i m pai rment may be d ue to granulomatous disease, tumors, cerebrovascular accident, or, rely, "essential hypernatrem ia " Essential hypernatremia represents an osmo-receptor defect in AVP release It is character ized by a lack of response to fOrced water intake Volume depletion from free water losses may be either renal or extra-rena l Rena l free water losses a re most com monly secondary to drugs, such a s loop 140 » • Nephrology SEIZURE BITE TO N G U E B l eed/h e m o rr h a g e I nfect i o n T u m a E t h a n o l/d rug s/toxi n s T u mor O xyge n l ack/i sch e m i a/hypoxia N o n c o m p l i a n ce ( s u bt h e p e u t i c m ed s ) G l u cose l ack/hypog lyc e m ia U re m i a/meta b o l i c E c l a m ps i a I CO NVU LS E B I G TI M E I nfec t i o n C oca i n e/d ru g s O xyg e n l a ck/i s ch e m i a/hypox i a N eoplasm Vascular ma lformatio n U re m ia L ytes (hypo N a , hypo M g , hypoCa) S i n u s t h ro m b o s i s E th a n o l w i t h d rawa l B l eed/h e m o r r h a g e I d i opath i c G l u cose l a ck/hypo g l yce m i a T u m a I n bo r n e rro r o f m eta b o l i s m M ed i cat i o n s (too m u ch , too l i tt l e ) E c l a m ps i a Neurology • 259 N otes A seizure is a clin ical man ifestation of excessive, a bnormal synchronous activity of neu rons in the cerebral cortex It is usua l ly transient, and man ifestations in clude alterations of consciousness, involuntary movements, sudden loss of motor tone, and sensory disturba nces (especially olfactory or g ustatory) Epilepsy is a term reserved for chronic, recurrent seizures A single seizure does not make a diagnosis of epilepsy The description of the seizure is helpful in diagnosis and treatment A good description of a seizure includes any premonitory symptoms reported by the pa tient, any foca l motor activity noted during the seizure, whether the motor activity was rhyth mic and synchronous, the presence and d i rection of eye deviation, res pi ratory pattern, whether the patient was a ble to respond to verbal sti m u l us, whether the patient bit h is/her tongue or experienced i ncontinence, and the presence and duration of post-ictal confusion Major types of seizures: a Absence - sta ring, blinking, very brief, preci pitated by hyperventilation , onset in chi ldhood , no post-ictal confusion b General ized ton ic-clon ic - a l l fou r extremities stiffen i n itially (ton ic!, then undergo rhyth m i c contraction and relaxation (clon ic); post-ictal confusion is a lways present (to some degree) ; may be assoc iated with cya nosis, tongue biti ng, and incontinence May often start as a focal/partial seizure and be sec ondarily generalized, particularly in adults c Simple partial- may be motor (focal motor twitching) or sensory (foca l sen sory disturbance!, with no alteration i n level of consciousness during episode, no post-ictal confusion May secondarily become generalized tonic-clonic d Complex partial - a lteration in consciousness, automatisms (lip-smacki ng, eye blinking, swallowi ng, picking at clothes!, preceded by aura (unusual smell, taste) May secondarily become generalized tonic-clonic Treatment by seizure type a Treatment of a bsence seizure is primarily with ethosuximide or valproic acid b Treatment of primarily generalized seizures is usually with valproic acid c Trea'i ment of seconda rily general ized seizures is pri m a ri ly with ca rba , mazepine, phenytoin, or valproic acid d Treatment of partial seizures (simple or complex) is pri mari ly with carba mazepine, phenytoin , or valproic acid I Other med ications used to treat epilepsy i nclude ch lorazepate, clonazepa m , felbamate, gaba penti n , phenoba rbita l , prim idone, tiagabine, topira mate, and lamotrigine It is i m porta nt to d i stinguish between seizure, syncope, and psychogenic seizure/ pseudoseizures I a Syncope is typically preceded by a lightheadedness, p recipitated by pos tural change, results in a fa ll/colla pse with loss of consciousness lasti ng only I 260 • Neurology seconds, and has no post-ictal confusion Occasionally, a few myoclonic twilches may accompany syncope Syncope is usually preci pitated by a vasovagal re action, but is also associated with arrhyth mia, orthostatic hypotension, low car diac output, and aortic valve disease See the Loss of Consciousness section b A generalized tonic-clonic seizure may also present with a fal l/collapse, but is associated with grunting or apnea, occasional cyanosis, tonic then clon ic motor activity, sometimes tongue-biting and inconti nence, and a lways post-ictal confusion (usually lasti ng m i n utes or longer) The d uration of a general ized seizure is usua lly longer than a syncopal event, lasting seconds to minutes c Pseudoseizures may be d ifficult to d isti ngu ish from epi lepti c seizures; indeed , the two disorders frequently overlap I n genera l , pseudoseizures occur in the presence of observers, are not stereotypic, have no post-ictal confusion , a n d a re not associated with self-in j u rious activity l i ke fa l l i n g or tongue-biting Motor activity incl udes com pletely asynchronous limb movements, struggling agai nst restra ints or resisting eye open ing, and repeated side-to-side head m ove ments None of these is d iagnostic, but carefu l observation helps avoid placing these patients on anticonvulsants or increasing dosages unnecessarily ' The most common couse of a seizure in a patient with a known seizure dis order is subtheropeutic medication This may be d ue to noncompliance (due to side effects or lack of understanding) or increased dosing requ i rements 6, I ndications for neuroimaging studies: a New focal-onset seizure or seizure with residual focal neurologic deficit b Status epilepticus of unknown etiology c New-onset seizure ( uncerta i n focalityJ without known precipitant d Any second seizure (except typical a bsence) not preViously i maged I t is not necessary to re-i mage a patient with a known seizure disorder after a typical seizure (see number above) It is not necessary to i mage a child with typical a bsence seizures Indications for lumbar puncture: a Status epilepticus of unknown etiology b Patients u nder suspicion for suba rachnoid hemorrhage c Patients u nder suspicion for CNS infection ( mening itis, encephalitis) For seizures secondary to alcohol withdrawal and meta bolic abnormalities, a nticonvulsants are always second-l i ne treatment; first-l ine treatment is d irected at the u nderlying process ( i e , treat withdrawa l , correct electrolyte a bnormal i ties, correct hypoglycemia , etc ) Generalized convulsive status epilepticus means contin uous general ized convulsions or repeated generalized convulsions without full recovery of mental status between seizures for a period lasti ng g reater than 30 minutes Protocol for treatment (Note: Items -4 are generally done nearly simultaneously) Carefully observe seizure activity ABCs Supplemental O2 if necessary IV l i n e with norma l sal i ne Send blood for CBC, electrolytes , BUN , Ca , Mg , glucose, anticonvulsant levels .Send ABG Send U/ A, consider tox screen ECG monitoring Accucheck, then 00 mg' thiamine , then 50 ml of 50% dextrose solu tion if ind icated Neurology 26 Lorazepam mg IV Do not exceed mg/m i n May repeat up to mg/kg Call neurologist Phenytoin (Fosphenytoin) 20 mg(pEl/kg IV When using phenytoin, not exceed mg/m i n When using Fosphenyto i n , not exceed 50 PE (phenytoi n-equivalents)/m i n Monitor ECG, respi ra tion and blood pressu re Phenytoin ( Fosphenyto i n ) 5- mg(PE)/kg IV Max i m u m rates per minute as descri bed a bove Maximum dose 30 mg(PE)/kg Consider intubation if not already i ntubated Phenobarbital 20 mg/kg IV Do not exceed 00 mg/m in Consider barbiturate coma (in consultation with neurologist) Common drugs having interactions with anticonvulsants include erythromycin, H2 blockers, isoniazid, methylphenidate, phenoth iazines, warfarin, oral contra ceptives, and other anticonvulsants Drug interactions may result in increased or decr.eased a nticonvulsant levels or altered efficacy of the concomitantly adminis tered drug In general, newer anticonvulsants have fewer drug-drug interactions 1 A rough clinica l gU ide to phenytoin levels: No nystagmus 0- Above 0: Gaze-evoked nystagmus Ga it ataxia Above 20: Above 30: limb ataxia Above 40: Stupor/confusion STR O KE SAV E D B RA I N u bsta n c e a b u se/d r u g s/m e d i ca t i o n s A lte red c oa g u l a t i o n/hype rc oa g u l a b i l ity V a sc u l i t i s E mboli i D i ss e ct i o n : B l ee d/h e m o rr h a g e/AVM R a re c a u ses ( e g , m ig i n e , i a t ro g e n i c ) A t h e roth rom b o s i s I nfect i o n s N eo p l a s m 262 • Neurology b D EA D H EA D S D ru gs/m e d i c a t i o n s E l evated b l ood p res s u re A rt e r i t i s/va s c u l it i s D ecreased p e rf u s i o n ( c a rd i a c a rrest, hypote n s i o n ) H e m o rrha g e o r H ypercoag u l a b i l ity E mbolism A t h e ro sc l e ro s i s D i s s e ct i o n S pa s m ( m i g i n e) Note: "DEAD HEADS" emphasizes the vascular causes o f stroke C VA S , D O I C T T H E M ? C oca i n e/d rugs V a s c u l i t i s/c o l l a g e n va s c u l a r d is e a s e A t h e roth ro m bos i s S yp h i l i s , t e rt i a ry/m e n i n g ova s c u l a r D is s ecti o n/dys p l a s i a (fi b ro m u s c u l a r) O l c o ntraceptives I ntra c n i a l b l e e d ( a n e u rys m , AVM ) C a ncer T h ro m b o s i s , s i n u s T u m a/h e r n i a t i o n H e ma to l og i c * /hyp e rcoa g u la b l e * * E m b o l i c ( i n c l u d i n g pa doxi ca l ) M ig i n e Neurology • 263 • DO SAVE T H E M B RA I N S D i s s e ct i o n/dys p l a s i a (fi b ro m u s c u l a r) O l c o n t c e pt ives S i n u s t h ro m b o s i s , ve n o u s A t h e roth r o m b o s i s V a s c u l i t i s/co l l a g e n va s c u l a r d i s e a s e E m b o l i s m ( i n c l u d i n g pa d ox i ca l ) T u m a/h e r n i a t i o n H e m a to l o g i c * /hypercoa g u l a b l e * * E xog e n o u s toxi n s/d r u g s ( e g , coca i n e ) M igraine B l e e d/AVM/a n e u rysm R a diation A ng i og p hy I nfect i o n s ( n e u rosyp h i l i s , m e n i n g i t i s ) N eo p l a s t i c ( b l e e d , m e n i n g it i s ) S yst e m i c hypote n s i o n/s h ock *Thrombocytosis, polycythemio, sickle cell anemia * * Protein C deficiency or resistance, protein S deficiency, ontithrombin III deficiency, malig nancy, onticordolipin antibody syndrome, factor V deficiency, homocystinuria N otes Stroke refers to the sudden onset of a focal neurologic deficit that does not re solve The etiology of a stroke is generally vascular, either hemorrhagic or is chemic The vascular event may be precipitated by a d ifferent underlying cause ( infection, tumor, hereditary condition) Transient ischemic attack (TIA) refers to the sudden onset o f a focal neuro logic deficit that resolves in 24 hours or less Reversible ischemic neurolog ic deficit (RIND) is a neurolog ic deficit that lasts longer than day and less than weeks; essentially, a mild stroke Hemiparesis refers to a weakness on one side of the body Hemiplegia refers to paralysis of one side of the body Astereognosis is the inability to identify obiects by touch only Agraphesthesio is the inabil ity to identify letters/numbers traced on the skin without visual cues 264 • Neurology cd Types of stroke a Hemorrhagic- refers to focal bleed i n g , usually i nto bra i n parenchyma Associated with acute hypertens ion , coagu lopathy, amyloid angiopathy, occa sionally trauma b T h romboti c - refers to g radual occl usion of cerebral a rteries by local plaques/thrombi Associated with longstanding hypertension, diabetes, athero sclerosis • Small vessel/ l acu n a r - occ lusion of m icrovessels, typica l ly in deep gray matter and/or brai nstem • Large vessel throm b osi s m ay not hea r carotid bruit with a low-g rade or a very high-grade stenosis c Embolic- refers to a sudden occlusion of cerebral arteries by blood clots that origi nate elsewhere in the vascular system May be a rtery-to-artery (carotid to middle cerebra l , aortic to carotid or vertebrobasilar), cardiogen ic ( heart to bra i n ) , or pa radoxical (venous system through atri a l septa l defect to a rterial system to bra i n ) Associated with cardiac arrhyth m ias (especially atrial fibril la tion) , right to left shunts, valvular heart d isease Hemorrhagic strokes can effectively be diag nosed by a noncontrast head CT Presentation is usually that of a very a brupt onset of neurologic deficit which may not fit wel l i nto the vascular patterns descri bed below Very la rge hemor rhagic strokes in the cerebrum could result in decreased mental status secondary to herniation; posterior fossa hemorrhages may lead to a very rapid decrease in level of consciousness Etiology is most often hypertension Treatment consists of gentle control of extreme hypertension, su pportive care, and occasionally (especially in posterior fossa/cerebel lar bleeds) surgical evacuation Anticoagu lation is contra i ndi cated Prognosis for functional recovery after hemorrhagic strokes is usua l ly better than after ischemic ( i e , th rombotic or embolic) infarcts Several stroke syndromes have been descri bed as lacu nar/small vessel thrombosis; that is, i nvolving small i nfa rcts as a result of occlusion of tiny pene trating vessels These presentations i nclude the following clin ical syndromes: a Pure hemisensory deficit (contralateral to a thalamic infarct) b Pure hemiparesis (contralateral to an i nternal capsule infarct) c Clumsy hand-dysarthria (multiple localizations) d Ataxia/hemiparesis (both contralateral to a pontine infarct) Onset of symptoms may be stuttering, stepwise deterioration or may be one of g radually worsening TIAs The typical d istri bution of a hem isensory deficit i n volves the face, arm , and leg equally, because the sensory fi bers a re closely compact in the tha lamus, so even a small ischemic lesion will l i kely affect a l l likewise for pure hemiparesis, which shou ld · be relatively equal i n the face, a rm , and leg, as the corticospinal fi bers a re crowded closely in the i nterna l capsule Etiology is most likely chron ic hypertensive damage to small penetrating ves sels Treatment acutely consi sts of avoiding hypotensio n , using a nti platelet agents, and supportive' care Long-term treatment i nvolves dimi n ishing risk factors such as smoki ng, hypertension , hyperli pidemia, and diabetes Anticoagulation - Neurology • 265 is unproven Tissue plasmi nogen activator (TPA) may be beneficial within the first hours Large vessel thrombosis may present with gradua lly worsening (crescendo) TIAs or an a brupt onset of symptoms Usually symptoms occur in a vascular d istri bution as descri bed below Carotid occlusion may presen t with o n ly m iddle cerebral a rtery infarction (due to collateral flow to the i psilateral anterior cere bral from the anterior com m u n icating a rtery ) Etiology is usually an atheroscle rotic plaque with loca l t h rom bus formation Treatment acutely i ncludes TPA, avoiding hypotension , and supportive care Ca rotid enda rterectomy is i nd i cated for symptomatic stenosis of 70% or g reater, often i n the setting of TIAs E mergent carotid enda rterectomy is u n proven Anticoagulation is u n p roven Ca rotid endarterectomy in the setting of com plete carotid occlusion is genera l ly nat ind icated Embolism classically presents with an a brupt neurolog ical deficit that is max imal at onset Symptoms occur in a vascu lar d istribution as described below The hemipa resis of m iddle cerebral artery (MCA) occlusion d iffers from that of lacuna r d isease in that MCA infarction causes hemiparesis that is greater in the face and arm than the leg a n d is usually associated with hemisensory loss in a s i m i lar d istribution Etiology is by occlusion of an a rtery by a blood clot from either another artery (e g , carotid to middle cerebra l ) , the heart (ca rd io genic), or the venous system via a right to left shunt ( pa radoxica l ) Treatment acutely may involve TPA, followed by a nticoagulation , especially in cases of atrial fibri llation and small cerebral infarcts Acute anticoagulation in the setting of a very large cerebral infarction has an i ncreased risk of precipitating hemor rhagic transformation Local ization of large vessel disease (thrombotic or embolic) a Specific signs/symptoms Monocular visual loss Hemi neglect • Anterior ( i e , carotid Aphasia Agraphesthesia artery) Visua l-spatial deficits Astereognosis Di plopia Nystagmus • Posterior ( i e , vertebral basi lar arteries) Ataxia Bi lateral sig ns/ symptoms Vertigo Face signs/symptoms Vom iting opposite arm/leg signs/symptoms Hemisensory loss • Either Hemiparesis Dysa rthria Visual field cut ('u sually PCA, but may be present with large MCA i nfarctions) b Vascular syndromes • Anterior cerebral artery Leg weakness > Contralateral face/ar� I ncontinence 266 • Neurology Middle cerebral artery Contralateral Face/ arm weakness > leg Hem isensory deficit Hemia nopsia Contralateral Hemianopsia • Posterior cerebral artery Mild hemiparesis Hemisensory deficit • Vertebral basilar arteries Contralateral Hemi pa resis Ipsi lateral Hemisensory deficit May be bi lateral C ranial nerve palsy Possibly hemiataxia Standard workup for stroke includes a head CT (hemorrhage!, CBC (throm bocytosis, polycythemia!, glucose (diabetes!, and lipids (hyperlipidem ia) Other blood tests which may be usefu l include PT/PTI (coagulopathy, inadequate a n ticoag u lation ! , ESR (vascul itis), and VDRL/RPR ( neu rosyph ilis) Carotid d uplex should be done in cases of anterior circu lation strokes and TIAs Tra nscranial Doppler is helpful in eva l uation of posterior circulation (vertebrobasi la r insuffi ciency) Echocardiography is performed to rule out valvular lesions and atrial or ventricular thrombi in patients suspected of having an embolic infa rct Magnetic resonance angiography is a noni nvasive method of visua lizing all of the cranial vasculature (a nterior and poste rior circulation!, and the resolution of MRA has greatly improved over the last few years In young patients « 45 years old) or patients with no clear etiology, the work-u p for stroke/cerebral infarction can be m uch more extensive and may in clude protein C, protein S, anticard iol i pin a nti body, antithrom bin I I I , factor V, and homocysteine (hypercoagulable states!, angiography (arterial dissection, fi bromuscular dysplasia, aneurysm!, MRI (tumor, AVM!, u rine drug screen (coca ine, amphetamines!, LP (i nfection, inflammation/vasculitis!, and transesophageal echo with bubble study (atrial septal defect with paradoxical embolism) Recently, the use of TPA has been recommended i n acute stroke Consider it in patients who present to med ical care within hours of onset of neurological sym ptoms, have sign ificant n eu rologic deficits, and have no evidence of in tracranial hemorrhage • Neu ro logy G lossary Agraphesthesia is the inability to identify letters/numbers traced on the skin with out visual cues Akathisia descri bes an involuntary restlessness a nd inability to sit still Altered mental status refers to any acute or subacute change in the level of con sciousness, n g i ng from m i ld confusion to deep coma Synonymous with Neurology • 267 + delirium Chronic problems such as dementia or menta l retardation a re not considered in th is category Amaurosis fugax is the subjective com plaint of transient visua l loss in one eye, oMen descri bed as a veil or shade coming over the eye Astereognosis is the inabil ity to identify objects by touch only Asterixis is a cond ition cha racterized by nonrhythmic, episodic loss of m uscle tone May be confused with tremor Ataxia is the subjective complaint or objective find ing of impaired coord ination, usua lly manifested as an i m pa irment of gait or dexterity in the a bsence of sig n ificant muscular weakness Autonomic disorgers constitute a wide range of neurologic derangements which may man ifest prima rily through symptoms of autonomic dysfu nction, including but not l i mited to orthostatic hypotension/syncope, card iac arrhythmias, a l tered lacri mation , i m pa i red temperature regulation , dia phoresis/a nhidrosis, sexual dysfunction, and bowel/bladder problems AVM is the acronym for a rteriovenous ma lformation ; on a bnormal ta ngle of blood vessels that can develop in the central nervous system Choreoathetosis is an i nvolu ntary movement disorder characterized by pid, jerky, dancing-l i ke movements (cho rea ) associated with or superi m posed upon writhing, flowing, continuous movements (athetosis) Clonus is an a brupt, unidirectional series of muscular contractions i n response to a sudden stretch Also used to describe repetitive, rhyth m i c muscle contrac tions seen i n some types of seizures Cogwheeling is a form of rigidity cha racterized by rhyth m i c , rachet-l ike resis tance throughout the range of motion CT is the acronym for computed tomography, a diagnostic neuroimaging test CVA is the acronym for cerebrovascu lar accident; refers to any acute cere brovascular pathology, generally ischemia or hemorrhage Dementia is an acquired condition characterized by chronic deterioration of i n tellectual function and associated with i m pairment in at least three of the fol lowing a reas : language, memory, visuospatial ski lls, personality, and cogn ition I t is not associated with on acute confusional state Diplopia is the subjective symptom of double vision Dizziness is a symptom with many meani ngs, but particularly used by patients to refer to feelings of fa intness/lig htheadedness, vertigo, a nd/or unsteadi ness/d isequili bri u m Dysconjugate gaze i s the objective exa m i nation finding of eye misalign ment, which may or may not be associated with symptoms of d i plopia Dysdiadochokinesis is on i m pai rment of the ability to perform rapid alternating movements Dysesthesia is an uncomforta ble sensation of ting l i n g , prickling, or burn i n g , often elicited by l ight (normally nonpa inful) touch Dyskinesia is o n a bnorm a l i ty o f movement T h i s usua l ly refers t o excessive motor activity ( L-dopa- i nd uced dyskinesias, tard ive dysk i nesia ) , but a lso may reflect a severe general ized slowing of move ment ( pa rki nson i a n bradykinesia) 268 • Neurology " T I Dysmetria is impa i rment i n the normal acceleration and deceleration of d irected movements Usually eva luated by finger-nose-finger and heel-knee-shin tests Dystonia is a condition of i m pa i red muscle tone, which usua l ly is i ncreased , persistent, and at an extreme of the range of motion for the affected area EMG is the acronym for electromyogra m , a d iagnostic test that exa m i nes the electrical properties of m uscle tissue (analogous to the electrocard iog ram for the heart) Epilepsy is a term reserved for chronic recurrent seizures A single seizure does not make a diagnosis of epilepsy Gegenhalten descri bes an inability to relax muscles subjected to passive move ment On exa m i nation, it feels as if patient is resisting the exam iner's motions Headache is a genera l term used to describe any pai nful sensation i nvolvi ng the structu res of the cranium-, face, and/or neck Hemiparesis refers to wea kness/pa rtial paralysis on one side of the body Hemiplegia refers to com plete paralysis of one side of the body Hypesthesia is a sensation of n u m bness; d i m i n ished sensation Synonymous with hypoesthesia I n}ention tremor is an exaggerated oscil lation of a l i m b most pronounced as it is approaching a target, and essentially absent at rest or at the beginning of a movement I ntention tremor is a man ifestation of dysmetria Lead-pipe is a form of rigidity characterized by uniform resistance throughout the range of motion LP refers to lumba r puncture; also known as a spinal ta p Monocular visuai loss is either a subjective report of transient visual loss i n one eye (as opposed to one visual field) or an objective find ing of decreased visual acu ity in one eye MRI is the acronym for mag netic resonance i maging, Q diag nostic neuroi mag ing test with higher resolution than CT, but which takes longer and is gener al ly more expensive Myelopathy is any pathologic process lead ing to spinal cord dysfunction Myoclonus refers to a sudden, nonrhyth mic contraction or spasm of a m uscle or g roup of muscles Contractions genera lly a re u n i d i rectional, asynchronous, and asymmetric Nerve conduction study is a diag nostic test that looks at the electrical function of peripheral nerves and roots Neuropathy is any d isorder which affects primarily peri phera l nerves a nd is manifested by symptoms of weakness or sensory d isturbance or both Paresthesia is a sensation of n u mbness or ti ngling Ptosis is a physical finding of one palpebral fissure being smaller than the other, i e , a drooping eyel id Reversible ischemic neurolog ic deficit (RIND) is a neurologic deficit that lasts longer than day and less than weeks; essential ly, a m i ld stroke Rigidity is a continuous or i nterm ittent increase in muscle tone throughout the full -ra nge of passive movement Seizure is a clinical manifestation of excessive, abnormal , synchronous activity of neurons in the cerebra l cortex It usually is transient, and manifestations Neurologv • 269 i nclude alterations of consciousness, i nvolu ntary movements, sudden loss of motor tone, and sensory disturbances (especially olfactory or gustatory) Spasticity is an increase in m uscle tone that is m i ld with slow movement and more pronounced with rapid movement Classically, rapid passive movement is met with i ncreasing resistance u ntil a point at which the resistance breaks (clasp knife phenomenon) Stroke refers to the sudden onset of a focal neurolog ic deficit that does not re solve The etiology of a stroke generally is vascular, either hemorrhagic or is chem ic The vascular event may be precipitated by a d i fferent underlying cause (e g , infection, tumor, hereditary condition) Syncope is defined as a tra nsient loss of consciousness and postural tone due to i m pai red cerebral blood flow Synonymous with fa inting Tics a re stereotypic, invol unta ry, repetitive spasmod ic muscular contractions Typically a ble to be suppressed briefly, o n ly to brea k out with increased severity Often a ppear purposeful or sem i purposeful Titubation i s a moderate-frequency head tremor, usua lly antero-posterior Torticollis is a form of focal dystonia involving persistent contraction of cervical muscles, leading to a head tilt Transient ischemic attack (TIA) refers to the sudden onset of a focal neurologic deficit that resolves in 24 hours or less Tremor is defined as an i nvolunta ry, rhythmic, oscillatory movement Weakness is the reported symptom or demonstrable sign of decreased strength of m uscular contraction 270 • Neurology Em A p PENDIX Ac ronym Dictiona ry ABG ALS ANA ARDS ATN AVM AVP BOOP BUN ClDP COPD CPK CVA CXR DDX DKA DVT ECG EEG ESR GERD GVH D ITP IVF LAM LP MCA MCV Arterial blood gas Amyotrophic lateral sclerosis Anti n uclear antibody Ad ult respi ratory d istress syndrome Acute tubular necrosis Arteriovenous ma lformation Arg i n i ne vasopressi n Bronchiol itis obl itera ns-org a n izing pneumon ia B lood u rea nitrogen C h ronic id iopath ic polyradiculopathy C h ronic obstructive pulmonary d i sease Creati ne phosphoki nase Cerebrovascu lar accident Chest x-ray Differential d iagnosis Diabetic ketoacidosis Deep vei n throm bos is Electroca rd iogram E lectroencepha log m E ryth rocyte sed i mentation rate Gastroesophageal reflux d isease Graft versus host d i sease Id iopath ic th rom bocytopen ic purpura I ntervertebral fora men Left atrial myxoma Lumbar puncture Middle cerebral artery Mean cell volume Appendix MI MS NCV PCA PIE PT PTI RDW RPR SIADH SLE TIA TPN TSH VDRL VOD Myocard i a l i n fa rction Multiple sclerosis Nerve cond uction velocity Posterior cerebra l a rtery Postinfectious encepha lomyel itis Prothrombin time Pa rtia l thromboplastin time Red blood cell d i stribution width i ndex Rapid plasma rea g i n Syndrome o f i n a ppropriate secretion o f anti d i u retic hormone System ic lupus erythematosus Tra nsient ischem ic attack Tota l pa renteral n utrition Thyroid-sti m u lati ng hormone Venera l disease research la boratory Veno-occlusive d isease 272 • Appendix DI FFERENTIAL D IAG NOS I S M N EM O N ICS is a memory aid to help you form comprehensive d ifferential d iagnoses for common i nternal medicine and neu rology problems Clever, often witty m nemon ics allow you to organize diagnostic possibilities quickly and effectively for a wide va riety of clinical scenarios The method succeeds because each m nemonic provides you with a framework on which to construct the d ifferential This book assures that you r eva l uations w i l l b e thorough , and d iagnoses will not be m issed! For More Memory Aids The SECRETS SER I ES ® has been extraordi na ri ly popular, and the distinctive approach has given birth to a wide range of books i n the major medical specialties and subspecia lties Questions and short a nswers as wel l as an i nformal tone a re employed to make the text enjoya ble as well as usefu l The l ist is constantly changi ng and expan d i ng H ere a re a few of the more than 50 titles: CARD I O LOGY SECRETS, 2/e CRITICAL CAR E SECRETS, 2/e EN DOCR I N E SEC R ETS, 2/e GI/LiVER SECRETS HEMATOLOGY/ON CO LOGY SECR ETS , 2/e I N FECTIOUS DISEAS E S EC R ETS N EP H RO LOGY SECR ETS N E U ROLOGY SECRETS N E U ROSCI ENCE SECR ETS P ULMONARY/RES P I RATO RY CAR E S ECRETS R H EU MATOLOGY SECR ETS S U RGICAL SECRETS , 4/e Hanley & Belfus, Inc , Medical Publishers South 3th Street Philadelphia , Pennsylvan i a www.hanleyand belfu$.com ... pC 02 [ 5(HC03) Full compensation Decreased Decreased (hyperventila+ 8) ± (patient HC03 pC 02 tion) may take with metabolic acidosis and HC03 2- 24 hours of should have pC 02 of [ 5( 0) + 8) ± 23 ... pC 02 of TORR may be normal from normal pC 02 Unusual for paof TORR, extients with pected change in pH is 0.03 un its pC 02 > 60 (patient with pC 02 TORR to have normal pH of 60 should have pH of 20 /... should have pC 02 of [ 5( 0) + 8) ± 23 ± 2 -25 TORR pC 02 last digits of pH x 00 = = = = Metabolic Increased HC03 alkalosis Increased pC 02 Compensation pC 02 0.9* less consistent (HC03) + than for