CHRONIC VENOUS DISEASE AND LYMPHEDEMA b.

Secondary
-result from venous HTN ; associated with:
CHRONIC VENOUS DISEASE deep venous insuff,
-range from telangiectasis and reticular veins, varicose veins, chronic deep venous obs, enlargement of superficial vein
venous insufficiency w/ edema, skin changes, ulceration incompetent perforating vein
-abnormality in deep venous system that will cause
1. Varicose veins superficial varicosities
-15% men; 30% women
2. CVI
2. CV insufficiency w/ edema: 7.5% men; 5% men -consequence of incompetent veins
Prevalence: <50 yo: 2%; 70 yo: 10% -there is venous HTN, edema
20% develop venous ulcers -may occur with varicose; usually cause by disease in deep
vein
VENOUS ANATOMY -categorized as:
a.Primary: abnormality in vein wall/valves->valvular reflux
Classified as:
1. Superficial b.Secondary: obstruction and/or valvular incompetence
- located bet. the skin and deep fascia; includes great from previous deep vein thrombosis; develops in distal
and small saphenous vein valves; large proximal vein remain occluded
- great saphenous vein is the longest vein; drains from -other causes:
medial foot-> ant.medial malleolus-> medial side of calf and thigh->  May-Thurner syndrome (left iliac vein is occluded or
common femoral vein stenosed by extrinsic compression of RCIA);
-small saphenous vein from dorsolateral aspect of foot->  arteriovenous fistula (inc.venous pressure);
post.malleolus-> posterolateral calf and thigh-> popliteal vein  congenital deep vein agenesis/hypoplasia;
2. Deep  Klippel-Trenaunay-Weber & Parkes-Weber syndrome
-includes peroneal, ant.tibial, post.tibial, popliteal (venous malformation)
-soleal tributary vein-> post tibial or peroneal v
-gastrocnemius t.v-> popliteal-> femoral v CLINICAL PRESENTATION
Perforating v- connects superficial and deep -often asymptomatic
-dull ache; throbbing or heaviness; pressure sensation after
In the arms prolonged standing; relieved w/ leg elevation
1.Superior: basilic, cephalic, median cubital -cramping, burning, pruritus, le swelling, skin ulceration
Basilic: medial -legs examined in both supine and standing position
cephalic: lateral both connects via median cubital -visual inspection & palpation in standing: presence of varicose vein
- superficial venous insufficiency and venous HTN: edema, statis
2.Deep: radial, ulnar, brachial, axillary, subclavian v-> converge with dermatitis, skin ulceration near ankle
internal jugular-> brachiocephalic v-> SVC -deep VI: inc. leg circumference, venous varicosities, edema, skin
changes
Bicuspid valve present in all venous system -edema is pitting; confined to ankles, knees, thighs
-venous stasis dermatologic fx:
PATHOPHYSIOLOGY OF CVD o Hyperpigmentation
1. Varicose vein o Erythema
Result from intrinsic weakness of vessel wall, inc. intraluminal o Eczema
pressure, congenital defects in the structure and fx of valves o Lipodermatosclerosis: combination of
-dilated, bulging, tortuous superficial vein, 3mm diameter induration, hemosiderin, deposition,
-reticular vein: less tortuous; dilated intradermal vein; inflammation; occurs in lower part of leg just
appear blue-green; 1-3mm diameter; DO NOT protrude in above the ankle
skin o Atrophie blanche: white patch of scar tissue;
-telaangiectasis: spider veins; small dilated veins; form near medial malleolus
blue, purple or red linear,branching, spider-web pattern o Phlebectasia corona: fan-shaped pattern of
Can be categorized into: intradermal vein near ankle or on foot
a. Primary -Maneuvers:
-originate in superficial system o Brodie-Trendelenber test: determine whether varicose
-defective structure and fx of valve, weakness of vein wall, vein are secondary to deep venous insufficiency
high intraluminal pressure -px lying supine, leg elevated, vein allowed to empty,
-fam hx of varicose vein tourniquet place on proximal part of thigh, px asked to
-other factors: aging, pregnancy, hormonal therapy, stand
obesity, prolonged standing -varicose vein fills w/in 30 sec: caused by DVI
-during pregnancy: high pressure w/in the legs contributes -refilling occurs promptly: primary varicose vein w/ SVI
to varicosities when there is underlying weakness of vessel
wall o Perthes test: assess possibility of deep venous obs.
-obesity: adipose tissue offer less structural support to -px asked to stand and alow vv to fill, torniquet placed
veins than lean mass midthigh, px instructed to walk for 5 min.
-patent and competent vein: collapse
-DV obs: distend
DIFFERENTIAL DX Interventional/Surgical Therapies
-duration of leg edema helps distinguish CVI and DVT -endovenous thermal ablation, sclerotherapy, surery: tx for VV;
-disorders that cause leg swelling should be considered and indicated when persistent sx, great saph insufficiency, complication
excluded of venous insuf (dermatitis, edema, ulcers)
- bilateral: CHF,hypoalbuminemia, myxedema, CCB use -ablative therapy: indicated for cosmetic reason
-unilateral: ruptured leg m.,hematoma, popliteal cyst -ETA: catheter placed percutaneously-> thermal energy is delivered-
> heat injures the endothelium-> media promotes thrombosis and
CLASSIFICATION OF CVD fibrosis
- adverse effects of thermal ablation:
o Pain
o Paresthesia
o Bruising
o Hematoma
o Hyperpigmentation
-sclerotherapy:injection of chemical to cause fibrosis and
obstruction; agents approved (Na tetraecyl sulphate, polidocanol,
glycerine, Na morrhuate)
: agent administered as liquid or mixed with CO2/02 to create foam
-surgical: stripping and ligation of saphenous vein
: incisions at groin and upper calf; great SV ligated below
saphenofemoral junction; wire inserted
:complications- DVT, bleeding, hematoma, nerve injury
-for DVI tx options:
Endovascular intervention, surgical bypass, valve reconstruction
-catheter-based intervention: chronic occlusion of iliac v.
-surgical bypass: chronic femoropopliteal v obs.
-valve reconstruction: valvular incompetence; transfer of
competent valve to incompetent valve
-valvuloplasty: tightening the valve by commissural
apposition

LYMPHEDEMA
-chronic condition caused by impaired lymph transport
-charac. by swelling of one or more limbs, trunk, genitalia
-imbalance lymph production and absorption-> lymph accumulates
in interstitium
-leads to inflammatory and immune response, adipose and collagen
DIAGNOSTICS deposition in skin and subcu
-Venous duplex ultrasound: principal dx test
-obstruction: absence of BF, presence of thrombus, failure to LYMPHATIC ANATOMY
collapse, ntraluminal thrombus Lymphatic capillaries: blind-ended tubes; single layer endothelial
-venous reflux: reversal of BF during Valsalva maneuver; severity cells; absent or fenestrated basement membrane allows access to
assessed by plethysmography interstitial particles
-MRI &CT scan: used to identify obs or stenosis of IVC and Precollector vessels: lymph cap.merge; few smooth m.
iliofemoral vein Collecting lymphatic vessel: comprise of endothelial cells, basement
membrane, smooth m., bileaflet valves
TREATMENT Lymphatic conduits: coll. Lymph vessel merge
Supportive measures
-VV: legs elevated periodically; avoid prolonged standing; elastic Direction of flow:
support hose (elastic stockings or stretch bandages; provide Lymphatic cap -> precollector vessels -> collecting lymphatic vessel->
counterbalance to hydrostatic pressure; they don’t prevent large lymphatic conduits
progression; 30-40 mmHg required for px with VI manifestation)
- CVI: avoid prolonged standing or sitting; leg elevation; compression -there are superficial and deep lymphatic vessels; communicates at
therapy (standard care or CEAP class C3-C6; 30-40 mmHg; calf- the popliteal and inguinal
length stockings tolerated by elderly; thigh-length for px w/ varicose -pelvic lymphatic vessels->thoracic duct->L brachiocephalic vein
extending to thigh); lose weight -lymphatic valves ensures unidirectional flow
-venous ulcers: low adherent absorbent dressing; antibiotic not
indicated unless infected; compression bandage put over the
dressing

Medical therapies
-diuretics for edema
-topical steroids for inflammation in stasis dermatitis
ETIOLOGY CLINICAL PRESENTATION
-painless condition, experience dull, heavy sensation in leg
-lympedema starts from foot and gradually progress up to
leg
-early stages: edema soft and pits easily with pressure
Over time: subcu adipose tissue accumulates, limb
enlarges, loss on normal contour, toes appear square
Chronic stages: edema no longer pits; woody textur limb
-Stemmer’s sign: inability to tent the skin at the base of
the toes
Detects thickening of the skin
-Peau d’orange: dimpling of the skin caused by
lymphedema

DDX
-should be distinguished from unilateral leg swelling in DVT and CVI.
-in CVI: edema is softer; evidence of stasis dermatitis,
hyperpigmentation, superficial venous varicosities
-myxedema and lipedema
-in lipedema: occurs usually in women; caused by accumulation of
adipose tissue in leg from the thigh to the ankle with sparing of feet

2 categories: DIAGNOSTICS
 Primary: caused by agenesis, hypoplasia, hyperplasia, -Abdominal and pelvic ultrasound & CT: detect obst lesions
obstruction. -MRI: may reveal honeycomb pattern (charac.of lymedema) &
-females more affected; 1.15 per 100k in <20 yo enlarged channels and nodes
-3 subtypes: : distinguish lympedema from lipedema
o Congenital: appears shortly after birth -lymphoschintigraphy & lymphangiography: confirm dx and
o Lymphedema precox: onset at puberty differentiate primary and secondary
o Lymphedema tarda: begins after age 35 Schintigraphy findings:
-familial form of congenital (Milroy’s disease) & precox -primary: absent or delayed filling or dermal dermal backflow
-secondary: dilated lymphatic vessels distal to an area of
(Meige’s disease) is inherited in AUTOMOSOMAL
obs.
DOMINANT Angiogrphy finding:
-mutations in VEGFR3 described in Milroy -primary: channels absent, hypoplastic, ecstatic
-mutation in choromosome 15q in cholestasis- -secondary: channels appear dilated beneath the level of
lymphedema syndrome obs.
-mutation in FOXC2 gene in lyphedema-distichiasis
syndrome; lympedema precox occirs in px with double row TREATMENT
of eyelashes -care of feet to prevent recurrent lymphangitis
-mutation in SOX18 -skin hygiene; use of emollients to prevent drying
-prophylactic antibiotics
 Secondary: acquired condition; results from damage or
-encourage physical act.
obst.of previously normal lymphatic channels -leg elevation
-recurrent bacterial lymphangitis: very common cause of -psychosocial support
lymphedema; result in chronic lymphedema -massage to facilitate lymphatic drainage; compressive bandage after
-lymphatic filiariasis: most common secondary lympedema massage to prevent recurrent edema
WORLDWIDE -DIURETICS ARE CONTRAINDICATED: may cause fluid depletion
-in DEVELOPED countries: surgical incisions or irradiation -liposuction may be considered
ARTERIAL DISEASE OF EXTREMTIES
most common cause
 -fewer than 50% are symptomatic
PERIPHERAL ARTERY DISEASE (PAD) -intermittent claudication: most common symptom; occurs during exercise,
-stenosis or occlusion in the aorta or the arteries of the limbs relieved by rest
-presence of flow-limiting lesions in an artery that supplies the limbs :site of claudication is distal to the location of
-atherosclerosis: leading cause of PAD in px >40 yo occlusive lesion
:prevalence: 6-7th decades -symptoms more common in lower x than upper x because of higher
-other causes: incidence of obs.lesions in lower x.
Thrombosis
Embolism
Vasculitis
Fibromuscular dysplasia
Entrapment
Cystic adventitial disease
Trauma
-increased risk in PAD:
smoking, DM, hypercholesterolemia, HTN, renal insufficiency

ETIOLOGY AND PATHOGENESIS

-large and medium-sized vessels: most segmental lesions that cause stenosis
are localized
-sites involved:
o Femoral and popliteal (80-90%)
- In severe arterial occlusive disease:
o Tibial and peroneal (40-50%) critical limb ischemia develops;
o Abdominal and iliac arteries (30%) REST pain; cold/numb foot or toes
-pathology: atheroslecrotic plaque with calcium deposit, thinning of media, Symptoms occur AT NIGHT when legs are horizontal; improves
patchy destruction of muscles and elastic fibers, internal elastic lamina when in dependent position
fragmentation, thrombi with platelets and fibrin
-AS lesions occur mostly at BRANCH POINTS (bec of increase turbulence, Important PE:
altered sheer stress and intimal injury)  Dec.or absent pulses distal to obs
-elderly an DM px DISTAL vasculature commonly involved  Bruits over narrowed artery
 Muscle atrophy
 In more severe: hair loss, thickened nails, smooth and shiny skin,
reduced skin temp, pallor or cyanosis, ulcers and gangrene in px
w/ critical limb ischemia
 Pallor of soles: when legs elevated and calf m. flexed
 Rubor: when legs are dependent
 Peripheral edema (bec px keep their legs in dependent position
much of the time)

Ischemic ulcers: more distal

venous insufficiency ulcers: more proximal, on the
medial portion, associated with reddish-brown
pigmentation and varicose vein

NONINVASIVE TESTING
-In stenosis systolic BP in leg is decreased
-ankle:branchial index (ABI)
1.00-1.40 = NORMAL
0.91-0.99 = BORDERLINE
<0.90 = ABNORMAL; DIAGNOSTIC OF PAD
>1.40 = noncompressible artery secondary to vascular calcification
-other noninvasive tests:
o Segmental pressure measurement: presence of
pressure gradients between sequential cuffs provide
evidence of stenosis
o Segmental pulse volume recordings: significant PAD ->
blunted amplitude in pulse volume contour
o Duplex ultrasonography: image and detect stenotic
lesion
o Transcutaneous oximetry
o Stress testing: assess functional limitiation objectively;
decline of ABI after exercise support dx of PAD.
-MRI and CT scan is not routinely used for dx testing; performed BEFORE
potential revascularization

PROGNOSIS
-influenced by coexisting CAD and cerebrovascular disease
-1/2 – 1/3 of px with PAD have CAD; px with PAD have 2fold to 5fold
increased risk of cardiovascular death compared with px who do not have
PAD.
-detection of PAD is useful in ID px at increased risk of adverse cardiovascular
events.
CLINICAL EVALUATION
-likelihood of symptomatic progression to PAD is lower than the chance of -B blockers and statins: reduce risk of postoperative cardiovascular
succumbing to CAD complications
-prognosis is worse in px who continue to smoke or have DM
FIBROMUSCULAR DYSPLASIA
TREATMENT -hyperplastic disorder
-risk factor modification -affects medium-size and small arteries; iliac areteries most affected
 Smoking cessation -predominant in female
 BP control: ACE-reduce the risk of cardiovascular events in px with -involves renal and carotid; iliac and subclavian
PAD; -string of beads appearance: thickened fibromuscular ridges; thin, less-
B-blockers- do not worsen claudication involved arterial wall
 Statin: treatment of hypercholesterolemia, reduce risk of MI, -histologic classification:
stroke, death; CC/AHA recommends high intensity statin  Intimal fibroplasias (focal)
-Antiplatelet therapy: aspirin and clopidogrel- reduce risk of cardiovascular  Medial dysplasia (multifocal)
events in px with AS; recommended in symptomatic PAD with o Medial fibroplasias
claudication or critical limb ischemia; prior lower x o Perimedial fibroplasias
revascularization o Medial hyperplasia- most common type; characterized
:dual therapy not effective than aspirin alone in reducing by alternating areas of thinned media and
cardiovascular morbidity and mortality in px with PAD fibromuscular ridges; preserved internal elastic lamina
-Anticougulant: warfarin- prevents adverse cardiovascular events; cause
major bleeding; not indicated to improve outcome in px with chronic PAD  Adventitial hyperplasia
-Intermittent claudicaton: -when limb vessels involved: manisfestationof AS (claudication and rest pain)
Meticulous care of feet, kept clean and avoid from drying -PTA and surgical reconstruction
Well-fitting shoes and protective shoes
Avoid elastic support hose (reduce BF) THROMBONGIITIS OBLITERANS (Buerger’s disease)
Shock block under the head and canopy over feet: improve -inflammatory occlusive vascular disorder
perfusion pressure, relieve rest pain -involves small and medium-size arteries and veins; distal upper and lower x
Exercise regularly, at more progressive strenuous level -rarely affected: cerebral, visceral and coronary vessels
-30-45 min, 3-5x/week for 12 weeks -frequent in men <40 yo
-Advise to walk to maximum distance until claudication -higher in Asians and Eastern European
occurs, rest until symptoms relieved, resume -no known cause but definite relationship to smoking
ambulation -histology:
Vasodilators, alpha adrenergic blockers, CCB have not proved to 1.infiltration of polymorphonuclear leukocytes in wall of vessels
be beneficial 2.internal elastic lamina is preserved, cellular inflammatory
Pharma thrombus develops in lumen
Cilostazol- phosphodiesterase inhibitor and increases cAMP and 3.mononuclear cells, fibroblast, giant cells replace neutrophils
has vasodilator and platelet-inhibiting properties 4. perivascular fibrosis, thrombus, recanalization
-increase claudication distance; improve exercise capacity CLINICAL FEATURES:
Pentoxyfylline- xanthine derivative; improve deformability of RBC Triad:
and may improve claudication symptoms; increases BF and 1.claudication – confined to calves and feet, hands/forerms; in severe digital
enhances oxygenation ischemia: nail chanes, ulceration, gangrene
-there is no definite therapy for critical limb ischemia 2.Raynaud’s phenomenon
Studies suggested that long-term parenteral administration of 3.migrating superficial vein thrombophlebitis
vasodilator prostaglandin: dec pain and facilitates healing of
ulcers PE
Revascularization -normal brachial and popliteal pulse
-indicated for px with: -reduces/absent radial, ulnar, and/or tibial pulses
 disabling, progressive, severe symptoms of -MRA and CTA: helpful in making dx
intermittent claudication DESPITE medical therapy; -characterize by smooth, tapering segmental lesions in the distal
 with critical limb ischemia vessels; collateral vessels at site of occlusion (corkscrew
-MRI and CT performed before revascularization appearance)
-nonoperatve intervention: -proximal AS is usually ABSENT
 Percutaneous transilumal Angiography (PTA) -dx confirmed: biopsy and pathologic exam
 Stent placement
TREATMENT
Iliac artery- higher success rate of PTA and stenting than femoral an -no specific treatment except smoking cessation
popliteal -antibiotics may be helpful
-Aortoiliac diasease procedures: -anticougulant and glucocorticoids ARE NOT HELPFUL
Aortobfemoral bypass, axillofemoral bypass, femoro-femoral -arterial bypass and local debridement in selected instances
bypass, aortoiliac endarterectomy -revascularization not usually an option because of the distal location
Aortobifemoral bypass- most frequently used procedure
-operative complications: ACUTE LIMB ISCHEMIA
 MI & stroke -sudden cessation of BF to an extremity bec of arterial occlusion
 Infection of graft -cause by:
 Peripheral embolization o Embolism:
 Sexual dysfunction (interruption of nerves in pelvis)
- heart, aorta, large arteries are most common source
-femoral-popliteal procedures:
-Cardiac disorders that cause thromboembolism:
Reverse autoenous saphenous vein bypass graft, PTFE,
AFib (chronic or paroxysmal), acute MI, ventricular aneurysm,
thromboendartherectomy
cardiomyopathy, infectious and marantic endocardidits, thrombi
-preoperative cardiac events high risk: (likely to experience adverse cardiac
associated with prosthetic valve, atrial myxoma
events during perioperative period)
-emboli originate from proximal sites of AS
 Px with angina HF
-less frequently, occlusion results from venous thrombus
 Prior MI DM
(paradoxical embolism) ie. Atrial septal defect
 Ventricular ectopy
-emboli lodge at vessel bifurcation
 -femoral artery > iliac > aorta > poplitel > tibioperoneal -blue toe syndrome
o thrombus situ- appear at site of atherosclerotic plaque or -Digital necrosis and gangrene
aneurysm, or within bypass grafts -localized tenderness
o arterial dissection- intimal flaps obstructs artery -pallor
o Trauma- may disrupt the continuity of BF and cause acute limb -livedo reticularis (purplish mottling of involved skin)
ischemia by formation of thrombus or disruption of artery and -kidney failure
extravasation of blood -intestinal ischemia
-Less common cause: TREATMENT
o Thoracic outlet compression syndrome (subclavian -ischemia resulting from atheroemboli is difficult to manage because of
a.occlusion) heterogenous composition, ultiplicity, distal location of emboli
o Entrapment of popliteal a.(abnormal placement of head of -statin: stabilize the plaque
gastrocnemius m) -surgical intervention to remove or bypass the atheroemboli
o Polycythemia and hypercougulable disorders
CLINICAL FEATURES: THORACIC OUTLET COMPRESSION SYNDROME
-severe pain, parenthesia, numbness, coldness w/in 1 hr -compression of neurovascular bundle (artery, vein, nerve) at the thoracic
-severe and persistent ischemia: paralysis outlet as it courses through the neck & shoulder
PE -compression through:
o -loss of pulse distal to occlusion Cervical ribs
o -cynosis Abnormality in scalenus anticus m.
o -pallor Proximity of clavicle to 1st rib
o -mottling Abnormal insertion of pectoralis minor
-divided into
o -decrease skin temp
Arterial: claudication, Raynaud’s phenomenon, ischemic tissue loss and
o -muscle stiffening
gangrene
o -loss of sensation
Venous: thrombosis of subclavian and axillary vein associate with effort
o -weakness
called Paget-Schroetter syndrome
o -loss/absent deep tendon reflex
neurogenic form: arm pain, weakness, parenthesia
6 P’S:
 PAIN APPROACH TO PATIENT
 PALLOR -distal pulses dec.or absent
 PARALYSIS -digital cyanosis & ischemia
 PARESTHESIA -subclavian a.bruits, diminished arm pulses
 PULSELESSNESS MANEUVERS:
 POIKILOTHERMIA (coolness)  Abduction and external rotation test: arm abducted at 90 deg,
- in the presence of collateral circulaton: symptoms less impressive; px shoulder is externally rotated
complains of less walking distance before claudication, pain, paresthesis  Scalene maneuver: neck extended, rotation of head at side of the
occur; pallor and coolness are evident, sensory and motor fx preserved symptoms
- MRA, CTA to confirm dx  Costaclavicular maneuver: posterior maneuver of shouder
 Hyperabuction maneuver: raising arm 180 deg
TREATMENT -chest X-ray indicate presence of cervical ribs
-IV heparin to prevent propagation of clot followed by oral warfarin (dose -Duplex ultrasonography, MRA, contast angiography: demonstrate TOC of
same with DVT) subclavian a.
-revascularization procedure (catheter-base thmboysis/thrombectomy, -electromyogram, nerve conduction studies, somatosensory evoked
thromboembolectomy, arterial bypass) indicated when: potential: abnormal if brachial plexus is involved
Limb viability at risk -shoulder girdle exercises
Severe ischemia of recent onset -surgical removal of first rib and resection of scalenus anticus m.
Large proximal vessel is occluded
Preferred when restoration must occur within 24hrs POPLITEAL ARTERY ENTRAPMENT
Symptoms present more than 2 weeks -affects young athletic men and women
-intraarterial thrombolytic therapy indicated in: -gastrocnemius or popliteal m. compresses the popliteal a.and causes
 Px contraindicated in surgery intermittent claudication
 Smaller distal vessels are occluded -pulse exam.normal unless maneuvers suck as ankle dorsiflexion and plantar
-tPA, reteplase, tenecteplase most effective when occlusion is recent flexion are performed
(<2 weeks) caused by thrombus in AS vessel, graft, occluded stent -dx confirmed by duplex ultrasound. CTA. MRA, anhiography
-percutaneous mechanical thrombectomy: use hydrodynamic force or -surgical release of popliteal a.or vascular reconstruction
rotating basket to fragment and remove clot
-amputation performed: POPLITEAL ARTERY ANEURYSYM
 Limb is not viable -most common peripheral artery aneurysm
 Loss of sensation, paralysis -50% are bilateral
 Absence of Doppler-detected BF -px may have aneurysm of other artery, esp.aorta
-emboli from infective endocarditis, prosthetic valve, atrial myxoma require -clinical presentation: limb ischemia secondary to thrombosis or embolism
surgery to remove -less frequent rupture
-detected by palpation; confirmed by duplex ultrasonography
ATHEROEMBOLISM -repair indication:
-another cause of limb ischemia  Symptomatic aneurysm
-fibrin, platelets, cholesterol embolize from proximal AS lesions or  Diameter >2-3 cm
aneurysmal sites
-source of emboli: large protruding aortic atheromas that leads to limb ARTERIOVENOUS FISTULA
ischemia, renal insufficiency, stroke -abnormal communication between artery and vein, bypassing capillary bed
-may occur after intraarterial procedure -congenital: result of persistent embryonic vessels that fail to differentiate
-lodge in small vessels; may not occlude large vessels; thats why distal pulses into arteries and veins; associated w/ birthmarks, located in any organ,
remain palpable frequently occur in extremities
CLINICAL MANIFESTATION
-acute pain and tenderness at site of occlusion
-acquired: created to provide vascular access for hemodialyisis; result of PE
penetrating inury susc as gunshot or surgical dissection -normal radial, ulnar, pedal pulses
-uncommon cause: rupture of arterial aneurysm into a vein -cool fingers and toes; may perspire excessively
CLINICAL MANIFESTATION -scleroctyly (thickening and tightening of digital subcu) in 10% of px
-palpable pulsatile mass -angiography not indicated
-thrill and bruit last throughout systole and diastole present over fistula -in general: mild manifestation; 1% lose a part of their digit
-long standing fistula: 15% resolves spontaneously; 30% progress
Peripheral edema Secondary
Varicose veins -occurs in 80-90% in px with scleroderma 20y(systemic sclerosis)
Stasis pigmentation -systemic lupus erythematous
-ischemia in distal x -in dermatomyotitis or polymyositis
-skin temp higher over arteriovenous fistula -in rheumatoid arthritis
-large arteriovenous fistula: inc.crdiac output->cardiomegaly-> high-output -AS in men >50 yo
HF -Buerger’s disease is uncommon; considered in young men who smokes
-Nicoladoni-Branham sign: reflex slowing of heart upon compresson of AV -occasionally, Raynaud’s follows acute occlusion of large arteries
fistula -hyperviscosity syndrome (Waldenstrom’s macroglobulinemia) should be
considered with Raynaud’s
TREAMENT -occurs in px whose vocation require vibrating hand tools
-surgery, radiotherapy, embolization (see table)
-congenital: elstic support hose reduce venous HTN, embolization with
autologous material to obliterate fistula TREATMENT
-acquired: excision of fistula, autogenous or synthetic grafting -mild and infrequent episodes
-dress warmly, avoid unnecessary cold exposure
RAYNAUD’S PHENOMENON -protect the trunk, head, feet with warm clothing
-episodic digital ischemia -tobacco contraindicated
-vasospastic disease of the digital arteries that occurs in susceptible people -drug tx reserved for severe cases
Vasospasm- EXTREME vasoconstrictor response Dihydropyridine CCB: dec.severity and frequency
-sequential development of digital blanching (pallor), cyanosis, rubor Postsynaptic alpha-adrenergic antagonist: doxazosin & terazosin
(reactive hyperaemia) of fingers and toes AFTER cold exposure & subsequent Phosphodiesterase type 5: sildenafil, taladafil in secondary
rewarming Raynaud’s
-also precipitated by emotional stress -digital sympathectomy: in px unresponsive to meds therapy
-triphasic color changes:
1.white- blood flow is interrupted; numbness & paresthesia ACROCYANOSIS
2.cyanotic-accumulation of dessaturated Hg; “ “ -arterial vasoconstriction and secondary dilation of capillaries and venules
3.ruddy-blood flow resumes, throbbing pain -PERSISTENT cyanosis of hands, less in feet.
Color response associated w/ numbess, paresthesia, pain -intensified in cool environment
Some px only develop pallor and cyanosis; others only cyanosis -categorized into:
a.Primary
2 categories: -women affected more than men
1. Primary (Idiopathic) -onset <30 yo
2. Secondary cause (Associated with other disease states) -asymptomatic; seek medical attention because of discoloration
-pain,ulcers, gangrene DO NOT occur
-normal pulses
-peripheral cyanosis and moist palms
-trophic skin changes and ulceration DO NOT occur
-distinguished from Raynaud’s:
-persistent not episodic
-discoloroation extends proximally
-no blanching
-distinguished from occlusive disease:
-presence of normal pulses
-central cyanosis & dec arterial oxygen saturation are NOT present
-pharma not indicated
b.Secondary
-result from hypoxemia, vasopressor meds, connective tissue disease,
atherembolism, antiphospholpid antibodies, cold gglutinins, cryoglobulins,
associate with anorexia, postural orthostatic tachycardia syndrome
-tx directed at underlying condition

LIVEDO RETICULARIS
-mottled or netlike appearance in localized areas of xtemities; more
prominent after cold exposure
-appears reddish to blue discoloration
Primary -primary: idiopathic form, benign or associated with ulceration
-50% have primary form More common in women; onset at 3rd decade
-5x in women than in men; between 20 and 40 yo Asymptomatic, take consult for cosmetic reason
-fingers involved more than toes Avoid cold environment
-initial episodes: involve one or two fingertips No drug indicated
-subsequent: all fingers Atrophie blanche en plaque: primary livedo with ulceration
-toes affected in 40%; vasospasm occurs with fingers or may happen alone -painful, take months to heal
-rarely: earlobes, penis, tip of nose -secondary: occur with atheroembolism, SLE, anticardiolipin antibodies,
-occurs in px with migraine headaches and variant angina hyperviscosity, cryoglobulinemia, Sneddon’s syndrome (ischemic stroke and
livedo reticularis); rarely ulceration develops
PERNIO (CHILBLAINS)
-vasculitic disorder associated with exposure to cold
-RAISED erythematous lesions on lower legs and feet in cold weather
-associated with pruritus and burning sensation; may blister and ulcerate
-pathology:
Angiitis; intimal proliferation and perivascular infiltration of monocluear &
polymotphonuclear leukocyte; giant cell in subcutaneous tissue
-px should avoid cold
-ulcers kept clean and protected
-sympatholytic drugs and dihydropyridines CCB effective in some px

ERYTHROMELALGIA
-burning pain and erthyma of the extremities
-feet involved more htna hnds
-males more than females
-occur most in middle age; ay occur at any age
-primaryor secondary
-inherited forms: mutations in SCN9A gene which encodes the Nav1.7
viltage-gated sodium channel expressed in sensory and sympathetic nerves
-secondary: cause by myeloproliferative such as polycythemia, essential
thrombocytosis
-burning in the xtremities precipitated by exposure to warm environment;
aggravated by dependent position; relieved: exposing affected area to cool
air or water or by elevation
-distinguished from ischemia secondary to PAD by presence of peripheral
pulses
-aspirin may produce relief

FROSTBITE
-tissue damage result from severe cold
-affects distal aspects of xtrmities or exposed part of face (ears, nose, chin,
cheeks)
-pain or parenthesia
-skin appears white and waxy
-after warming: cyanosis and eythema, wheel-and-flare formation, edema,
superficial blisters
TREATMENT
-rewarming of affected part in water bath at 40-44 C
-massage, ice water is contraindicated
-analgesics often required during rewarming
-antibiotic if evidence of infection
 DISEASES OF AORTA

Aorta
-conduit where blood from LV is delivered to the systemic circulation
-3cm at origin and ascending
-2.5cm in descending portion
-1.8-2cm in abdomen
-buffering fx
-wall consist of:
Thin intima- endothelium, subendo, internal elastic lamina
Thick tunica media- smooth muscles
Tunica adventitia- vasa vasorum and nervi vascularis

CONGENITAL ANOMALIES
-involved aortic arch and branches
-dysphagia, stridor, cough
-Kommerell’s diverticlum: anatomic remnant of R aortic arch
-most do not cause symptoms
-dx confirmed by CT or MR angiography

AORTIC ANEURYSYM
Aneurysm- dilation of a segment of blood vessels
 True- all 3 layers involved
 False/pseudoaneurysm- disrupted intimal and medial, lined by a
layer of adventitia only and at times, perivascular clot ; prone to
rupture completely
In appearance:
 Fusiform: affects entire circumference
 Saccular: involves only a portion; outpoutching of a vessel wall
Diffuse ectasia: generalized yer lesser increase in aortic diameter; developd
in older px

ETIOLOGY & PATHOGENESIS

- degenerative AA: AS most common cause
-Risk factors asscociated with degenerative AA: aging, smoking,
hypercholesterolemia, HTN, male
-abdominal and descending thoracis most affected
-cystic medial necrosis: usually affects proximal aorta, ascending aorta,
sinuses of Valsalva; condition of degeneration and fragmentation
of elastic fibers with subsequent accumulation of collageous and
mucoid material within the medial layer; occurs normally with
aging, associated with HTN; prevalent in px with:
o Marfan syndrome: abnormal fibrillin-1
o Loeys-Dietz syndrome: genetic mutation in TGF-beta
receptors
o Ehlers-Danlos type IV: mutations ecoding type 3
collaen

-infectious causes: syphilis, TB

Syphilis: damage in elastic fibers, thickening and weakening of
aortic wall; located in ascending and aortic
arch
Tuberculos: affect thoracic aorta; loss of aortic wall elasticity->
granulumatous destruction of medial layer
Mycotic: staph, strep, Salmonella; usually saccular
-vasculitis: Takayasus, giant cell arteritis
:aortic arch and descending thoracic
-sponydylarthopthies: ascending aorta
-trauma: affect descending just beyond the site of insertion of the
ligamentum arteriosum
-chronic aortic dissection: weakening of aortic wall-> develops aneurismal
diltation
THORACIC AORTIC ANEURYSM
-0.1-0.2 cm/yr: ave.growth rate ACUTE AORTIC SYNDROMES
-risk of rupture: 2-3%/yr in <4.0 cm; 7%/yr in >6 cm -4 major AAS:
-most asymptomatic  Aortic rupture
-compression of adjacent tissue:  Aortic dissection
 Chest pain  Intramural hematoma
 shortness of breath- compress trachea/mainstem bronchus  Penetrating atherosclerotic ulcers
 cough- compress trachea/mainstem bronchus -Aortic dissection
 hoarseness-recurrent laryngeal nerve involvement -Life threatening condition
 dysphagia- compression of esophagus -Blood passes through a tear in the intima passes to the media
 CHF: aortic regurgitation from dilation of ascending aorta and spreads along the artery forming a false lumen; OR
 Congestion of head, neck, upper x: compression of SVC Ruptured vasa vasurom with haemorrhage in the media, forms
-X-ray suggest dx hematoma in arterial wall that subsequently tears through
 Widening of mediastinal shadow through intima and into the vessel’s lumen
 Displacement/compression of trachea or left main stem bronchus 2 variants of Aortic dissection:
-contranst enhance CT or MRI: asymptomatic px; every 6-12 mos to monitor a.Intramural hematoma: hemorrhage in the wall of aorta w/o
expansion evidence of intimal tear; thought to result from rupture of casa vasorum;
TREATMENT descending thoracic aorta mostly affected
-B-blockers: reduce rate of expansion b.penetrating atherosclerotic ulcers: erosion of plaque into the
-ARB’s and ACEI: reduce rate of aortic dilation in Marfan’s by blocking TGF- aortic media; localized not extensive; middle and distal portion of descending
signalling thoracic aorta
-prosthetic graft indicated in:
 symptomatic ascending thoracic AA
 diameter of >5.5 cm in asymptomatic -
 4-5 cm diameter in Marfan and bicuspid aortic valve
 >6cm diameter descending TAA or >5.5 cm (f feasible)
Increases diameter of >1cm/yr
ABDOMINAL AORTIC ANEURYSM
-more males than females
-incidence increases with age
->4.0 cm affect 1-2% of men older than 50 yrs
-90% related to AS
-most are below the level of renal arteries (infrarenal)
-commonly asymptomatic
-detected as: palpable, pulsatile, expansile, nontender mass
-some complain of strog pulsation in abdomen
-pain in chest, lower back, scrotum
-pain is a harbinger of rupture and represents a medical emergency
-more often rupture w/o prior warning (always life-threatening)
Hypotension
Acute abdominal pain
Pulsatile mass
-screening recommended in:
 Men 65-75 yo who have ever smoked
 Siblings or offspring of px with AAA
 Individuals with thoracic r peripheral arterial aneurysm
TREATMENT
-operative repair indication:
 Any size that are expanding rapidly and/or associated with
symptoms factors that predispose: medial degeneration, HTN
 >5.5 cm in asymptomatic -major cause of morbidity and mortality in Marfan’s Loeys-Dietz, Ehlers-
-careful preoperative cardiac and general medical evals are essential; added Danlos
risk of surgery: -incidence increase in aortitis, congenital aortic valve anomalies, coarctation
Pre-existing CAD, CHF, pulmonary disease, DM, advanced age of aorta, hx of trauma, 3rd trimester of pregnancy, weightlifting, cocaine use,
-B-blockers: dec perioperative cardiovascular morbidity and mortality deceleration injury
-after acute rupture: mortality rate of emergent operation is 45-50%
-edovascular repair w/ stent placement: alternative approach to treat CLINICAL MANIFESTATION
rupture aneurysm -peak incidence in the 6th and 7th decades
-men affected more than women 2:1
-sudden onset of pain; very severe, tearing associated w/ diaphoresis
-pain localized to front and back of chest, interscapular region,
-syncope, dyspnea, weakness
-compression of adjacent structure:
Horner’s syndrome
Superior vena cava syndrome
Hoarseness
Dysphagia
Airway compromise
PE
-HTN or hypotension
-loss of pulses
-aortic regurgitation: most common complication of proximal dissection
 Signs: bounding pulse; wide pulse pressure; diastolic murmur -loss of hair
radiating along the R sterna border, CHF -coolness of lower x
-pulmonary edema -advanced ischemia: rubor on dependency; pallor on elevation
-neurologic fx due to carotid a obs (hemiplegia, hemianesthesia) -surgery tx in px with lifestyle-limiting or debilitating symptoms of
-spinal cord ischemia (paraplegia) claudication and px with critical limb ischemia
-bowel ischemia, hematuria, MI
-X-ray: widened superior mediastinum in ascending aortic dissection ACUTE AORTIC OCCLUSION
:pleural effusion; typically serosanguineous; not indicative of rupture -distal abdominal aorta
unless accompanied with hypotension and falling hematocrit -mdical emergency bec it threatens viability of lower x
: widened descending aorta than ascending portion -result from occlusive embolus almost always originate from the heart
-transthoracic echocardiography: sensitive for ascending aortic dissection; -rarely: in situ thrombosis in narrowed segment of aorta
less useful in detecting dissection in aortic arch and descending -severe rest pain, coolness, pallor on lower x, absence of distal pulses
-CT and MRI not suitable for unstable px; highly accurate in ID intimal flap bilaterally
-emergency thrombectomy or revascularization indicated

AORTITIS
-inflammatory disease of the aorta
-may result in aneurismal dilation and aortic regurgitation, occlusion, acute
aortic syndrome

1.TAKAYASU’S ARTERITIS
-often affects ascending aorta and aortic arch and braches
-termed as pulseless diseases: diminished or absent pulse at the time of dx
-pathology: panarteritis; charac. by mononuclear cells and occasionally giant
cell, with marked intimal hyperplasia, medial and adventitial thickening,
fibrotic occlusion
-most prevalent in young females of Asian descent
-systemic complaints: fever , malaise, weight loss
Elevation of sedimentation rate and C-reactive protein
-chronic stages: upper x claudication (brachiocepahlic or subclavian a.),
cerebral ischemia (brachicephalic or carotid a); HTN (renal artery), syncope
-progressive process; no definitive therapy
TREATMENT -glucocorticoids effective in some px during acute stage
-medical therapy indicated as soon as dx considered
-unless hypotensive: therapy aimed at reducing cardiac contractility and 2.GIANT CELL ARTERITIS
systemic arterial pressure -older individuals
-B-blockers administered parenterally: propanolol, metoproplol, short-acting -women more than men
esmolol to achieve HR of 60beats/min -affects medium to large size artery
Accompanied by sodium nitroprusside infusion: lower systolic BP -pathology: focal granulomatous lesions; involves entire arterial wall;
to <120 mmHg associated with polymyalgia rheumatic
Labetalol: both B-and a-blocking properties used parenterally for SIGNS & SYMPTOMS:
acute dissection -diminished temporal pulses
-verapamil and diltiazem: if nitroprusside or B-blockers not employed -prominent headache (temporal artey involved)
-addition of ACE (enalaprilat) to B-blockers may be considered -facial pain and claudication of jaw while chewing (facial a.involvemet)
-isolated use of hydralizine is CONTRAINDICATED because it can inc hydraulic -impaired vision (ophthalmic a. arteritis)
shear and propagate dissection
-surgical correction indicated in: -aortic regurgitation: important complication
 acute ascending dissection and intramural hematoma (TYPE A) -self-limited course of 1 to 5 yrs
 complicated type B (propagation, compromise of major aortic
branches, imoending rupture, continued pain 3.RHEUMATIC AORTITIS
major cause of perioperative mortality/morbidity: -associated with aortitis involving ascending aorta
 MI -extends to sinuses of Valsalva, mitral valve leaflets, myocardium
 Paraplegia -clinical manifestation: aneurysm, aortic regurg, cariac conduction system
 Renal failure
 Tamponade 4.IDIOPATHIC AORTITIS
 Hemorrhage -adventitial and periaortic inflammation with thickening of aortic wall
 Sepsis -assoc with abdominal aortic aneurysim & idiopathic retroperitoneal fibrosis
-medical therapy: SIGNS AND SYMPTOMS
 Uncomplicated and stable dissection type B -fever
-long-term therapy: -abdominal pain
Control of HTN: B-blockers, ACEI or CCB -retroperitoneal fibrosis: ureteral obstruction and hydronephrosis
Chronic type b: follow up every 6-12 mos -glucocorticoids: reduce inflammation

CHRONIC ATHEROSCLEROTIC OCCLUSIVE DISEASE 5.INFECTIVE ENDOCARDITIS

-confined to distal abdominal aorta below renal arteries (infrarenal) -invasion of aortic wall by Staph, Strep, Salmonella, fungi
-frequently extends to iliac -infects sites of atherosclerotic plaques
-claudication in buttocks, thighs, calves, impotence in males (Leriche’s -protease: degrades collagen-> formation of saccular aneurysym (mycotic
syndrome) aneurysm)
-mycotic aneurysym: suprarenal abdominal aorta
PE -pathology: acute and chronic inflammation, abscess hemorrhage, necorsis
-absence femoral and distal pulses bilaterally -affects elderly
-bruit over abdomen (at or below the umbilicus) & common femoral arteries -men 3x more than women
-atrophic skin -signs &symptoms: fever, sepsis, ches,back abdominal pain, diarrheal illness
-antibiotic and surgical removal of affected aorta
-syphilitic aortitis: late manifestation of luetic infection
:usually proximal ascending aorta particularly aortic root
: may involve aortic arch or descending aorta
:saccular or fusiform
:presents in chest radiograph 15-30 yrs after initial infection
:symptoms from: arotic regurgitation, narrowing of coronary
ostia, compression of esophagus, or rupture
:dx is by positive serologic test ie. Rapid plasmin regain (RPR) or
fluorescent treponemal antibody
:tx includes antibiotic and surgical excision and repair
DEEP VENOUS THROMBOSIS & PULMONARY EMBOLISM -vasoactive released by platelets-> induce constriction
-venous thrombosis or thrombophlebitis: thrombus formation w/in -bronchoconstrictive mediators-> bronchospasm
superficial or deep vein and the inflammatory response in the vessel wall -arterial hypoxemia
that it incites -inc. alveolar-arterial O2 tension gradient
-2 major consequences of DVT are: (1) PE and (2) postphlebitic sydrome -inc. anatomic dead space
-inc physiologic dead space
Epidemiology -inc. pulmonary vascular resistance
-venous thromboemblism (VTE) encompasses DVT & PE -impaired gas exchange
-chronic thromboembloic pulmonary HTN cause breathlessness with exertion -alveolar hyperventilation
-chronic venous insufficiency or postthrombotic syndrome: damage valves of -inc airway resistance
leg and cause anke or calf swelling and leg aching after prolonged standing, -dec.pumonory compliance
skin ulceration in severe form
PULMONARY HTN, RV DYSFX, RV MICROINFARCTION
PATHOPHYSIOLOGY -pulmonary obs -> rise pulmonary artery pressure and pul. vascular
Inflammation and Paltelet Activation resistance -> RV wall tension rises RCA compress -> limit myocardial O2
Virchow’s triad of inflammation supply-> RV schemia -> RV
 Hypercougulability microinfarction
 Endothelial injury (vascular damage)
 Inflammation( stasis of blood flow) RV dilation &dysfunction -> release of cardiac
biomarkers and brain natriuretic peptide

Interventrcular septum bulges -> compress LV -> diastolic LV dysfx -> reduce
LV filling-> fall in LV CO-> low systemic arterial pressure

CLASSIFICATION
1.PE
a.Massive PE:
-extensive thrombosis; affects at least hlaf of pulmonary vasculature
-hallmarks: dyspnea, syncope, hypotension, cyanosis
-present in cardiogenic shock and die from multisystem organ failure
b.Submassive PE
-RV dysfx despite normal systemic arterial pressure
-RH failure plus release of cardiac biomarkers
c. Low-risk PE
-excellent prognosis

2.DVT
a. Lower x DVT
-begins inthe calf; propgates proximally to the popliteal vein, femoral and
iliac v
-leg DVT 1x common than upper X DVT
b.Upper X DVT
-precipitated by pacemakers, cardiac defib, central venous catheter
-likelihood inc with inc diameter and lumen of catheter
c. Superficial VT
-erythema, tenderness, palpable cord
-at risk of ectension of thrombosis to deep venous system

DIAGNOSIS
Clinical Evaluation
-PE is known as “the Great Masquerader”; signs and symptoms are
nonspecific;difficult to dx
Virchow’s triad -> recruitment of activated platelets -> release microparticles -breathlessness is most common symptoms
-> microparticles contain proinflammatory mediators -> stimulates release of -with DVT most common symptom is cramp or “charley horse” in lower calf;
neurtrophil extracellualr traps -> these traps contain histoms that stimulate persisting and intensifies over several days
platelet aggregation and thrombin generation -px DVT may be asymptomatic
Calf or thigh discomfort when standing or walking
-Venous thrombi form in an environment of stasis, low O2 tension, Unilateral leg swelling
upregulation of proinflammatory genes Tenderness over the phlebitic vein
Palpable deep venous cord (induratin along the thrombosed
Prothrombotic states vessel)
-antiphospholipid antbody sydrome: most common acquired cause of Homan’s sign: calf pain produced by dorsiflexion of foot;
thrombophilia nonspecific and unreliable sign of DVT
In Proximal DVT: edema of involved leg
Embolization Localized warmth and erythema
-detach deep venous thrombi, lodged to pulmonary circulation causing acute -in px with PE
PE. Dyspnea
Pleuritic chest pain (pleural irritation)
Physiology Hemoptysis, cough, syncope (reduced CO)
-in px w/ PE, gas exchnage is often impaired bec of anatomic dead space and Tachypnea
ventilatoin-perfusion mismatches. As a result alveolar-arterial O2 gradient Bronchospasm
increases and hypoxemia may occur. Elevated pulmonary a.pressure
-mechanical obstruction-> rise in pulmonary vascular resistance Jugular venous distension
 Second heart sound accentuated
-low-to-moderate likelihood of DVT: D-dimer testing ALONE w/o imaging test
-high likelihood of DVT: skip D-dimer; undergo imaging

Cinical pearls
-ruptured Baker’s cyst: sudden, severe calf discomfort
-cellulitis: fever and chills
-DVT: only mild discomfort in ower calf; or in massive PE marked thigh
swelling, tenderness, erythema
if leg DIFFUSELY edematous: DVT is unlikely
upper x DVT: assymetry in supraclavicular fossa or cicumference
of arm
-pulmonary infarction: indicate small PE
-exquisitely painful (thrombus lodges peripherally, near
innervation of pleural nerves)
-nonthrombotic PE: fat embolism (after pelvic/long bone fracture)
Tumor embolism, bone marrow air embolism, cement embolism,
bony fragment embolism
-IV drug users: embolize such as hair, tac, cotton
-amniotic fluid emobolism: leak or tear of fetal membrane at placental
margin
Nonimaging Diagnostic Modalities
a.Blood test
-D-dimer ELISA: rises in DVT and PE bec of breakdown of fibrin by plasmin -consider when:
-D-dimer is a byproduct of fibrin degradation that can be CT facilities not available
measured in a peripheral blood sample Px has renal failure
-highly senstive for dx of DVT/PE Contrast allergy
-nonspecific for DVT Invasive Diagnostic Modalities
POSITIVE result in cancer, inflammation, infection, a.Pulmonary Angiography
necrosis, MI, pneumonia, sepsis, postoperative state, -reserved for:
2nd or 3rd trimester pregnancy Unsatisfactory chest CT
-useful “rule out” test Planned catheter-directed thombolysis procedure
b.Elevated cardiac biomarkers -definitive dx: intraluminal filling defect in more than one projection
-inc. troponin and plasma heart-type fatty acid-binding protein level -secondary signs of PE:
-release of brain natriuretic peptide: myocardial stretch Abrupt occlusion
c.ECG Segmenatl oligemia
-sinus tachycardia Avascularity
-S1Q3T3: S wavein lead I; Q wave in lead 3; inverted T-wave in lead 3 Prolonged arterial phase slow filling
-specific but insensitive Tortous, tapering peripheral vessels
-inverted T waves in v1-v4: RV strain and ischemia Integrated Diagnostic Approach

Noninvasive Imaging Modalitites

a.Venous ultrasonography
-normal vein: collapses woth gentle pressure; creates a “wink”
-DVT: loss of vein compressibility bec of passive distension of acute thrombus
-thrombus appears homogenous, low echogenocity
-vein dilated; absent collateral channels
-px with poor or nondiagnostic venous ultrasound: consider CT and MRI
b.Chest Roentgenography
-Westermark’s sign: focal oligemia (total volume of blood reduced)
-Hampton’s hump: peripheral wedged-shaped density above the diaphragm
-Palla’s sign: enlarged R descending pulmonary artery
c. Chest CT
-principal imaging test for dx of PE
-RV enlargemet on chest CT indicates inc.death w/in next 30 days
d. Lung scanning
-second-line diagnostc test for PE
-px who can’t tolerate IV contrast
-absent or decreased blood flow, possibly due to PE
-high probabilty PE: 2 or more segmental perfusion defects in the presence of
normal ventilation
e.MRI
-when ultrasound is equivocal
-detect large proxmal PE
-not reliable for smaller segmental and subsegmental PE
f. Echocardiography
-not reliable; most px with PE have normal result
-helpful for detecting conditions That may mimic PE (acute MI, pericardial
tamponade, aortic dissection)
-McConnel’s sign: hypokinesis of RV free wall with normal or hyperkinetic
motion of RC apex
DVT TREATMENT
-Primary therapy:
-clot dissolution; low-dose catheter-directed thrombolysis
-reserved for px with extensive femoral, iliofemoral, upper x DVT
Open vein hypothesis: postulates that px who receive primary therapy will
sustain less long-term damage to venous valves, with consequent lower rates
of posttrhombotic sydrome
-Secondary prevention:
-anticouagulation; palcement of IVC filter
-compression stockings, 30-40 mmHg, for 2 yrs after DVT
episodes, replaced every 3 mos

PE TREATMENT
Risk stratification
-high risk: hemodynamin instab, RV dysfx, RV enlargment, elevated troponin
-RV fx normal in hemostable px: anticougulation alone
Anticougulation
-foundation for succesful tx
-3 options:
1. parenteral therapy “bridged” to warfarin
2.parenteral therapy “bridged” to NOAC (dabigatran, edoxaban)
3.NOAC (rivaroxaban, apixaban) followed by maintenance dose
w/o parenteral
-3 heparin-based anticoug:
1.UFH
2.LMWH
3.Fondaparinux
Argatroban & bivalirudin: px with suspected heparin-induced
thrombocytopenia
UFH
-bind and accelerates antithrombin, prevents additional thrombus formation
-activated partial thromboplastin time (aPPT): 60-80 s
-80 U/kg: initial bolus; followed by infusion rate of 18 U/kg per h
-disadvantage: short half-life

LMWH
-less binding to plasma protein & endothelial cells; greater bioavailabilty
-more predictable dose response
-longer half-life thn UHF
-no monitoring or dose adjustment UNLESS px obsese or CKD
Complications of anticougulant
Fondaparinux -hemorrhage
-anti Xa-pentasaccharide -intracranial hemorrhage: Heparin and LMWH
-adminis. Wieght-based OD subcu -heparin-induced thrombocytopenia: UFH
-no lab monitoring required -no reversal agent n bleeding caused by fondaparinux, direct throbin or
-not derived form animal product factorX inhibitors
-does not cause heparin-induce thrombocytopenia -warfarin: antidote is prothrombin complex concentrate; freh frozen plasma,
-dose adjustment with renal dysfx IV vit K
Oral vit K (minor bleeding)
Warfarin Recombinant human cougulation factor VIIa (catastrophic
-vit K antagonist of cofactors 1972 (9, 10, 7, 2) bleeding; although is prothrombin complex concentrate is a better choice)
-full effect requires 5 days
-if monotherapy: paradoxical exacerbation of hypercougulability-> Duration of Anticougulation
thrombosis -3 mos: DVT isolated in upper x or calf
-UFH, LMWH, fondaparinux, parenteral direct thrombin inhibitors plus -3-6 mos: initial episode of provoked proximal leg DVT
warfarin for at least 5 days will NULLIFY the procougulant effect -indefinitely (LMWH as monotherapy w/o warfarin): cancer with DVT
-5mg: adult-size -indefinite duration: idiopathic, unprovoked VTE (ie.long haul air travel); INR
-INR of 2.5; with range of 2-3 between 2-3
-increasing age, sytemc illness: reduce required warfarin dose Alternative approach: first 6 mos of anticoug; reduced intensity
-pharmacogenomics provide more precise dose and lower target NR between 1.5-2.
-presence of genetic mutation: not appear to inc risk of recurrent VTE
NOAC -antiphospholipid antibody syndrome: indefinite durtion
-adminis in fixed dose INFERIOR VENA CAVA FILTERS
-effective anticougulation within hours after ingestion -2 indications:
-no lab monitoring 1.active bleeding that precludes anticougulation
-few drug-drug & drug-food interaction 2. recurrent venous thrombosis despite intensive anticoug
-Rivaroxaban & apixaban: approved for DVT and PE tx as MONOTHERAPY -soft indication: px w/ R HF not indicated for fibrinolytics and phrophylaxis
w/o parenteral bridging -caval thrombosis with bilateral leg swelling: common complication
-Dabigatran and edoxaban: approved tx for VTE after initial course of -paradoxically, filters increase DVT rate
parenteral anticougulation -retrievable filters can be placed with anticipated temprary bleeding disprder
at high risk of PE (in bariatric surgery)
-retrieved after several mos

MANAGEMENT OF MASSIVE PE
-replete 500 ml NSS
-infused with caution: excessive fluid exacerbates RV wall stress
-Dopamine & dobutamine: first-line inotropic agents
-maintain low threshold
-other agents: NE, vasopressin, phenylephrine
FIBRINOLYSIS PULMONARY THROMBOENDARTERECTOMY
-succesful therapy reverses R HF by: -acute PE px develops chronic thromboembolic pulmonary HTN
 1.dissolving the pulmonary thrombus -follow up for 6 weeks with repeat echocardiogram
 2.prevents secretion of serotonin and others that exacerbates -considered in px impaird by dsypnea
pulmonary HTN -inoperable px: mananged with pulmonary vasodilator therapy
 3.lyse pelvic or deep lef vein thrombus
-100mg tPA IV for 2hrs; used for at least 14 days after PE occured PREVENTION OF VTE
-indicated for MASSIVE PE -low-dose UFH or LMWH: most common prophylaxis
-px who undergo total hip or knee replacement or cancer surgery will benifit
PHARMACOMECHANICAL CATHETER-DIRECTED THERAPY form extended pharma VTE prophylaxis
-combines physical fragmentation or pulverization of thrombus with -at least 1 mos duration
catheter-dircted low-dose thrombolysis
-alteplase 20-25 mg
DISEASES OF THE ESOPHAGUS -occurs in anxiety or obessive/compulsive disorder; often
atrritubed by GERD
Key fx impairments: g.Water brush
1.Swallowing disorders -esophagea mucosa acidification->vagal reflex-> excessive
2.Gastroesophageal reflux salivation
-not common symptom
Symptoms of Esophageal Disease -unpleasant sensation in mouth; rapidly filled with salty thin fluid;
-obtain a careful clinical hx; details on: concominant with heartburn
 Weight gain/loss
 GI bleeding DIAGNOSTIC STUDIES
 Dietary habits (timing of meals) a.Endoscopy
 Smoking -aka esophagogastroduodenoscopy (EGD)
 Alcohol consumption -most uselful test tor evals of proxiaml GI tract
-major symptoms: -advantages:
 Heartburn  Sensitivity in detecting mucosal lesion
 Regurgitation  “ “ abnormalities (eg. Barret metaplasia, vascular
 Chest pain lesion)
 Dysphagia  Obtain biopsyspecimen
 Odynophagia  Dilate strictures
 Globus sensation -disadvantage: COST
a.Heartburn b.Radiography
-MOST common esophageal symptoms -demostrate reflux, hiatal hernia, mucoal granularity, erosions,
-discomfort/burning sensation behind the sternum ulceration, strictures
-arise: epigastrium; radiate: towards the neck -22-95% senstivity in detecting reflux esophagitis vs endoscopy;
-intermittent symptom; higher grades of esophagitis = greater dection rates
-aggravated/experienced: after eating, during -greater sensivity for detecting strictures than edoscopy
exercise,lying in recumbent, -provides assessment of esophageal fx &morphology undetected
-relieved: drinking water or antacid by endoscopy
-interfere w/ normal activity like sleeping -best in hypophrayngeal pathology & cricopharyngeus m disorders
b.Regurgitation -radiography + endoscopy:
-return of food or fluid into the pharynx w/o nausea or retching  Tracheoesophageal fistula
(gag)  Altered postsurgical anatomy
-sour or burnn fluid in throat or mouth; may contain udigested  Extrinsic esophageal compression
food -shortcoming: endoscopy is almost always needed to obtain
-provoked by:bending, belching, maneuvers that inc. intrabominal biopsies, provide therapy, clarify findings
pressure c.Endoscopic ultrasound
Vomiting: preceded by nausea and accompanied by retching -endosope + ultrasound transducer
Rumination: behaviorin w/c recently swallowed food is regurgitated and then -create transmural image of the surrounding tissue
reswallowed repetitivey for an hour; link with mental deficiency -advantage: greater resolution
c.Chest pain -applications: esophageal cancer, Barret’s esophagus, submucosal
-charac.similar to cardiac pain
-Esophageal pain: pressure type sensation in midchest, radiatng to lesion
mid back, arms or jaw d.Esophageal manometry
-similar w/ cardiac bec they share nerve plexus and nerve endings -motility testing
in the esophageal wall -pressure-sensing catheter positioned in esophagus & observng
-esophageal distension & chemostimulation-> perceive as cehst contractility follwing test swallows
pain -UES & LES relax during swallowing; intersphincteric esophagus
-gastroesophageal reflux: the most common cause of esophageal exhibits peristaltic contraction
chest pain -used to dx:
d.Dysphagia  Motility disorders (e.g achalasia, diffuse
-feeling of “food sticking” or lodging in the chest esophageal spasm)
-differetiate between:  Assess peristaltic integrity prior to surgery
Solid food or solid and liquid -combined w/ impedance monitoring (catheter w/ paired
Episodic or constant electrode)
Progressive or static  Contents in lumen in contact w/ electrode dec
-achalasia (motility disorder): solid & liquid (liquid) inc (air) the impedance signal
-stricture, ring, tumor: solid  Allows detection of anterograde or retrograde
-30% of distal esophageal obstruction present wth cervical esophageal bolus transit
dysphagia e.Reflux testing
- oropharyngeal dysphagia symptoms: aspiration, nasopharyngeal -demostrate excessive esophageal exposure to refluxed gastic
regurgitation, cough, drooling, neuromascular compromise juice
e.Odynophagia -ambulatory 24-48-h esophageal pH recording using:
-pain cause by or exacerbated by swallowing  Wireless pH-sensitive tranmitter: anchored in
-may manifest concurrently with dysphagia esophageal mucosa
-common with pill or infectious esophagitis than reflux  Wire electrode: positioned transnasally w/ tip in distal
esophagitis esophagus
-odynophagia in GERD: likely related to esophageal ulcer or deep -result expressed as percentage of the day
erosion  <4 pH: recent acid reflux
f.Globus sensation  >5%: GERD
-globus hystericus -useful w/ atypical syptoms or poor response to therapy
-perception of lump or fullness in throat felt IRRESPECTIVE of
swallowing
-relieved by swallowing
 STRUCTURAL DISORDERS

HIATAL HERNIA
- herniation of viscera,
-most common: stomach in esophageal hiatus of the diaphragm
-4 types:
 Type 1
-sliding hiatal hernia; 95% of the types
-weakening of the phrenoesophageal ligament & dilatation
of the diaphragmatic hiatus -> cephalad translocation of
gastroesophageal junction and gastric cardia
-inc. with age
-enlarge w/ increased intraabdominal pressure, swallowing,
and respiration
- abdominal obesity, pregnancy -> increased intraabdominal
pressure -> wear and tear -> sliding hernias
-inc risk of developing GERD
 Paraesophageal hernia (herniation includes visceral structure
other than gastric cardia):
 Type II: gastric fundus herniates; fixed GEJ;
stomach inverts as it herniates
 Type III: gastric fundus herniates; sliding +
paraesophageal hernia; stomach inverts as it
herniates
 Type IV: viscera (colon) herniates other than
stomach

DIVERTICULA
- categorized by location
- most common:
 Epiphrenic- associated with achalasia or a distal esophageal
stricture; asymptomatic until enlarge to cause dysphagia and
regurgitation.
 hypopharyngeal (Zenker’s)- stenotic cricopharyngeus muscle
(UES); most common in an area of natural weakness known as
Killian’s triangle
- Small Zenker’s diverticula
-large: associated with dysphagia, halitosis, and aspiration
-tx: surgical diverticulectomy and cricopharyngeal myotomy
or a marsupialization
 midesophageal- traction from adjacent inflammation (classically
tuberculosis); asymptomatic asymptomatic until enlarge to cause
dysphagia and regurgitation.
- true diverticula involving all layers of the esophageal wall
-false diverticula: Epiphrenic & hypopharyngeal (Zenker’s); herniation of the
mucosa and submucosa
Result: increased intraluminal pressure; associated: distal
obstruction
- myotomy: if large diverticula; if the underlying cause is achalasia
-diffuse intramural esophageal diverticulosis: results from dilatation of the
RINGS AND WEBS excretory ducts of submucosal esophageal glands
-B ring: distal esophageal mucosal ring; thin membranous narrowing -associated with: esophageal candidiasis & proximal esophageal strictures
at the squamocolumnar mucosal junction; asymptomatic;
protrusion of mucosa/submucosa TUMORS
Schatzki rings: when the lumen diameter <13 mm; associated -esophageal cancer less common than colorectal cancer
with episodic solid food dysphagia - rare and lethal
- older than 40 years -squamous cell carcinoma & adenocarcinom linked to reflux disease and
- acquired rather than congenital Barrets esophagus
- most common causes of intermittent food -adenocarcinoma: affect distal esophagus; white male
impaction -squamous cell: more proximal; black males; risk factors: smoking, alcohol,
- “steakhouse syndrome” because meat is typical HPV
instigator -esophageal cancer manifestation:
- easily treated by dilation  Progressive SOLID food dysphagia
-Web-like constriction: congenital or inflammatory origin (proximal  weight loss
esophagus); protrusion of mucosa -associated symptoms:
 Cervical esophageal webs: originate anterior aspect of the  odynophagia,
esophagus; asymptomatic  iron deficiency
-when circumferential: intermittent dysphagia to solids similar to  midesophageal tumors
Schatzki rings hoarseness (left recurrent laryngeal nerve injury)
- treated with dilatation -benign esophageal tumors (dec. frequency):
-Plummer-Vinson syndrome: symptomatic proximal  leiomyoma,
esophageal webs + iron-deficiency anemia in middle-aged  fibrovascular polyps
women  squamous papilloma
  granular cell tumors -Chagas’disease: endemic in areas of central Brazil, Venezuela, and northern
 lipomas Argentina
 neurofibromas : spread by the bite of the reduviid (kissing) bug that transmits
 inflammatory fibroid polyps the protozoan Trypanosoma cruzi
 become symptomatic only when they are associated with : chronic phase: develops years after infection; results from
dysphagia destruction of autonomic ganglion cells throughout the body, including
the heart, gut, urinary tract, and respiratory tract
CONGENITAL ANOMALIES - pseudoachalasia: tumor infiltration in the gastric fundus or distal
- esophageal atresia: most common esophagus; mimic idiopathic achalasia
-Developmental failure of fusion between the proximal and : advanced age, abrupt onset of symptoms (<1 year), and
distal esophagus weight loss
- Associated with: tracheoesophageal fistula (distal segment : computed tomography (CT) scanning or EUS: when the clinical
excluded) suspicion for pseudoachalasia is high :pseudoachalasia can result
-H-type configuration: esophageal fusion but with a from a paraneoplastic syndrome
tracheoesophageal fistula with circulating antineuronal antibodies
-corrected surgically within the first few days of life
-complications: DIAGNOSTICS
 dysphagia - diagnosed by barium swallow x-ray and/or esophageal manometry
 absent peristalsis -dilated esophagus with poor emptying
 reflux -an air-fluid level
-less common anomaly: congenital esophageal stenosis, webs, and -tapering at the LES giving it a beak-like appearance
duplications - epiphrenic diverticulum is observed
-dysphagia: extrinsic compression of the esophagus - sigmoid configuration
dysphagia lusoria- esophagus is compressed by right subclavian - esophageal manometry:
artery arising from the descending aorta and passing behind the - impaired LES relaxation and absent peristalsis
esophagus -3 SUBTYPES:
- Heterotopic gastric mucosa: aka esophageal inlet patch a.classis achalasia: minimal pressure of esophageal body
-gastric type epithelium in the proximal cervical esophagus b.achalasia w/ compression: substantial pressurization
-incomplete replacement of embryonic columnar epithelium c.spastic achalasia: spastic contraction
with squamous epithelium -endoscopy: to exclude pseudoachalasia
-asymptomatic; but acid production can occur
TREATMENT
ESOPHAGEAL MOTILITY DISRODER - no known way of preventing or reversing achalasia
- attributable to esophageal neuromuscular dysfunction - directed at reducing LES pressure by:
- associated with dysphagia, chest pain, or heartburn  pharmacologic therapy: nitrates or CCB before eating; botulinum
- major entities: toxin improves dysphagia; sidenafil & other phosphodiesterase
 Achalasia inhibitors
 diffuseesophageal spasm (DES)  pneumatic balloon dilatation: durable therapy; balloon dilator
 GERD positioned across the LES and inflated to a diameter of 3–4 cm;
-secondary to disease process: 2yr follow-up
 Pseudoachalasia -major complication: perforation
 Chagas’ disease  surgical myotomy: most common is laparoscopic Heller myotomy:
 Scleroderma performed in conjunction with an antireflux procedure; 2yr
follow-up
ACHALASIA -in unresponsive px:
- loss of ganglion cells within the esophageal myenteric plexus: autoimmune esophageal resection with gastric pull-up or interposition of a
process attributable to a latent infection with human herpes simplex virus 1 segment of transverse colon
combined with genetic susceptibility. -per oral esophageal myotomy: endoscopic approach to LES
- present: age 25 and 60 myotomy; creation of a tunnel within the esophageal wall through
- aganglionosis: noted in long-stading disease which the circular muscle of the LES and distal esophagus are
-involves: transected with electrocautery.
 excitatory (cholinergic) Advantage:
 inhibitory (nitric oxide) ganglionic neuron  avoidance of surgical disruption of
- impaired deglutitive LES relaxation and absent peristalsis thediaphragmatic hiatus
-characterized by:  more rapid recovery
 progressive dilatation and sigmoid deformity of the esophagus -untreated achalasia->esopahageal dilation-> stasis esophagitis-> esophageal
 hypertrophy of the LES squamous cell cancer
-clinical manifestation:
 Dysphagia- solid and liquid food DIFFUSE ESOPHAGEAL SPASM (DES)
 Regurgitation -episodes of dysphagia and chest pain
 chest pain- early in the course; from esophageal spasm; -normal deglutitive LES relaxation
squeezing, pressure-like retrosternal pain; radiates: neck, arms, -characterized by:
jaw, and back corkscrew esophagus
 weight loss achalasia (in many instances)
-risk for: -manometrically:
 bronchitis Uncoordinated (spastic) activity in distal esophagus
 pneumonia Spontaneous and repetitive contraction
 lung abscess High-amplitude & prolonged contraction
- Treatment less effective in relieving chest pain than it is in relieving -current consensus: define spasm by the occurrence of
dysphagia or regurgitation contractions in the distal esophagus with short latency relative to
the time of the pharyngeal contraction, a dysfunction indicative of
DDx impairment of inhibitory myenteric plexus neurons
- DES, -much less common than achalasia
-esophageal chest pain: -potential mechanisms for symptom genesis:
 nonexertional, prolonged, interrupts sleep, meal-related,  mucosal erosion
relieved with antacids  activation of afferent sensory nerve,
 accompanied by heartburn, dysphagia, or regurgitation  hypersensitivity
-diagnosed by manometry  functional pain
-radiograph: - dominant clinical strategy: tx w/ acid inhibitor; exceptions:
 Corkscrew esophagus  patients with chest pain (consider cardiac disease)
 rosary bead esophagus  persistent dysphagia (chronic reflux -> peptic stricture &
 pseudodiverticula adenocarcinoma
 curling -extraesophageal syndromes associated w/ GERD:
 these are also found in spastic achalasia  chronic cough
-respond to nitrates, calcium channel blockers, hydralazine, botulinum toxin,  laryngitis
and anxiolytic (effective in controlled trial)  asthma
-surgical therapy:considered only with severe weight loss or unbearable pain  dental erosions
 pharyngitis
GASTROESOPHAGEAL REFLUX DISEASE (GERD)  chronic bronchitis
-encompass a spectrum of condition caused by gastroesophageal reflux:  pulmonary fibrosis
 Esophagitis  chronic sinusitis
 Stricture  cardiac arrhythmias
 Barret’s esophagus  sleep apnea
 Adenocarcinoma  recurrent aspiration pneumonia
PATHOPHYSIOLOGY - mechanisms for extraesophageal GERD manifestations:
 regurgitation with direct contact between the refluxate and
supraesophageal structures
 vagovagal reflex wherein reflux activation of esophageal afferent
nerves triggers efferent vagal reflexes such as bronchospasm,
cough, or arrhythmias
DDx
- addressed by endoscopy, upper gastrointestinal series, or biliary tract
ultrasonography
 endoscopy with mucosal biopsies: to evaluate for infection or
eosinophilic inflammation
- infectious esophagitis: diffuse; involve the proximal esophagus than
does reflux esophagitis; ulcerations are punctate and diffuse.
- peptic esophagitis : ulcerations solitary and distal
-eosinophilic esophagitis: multiple esophageal rings, linear furrows,
or white punctate exudates
- pill esophagitis: esophageal ulcerations are singular and deep at points of
luminal narrowing, especially near the carina, distal esophagus is
spared

COMPLICATIONS
- bleeding and stricture & esophageal adenocarcinoma
- Barrett’s metaplasia : most severe histologic consequence of GERD &
associated risk of developing esophageal adenocarcinoma
 inc.risk in: obese white male in 6th decade of life
 no evidence confirms that aggressive antisecretory therapy or
antireflux surgery causes regression of Barrett’s esophagus or
prevents adenocarcinoma
Histology:
 tongues of reddish mucosa extending proximally from
the gastroesophageal junction
 columnar metaplasia
Treatment:
 Esophagectomy- gold standard treatment for high-grade dysplasia
in healthy patient with minimal surgical risk.
 intensive endoscopic surveillance
 mucosal ablation
 endoscopic therapy with purpose-built radiofrequency ablation
devices: many to favor this therapy as a preferable
management strategy

TREATMENT
- Lifestyle modifications:
 avoidance of foods that reduce LES pressure, making them
“refluxogenic” (fatty foods, alcohol, spearmint, peppermint,
tomato based foods, and possibly coffee and tea);
 avoidance of acidic foods that are inherently irritating
 adoption of behaviors to minimize reflux and/or heartburn
- sleep disturbance from nighttime
SYMPTOMS heartburn: elevation of the head of the bed
- typical symptoms: heartburn and regurgitation and avoidance of eating before retiring
- less common: dysphagia and chest pain
  weight reduction: most broadly applicable recommendation;  common food allergies e.g. milk, wheat, egg, soy,
strong epidemiologic relationship between body mass index and nuts, and seafood) followed by systematic
GERD reintroduction
Pharmacology -swallowed topical glucocorticoids
- Proton pump inhibitors (PPIs) & histamine receptor  fluticasone propionate or budesonide
antagonists (H2RAs)  Systemic glucocorticoids: reserved for severely
-frequency and severity of heartburn correlate poorly with the presence or afflicted patients
severity of esophagitis - Esophageal dilation: very effective at relieving dysphagia in patients with
-reflux symptoms tend to be chronic, irrespective of esophagitis fibrostenosis; dilation should be approached conservatively
- indefinite treatment with PPIs or H 2RAs for symptom control
-side effects of PPI: INFECTIOUS ESOPHAGITIS
 Dec.Vitamin B12 and iron absorption -in immunocompromised: infections with Candida species,
 susceptibility to enteric infections (Clostridium difficile colitis) herpesvirus, and cytomegalovirus (CMV)
 bone fracture (suggesting an impairment of calcium) -in non immunocompromised: herpes simplex and Candida albicans -> the
Surgical most common pathogens
-Laparoscopic Nissen fundoplication: proximal stomach is wrapped around -in AIDS: infectious esophagitis common: when <100 CD4 count; rare with a
the distal esophagus to create an antireflux CD4 count >200
barrier - in HIV: self-limited syndrome acute esophageal ulceration with oral ulcers
-complications: and a maculopapular skin rash;
 surgical morbidity and mortality patients with advanced disease: deep, persistent esophageal
 postoperative dysphagia ulcers treated with oral glucocorticoids or thalidomide
 failure or breakdown requiring reoperation SIGNS & SYMPTOMS
 inability to belch - odynophagia: characteristic symptom;
 increased bloating, flatulence, and bowel symptoms -also common: dysphagia, chest pain, and hemorrhage
- odynophagia: uncommon with reflux esophagitis; presence should always
EOSINOPHILIC ESOPHAGITIS raise suspicion of an alternative etiology
- recognized in adults and children
- predilection for white males CANDIDA ESOPHAGITIS
- overlap between EoE and GERD confuses diagnosis of the disease - Candida: normally found in the throat, pathogenic and produce esophagitis
- diagnosed based on: in a compromised host
 typical esophageal symptoms - C. albicans is most common
 esophageal mucosal biopsies: squamous epithelial - occurs with esophageal stasis secondary to esophageal motor disorders and
eosinophil-predominant inflammation diverticula
- alternative etiologies: GERD, drug hypersensitivity, connective tissue
disorders, hypereosinophilic syndrome, and infection SIGNS & SYMPTOMS
- is an immunologic disorder: induced by antigen sensitization in susceptible - odynophagia and dysphagia
individuals - if oral thrush is present: empirical therapy but co-infection is common
-Dietary factors play an important role in both the pathogenesis - endoscopy with biopsy: in persistent symptoms; the most useful diagnostic
and treatment evaluation
-Aeroallergens may also contribute  white plaques with friability
SIGNS & SYMPTOMS - complication (rare)
- dysphagia and esophageal food impactions: strongly considered in children  bleeding,
and adults  perforation
- chest or abdominal pain, nausea, vomiting, and food aversion:  stricture
preadolescent children  systemic invasion
- other symptoms in adult: atypical chest pain and heartburn (that is
refractory to PPI therapy) TREATMENT
- atopic history of food allergy, asthma, eczema, or allergic rhinitis - Oral fluconazole (200–400 mg on the first day, followed by 100–200 mg
- Peripheral blood eosinophilia: demonstrated in upto 50% of patients; not daily) for 14–21 days: PREFERRED treatment
specific findings - itraconazole, voriconazole, or posaconazole: px refractory to fluconazole
-endoscopy: - intravenous echinocandin (caspofungin 50 mg daily for 7–21 days): poorly
 loss of vascular markings (edema) responsive patients or those who cannot swallow medications
 multiple esophageal rings
 longitudinally oriented furrows HERPETIC ESOPHAGITIS
 punctuate exudates - Herpes simplex virus type 1 or 2
-histology: - Vesicles on the nose and lips: suggestive of a herpetic etiology
 esophageal mucosal eosinophilia (greatest density ±15 eosinophils -endoscopy:
per high-power field)  vesicles and small, punched-out ulcerations
-complications: - limited to squamous epithelium. In biopsy, ulcer margin reveal:
 esophageal stricture  ground-glass nuclei,
 narrow-caliber esophagus  eosinophilic Cowdry’s type A inclusion bodies
 food impaction  giant cells
 esophageal perforation
TREATMENT
MANAGEMENT - Acyclovir (200 mg orally five times a day for 7–10 days) for
- goal: symptom control and prevention of complications immunocompetent hosts
- trial of PPI therapy: to exclude contribution of GERD to the esophageal disease is typically self-limited after a 1- to 2-week
mucosal inflammation - Immunocompromised patients:
- px with persistent symptoms and eosinophilic  Acyclovir (400 mg orally five times a day for 14–21 days)
inflammation following PPI therapy are subsequently considered for EoE  famciclovir (500 mg orally three times a day)
treatments:  valacyclovir (1 g orally three times a day)
- elimination diets - In patients with severe odynophagia:
 allergy testing: skin prick and atopy patch  intravenous acyclovir, 5 mg/kg every 8 h for 7–14 days
 -complication:
CYTOMEGALOVIRUS  esophageal perforation
- occurs primarily in immunocompromised patients particularly organ  bleeding
transplant recipients  stricture
- activated from a latent stage  death
-endoscopy: - Glucocorticoids; have not been shown to improve; not recommended.
lesions appear serpiginous ulcer; particularly in the distal esophagus - healing is commonly associated with severe stricture formation and often
-biopsy: requires repeated dilatation
large nuclear or cytoplasmic inclusion bodies
-diagnosed by: immunohistology with monoclonal antibodies to CMV and PILL ESOPHAGITIS
insitu hybridization tests - occurs when a swallowed pill fails to traverses the entire esophagus and
lodges within the lumen
TREATMENT - poor “pill taking habits”: inadequate liquid with the pill or lying down
- anciclovir (5 mg/kg every 12 h intravenously) and foscarnet (90 mg/kg every immediately after taking a pill
12 h intravenously) - mid-esophagus near the crossing of the aorta or carina: most common
- oral formulation of ganciclovir: Valganciclovir (900 mg two times a day) can location for the pill to lodge
also be used -common medications involved:
- Therapy is continued until healing, which may take 3–6 weeks  doxycycline, tetracycline, quinidine, phenytoin, potassium
-Maintenance therapy may be needed for patients with relapsing disease chloride, ferrous sulfate, nonsteroidal anti-inflammatory drugs
MECHANICAL TRAUMA & IATROGENIC INJURY (NSAIDs), and bisphosphonates

ESOPHAGEAL PERFORTION SIGNS & SYMPTOMS

- instrumentation of the esophagus or trauma: most cases of esophageal - sudden onset of chestpain and odynophagia
perforation - pain: develop over a period of hours or will awaken the individual from
- Boerhaave’s syndrome: forceful vomiting or retching that lead to sleep
spontaneous rupture at the gastroesophageal junction -endoscopy:
- corrosive esophagitis or neoplasms  localized ulceration or inflammation
- Instrumentation :occurs in the hypopharynx or at the gastroesophageal  esophageal thickening consistent with transmural inflammation
junction; perforation may also occur at the site of a stricture (chest CT)
-histology:
SIGNS & SYMPTOMS  acute inflammation
- pleuritic retrosternal pain - resolves within days to weeks; symptoms may persist for months; stricture
- associated with: pneumomediastinum and subcutaneous emphysema can develop in severe cases
- Mediastinitis: major complication - no specific therapy is known to hasten the healing process
-chest CT scan: most sensitive in detecting mediastinal air  antisecretory medications: frequently prescribed to remove
-confirmed by: contrast swallow (Gastrografin) followed by thin barium concomitant reflux as an aggravating factor.
-when healing results in stricture formation, dilation is indicated
MANAGEMENT
- nasogastric suction, parenteral broad-spectrum antibiotics, prompt surgical FOREIGN BODY & FOOD IMPACTION
drainage and repair in noncontained leaks - complete obstruction
- contained perforation: NPO status and antibiotics without surgery - cause foaming at the mouth and severe chest pain
- Endoscopic clipping or stent placement -occur due to:
indicated: nonoperated iatrogenic perforations or  Stricture
nonoperable cases such as perforated tumors  Carcinoma
 Schatzki ring
 eosinophilic esophagitis
MALLORY-WEISS TEAR  simply inattentive eating
-nontransmural tear that cause upper GI bleeding, due to: - dislodged endoscopically if not spontaneously resolve impacted food can be
 Vomiting -Use of meat tenderizer enzymes is discouraged because of
 retching potential esophageal injury
 vigorous coughing -Glucagon (1 mg IV) is sometimes tried before endoscopic dislodgement
- patients present with hematemesis
- bleeding usually abates spontaneously ESOPHAGEAL MANIFESTATION OF SYSTEMIC DISEASE
-protracted bleeding: local epinephrine or cauterization therapy, endoscopic
clipping, or angiographic embolization SCLERODERMA & COLLAGEN VASCULAR DISEASE
-surgery is rarely needed - Scleroderma esophagus (hypotensive LES and absent esophageal
peristalsis) : manifestation of scleroderma or other collagen vascular diseases
RADIATION ESOPHAGITIS BUT half of qualifying patients do not have an identifiable systemic disease;
-drugs that inc risk: doxorubicin, bleomycin, cyclophosphamide, and cisplatin reflux disease is often the only identifiable association
-scleroderma esophagus in collagen vascular
SIGNS & SYMPTOMS disease:
- Dysphagia and odynophagia may last weeks to months after therapy  infiltration and destruction of the esophageal muscularis propria
- esophageal mucosa :erythematous, edematous, and friable with collagen deposition and fibrosis
- years after the radiation exposure : submucosal fibrosis and degenerative -predispose to GERD
tissue changes and structuring may occur - dysphagia: generally mild; alleviated: eating in an upright position and using
- excess of 5000 cGy: increased risk of esophageal stricture liquids to facilitate solid emptying
-treatment for acute radiation esophagitis is supportive
- esophageal dilation: chronic strictures
CORROSIVE ESOPHAGITIS DERMATOLOGIC DISEASE
- ingestion of alkali, acid -affects oropharynx & esophagus:
- can be accidental or from attempted suicide  pemphigus vulgaris
- early endoscopic evaluation is recommended to assess and grade the injury  bullous pemphigoid
to the esophageal mucosa  cicatricial pemphigoid
  Behçet’s syndrome
 epidermolysis bullosa
 Erosive lichen planus
 Stevens-Johnson syndrome
 graft-versus-host disease
- blisters, bullae, webs, and strictures in proximal esophagus
- Glucocorticoid treatment is usually effective
- Esophageal dilatation may be necessary to treat strictures

ESOPHAGEAL CANCER
-extremely lethal malignancy
-either: SCC or adenocarcinoma
 similar clinical presentation but different causative factor

a.Squamous cell carcinoma Associated w/:
-most common worldwide; associated with geographic location  odynophagia
-occurs frequently within a region extending from the southern  pain radiating to the chest and/or back,
shore of the Caspian Sea, to northern China, Iran, central Asia,  regurgitation or vomiting,
Afghanistan, Siberia, and Mongolia, Finland, Iceland, Curaçao,  aspiration pneumonia
southeastern Africa, and northwestern France  Weight loss
-familial increased risk in regions with high incidence -tracheoesophageal fistulas: develop in patients with upper and
-more common in blacks midesophageal tumors.
-males than females - hypercalcemia: occur in the absence of osseous metastases, probably
-after age 50 from parathormone-related peptide secreted by tumor cells
-associated with a lower socioeconomic status
-generally in cervical and thoracic portions of the esophagus DIAGNOSIS
-primarily related to excess alcohol consumption and/or - endoscopic and cytologic screening: not yet been shown to reduce the
cigarette smoking likelihood of death
-whiskey > wine or beer - esophagoscopy: should be performed in all suspected patients
-patients with head and neck cancer are at increased risk of  to visualize and identify a tumor
squamous cell cancer of the esophagus  to obtain histopathologic confirmation of the diagnosis
-examination of the fundus of the stomach
-chest & abdomen CT scan: to assess extent of tumor spread to the
mediastinum and para-aortic lymph nodes
-PET: assessment of the presence of distant metastatic disease

TREATMENT
- prognosis for patients with esophageal carcinoma is poor
- management focuses on symptom control (palliation)
-surgical resection: feasible in only 45%; postoperative mortality rate of
approximately 5% due to:
 Anastomotic fistulas
 subphrenic abscesses
 cardiopulmonary complications
 transthoracic esophagectomies > transhiatal
 fundoplication surgery: the removal of the
gastroesophageal junction as a means of cancer
prevention in patients with Barrett’s esophagus
- monoclonal antibody trastuzumab (Herceptin): in patients whose tumors
overexpress the HER2/neu gene
- bevacizumab (Avastin): antiangiogenic agent; limited value in the setting of
esophageal cancer
- radiation therapy + chemotherapy > radiation therapy
-incurable px: palliative tx include: (1) repeated endoscopic dilatation (2)
b.Adenocarcinoma gastrostomy or jejunostomy for hydration and feeding (3)endoscopic
- rate of adenocarcinoma risen sevenfold placement of an expansive metal stent to bypass the tumor & dysphagia
- white males management (4) radiation therapy
-more distal; associated with chronic gastric reflux; often in
Barrett’s esophagus (common in obese)
- dysplastic columnar epithelium in the distal esophagus
aneuploidy and p53 mutations
- behave clinically like gastric adenocarcinomas
- not associated with Helicobacter pylori
- overexpress the HER2/neu gene

CLINICAL MANIFESTATION
-occur in:
 cervical esophagus: 5%
 middle third: 20%
 lower third: 75%
-both cannot be distinguished radiographically or endoscopically
-manifestations:
 Progressive dysphagia- w/ solid foods; gradually semisolid and
liquids;
 by the time these symptoms develop, the
disease is already very advanced
 60% esophageal infiltration: dysphagia occur
PEPTIC ULCER DISEASE -classification:
-burning epigastric pain  Type I: body; low gastric acid production
-exacerbated: fasting; relieved: with meals  Type II: antrum; low to normal gastric
-ulcer: disruption of the mucosal integrity of the stomach and/or duodenum  Type III: 3 cm of the pylorus; normal or high acid production;
-> active inflammation -> local defect or excavation accompanied by DUs
often chronic in nature  Type IV: cardia; low gastric acid production
men > women
H.PYLORI & PUD
PATHOPHYSIOLOGY - infection cause majority of PUD
-encompass both gastric and duodenal ulcers -play role in development of:
-ulcers: breaks in the mucosal surface  gastric mucosa-associated lymphoid tissue (MALT) lymphoma
>5 mm in size  gastric adenocarcinoma
depth to the submucosa The bacterium
-DUs & GUs share many common features but several factors distinguish - initially named Campylobacter pyloridis
them from one another - gram-negative microaerophilic rod
-common risk factors: Helicobacter pylori (37 ratio) and NSAIDs (3.3) - found most commonly in the mucous gel or between the mucous layer and
- additional risk factors: the gastric epithelium
 chronic obstructive lung disease (2.34) - may attach to gastric epithelium but does not invade
 chronic renal insufficiency (2.29) - S-shaped (~0.5–3 μm in size)
 current tobacco use (1.99) - contains multiple sheathed flagella
 former tobacco use (1.55) -initially in the antrum-> migrates to proximal segment of stomach
 older age (1.67) - can transform into a coccoid: dormant state; able to survive adverse
 three or more doctor visits in a year (1.49) conditions
 coronary heart disease (1.46) -factors that contribute to its pathogenicity:
 former alcohol use (1.29)  outer membrane protein (Hop proteins)
 African-American race (1.20)  urease
 obesity (1.18),  vacuolating cytotoxin (Vac A)
 diabetes(1.13) - cag pathogenicity island (cag-PAI): genomic fragments encoded by H.pylori
strains; encodes virulence factors
EPIDEMIOLOGY -encodes type IV secretion island: translocates Cag A into
a.DU host cells -> Cag A activates series of cellular events important
-DUs reduced because of decreasing H.pylori infection in cell growth and cytokine production
-natural history of DUs: frequent recurrences after initial -first teps in infection:
therapy dependent on the bacteria’s motility and its ability to produce urease
b.GU Urease-> ammonia -> alkalinize surrounding pH
- occur later in life than duodenal lesions; peak in the sixth Additional bacterial factors:
decade  catalase
- occur in males  lipase
- less common than DUs  adhesins
- presents after complication develops  platelet-activating factor
 pic B (induces cytokines)
PATHOLOGY
a.DU EPIDEMIOLOGY
- >95%: first portion of the duodenum - 80% of the population: infected by the age of 20
-~90%: within 3 cm of the pylorus -rare in childhood
- ulcers: ≤1 cm in diameter but reach 3–6 cm (giant ulcer) -risk factors:
-sharply demarcated  poor socioeconomic status
-depth reach the muscularis propria  less education
-base: consists of a zone of eosinophilic necrosis with surrounding  birth or residence in a developing country
fibrosis  domestic crowding
- malignant DUs are extremely rare  unsanitary living conditions
b.GU  unclean food or water, and
-represent a malignancy  exposure to gastric contents of an infected individual
-should be biopsied upon discovery -transmission: person to person via oral-oral or fecal-oral route
-benign GUs: found distal to the junction between the antrum and the acid
secretory mucosa; rare in the gastric fundus PATHOPHYSIOLOGY
- GUs associated with H. pylori: antral gastritis - always associated with chronic active gastritis; only 10–15% of infected
- NSAID-related GUs: no chronic active gastritis individuals develop frank peptic ulceration
-evidence of a chemical gastropathy: foveolar hyperplasia, edema -end result of infection:
of the lamina propria, epithelial regeneration in the absence of H.  gastritis
pylori, of smooth-muscle fibers extended into the upper portions  PUD
of the mucosa gastric MALT lymphoma
 gastric cancer
PATHOPHYSIOLOGY
a.DUs 1.Bacterial factors
- H. pylori and NSAID-induced injury: majority of DUs - virulence factors: Cag A, pic B & Vac A ( not encoded in pathogenicity island)
- increased average basal and nocturnal gastric acid secretion -Vac A: targets human CD4 T cells, B cells, CD8 T cells,
- decreased Bicarbonate secretion in the duodenal bulb macrophages, and mast cells
 H. pylori infection may also play a role in this process - cag-PAI positive strains = higher risk of PUD, premalignant gastric lesions,
b.GUs and gastric cancer
- either H. pylori or NSAID-induced mucosal damage -Cag A: inhibit parietal cell H+,K+-ATPase activity-> low acid production
-normal or decreased basal and stimulated -urease-> produce ammonia-> cell damage
-GUs in minimal acid levels -> impairment of mucosal defense
-surface factors-> chemotactic for neutrophils & monocytes -> epithelial (6) α1- antitrypsin deficiency
injury (7) systemic mastocytosis
-proteases & phopholipase -> break down the glycoprotein lipid complex of
the mucous gel -> reduce first line of mucosal defense
2. Host factors:
- genetic predisposition to acquire H. pylori
- recruitment of neutrophils, lymphocytes (T and B), macrophages, and
plasma cells -> inflammation
-binding to class II major histocompatibility complex (MHC)-> cell death
(apoptosis)
-additional mechanism:
(1) production of reactive oxygen or nitrogen species and
enhanced epithelial cell turnover
(2) apoptosis related to interaction with T
(3) colonization of commensal organisms
 gastric metaplasia in duodenum of DU: permits H pylori to bind
 antral-predominant gastritis: DU formation
 gastritis in body: GUs, gastric atrophy, gastric carcinoma

NSAID-INDUCED DISEASE
-NSAID-induced spectrum:
 nausea and
-Disorders with possible association:
 dyspepsia
(1) hyperparathyroidism
 peptic ulceration
(2) coronary artery disease
- dyspeptic symptoms do not correlate with NSAID-induced pathology
(3) polycythemia vera
- no dose of NSAID is completely safe; even 75 mg/d of aspirin lead to serious
(4) chronic pancreatitis
GI ulceration
(5) former alcohol use
- H. pylori infection: increases the risk of GI bleeding in chronic users of low-
(6) obesity
dose aspirin
(7) African-American race
-risk factors:
(8) three or more doctor visits in a year
 advanced age
 history of ulcer
 concomitant use of glucocorticoids
 high-dose NSAIDs
 multiple NSAIDs
 concomitant use of anticoagulants
 clopidogrel
 serious or multisystem disease
 concomitant infection with H. pylori
 cigarette smoking
 alcohol consumption
Pathophysiology
- Prostaglandins: maintaines gastroduodenal mucosal integrity and repair;
interruption of prostaglandin synthesis can impair mucosal defense and
repair, thus facilitating mucosal injury via a systemic mechanism
- initiated by: neutrophil adherence to gastric
- Injury to the mucosa also occurs as a result of the topical encounter
with NSAIDs
 Aspirin and many NSAIDs in nonionized lipophilic form-
> migrate across lipid membrane-> trapped
intracellularly in an ionized form-> leading to cell injury
 Topical NSAIDs: permits back diffusion of H+ and
pepsin -> further epithelial cell damage
PATHOGENETIC FACTORS OTHER THAN HP & NSAID
-cigarette smoking
 decrease healing rates, impair response to therapy, and increase
ulcer-related complications such as perforation
- genetic predisposition
 First-degree relatives of DU patients are three times aslikely to
develop an ulcer
- blood group O CLINICAL FEATURES
 H. pylori preferentially binds to group O antigens
- psychological stress History
 associated with certain personality traits (neuroticism) -abdominal pain: common but not predictive
-diet -NSAID-induce present w/ complication (bleeding, perforation, obstruction)
 no convincing studies indicate an association between ulcer w/o symptoms
formation and a specific diet - Often patients complain of dyspeptic symptoms
-specific chronic disorders: such as a bloated sensation and fullness
(1) advanced age -epigastric pain
(2) chronic pulmonary disease -burning or gnawing discomfort (in DU & GU)
(3) chronic renal failure - ill-defined, aching sensation or hunger pain
(4) cirrhosis -pain pattern in DU:
(5) nephrolithiasis  90 minutes to 3 hours after a meal
  relieved by antacids or food -gastroduodenal Crohn’s disease
 Pain that awakes the patient from sleep (between
midnight and 3 A.M.) : also manifest in NUD Diagnostic Evaluation
 Elderly px: less likely to have abdominal pain; present - radiographic (barium study)
w/ ulcer bleeding or perforation  used as first test for documenting an ulcer (proximal GI tract)
-pain pattern in GU:  sensitivity: decreased in small ulcers (<0.5 cm), with presence of
 Precipitated by food previous scarring, or in postoperative patients
 Nausea & weight loss  DU appears: well-demarcated crater seen in the bulb
 <30% have dyspepsia  GU: discrete crater with radiating mucosal folds originating from
-mechanism of development: the ulcer margin
 Acid-induced activation of chemical receptors in the -8% of GUs that appear to be benign by
duodenum radiographic appearance are malignant by endoscopy
 Enhanced duodenal sensitivity to bile acids or surgery
& pepsin - GU must be followed by endoscopy and biopsy
 altered gastroduodenal motility -endoscopic procedure
-indicative of ulcer complication:  the most sensitive and specific approach
 variation in the intensity or distribution of the abdominal pain  direct visualization of the mucosa
 onset of associated symptoms (nausea & vomiting)  facilitates photographic documentation of a mucosal defect
-penetrating ulcer (pancreas): constant dyspepsia , no longer relieved  tissue biopsy: rule out malignancy (GU) or H. pylori
by food or antacids, or radiates to the back - testing for H. pylori and antibiotic therapy
- perforation: sudden onset of severe, generalized abdominal pain
-gastric outlet obstruction: pain worsening with meals, nausea, and  for individuals who are otherwise healthy and <45 years of age
vomiting of undigested food  before using diagnostics
PE
- Epigastric tenderness: with GU or DU - individuals with complicated or refractory PUD (ZES)
- Pain in the right of the midline: predictive value is low  serum gastrin and gastric acid analysis or sham feeding
-evidence of complication:  Screening for aspirin or NSAIDs (Hp-negative)
 Tachycardia and orthostasis: dehydration secondary to vomiting
or active GI blood loss
 severely tender, board-like abdomen: perforation
 succussion splash indicates retained fluid in the stomach: gastric
outlet obstruction

PUD-RELATED COMPLICATIONS
a.GI bleeding
- most common complication
- occur in individuals >60 years of age
 likely due to the increased use of NSAIDs
-PUD-related bleeding mortality due no nonbleeding causes:
 multiorgan failure (24%)
 pulmonary complications (24%)
 malignancy (34%)
- ulcer-related hemorrhage may bleed without any preceding warningsigns or
symptoms
b. Perforation
- second most common
- incidence increase in the elderly
-penetration: form of perforation; ulcer bed tunnels into an adjacent organ
-DU: penetrate into the pancreas
- GUs: penetrate into the left hepatic lobe; associated with gastrocolic fistulas
c. Gastric Outlet Obstruction
- least common
- RELATIVE obstruction secondary to ulcer-related inflammation and edema
in the peripyloric region
 resolves with ulcer healing
-FIXED, mechanical obstruction secondary to scar formation in the peripyloric
areas
 requires endoscopic (balloon dilation) or surgical intervention
-clinical manifestation for possible dx:
 New onset of early satiety
 Nausea
 Vomiting
 increase of postprandial abdominal pain
 weight loss

DDx
-NUD: aka functional dyspepsia or essential dyspepsia
group of heterogeneous disorders
upper abdominal pain without the presence of an ulcer
- proximal GI tumors
- gastroesophageal reflux
-vascular disease
TREATMENT
- pancreaticobiliary disease (biliary colic, chronic pancreatitis)
- mainstay of treatment: eradication of H. pylori and therapy/prevention of  Nizatidine-300 mg
NSAID-induced disease -Patient may develop tolerance to H 2 blockers
- Cimetidine and ranitidine:bind to hepatic cytochrome P450;
famotidine and nizatidine do not
c.Proton Pump (H=,K+-ATPase) Inhbitors
 Omeprazole: nonenteric-coated granules mixed with sodium
bicarbonate (1) to protect from acid degradation (2) promote
rapid gastric alkalinization and subsequent proton pump
activation for rapid action of the PPI
 Esomeprazole: newest members
 Lansoprazole: dexlansoprazole, R-isomer of lansoprazole, --most
recent PPI approved for clinical use
-orally disintegrating tablet
-lansoprazole-naproxen: targeted at decreasing NSAID related GI
injury
 Rabeprazole- enteric-coated tablets
 Pantoprazole- enteric-coated tablets; parenteral formulation for
IV use
- Omeprazole and lansoprazole: used for the longest time
acid-labile; enteric-coated granules; sustained-release capsule; dissolves
within the small intestine at a pH of 6
- MOA: inhibit all phases of gastric acid secretion
-Onset of action: rapid
- maximum effect: between 2 and 6 h after administration
-duration of inhibition: 72–96 h
-half-life: ~18 h
 Take between 2 and 5 days for gastric acid secretion to return to
normal levels once discontinued
ACID-NEUTRALIZING/INHIBITORY DRUGS - efficacy is maximized if they are administered before a meal
a.Antacids  Except immediate-release omeprazole
-main form of therapy for peptic ulcers -side effects:
-often used by patients for symptomatic relief of dyspepsia  Hypergastrinemia
-most commonly used agents:  Risk of fracture
 aluminum hydroxide- constipation and phosphate depletion  Iron and magnesium deficiency
 magnesium hydroxide-cause loose stools  Negative effect on clopidogrel
 combination of both aluminum and magnesium hydroxide-  Recommendation:
Maalox, Mylanta; to avoid side effects -Patients taking clopidogrel with aspirin should receive
 magnesium-containing: not used in chronic renal GI protective therapy; 12-h separation between
failure (possible hypermagnesemia) administration of the PPI and clopidogrel; give the PPI
 aluminium: chronic neurotoxicity in renal failure 30 min before breakfast, clopidogrel at bedtime
 Calcium carbonate- converts to calcium chloride in the stomach; - Patients 65 years of age or older have a higher risk for
can lead to milk-alkali syndrome: side effects
Hypercalcemia - 1–2 weeks after drug cessation: Serum gastrin levels return to normal
Hyperphosphatemia with possible renal - Rebound gastric acid hypersecretion: in H. pylori–negative individuals after
calcinosis discontinuation
Renal insufficiency  gastrininduced hyperplasia and hypertrophy of ECL cells
 sodium bicarbonate- induce systemic alkalosis  worsening symptoms of GERD or dyspepsia upon stopping
b.H2 receptor antagonist - interfere with absorption of : ketoconazole, ampicillin, iron, and digoxin
-cimetidine, ranitidine, famotidine, and nizatidine - omeprazole, lansoprazole: inhibit hepatic cytochrome P450
-inhibit basal and stimulated acid secretion; ulcer-healing - Caution using theophylline, warfarin, diazepam, atazanavir, and phenytoin
- treatment of active ulcers (4–6 weeks) + antibiotics directed at eradicating w/ PPI
H. pylori - long-term use associated with:
-Cimetidine:  a higher incidence of community-acquired pneumonia
 first H2 receptor antagonist;  community and hospital acquired Clostridium difficile–associated
 recommended dose: 300 mg qid disease
 800 mg at bedtime for treatment of active ulcer t 4 weeks -2 new formulations:
 Side effects:  Tenatoprazole: PPI containing an imidazopyridine ring; PPI
 Gynecomastia containing an imidazopyridine ring; longer half-life than the other
 Impotence PPIs; beneficial for inhibiting nocturnal acid secretion (GERD)
 Confusion  potassium-competitive acid pump antagonists (P-CABs): inhibit
 Elevated levels of serum aminotransferases, creatinine, gastric acid secretion via potassium competitive binding of the
and serum prolactin H ,K+-ATPase
 Pancytopenia d.CYTOPROTECTIVE AGENTS
 Neutropenia Sucralfate
 Anemia - complex sucrose salt in which the hydroxyl groups have been substituted by
 Thrombocytopenia aluminum hydroxide and sulphate
 inhibit cytochrome P450- careful monitoring of drugs such as
warfarin, phenytoin, and theophylline is indicated
-Ranitidine, famotidine, and nizatidine are more potent H 2 receptor
antagonists
 once a day at bedtime for ulcer prevention
 Ranitidine- 300 mg
 Famotidine- 40 mg
- insoluble in water - H. pylori resistance >15–20%: Clarithromycin-based triple therapy should be
- becomes a viscous paste within the stomach and duodenum avoided
- binding primarily to active ulceration
- physicochemical barrier, promoting a trophic, enhancing prostaglandin
synthesis, stimulating mucus and bicarbonate secretion, and enhancing
mucosal defense and repair
- avoided in patients with chronic renal insufficiency : aluminum-induced
neurotoxicity
- hypophosphatemia and gastric bezoar formation
- Standard dosing: 1 g qid

Bismuth-containing preparation
- effective against H. pylori; induce ulcer healing
- widely use
 Colloidal bismuth subcitrate (CBS)
 Bismuth subsalicylate (BSS, Pepto-Bismol)
-adverse effect:
 black stools
 constipation
 darkening of the tongue
 neurotoxicity (CBS)

Prostglandin Analogues
- enhancement of mucosal defense and repair (prostaglandin maintains
mucosal integrity and repair)
-side effects:
Diarrhea
Uterine bleeding and contractions -side effects:
 Contraindicated in women who may be pregnant  Bismuth: black stools, constipation, or darkening of the tongue.
- standard therapeutic dose: 200 μg qid  Amoxicillin: pseudomembranous colitis, antibiotic-associated
diarrhea, nausea, vomiting, skin rash, and allergic reaction
THERAPY FOR H.PYLORI  Tetracycline: rashes, hepatotoxicity and anaphylaxis
- H. pylori should be eradicated in patients with documented PUD - Culture and sensitivity testing of H. pylori is not performed routinely
- Maastricht IV/Florence Consensus Report recommends: - Quadruple therapy: Failure of H. pylori eradication with triple therapy
 test-and-treat approach: patients with uninvestigated dyspepsia if  clarithromycin is substituted for metronidazole (or vice versa) OR
the local incidence of H. pylori is >20%  combination of pantoprazole, amoxicillin, and rifabutin for 10
 patients who will be using NSAIDs (including low-dose aspirin) on days
a long-term basis: PPI treatment & eradication treatment  levofloxacin-based triple therapy (levofloxacin,
 H. pylori treatment in gastric cancer prevention; considered in: amoxicillin, PPI) for 10 days
-first-degree relatives of family members with gastric  furazolidone-based triple therapy (furazolidone, amoxicillin, PPI)
cancer for 14 days
-patients with previous gastric neoplasm treated by  If eradication is still not achieved in a compliant patient, then
endoscopic or subtotal resection culture and sensitivity of the organism should be considered
individuals with a risk of gastritis (severe pangastritis - factors that may lower eradication rates:
or body-predominant gastritis) or severe atrophy  patient’s country of origin (higher in Northeast Asia than other
-patients with gastric acid inhibition for more than 1 parts of Asia or Europe)
year  cigarette smoking
-individuals with strong environmental risk factors for - sequential therapy: patients treated with first-line therapy may still remain
gastric cancer (heavy smoking; high exposure to dust, infected
coal, quartz, or cement; and/or work in quarries)  5 days of amoxicillin and a PPI, followed by an additional 5 days of
-H. pylori–positive patients with a fear of gastric cancer PPI plus tinidazole and clarithromycin or levofloxacin
- American College of Gastroenterology suggest eradication of H. pylori in  5 days of concomitant therapy (PPI twice daily, amoxicillin 1 g
patients who have undergone resection of early gastric cancer twice daily, levofloxacin 500 mg twice daily, and tinidazole 500 mg
- No single agent is effective in eradicating the organism twice daily)
 Combination therapy for 14 days provides the greatest efficacy - use of certain probiotics, such as Lactobacillus spp., Saccharomyces spp.,
 shorter administration course (7–10 days) Bifidobacterium spp., and Bacillus clausii, did not alter eradication rates but
 amoxicillin, metronidazole, tetracycline, clarithromycin, and importantly decreased antibiotic-associated side effects
bismuth compounds
NSAID-RELATED GASTRIC OR DUODENAL INJURY THERAPY
- Dual therapy is not recommended - treatment of an active ulcer and primary prevention of future injury
- first triple regimen found effective: combination of bismuth, metronidazole,
and tetracycline; OR
- combination of two antibiotics plus either a PPI, H 2 blocker, or bismuth
compound
- Simpler (dual therapy) and shorter regimens (7 and 10 days) are not as
effective as triple therapy for 14 days
- anti-H. pylori regimens prepackaged formulation:
 Prevpac (lansoprazole, clarithromycin, and amoxicillin)
- twice per day for 14 days
 Helidac (BSS, tetracycline, and metronidazole)
- four times per day + antisecretory agent (PPI or H 2 blocker),
also for at least 14 days.
  2 approaches for documenting eradication:
- Only PPIs can heal GUs or DUs, independent of whether NSAIDs are (1) Test for eradication only in individuals with a complicated
discontinued course or in individuals who are frail or with multisystem disease
- nonselective NSAIDs that are associated with a lower likelihood of GI (2) test all patients for successful eradication
toxicity: -Approach in GU:
 Diclofenac Initial multiple biopsies
 aceclofenac Repeat endoscopy at 8–12 weeks (to document healing)
 ibuprofen  70% of GUs eventually found to be malignant
-prophylaxis: undergo significant (usually incomplete) healing
 misoprostol (200 μg qid)  Repeat endoscopy: patients with DU if symptoms persist
 High-dose H 2 blockers (famotidine, 40 mg bid) despite medical therapy or a complication is suspected
 Highly-selective COX-2: celecoxib and rofecoxib- leads to gastric or -refractory: GU that fails to heal after 12 weeks; DU that does not heal after 8
duodenal mucosal injury; increase in cardiovascular events; weeks of therapy
withdrawn from the market  heal after 8 weeks of treatment with higher doses of PPI
-px considered for long-ter NSAID therapy: also considered for H. pylori (omeprazole, 40 mg/d; lansoprazole 30–60 mg/d)
testing and treatment if positive  rare causes of refractory ulcers:
o ischemia
o Crohn’s disease
o aamyloidosis,
sarcoidosis
o lymphoma
o eosinophilic gastroenterition
o infection (cytomegalovirus [CMV], tuberculosis, or
syphilis)
SURGICAL THERAPY
-either:
 elective: for treatment of medically refractory disease, or as
 urgent/emergent: for the treatment of an ulcer-related
complication

Specific Operations for DUs

-operations performed:
(1)vagotomy and drainage (by pyloroplasty, gastroduodenostomy,
or gastrojejunostomy)
SUMMARY OF TREATMENT (2) highly selective vagotomy (which does not require a drainage
procedure)
(3) vagotomy with antrectomy
 lowest rates of ulcer recurrence; highest complication
rate
 antrectomy: eliminating an additional stimulant of
gastric acid secretion, gastrin
 indicated: ulcer recurrence rates are high (prepyloric
ulcers and those refractory to medical therapy)

2 types of reanastomoses after antrectomy:

-Billroth I (gastroduodenostomy)
- Billroth II (gastrojejunostomy)
- Billroth I is often preferred over II

- Hp positive: triple therapy for 14 days, followed by continued acid-

suppressing drugs (H 2 receptor antagonist or PPIs) for a total of 4–6 weeks
- The test of choice for eradication: monoclonal stool antigen test or a urea
breath test (UBT)
 Serologic testing: not useful for the purpose of documenting
eradication because antibody titers fall slowly and often do not
become undetectable
-Vagotomy: component of each procedures; and is aimed at decreasing acid -cornerstone of therapy: diet modification
secretion through ablating cholinergic input to the stomach  small, multiple (six) meals devoid of simple carbohydrates
-gastric atony: results of truncal and selective vagotomy; drainage coupled with elimination of liquids during meal
compensate for the vagotomy-induced gastric motility disorder  Guar and pectin: increase the viscosity of intraluminal
-highly selective vagotomy (also known as parietal cell, super-selective, or contents
proximal vagotomy) - Antidiarrheals and anticholinergic agents
 developed to minimize gastric motility disorder - Acarbose: delays digestion of ingested carbohydrates (late phases of
 Only the vagal fibers innervating the portion of the stomach that dumping)
contains parietal cells is transacted - octreotide: somatostatin analogue; dministered subcutaneously (50 μg tid);
 Higher rates of ulcer recurrence long-acting octreotide: administered once every 28 days
 Not indicated: ulcer recurrence rates are high (prepyloric ulcers
and those refractory to medical therapy) d.Postvagotomy Diarrhea
- most commonly observed after truncal vagotomy
Specific Operations for GUs - intermittent diarrhea 1–2 h after meals
-indicated when there is concominant DU -due to:
-treatment of choice (antral ulcer): antrectomy with Billroth I  interruption of the vagal
-if only DU is present: vagotomy  decreased absorption of nutrients
- Ulcers located near the esophagogastric junction: subtotal gastrectomy  increased excretion of bile acids
with a Roux-en-Y esophagogastrojejunostomy (Csendes’ procedure) release of luminal factors that promote secretion
-fragile px w/ high GU: - Diphenoxylate or loperamide: use for symptom control
 Antrectomy - cholestyramine: bile-salt binding agent
 intraoperative ulcer biopsy
 vagotomy (Kelling-Madlener procedure) e.Bile reflux gastropathy
- abdominal pain, early satiety, nausea, vomiting, mucosal erythema of the
SURGERY COMPLICATION gastric remnant
- highly selective vagotomy: higher rates of ulcer recurrence and less GI
disturbance f. Maldigestion and Malabsorption
- More aggressive surgical procedures: lower rate of ulcer recurrence but a - Weight loss: due to decreased oral intake; stabilizes 3 months
greater incidence of GI dysfunction postoperatively
- mild steatorrhea
a. Recurrent ulceration -reasons:
- develop at the anastomosis (stomal or marginal ulcer)  decreased gastric acid production
- Epigastric abdominal pain: most frequent presenting complaint  rapid gastric emptying
-ulcer recur because:  decreased food dispersion in the stomach
 incomplete vagotomy: ruled out by gastric acid analysis coupled  reduced luminal bile concentration
with sham feeding  reduced pancreatic secretory response to feeding
 gastric acid output is measured while the patient sees,  rapid intestinal transit
smells, and chews a meal - Decreased serum vitamin B12
 cephalic phase of gastric secretion is assessed - Iron-deficiency anemia: Billroth II
 increase in gastric acid output in response to sham - Folate deficiency
feeding: vagus nerve is intact - Malabsorption of vitamin D and calcium: partial gastrectomy and
 rise in serum pancreatic polypeptide >50% within 30 gastrojejunostomy (Billroth II)
min of sham: intact vagus nerve  Osteomalacia: Elevated alkaline phosphatase, reduced serum
 inadequate drainage calcium, bone pain, and pathologic fractures
 retained antrum: elevated plasma gastrin levels  Bone fractures: common in men
 persistent or recurrent H. pylori infection - Copper deficiency
 Surreptitious use of NSAIDs: important reason for recurrent
ulcers after surgery g. Gastric adenocarcinoma
- increased 15 years after resection
b.Afferent Loop Syndromes - due to: alkaline reflux, bacterial proliferation, or hypochlorhydria
- bacterial overgrowth in the afferent limb secondary to stasis
 postprandial abdominal pain, bloating, and diarrhea with h.Other complications
concomitant malabsorption of fats and vitamin B12 - Reflux esophagitis
-severe abdominal pain and bloating that occur 20–60 min after meals; - gallstones
followed by nausea and vomiting bile-containing material - cholecystitis: due to decreased gallbladder contractility associated with
vagotomy and bypass of the duodenum -> decreased postprandial release of
c.Dumping syndrome cholecystokinin
- series of vasomotor and GI signs and symptoms and occurs in patients who
have undergone vagotomy and drainage RELATED CONDITIONS
-2 phases: a.Zollinger-Ellison Syndrome
 Early: - unregulated gastrin release from a non-β cell endocrine
-15–30 min after meals tumor (gastrinoma) -> gastric acid hypersecretion -> severe peptic ulcer
-crampy abdominal discomfort, nausea, diarrhea, belching, diathesis
tachycardia, palpitations, diaphoresis, light-headedness, syncope
- arise from the rapid emptying of hyperosmolar gastric Epidemiology
contents into the small intestine -> fluid shift - 0.1–1% of individuals presenting with PUD
 Late -males > females
- occurs 90 min to 3 h after meals -ages 30 and 50
- vasomotor predominates: light-headedness, diaphoresis, -gastrinoma classified into: (1) sporadic tumors (most common); (2) multiple
palpitations, tachycardia, and syncope endocrine neoplasia (MEN type 1)
- secondary to hypoglycemia from excessive insulin release
- most noticeable after meals rich in simple carbohydrates (especially
sucrose) and high osmolarity
Pathophysiology Diagnosis
- - Biochemical measurements of gastrin and acid secretion
- obtain a fasting gastrin level
- <150 pg/Ml: normal fasting gastrin
-normal fasting gastrin, on two separate occasions, especially if the patient is
on a PPI: excludes this diagnosis
- >150–200 pg/mL: gastrinoma patients
- Gastric acid induces feedback inhibition of gastrin release; decrease in acid
production will subsequently lead to failure of the feedback inhibitory
pathway -> hypergastrinemia
 process that leads to elevated fasting gastrin:
 gastric hypochlorhydria and achlorhydria
 patients using antisecretory agents
 H. pylori infection
 retained gastric antrum
Tumor Distribution  G cell hyperplasia
- majority of gastrinomas: within the pancreas; also extrapancreatic  gastric outlet obstruction
-80%: gastrinoma triangle  renal insufficiency
- Duodenal tumors: most common nonpancreatic lesion  massive small-bowel obstruction
 smaller, slower growing and less likely to metastasize than  rheumatoid arthritis
pancreatic lesion  vitiligo
-less common extrapancreatic sites:  diabetes mellitus
 Stomach  pheochromocytoma
 Bones - effects of PPI on gastrin levels and acid secretion will linger several days:
 Ovaries stopped for a minimum of 7 days before testing
 Heart  patient should be placed on a histamine H2 antagonist during this
 Liver period
 lymph node  patient may take antacids for the final day: stopped
-histology: gastrin-producing cells appear well-differentiated, expressing approximately 12 h before testing
markers typically found in endocrine - pH <3 is suggestive of a gastrinoma
neoplasms (chromogranin, neuron-specific enolase) - Normal <5 meq/h
 BAO >15 meq/h in the presence of hypergastrinemia is considered
Clinical Manifestation pathognomonic of ZES
- Peptic ulcer: the most common, may be indistinguishable from common - secretin study: most sensitive and specific gastrin provocative test
PUD  increase in gastrin of ≥120 pg within 15 min of
-situations that create suspicion: secretin injection has a sensitivity and specificity of >90% for ZES
 unusual locations (second part of the duodenum and beyond),  PPI must be stopped for 1 week before testing: to avoid false-
 ulcers refractory to standard medical therapy positive
 ulcer recurrence after acid-reducing surgery
 ulcers presenting with frank complications (bleeding, obstruction,
and perforation)
 ulcers in the absence of H. pylori or NSAID ingestion
-esophageal symptoms:
 mild esophagitis
 frank ulceration with stricture
 Barrett’s mucosa
-diarrhea: next common symptoms
-gastrinoma in MEN 1 syndrome; autosomal dominant; involves 3 organs:
 parathyroid glands (80–90%),
 pancreas (40–80%)
 pituitary gland Tumor Localization
 syndrome is caused by inactivating mutations of the
MEN1 tumor suppressor gene found on the long arm
of chromosome 11q13
 gene encodes for Menin
 calcium has stimulatory effect of on gastric secretion
 higher incidence of gastric carcinoid tumor
development
-sporadic ZES: gastrinomas tend to be smaller, multiple, and located in the
duodenal wall

- Endoscopic ultrasound (EUS): imaging of the pancreas with a high degree of

resolution (<5 mm); helpful in excluding small neoplasms within the
pancreas; assessing lymph nodes and vascular involvement; not very
sensitive for finding duodenal lesions
-confirmed biochemical dx -> abdominal (CT) scan, MRI, or OctreoScan to  Sucralfate slurry (1 g every 4–6 h): but lead to
EXLUDE metastatic disease -> laparotomy constipation and aluminum toxicity; aspiration
with intraoperative ultrasound or transillumination OR examination of the pneumonia
peripancreatic area with EUS + endoscopic exploration of the duodenum for  PPIs are the treatment of choice for
primary tumors -> surgery stress prophylaxis
- Pantoprazole: IV
TREATMENT  If bleeding still occurs: endoscopy, intraarterial
- PPIs are the treatment of choice vasopressin, and embolization
 doses tend to be higher than those used for treatment of GERD or  If all else fails, then surgery should be considered
PUD - total gastrectomy
 initial dose of omeprazole, lansoprazole, rabeprazole, or
esomeprazole should be in the range of 60 mg in divided doses in C.GASTRITIS
a 24-h period - should be reserved for histologically documented inflammation of the
 Dosing adjusted to achieve: gastric mucosa
BAO <10 meq/h: surgery-naive patients - not the mucosal erythema seen during endoscopy
<5 meq/h: px undergone an acid-reducing operation - not interchangeable with “dyspepsia.”
-poor prognosis: - no typical clinical manifestation of gastritis
 shorter disease duration a.Acute gastritis
 higher gastrin levels (>10,000 pg/mL) - H. pylori induces gastritis: most common causes
large pancreatic primary tumors (>3 cm)  sudden onset of epigastric pain, nausea, and vomiting
 metastatic disease to lymph nodes, liver, and bone  histologic studies: marked infiltrate of neutrophils with edema
 Cushing’s syndrome and hyperaemia
hepatic metastases  If not treated -> chronic gastritis
 Hypochlorhydria lasting for up to 1 year may follow acute H.
B.STRESS-RELATED MUCOSAL INJURY pylori infection
- Patients suffering from shock, sepsis, massive burns, severe trauma, - Bacterial infectionor phlegmonous gastritis
or head injury can develop acute erosive gastric mucosal changes or  rare; potentially life-threatening disorder
frank ulceration with bleeding  histology: marked and diffuse acute inflammatory infiltrates of
- injury most commonly observed in fundus and body the entire gastric wall; at times ccompanied by necrosis
- GI bleeding: most common presentation  affects: Elderly individuals, alcoholics, and AIDS px
- risk factors for bleeding: - iatrogenic causes:
 Respiratory failure  polypectomy
 Coagulopathy  mucosal injection with India ink
 occur 48–72 h after the acute injury  Associated with:
-histology: does not contain inflammation or H. pylori streptococci, staphylococci, Escherichia coli, Proteus,
-inc.gastric acid in px after: and Haemophilus species
 Head trauma: Cushing’s ulcer and -CMV gastritis: intranuclear inclusions
 severe burns: Curling’s ulcer
 mucosal ischemia b.Chronic gastritis
 breakdown of protective barriers of the stomach - histology: inflammatory cell infiltrate consisting primarily of lymphocytes
 systemic release of cytokines and plasma cells, with very scant neutrophil involvement
 poor GI motility - patchy, initially involving superficial and glandular portions of the gastric
 oxidative stress mucosa -> glandular destruction (atrophy and metaplasia)
-high-risk px who needs preventive measures (prophylaxis): -classified into:
 Mechanicall ventilated  superficial atrophy
 coagulopathy - early phase
 multiorgan failure - inflammatory changes are limited to the lamina propria of the
 severe burns surface mucosa, with edema and cellular infiltrates separating
 Maintain: gastric pH >3.5; intact gastric glands
Continuous infusion of H 2 blockers or liquid antacids  atrophic gastritis
administered every 2–3 - inflammatory infiltrate extends deeper into the mucosa
-with progressive distortion and destruction of the glands
 gastric atrophy
- Glandular structures are lost
- paucity of inflammatory infiltrates.
-thin mucosa: permitting clear visualization of the underlying
blood vessels
- gastric glands may undergo morphologic transformation:
 intestinal metaplasia: conversion of gastric glands to
mucosal glands containing goblet cells; important
predisposing factor for gastric cancer
-classified base on site involved:
 Type A: body-predominant form (autoimmune)
 Type B: antral-predominant form (H. pylori–related)
 AB gastritis: mixed antral/body picture
Type A
- less common
- associated with pernicious anemia
- also called autoimmune gastritis
- detection of antibodies to parietal cells
 directed against H+,K+-ATPase
 observed: individuals over age 60 & px with vitiligo and
Addison’s disease
- observed in family members of patients with pernicious anemia - overexpression of TGF-α -> overstimulation of the epidermal growth factor
 one-half of patients have antibodies to thyroid antigens receptor (EGFR) pathway -> increased proliferation of mucus cells -> foveolar
 30% of patients with thyroid disease have circulating antiparietal hyperplasia
cell antibodies
 leads to hypergastrinemia CLINICAL MANIFESTATION
Type B  Epigastric pain
- antral-predominanT  nausea,
-More common form  vomiting
- progression toward the body and fundus  anorexia,
- 15–20 years: conversion to a pangastritis  peripheral edema
- increases with age: 100% of persons over age 70  weight loss
-histology: dense chronic inflammatory infiltrate of the lamina propria; - Occult GI bleeding may occur; overt bleeding (due to superficial mucosal
epithelial cell infiltration with polymorphonuclear leukocytes erosions)
- chronic H. pylori–induced gastritis -> gastric adenocarcinoma - gastric polyposis: common mimics of MD; bleeding is overt
- Tumor growth remains dependent on the presence of H. pylori - develop a protein-losing gastropathy
 follow-up EUS every 2–3 months - Gastric acid secretion: reduced or absent because of the decreased parietal
-treatment: cells
 aimed at the sequelae and not the underlying inflammation - Endoscopy with deep mucosal biopsy, preferably full thickness
 pernicious anemia: long-term parenteral vitamin B12 with a snare technique: required to establish the diagnosis and exclude other
supplementation entities
 Eradication of H. pylori even if PUD or a low-grade MALT - initial evaluation:
lymphoma is not present  Complete blood count
c.Miscellaneous Gastritis  serum gastrin
- Lymphocytic gastritis  serum albumin
 intense infiltration of the surface epithelium with lymphocytes  CMV and H. pylori serology
 body of the stomach  pH testing of gastric aspirate during endoscopy
 mature T cells and plasmacyte
 described in patients with celiac sprue TREAMENT
 H. pylori probably plays no significant role - cetuximab: EGF inhibitory antibody; first-line treatment for
- varioliform gastritis MD
 thickened folds noted on endoscopy - total gastrectomy: severe disease with persistent and substantial protein
 folds capped by small nodules that contain a central depression or loss despite therapy
erosion
- eosinophilic gastritis
 eosinophilic infiltration in mucosa, muscularis propria, and serosa
 circulating eosinophilia
 clinical manifestation of systemic allergy
 Antral involvement predominates with edematous folds -> outlet
obstruction
 epigastric discomfort, nausea, and vomiting
- granulomatous gastritis
 observed in Crohn’s disease
 granulomatous infiltrates
 infectious processes can lead to granulomatous gastritis:
 histoplasmosis
 candidiasis
 syphilis
 tuberculosis
sarcoidosis
 idiopathic granulomatous gastritis
 eosinophilic granulomas
- Russell body gastritis (RBG)
 a pseudotumoral endoscopic appearance
 presence of numerous plasma cells containing Russell
bodies (RBs) that express kappa and lambda light chains
 benign in nature

D.MÉNÉTRIER’S DISEASE
- very rare gastropathy
- characterized by large, tortuous mucosal folds
- age of onset of 40–60 years
- male predominance
- differential diagnosis: ZES, malignancy (lymphoma, infiltrating carcinoma),
infectious etiologies (CMV, histoplasmosis, syphilis,
tuberculosis), gastritis polyposa profunda, and infiltrative disorders such as
sarcoidosis
- mucosal folds: most prominent in the body and fundus, sparing the antrum
-histology: massive foveolar hyperplasia (hyperplasia of surface and glandular
mucous cells); reduction in oxyntic glands and parietal cells and chief cells
- MD is not considered a form of gastritis
- CMV: common etiology in children
GASTROINTESTINAL BLEEDING - have poorer outcomes
-UGIB > LGIB - cirrhotics with UGIB: urgent endoscopy within 12 h
-GIB present as : “ “ + varices: endoscopic ligation; IV vasoactive medication (e.g., octreotide
 overt 50 μg bolus and 50 μg/h infusion) is given for 2–5 days
-manifested by: - advanced liver disease: transjugular intrahepatic portosystemic shunt (TIPS)
 Hematemesis: vomitus of red blood or “coffee- w/in first 1-2 days
grounds” material - persistent or recurrent bleeding despite endoscopic and medical therapy:
 Melena: black, tarry, foul-smelling stool TIPS
 Hematochezia: passage of bright red or maroon blood - well-compensated cirrhosis: Decompressive surgery
from the rectum - Portal hypertension: responsible for bleeding from gastric varices
 occult
- symptoms of blood loss or anemia: HEMORRHAGIC & EROSIVE GASTROPATHY
 Lightheadedness - often labeled gastritis
 Syncope - endoscopically visualized subepithelial hemorrhages and erosions
 Angina -no major bleeding: due to the absence of arteries and veins in the mucosa
 Dyspnea -erosions develop: NSAID use, alcohol intake, and stress
 diagnostic evaluation: reveals iron deficiency anemia &
positive fecal occult blood test OTHER CAUSES:
- erosive duodenitis, neoplasms, aortoenteric fistulas, vascular lesions
SOURCES OF GIB (including hereditary hemorrhagic telangiectasias [Osler-Weber-Rendu] and
a.UGIB gastric antral vascular ectasia [“watermelon stomach”]), Dieulafoy’s lesion (in
which an aberrant vessel in the mucosa bleeds from a pinpoint mucosal
defect), prolapse gastropathy (prolapse of proximal stomach into esophagus
with retching, especially in alcoholics), and hemobilia or hemosuccus
pancreaticus (bleeding from the bile duct or pancreatic duct)

b.LGIB
Small intestine source
-bleeding from sites beyond the reach of the standard upper endoscope
- bleeding is uncommon
-most common cause:
 Vascular ectasias
 tumors (e.g., GI stromal tumor, carcinoid,
adenocarcinoma, lymphoma, metastases)
 NSAID-induced erosions and ulcers
- Hemorrhagic or erosive gastropathy and erosive esophagitis: mild UGIB; - Meckel’s diverticulum: is the most common cause of significant LGIB in
major bleeding is rare children
- small-bowel tumors: adults <40–50 years; often account for obscure GIB
PUD - vascular ectasias and NSAIDinduced lesions: patients >50–60 years
- remain in the hospital for 3 days: patients without clean-based ulcers; most  Vascular ectasias: treated with endoscopic therapy
episodes of recurrent bleeding occur within 3 days  Tumors: surgical resection
-high-risk ulcers: Colonic source
 active bleeding - Hemorrhoids: most common
 nonbleeding visible vessel - anal fissures: minor bleeding and pain
 adherent clot  Both rarely require hospitalization. If excluded, most
 high-dose, constant infusion IV PPI (80-mg bolus and 8- common cause of LGIB in adults:
mg/h infusion) to sustain intragastric pH >6 and  Diverticula- abrupt, painless, sometimes
enhance clot stability massive, and often from the right colon
-low-risk ulcers:  vascular ectasias (especially in the proximal
 flat pigmented spot colon of patients >70
 clean base years)- overt or occult
 do not require endoscopic therapy  neoplasms (primarily adenocarcinoma),
 receive standard doses of oral PPI  colitis (ischemic,infectious, idiopathic
-next 1-2 yrs: ulcers rebleed if no preventive strategies inflammatory bowel disease)
-preventve strategies focus on:  postpolypectomy bleeding
 Eradication of Hp
 NSAID discontinuation APPROACH TO PX WITH GIB
 If NSAIDs must be given: COX-2 selective inhibitor -initial assessment: measure HR & BP
(coxib) plus a PPI should be used  postural changes in clinically significant bleeding
 PPI co-therapy alone or a coxib alone is associated with - hemoglobin below 7 g/dL: transfusion is recommended
an annual rebleeding  hemoglobin does not fall immediately with acute GIB
 px w/ CAD who developed ulcers after takin aspirin:  may be normal or only minimally decreased at the initial
restart aspirin ASAP 1-7 days after bleeding episode presentation
 Acid reduction  may take 72 hrs to fall as extravascular fluid enters the vascular
 bleeding ulcers unrelated to H. pylori or NSAIDs: PPI space to restore volume
therapy indefinitely - Hematemesis:indicates an upper GI source of bleeding (above the
ligament of Treitz)
MALLORY-WEIS TEARS - Melena: blood present in the GI tract for at least 14 h, and as long as 3–5
- vomiting, retching, or coughing preceding hematemesis; alcoholic px days
- Bleeding: gastric side of the gastroesophageal junction; stops spontaneously  more proximal = more melena
and recurs in only 0–10% - Hematochezia: lower GI source of bleeding; although UGIB lesion bleeds
- actively bleeding tears: endoscopic therapy briskly blood flow to the bowel before melena develops
 when presenting symptom of UGIB: dropping hemoglobin
ESOPHAGEAL VARICES
-UGIB: hyperactive bowel sounds and an elevated blood urea nitrogen - persistent or recurrent bleeding for which no source has been identified
(volume depletion and blood proteins absorbed in the small intestine) - initial tests:
 angiography:for massive obscure bleeding
EVALUATION & MGMT  video capsule endoscopy: allows examination of the entire small
a.UGIB intestine
- characteristics predictive of rebleeding and death: - Push enteroscopy: inspect the entire duodenum and
 tachycardia or hypotension proximal jejunum; may be considered as an initial evaluation
 increasing age - Deep” enteroscopy: next test undertaken
 comorbidities
- PPI infusion at presentation Fecal occult blood testing:
- to improve endoscopic visualization: erythromycin, 250 mg  only for colorectal cancer screening
intravenously ~30 min before endoscopy  used beginning at age 50: in average-risk adults
- Cirrhotic patients: start antibiotics & vasoactive medication (octreotide,  begin at age 40: first-degree relative with colorectal neoplasm at
terlipressin, somatostatin, vapreotide) upon presentation, even before ≥60 years
endoscopy  two second-degree relatives with colorectal cancer
- low-risk: Upper endoscopy within 24 h
-hight-risk: within 12 h

b.LGIB
- upper endoscopy before evaluation of the lower GI tract in px with
hematochezia and hemodynamic instability
- Colonoscopy: procedure of choice; nonmassive bleeding
-Angiography: in massive bleeding
- Sigmoidoscopy: patients <40 years old with minor bleeding
- imaging studies: no source identified on colonoscopy

c.OBSCURE GIB
SALMONELLOSIS ENTERIC (THYPOID) FEVER
- grow in both humans and animals - systemic disease characterized by fever and abdominal pain
- Salmonella typhi and Salmonella paratyphi: restricted to - enlarged Peyer’s patches and mesenteric lymph nodes
human hosts; cause enteric (typhoid) fever
- nontyphoidal Salmonella, or NTS: colonize the GI tracts of a broad range of Epidemiology
mammals, reptiles, birds, and insects - S. typhi and S. paratyphi serotypes A, B, and C: human is ONLY host
- food-borne or waterborne transmission from fecal contamination
Etiology - Sexual transmission between male partners
- gram-negative bacilli - high incidence:
- family Enterobacteriaceae poor sanitation and
- non-spore-forming, facultatively anaerobic lack of access to clean drinking water
- measure 2–3 μm by 0.4–0.6 μm urban > rural areas
- produce acid on glucose fermentation, reduce nitrates young children and adolescents
- do not produce cytochrome oxidase -risk factors:
-2 species: contaminated water or ice, flooding, food and drinks purchased from street
 Salmonella enterica vendors, raw fruits and vegetables grown in
-contains six subspecies fields fertilized with sewage, ill household contacts, lack of hand washing and
- S. enterica subspecies I includes almost all the serotypes (>2500 toilet access, and evidence of prior Helicobacter pylori infection
serotypes) pathogenic for humans - 1 paratyphoid fever: 4 cases of typhoid fever
- Serotyping is based on:
 somatic O antigen: lipopolysaccharide cellwall Clinical course
components - fever: >75% of cases; abdominal pain: only 30–40%
 surface Vi antigen: restricted to S. typhi and S. -incubation period: averages 10–14 days but ranges from 5 to 21 days
paratyphi C - most prominent symptom:
 flagellar H antigen  prolonged fever (38.8°–40.5°C; 101.8°–104.9°F); up to 4 weeks if
 Salmonella bongori untreated
- except Salmonella gallinarum-pulloru: ALL are motile by means - S. paratyphi A is thought to cause milder disease; predominantly GI
of peritrichous flagella symptoms
-except S. typhi: ALL produce gas (H2S) on sugar fermentation  enteric fever caused by these organisms were clinically
- only 1% of clinical isolates ferment lactose indistinguishable
- ~99% of Salmonella infections in humans cause by specific O-antigen -symptoms: GI symptoms:
serogroups: A, B, C1, C2, D, and E  Headache -anorexia
chills -abdominal pain
Pathogenesis  Cough - nausea
-begin with ingestion of organisms from contaminated food or water  Sweating -vomiting
-infectious dose: 200 colony-forming units (CFU) to 106 CFU  Myalgias -diarrhea
-increase susceptibility: conditions that decrease stomach acidity (age <1  malaise -constipation
year, antacid ingestion) & decrease intestinal integrity  Arthralgia
- initial incubation stage: few or no signs and symptoms -PE:
- fever and abdominal pain: result from secretion of cytokines by  rash (“rose spots”)
macrophages and epithelial cells in response to bacterial products -faint, salmon-colored, blanching, maculopapular rash; located on
- hepatosplenomegaly: recruitment of mononuclear cells and the trunk and chest
development of a specific acquired cell-mediated immune response to S. - evident at end of the 1st week; resolves: w/o a trace after 2–5
typhi colonization days
-enteric fever: characterized by an infiltration of mononuclear cells into the  hepatosplenomegaly
small-bowel mucosa  epistaxis
- NTS gastroenteritis:  relative bradycardia (peak of high fever)
 massive polymorphonuclear leukocyte infiltration into both the - third and fourth weeks:
large- and small-bowel mucosa (depend on interleukin 8)->  gastrointestinal bleeding and intestinal perforation result from
degranulation and release of toxic substances by neutrophils -> hyperplasia, ulceration, and necrosis of the ileocecal Peyer’s
damage to the intestinal mucosa -> nontyphoidal gastroenteritis patches
-nontyphoidal salmonellae: ability to utilize the sulfur-containing - Neurologic manifestations:
compound tetrathionate (generated from thiosulfate produced by epithelial  Meningitis
cells through inflammatory cell production of reactive oxygen species)  Guillain-Barré syndrome
 Neuritis
 neuropsychiatric symptoms
- Rare complications:disseminated intravascular coagulation,
hematophagocytic syndrome, pancreatitis, hepatic and splenic abscesses and
granulomas, endocarditis, pericarditis, myocarditis, orchitis, hepatitis,
glomerulonephritis, pyelonephritis and hemolytic-uremic syndrome, severe
pneumonia, arthritis, osteomyelitis, endophthalmitis, and parotitis
- Chronic carriage:common women, infants, and persons who have biliary
abnormalities or concurrent bladder infection with Schistosoma
haematobium

DIAGNOSIS
- considered in any febrile traveller
 other diagnosis: malaria, hepatitis, bacterial
enteritis, dengue fever, rickettsial infections, leptospirosis, amebic
liver abscesses, and acute HIV infection
- no specific laboratory test is diagnostic
- Leukocytosis: children, during the first 10 days of illness
- nonspecific laboratory findings: moderately elevated liver function tests and -not recommended: (1) adults residing in typhoid-endemic areas or (2)
muscle enzyme levels management of persons who may have been exposed in a common source
-definitive dx: requires the isolation of S. typhi or S. paratyphi from blood, outbreak
bone marrow, other sterile sites, rose spots, stool, or intestinal secretions
- Stool cultures: negative in first week; positive during the third week of NONTYPHOIDAL SALMONELLOSIS
infection in untreated patients
- Serologic tests: Widal test for “febrile agglutinins”, tests to detect Epidemiology
antibodies to outermembrane proteins or O:9 antigen -Five serotypes:
 typhimurium (23%)
TREATMENT  enteritidis (16%)
- Prompt antibiotic therapy  newport (10%)
- fluoroquinolones: most effective class of agents for treatment of drug-  heidelberg (6%)
susceptible typhoid fever  javiana (5%)
- persistent vomiting, diarrhea, and/or abdominal distension: arenteral -highest during the rainy season (tropical); during the warmer months
third-generation cephalosporin or fluoroquinolone; administered for at least (temperate)
10 days or for 5 days after fever resolution -highest among the elderly, infants, and immunocompromised individuals,
- dexamethasone (an initial dose of 3 mg/kg followed by including those with hemoglobinopathies, HIV infection, or infections that
eight doses of 1 mg/kg every 6 h) with chloramphenicol: lower mortality rate cause blockade of the reticuloendothelial system (e.g., bartonellosis, malaria,
- chronic carriage of Salmonella: treated for 4–6 week; amoxicillin, TMP-SMX, schistosomiasis, histoplasmosis)
ciprofloxacin, or norfloxacin -Transmission: associated with food products of animal origin, fresh produce
- anatomic abnormality: antibiotic therapy + surgery contaminated with animal waste, contact with animals or their environments
 chicken eggs: major cause of food-borne disease
-Reptile-associated Salmonella > other Salmonella infections
-ceftriaxone: choice for treatment of invasive NTS infection

Clinical Manifestation
a.Gastroenteritis
- most often with NTS (but indistinguishable)
- Nausea, vomiting, and diarrhea: occur 6–48 h after the ingestion of
contaminated food/water
 Diarrheal stools: loose, nonbloody, and of moderate volume
 Large volume watery stools, bloody stools, or symptoms of
dysentery may occur
- abdominal cramping
- fever (38–39°C; 100.5–102.2°F)
- Rarely causes pseudoappendicitis
- usually self-limited
 Diarrhea resolves within 3–7 days
 fever within 72 h
- Stool cultures positive
 4–5 weeks after infection
 >1 year chronic carriage
- Antibiotic treatment usually is not recommended; prolong fecal carriage
- susceptible: neonates, the elderly, and immunosuppressed patients

b.Bacteremia and Endovascular Infections

- 8% of patients: bacteremia
- 5–10%: localized infections
- Bacteremia most common with:
 Salmonella choleraesuis and Salmonella Dublin
 Infants
 Elderly
 immunocompromised patients
- NTS endovascular infection: suspected in highgrade or persistent
bacteremia, especially with preexisting valvular heart disease, atherosclerotic
vascular disease, prosthetic vascular graft,
or aortic aneurysm
 Arteritis: suspected in elderly patients with prolonged fever and
PREVENTION & CONTROL back, chest, or abdominal pain after an episode of gastroenteritis
- Two typhoid vaccines:  Endocarditis and arteritis: associated valve perforation,
(1) Ty21a endomyocardial abscess, infected mural thrombus, pericarditis,
-oral live attenuated S. typhi vaccine mycotic aneurysms, aneurysm rupture, aortoenteric fistula, and
-given on days 1, 3, 5, and 7, with a booster every 5 years vertebral osteomyelitis
- minimal age for vaccination: 6 years
(2) Vi CPS c.Localized infection
-parenteral vaccine Intraabdominal infection
-purified Vi polysaccharide from the bacterial capsule -rare and usually manifest as hepatic or splenic abscesses or
-given in a single dose, with a booster every 2 years cholecystitis
- minimal age for vaccination: 2 years - Risk factors:
-no licensed vaccine for paratyphoid fever  Hepatobiliary anatomic abnormalities (e.g., gallstones)
-immunization is an adjunct and not a substitute for the avoidance of high-  abdominal malignancy
risk foods and beverages sickle cell disease (especially with splenic abscesses)
- surgical correction and percutaneous drainage of abscesses
  with HIV/AIDS and NTS bacteremia: 1–2 weeks of IV antibiotic
CNS infection therapy followed by 4 weeks of oral therapy with a
- meningitis: most common; in infants 1–4 months of age fluoroquinolone
- others: ventriculitis, subdural empyema, and brain abscesses  infections relapse after this regimen: long-term suppressive
therapy with a fluoroquinolone or TMP-SMX
Pulmonary infection
- present as lobar pneumonia
- complications:
 lung abscess
 empyema,
bronchopleural fistula
GU infection
- present as either cystitis or pyelonephritis
- Risk factors:
 malignancy
 Urolithiasis
 structural abnormalities
 HIV infection
renal transplantation
- genital infections:
 ovarian and testicular abscesses
 prostatitis
 epididymitis

Bone, joint, soft tissue infection

- Salmonella osteomyelitis most commonly affects:
 femur
 tibia
 humerus
 lumbar vertebrae
-associated w/:
 sickle cell disease
 hemoglobinopathies
 preexisting bone disease (e.g., fractures)
- Septic arthritis involves:
 Knee
 Hip
 shoulder joints
- Reactive arthritis: frequent in persons with the HLA-B27
histocompatibility antigen

DIAGNOSIS
- based on isolation
- Endovascular infection: suspected if highgrade bacteremia (>50% of 3 or
more positive blood cultures)
- to identify localized infection:
Echocardiography, computed tomography (CT), and indium-labeled
white cell scanning
TREATMENT
- Antibiotics should not be used routinely to treat uncomplicated NTS
gastroenteritis
 symptoms are usually self-limited
 duration of fever and diarrhea is not decreased by antibiotic
therapy
 associated with: increased rates of relapse, prolonged
gastrointestinal carriage, and adverse drug reactions
- fluid and electrolyte replacement: dehydration secondary to diarrhea
- Preemptive antibiotic treatment:
 increased risk for invasive NTS infection: including neonates
(probably up to 3 months of age)
 persons >50 yo with suspected atherosclerosis
 immunosuppression
 cardiac valvular or endovascular abnormalities
 significant joint disease
 oral or IV antibiotic administered for 48–72 h or until
the patient becomes afebrile
 Immunocompromised: up to 7–14 days
 chronic carriage of NTS: prolonged antibiotic course
-third-generation cephalosporin or a fluoroquinolone: life-threatening NTS
bacteremia or focal NTS infection
 bacteremia is low-grade: treated for 7–14 days