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SECTION A: ANORECTAL SURGERY

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1. Carcinoma of the Anal Canal [2+2+3+3]

Etiology [2]

• HPV infection (types 16, 18) - the most important etiologic factor; responsible for ~90% of anal SCCs
• HIV infection / immunosuppression - HIV+ individuals have 30-fold increased risk
• Receptive anal intercourse - increases HPV exposure
• Multiple sexual partners
• History of other HPV-related malignancies (cervical, vulvar, vaginal)
• Smoking - independent risk factor (2-5x increased risk)
• Chronic inflammatory conditions - Crohn's disease, chronic fistulae (rare malignant transformation)
• Immunosuppression after solid organ transplantation

• SCC (majority, 80%) - arising from transitional zone/dentate line area
• Adenocarcinoma (rare, from anal glands or rectal-type mucosa)
• Melanoma (rare, 1-2%)
• Basal cell carcinoma (rare)
• GIST (very rare)

Differential Diagnosis [2]

Investigations [3]

• History + examination under anesthesia (EUA) with biopsy - gold standard for diagnosis
• Digital rectal examination (DRE), anoscopy, proctoscopy

• MRI pelvis - most important; defines local tumor extent, lymph node status, sphincter involvement
• CT chest-abdomen-pelvis - distant metastases (liver, lung)
• PET-CT - increasingly used for staging and treatment planning; detects occult nodal disease
• Endoanal ultrasound (EAUS) - assesses sphincter involvement and perirectal nodes
• Transrectal ultrasound

• FBC, LFTs, renal function
• HIV serology (all patients)
• HPV genotyping / anal cytology (in screening programs)
• SCC antigen as tumor marker (limited utility)

• T1: ≤2 cm; T2: 2-5 cm; T3: >5 cm; T4: invades adjacent organs
• N0-N1 based on regional nodal involvement
• M1: distant metastasis

Treatment [3]

• Radiotherapy: 45-54 Gy to pelvis (inguinal nodes included if involved)
• Chemotherapy: 5-Fluorouracil (5-FU) + Mitomycin C (MMC) concurrently
  • 5-FU 1000 mg/m²/day on days 1-4 and 29-32
  • MMC 10 mg/m² IV bolus on day 1 (and day 29)
• Response assessment: 8-12 weeks post-CRT (biopsy if residual disease suspected)
• Complete response rate: ~80-90%

• Abdominoperineal resection (APR): Reserved for:
  • Residual/recurrent disease after CRT
  • T4 tumors with sphincter invasion requiring palliation
  • Failure of CRT
  • Contraindications to CRT
• Local excision: Only for small (T1), well-differentiated, superficial lesions NOT involving sphincter

• Inguinal node metastases: included in radiation field ± groin dissection
• HIV+ patients: treat with standard CRT (ART to be optimized)
• Anal melanoma: APR, poor prognosis; adjuvant immunotherapy (pembrolizumab) being studied

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2. Surgical Anatomy of the Anal Sphincters [5]

Internal Anal Sphincter (IAS)

• Origin: Continuation of the circular smooth muscle of the rectum
• Characteristics: Involuntary (autonomic); smooth muscle; tonically contracted
• Extent: Extends from the anorectal junction to 1-1.5 cm below the dentate line; approximately 3-4 cm in length, 5 mm thick
• Nerve supply:
  • Sympathetic (L1-L2) via hypogastric plexus - maintains tonic contraction
  • Parasympathetic (S2-S4) via pelvic splanchnic nerves - causes relaxation (rectoanal inhibitory reflex - RAIR)
• Function: Responsible for 80-85% of resting anal canal pressure (15-25 mmHg of the total 90 mmHg)
• Clinical: Disruption causes passive fecal incontinence

External Anal Sphincter (EAS)

• Origin: Puborectalis and deep EAS are continuous with the levator ani (pubococcygeus)
• Characteristics: Voluntary (somatic); striated muscle; can be consciously contracted
• Three parts (from deep to superficial):
  1. Deep part: Blends superiorly with puborectalis; surrounds upper anal canal
  2. Superficial part: Elliptical; attached anteriorly to the perineal body and posteriorly to the anococcygeal ligament
  3. Subcutaneous part: Below the IAS; encircles lower anal canal; no bony attachments
• Nerve supply: Inferior rectal branch of the pudendal nerve (S2, S3, S4)
• Function: Responsible for squeeze pressure; maintains continence during urgency
• Clinical: Disruption causes urgency fecal incontinence

Puborectalis Muscle

• Part of the levator ani group (pelvic diaphragm)
• U-shaped sling of striated muscle from pubic symphysis, looping posterior to the anorectal junction
• Creates the anorectal angle (90-110°) - essential for continence
• Nerve supply: Pudendal nerve + direct branches from S3, S4

Intersphincteric Space

• Located between IAS and EAS
• Contains anal glands (cryptoglandular origin of most fistulae)
• Site of primary infection in most anorectal sepsis (Park's cryptoglandular theory)

Conjoined Longitudinal Layer

• Forms between IAS and EAS
• Derived from longitudinal smooth muscle of rectum + fibers of levator ani
• Penetrates EAS to anchor perianal skin as "corrugator cutis ani"
• Divides the intersphincteric space

Dentate (Pectinate) Line

• Key anatomical landmark at junction of endoderm and ectoderm (8 columns of Morgagni)
• Above: Columnar epithelium; visceral innervation; autonomic; superior rectal artery; drainage to inferior mesenteric lymph nodes
• Below: Squamous epithelium; somatic innervation (pudendal nerve) - pain sensitive; inferior rectal artery; inguinal lymph node drainage

Clinical Zones of the Anal Canal

• Surgical anal canal: 4 cm; from anorectal junction to anal verge (used surgically)
• Anatomical anal canal: 2 cm; from dentate line to anal verge
• Transitional zone (ATZ): Above dentate line; contains transitional/cloacogenic epithelium; origin of transitional cell (basaloid) carcinomas

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3. VAAFT (Video-Assisted Anal Fistula Treatment) [5]

Principle

Instruments

• Fistuloscope: 8 Fr, 0° rigid scope with working channel; connects to camera, light source, and irrigation
• Monopolar electrode for coagulation of fistula epithelium
• Forceps for removal of debris
• Stapler or suture materials for internal opening closure

Two-Phase Technique

1. Insert fistuloscope from external opening with continuous glycine/saline irrigation
2. Navigate the fistula tract under direct vision
3. Identify internal opening (confirmed by transanal visualization)
4. Identify secondary tracts, cavities, abscesses
5. Determine relationship to sphincters

1. Under direct vision, use monopolar electrode to electrocoagulate the fistula tract from inside
2. Destroy epithelial/granulation tissue lining with electrode (or laser)
3. Remove all necrotic material with forceps
4. Close internal opening: options include
   • Stapled closure (mucosal flap advance by endostapler)
   • Hand-sewn closure
   • Suture ligation
5. External opening left open for drainage

Advantages

• Sphincter-preserving (no sphincter muscle cut)
• Minimal risk of fecal incontinence
• Can treat complex and recurrent fistulas
• Identifies secondary tracts not seen on imaging
• Lower morbidity than conventional surgery
• Day-case procedure; quick recovery

Disadvantages/Limitations

• High recurrence rate: 30-50% (main limitation)
• Steep learning curve
• Not suitable for very tight, tortuous, or calcified tracts
• Cannot be used for suprasphincteric/extrasphincteric fistulae easily
• Limited long-term data

Indications

• Complex anal fistulas (trans-sphincteric, suprasphincteric)
• Recurrent fistulas after previous surgery
• Patients at high risk of incontinence (anterior fistulas in women, multiple prior surgeries)
• Crohn's fistulas (selected cases)

Results

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4. EPSiT for Pilonidal Sinus [5]

Principle

Instruments

• Fistuloscope (same Karl Storz device as VAAFT) introduced through the external pit
• Monopolar electrode or Nd:YAG laser for coagulation
• Forceps for hair/debris extraction

Technique (Step-by-Step)

1. Patient position: Prone jack-knife
2. Identification: Probe the sinus; inject hydrogen peroxide to identify pits
3. Diagnostic phase: Insert fistuloscope through the largest pit; irrigate with saline
4. Under direct vision, identify:
   • Entire sinus cavity and tracts
   • Hair content, granulation tissue
   • Blind extensions
5. Operative phase:
   • Remove all hair using forceps (crucial - hair is the primary driver of recurrence)
   • Coagulate the sinus walls and granulation tissue with monopolar electrode or laser
   • Destroy all epithelial lining systematically
   • Ensure all secondary tracts are treated
6. Closure: Small pits are curetted; may be excised minimally or left to heal by secondary intention; no large excision needed

Advantages

• Minimal tissue excision - no wide excision/flap required
• Preserves natal cleft anatomy
• Short procedure (~20-30 min)
• Outpatient/day-case
• Quick return to work (1-2 weeks vs. 4-6 weeks for excision)
• Low postoperative pain
• Good cosmesis
• Can be repeated if recurrence occurs
• Suitable for extensive/recurrent disease

Disadvantages

• Higher recurrence rate (~20-30%) vs. flap procedures (5-10%)
• Requires specialized equipment and training
• Not suitable for very acute, infected sinuses (must treat sepsis first)

Indications

• Primary pilonidal sinus disease
• Recurrent pilonidal sinus
• Patients wishing to avoid wide excision
• Multiple pit disease

Results

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5. Pilonidal Sinus [5]

Definition

Epidemiology

• Incidence: 26/100,000; predominantly affects young adults (18-35 years)
• Male:Female = 3:1
• More common in hirsute individuals with sedentary occupations

Pathogenesis

• Berliner/Patey theory: Loose hairs penetrate skin in natal cleft due to:
  • Friction from buttock movement
  • Suction effect of natal cleft during walking
  • Hair enters a stretched follicle or creates a new pit
• Once hair enters subcutaneous tissue, foreign body reaction and secondary infection creates the sinus cavity
• "Jeep driver's disease" - originally described in WWII soldiers

Clinical Features

• Asymptomatic pit(s) in natal cleft
• Acute presentation: painful, fluctuant abscess with surrounding cellulitis
• Chronic: intermittent discharge (serous, purulent, or bloody) from pits; may be odorous
• Pits characteristically contain tufts of hair
• External pits are off-midline (usually)

Differential Diagnosis

• Perianal abscess, anal fistula (with perianal skin opening)
• Hidradenitis suppurativa
• Carbuncle, furuncle
• Tuberculosis of the sacrum
• Coccydynia
• Sacral dermoid/teratoma
• Actinomycosis

Investigations

Treatment

1. Conservative: Depilation (shaving, laser), hygiene, 10% phenol injection - for minimal disease
2. Lay open (Lord-Millar): Simple unroofing; high recurrence
3. Excision and primary closure: High wound breakdown; not recommended
4. Excision with secondary healing: Wide excision to sacral fascia; long healing time (8-10 weeks) but low recurrence
5. Karydakis flap: Excision with eccentric midline closure; moves scar off midline; recurrence ~5%
6. Bascom procedure: Pit excision + off-midline drainage
7. Cleft lift procedure (Bascom): Advances skin to flatten natal cleft; very low recurrence
8. Limberg/Rhomboid flap: Excision + fasciocutaneous transposition flap; low recurrence
9. Minimally invasive: EPSiT, SiLaT (Sinus Laser Treatment), EPSIT+laser

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6. Treatment Options for Fistula-in-Ano [5]

Principles of Treatment

Classification First (Parks' - determines management):

1. Intersphincteric (~45%) - passes between sphincters
2. Trans-sphincteric (~30%) - crosses EAS
3. Suprasphincteric (~20%) - passes above puborectalis
4. Extrasphincteric (~5%) - passes outside both sphincters

Treatment Options

• Gold standard for low (intersphincteric, low trans-sphincteric involving <30% EAS) fistulas
• Entire tract laid open; granulation tissue curetted
• Wound heals by secondary intention
• Success rate: 90-97%; Incontinence risk: <5% for low fistulas
• Contraindicated for high fistulas (incontinence risk unacceptable)

• A suture (silk, silastic) passed through fistula tract
• Loose/Draining seton:
  • Maintains drainage; controls sepsis
  • Used in Crohn's fistulas (long-term palliation)
  • First-stage in two-stage procedures for complex fistulas
  • Allows fibrosis around sphincter before definitive repair
• Cutting seton (Kshara sutra in Ayurveda):
  • Slowly tightened to cut through sphincter gradually, allowing fibrosis as it cuts
  • Minimal incontinence due to slow division with simultaneous scarring
  • High success; prolonged treatment course (weeks)

• Mucosal advancement flap raised to cover internal opening
• Core of fistula tract excised/curetted
• Suitable for trans-sphincteric, suprasphincteric fistulas
• Success: 65-80%; Recurrence: 20-35%
• Sphincter-preserving

• Intersphincteric approach; fistula tract identified and ligated/divided in intersphincteric plane
• Success: 57-94%; sphincter-preserving
• Suitable for trans-sphincteric fistulas

• Biological glue (thrombin + fibrinogen) injected to obliterate tract
• Minimally invasive, repeatable
• Success: 14-55%; Higher success for short, simple tracts
• No sphincter risk; low success for complex fistulas

• Bioprosthetic porcine small intestine submucosa plug inserted to occlude tract
• Promotes tissue ingrowth
• Success: 50-80% (variable in literature)
• Sphincter-preserving; can be used for complex fistulas

• Endoscopic treatment (detailed above)
• Success: 40-87%; sphincter-preserving

• FiLaC (Fistula-tract Laser Closure): Radially emitting laser destroys fistula epithelium
• SiLaT: Laser treatment of fistula under scope guidance
• Success: 60-70%; minimal sphincter damage

• Endoscopic clip closes internal opening
• Emerging technique

• Darvadstrocel (Alofisel) - allogeneic adipose-derived mesenchymal stem cells
• EU-approved for complex perianal Crohn's fistulas
• Injected around internal opening after curettage
• Success (combined remission): ~51% vs 36% placebo (ADMIRE-CD trial)

• Last resort for intractable Crohn's/radiation fistulas
• Permanent stoma required

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7. Surgical Anatomy of the Anal Canal [5]

Boundaries

• Above: Anorectal junction (level of puborectalis sling, ~15 cm from anal verge)
• Below: Anal verge (junction with perianal skin)
• Length: 3-4 cm (surgical anal canal)

Lining (from Above to Below)

1. Upper zone (above ATZ): Columnar epithelium (rectal type) - insensate
2. Transitional/ATZ zone: Junctional epithelium (6-12 mm above dentate); variable - columnar, cuboidal, squamous
3. Dentate/pectinate line: Key surgical landmark
4. Pecten (anoderm): Squamous epithelium, hairless; highly pain-sensitive; extends 1.5 cm below dentate
5. Anal verge: Junction with hair-bearing perianal skin

Columns of Morgagni

• 8-12 longitudinal mucosal folds above the dentate line
• Each column contains terminal branch of superior rectal artery + vein
• Anal crypts (sinuses of Morgagni): Pockets at the base of each column
• Anal glands: Open into crypts; 4-8 in number; penetrate IAS into intersphincteric space (source of cryptoglandular sepsis)
• Anal valves: Semilunar folds connecting bases of adjacent columns

Blood Supply

• Superior rectal artery (from inferior mesenteric artery): Main supply above dentate
• Middle rectal artery (from internal iliac): Midzone
• Inferior rectal artery (from internal pudendal artery): Below dentate
• Three terminal branches of superior rectal artery at 3, 7, 11 o'clock (corresponds to primary hemorrhoidal positions)

Venous Drainage

• Internal hemorrhoidal plexus: Portal system (superior rectal vein → inferior mesenteric vein)
• External hemorrhoidal plexus: Systemic (inferior rectal vein → internal pudendal → internal iliac)
• Portosystemic anastomosis at dentate line (clinically: ectopic varices in portal hypertension)

Lymphatic Drainage

• Above dentate line: To inferior mesenteric and internal iliac nodes
• Below dentate line: To inguinal lymph nodes (superficial inguinal) then external iliac

Nerve Supply

• Above dentate: Autonomic (insensate to pain); parasympathetic (S2-S4 - relaxation); sympathetic (L1-L2 - contraction/closure)
• Below dentate: Somatic innervation via inferior rectal nerve (branch of pudendal nerve, S2-S3-S4) - exquisitely sensitive to pain, temperature, touch
• Clinical significance: Injections below dentate are painful; sclerotherapy must be above dentate

Muscles (Summary)

• IAS (involuntary, smooth)
• EAS - deep, superficial, subcutaneous (voluntary, striated)
• Puborectalis (voluntary, striated) - creates anorectal angle
• Corrugator cutis ani (subcutaneous)

Spaces

• Perianal space: Surrounds lower anal canal
• Ischiorectal/Ischioanal space: Lateral, contains fat; connects posteriorly via deep postanal space (Courtney's space) - important in horseshoe abscess formation
• Intersphincteric space: Between IAS and EAS
• Supralevator space: Above levator ani

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8. Parks' Classification for Fistula-in-Ano [5]

Cryptoglandular Theory (Basis)

The Four Types

• Track passes through IAS, traverses intersphincteric space, opens in perianal skin
• Does NOT cross the EAS
• Most common type
• Usually simple; low risk of incontinence
• Treatment: Fistulotomy (safe)

• Track crosses both IAS and EAS
• Opens in ischiorectal fossa
• High variety: crosses high in EAS (most at risk for incontinence)
• Low variety: crosses low in EAS (fistulotomy feasible)
• Treatment: LIFT, seton, flap, VAAFT (depending on level)

• Track passes upward through intersphincteric space, over the top of puborectalis muscle, then downward through levator ani into ischiorectal fossa
• Rare; complex management
• Treatment: Seton, advancement flap, staged procedures

• Track passes from rectum (above levator ani), through levator ani, into ischiorectal fossa, to perineal skin
• Completely outside sphincter complex
• Causes: Pelvic sepsis, Crohn's disease, iatrogenic (probing injury), foreign body, pelvic malignancy
• Treatment: Seton, flap, colostomy may be needed

AGA Simplified Classification

• Simple fistula: Intersphincteric or low trans-sphincteric; single tract; no previous surgery; no radiation; no Crohn's; continent
• Complex fistula: High trans-sphincteric or above; multiple tracts; prior repairs; radiation; Crohn's; or pre-existing incontinence

Additional Classification Points

• Goodsall's Rule: External opening anterior to transverse anal line → fistula runs directly to nearest crypt; external opening posterior → fistula runs in a curved track to posterior midline crypt (6 o'clock position)
• Exceptions to Goodsall's Rule: Anterior fistulas >3 cm from anus often follow the posterior rule

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9. Recent Advances in Fistula-in-Ano Management [5]

Imaging Advances

• 3D Endoanal Ultrasound (3D-EAUS): Superior delineation of sphincter anatomy and tract anatomy vs. 2D EAUS
• MRI with fistula protocol: Gold standard; STIR/T2 sequences identify secondary tracts, horseshoe extensions, undrained collections; increasingly used pre- and post-operatively

Sphincter-Preserving Surgical Techniques

1. LIFT Procedure - increasingly popular sphincter-preserving option with improving results; modifications include LIFT-plug
2. FiLaC (Fistula-tract Laser Closure): Radially emitting laser probe destroys tract epithelium from inside; 60-70% success; day case
3. VAAFT (see above)
4. Over-the-scope clip (OTSC): Endoscopic clip applied to internal opening via flexible sigmoidoscope; early data promising
5. Video-assisted variants (VAAFT + LIFT): Combined approaches

Biological and Regenerative Therapies

• Stem cell therapy: Darvadstrocel (Alofisel, Cx601) - adipose mesenchymal stem cells - EU approved for refractory perianal Crohn's fistula; phase 3 ADMIRE-CD trial showed combined clinical remission in 51% vs 36% placebo
• Platelet-Rich Plasma (PRP): Autologous growth factors to promote healing; adjunct therapy
• Amnion-derived stem cells

Newer Sphincter-Preserving Concepts

• TROPIS (Trans-sphincteric Redo Operating Procedure for Intersphincteric Sepsis): For recurrent complex fistulas
• Balloon dilatation of internal opening combined with tract ablation

Management of Crohn's Fistulas

• Anti-TNF agents (infliximab, adalimumab): First-line medical therapy; maintain remission
• Combination medical + surgical (seton drainage + biologics): Superior to either alone
• Ustekinumab, vedolizumab: Second-line biologics with fistula data
• Stem cell therapy (as above)

Rectal Advancement Flap Improvements

• Improved outcomes with full-thickness (not just mucosal) flap
• Combined with intersphincteric closure of internal opening

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10. Stapler Haemorrhoidopexy (Procedure for Prolapse and Haemorrhoids - PPH) [5]

Principle

Indications

• Grade III hemorrhoids (preferred indication)
• Grade IV hemorrhoids (selected cases)
• Circumferential prolapsing hemorrhoids
• Not suitable for isolated Grade I-II hemorrhoids (conservative management sufficient)

Technique

1. Examination under anesthesia (EUA); patient in lithotomy or prone jack-knife
2. Dilate anal canal; insert Park's anal retractor/anal dilator (CAD - Circular Anal Dilator)
3. Place purse-string suture (2/0 monofilament) at least 4 cm above dentate line (critical - too low = painful/stricture)
4. Introduce PPH 03 circular stapler (33 mm) with anvil into rectum above purse-string
5. Tighten purse-string around central rod of anvil; prolapsed mucosa is drawn into the housing
6. Fire stapler: resects a ring of mucosa and creates a circular titanium staple anastomosis
7. Inspect doughnut of resected tissue; check completeness
8. Suture any bleeding points on staple line

Advantages over Conventional Haemorrhoidectomy

• Less postoperative pain (incision above dentate; somatic nerve-free zone)
• Faster return to work (1 week vs. 4 weeks)
• Shorter operative time
• Lower urinary retention rates
• Suitable for circumferential disease

Complications

• Early: Bleeding (1-5%), urinary retention, pain, pelvic sepsis (rare)
• Late: Recurrence (5-10% at 5 years - higher than Milligan-Morgan)
• Rare but serious:
  • Retroperitoneal/pelvic sepsis: Life-threatening; requires emergency laparotomy
  • Rectovaginal fistula: If posterior vaginal wall inadvertently incorporated
  • Rectal stricture/stenosis
  • Proctalgia/STARR syndrome: Chronic pain; uncommon
  • Fecal urgency/incontinence

Current Status

• Higher long-term recurrence vs. conventional haemorrhoidectomy
• Risk of rare but catastrophic complications
• Transanal Haemorrhoidal Dearterialisation (THD) with mucopexy gaining popularity as alternative

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11. Recurrent Fistula-in-Ano [5]

Definition

Causes of Recurrence

1. Missed/untreated secondary tracts - most common cause; inadequate preoperative imaging
2. Failure to identify true internal opening
3. Incomplete destruction/excision of the primary tract
4. Underlying disease: Crohn's disease (always consider), tuberculosis, actinomycosis
5. Iatrogenic: Injury creating a new false internal opening during probing
6. Immune deficiency: HIV, diabetes mellitus, immunosuppression
7. Radiation proctitis

Assessment

• Detailed history of previous surgery and outcome
• EUA + gentle probing + hydrogen peroxide injection
• MRI pelvis (fistula protocol): Mandatory for complex/recurrent fistulas; STIR sequences
• 3D Endoanal ultrasound
• Consider colonoscopy if Crohn's disease suspected
• Review previous operation notes and histology

Management Principles

1. Ensure complete drainage before definitive repair: Drain any undrained collection; insert seton if needed
2. Define anatomy precisely with MRI
3. Exclude underlying cause (Crohn's, TB, malignancy)
4. Allow adequate healing (minimum 3-6 months after previous surgery)
5. Sphincter assessment: Endoanal ultrasound + manometry if continence is a concern

Treatment Options (Recurrent Fistula)

• Simple recurrence (low fistula): Repeat fistulotomy if no continence risk
• Complex recurrence: Choose sphincter-preserving technique:
  • LIFT or modified LIFT
  • Advancement flap (full-thickness)
  • VAAFT - particularly useful to visualize missed tracts
  • FiLaC laser treatment
  • Staged seton → definitive repair
• Crohn's fistula recurrence: Optimize medical therapy (anti-TNF) + seton; stem cell therapy (Alofisel)
• Intractable recurrence: Temporary defunctioning loop colostomy + definitive repair; may require proctectomy

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12. Classification and Clinical Assessment of Fistula-in-Ano [5]

Classification

• Simple vs. Complex (clinical utility for treatment planning)

• Low vs. High: Based on amount of sphincter involved; "high" = >30-50% EAS
• Simple vs. Horseshoe: Horseshoe = bilateral extension via deep postanal space (Courtney's space)
• Anterior vs. Posterior: Anterior fistulas in women at greater risk of sphincter damage

Clinical Assessment

• Duration, previous anorectal operations, history of abscess
• Discharge characteristics (purulent, serous, faecal - faecal suggests rectal internal opening)
• Incontinence assessment (pre-existing)
• Systemic symptoms (weight loss, diarrhea - Crohn's?)
• TB contacts, HIV risk factors
• Diabetes, immunosuppression

• External opening: location (anterior/posterior to transverse anal line), number, distance from anus
• Goodsall's Rule application
• Induration/scarring along tract (palpable cord)
• Perineal/perianal skin condition (skin tags, edema of Crohn's)
• Gentle probing under anesthesia (EUA): direction, depth, relationship to sphincters
• Internal opening identification: probe + proctoscopy; hydrogen peroxide injection through external opening (bubbles identify internal opening)
• DRE: sphincter tone, masses

• MRI pelvis (fistula protocol)
• 3D EAUS
• Anorectal manometry (if incontinence or complex surgery planned)
• Colonoscopy/CT colonography if Crohn's/malignancy suspected
• Serum markers: CRP, ESR, calprotectin

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13. Role of Seton and VAAFT in Fistula-in-Ano [5]

Seton

• Material: Silastic sling, silk suture, vessel loop
• Passed through entire fistula tract, tied loosely
• Purposes:
  1. Controls sepsis by maintaining drainage
  2. Promotes fibrosis around sphincter (reduces incontinence risk)
  3. Marks and maintains the tract for staged second procedure
  4. Long-term palliation in Crohn's fistulas
• Process: Left in situ for weeks to months until all sepsis controlled and sphincter fibrous → removed or tightened

• Gradually tightened (weekly or fortnightly) to slowly cut through sphincter
• Sphincter divides slowly while simultaneously developing fibrosis
• Kshara Sutra (Ayurvedic): Alkali-coated linen thread; cutting + chemical destruction of tract; popular in India; success ~96% for low fistulas
• Minimal incontinence due to gradual nature of division

• High trans-sphincteric, suprasphincteric fistulas (before definitive repair)
• Crohn's fistulas (long-term)
• Complex/recurrent fistulas
• Initial management of undrained sepsis with complex fistula
• Two-stage procedure: Stage 1 = seton drainage; Stage 2 = advancement flap/LIFT

VAAFT in Fistula-in-Ano

1. Diagnostic: Identifies missed secondary tracts; defines exact internal opening location; assesses relation to sphincters - superior to MRI for secondary tracts in some series
2. Therapeutic: Destroys fistula lining under direct vision with electrode/laser; removes all hair and debris
3. Staging tool: Can be used before definitive surgery to map complex anatomy

• Increasingly used in combination: VAAFT to destroy/ablate main tract + seton for remaining internal opening closure = improved results

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14. Anal Incontinence: Causes and Treatment [5]

Definition

Classification

• Passive incontinence: Loss without awareness; IAS dysfunction
• Urge incontinence: Unable to defer; EAS/puborectalis dysfunction
• Mixed: Both components (most common)

Causes (Etiology)

• Obstetric trauma (most common cause in women): 3rd/4th degree perineal tears, prolonged labor, forceps delivery - occult IAS/EAS tears
• Anorectal surgery: Fistulotomy, hemorrhoidectomy, lateral sphincterotomy, Thiersch wire
• Trauma: Pelvic fractures, penetrating injuries, impalement

• Pudendal neuropathy: Prolonged straining, obstetric stretch injury
• Spinal cord lesions: Myelomeningocele, spinal cord injury, cauda equina syndrome
• Multiple sclerosis, diabetes mellitus (autonomic neuropathy)
• Stroke, dementia

• Rectal prolapse (stretches pudendal nerve + disrupts sphincters)
• Radiation proctitis
• Inflammatory bowel disease (Crohn's, UC - urgency/frequency)
• Rectal carcinoma

• Faecal impaction (common in elderly): High volume liquid stool bypasses impacted mass
• Hirschsprung's disease (paradoxical overflow)

• "Descending perineum syndrome"
• Chronic straining, constipation → pudendal nerve stretch neuropathy

• Anorectal malformations, spina bifida

Assessment

• History: Frequency, type (gas/liquid/solid), pad use, urge vs. passive, obstetric/surgical history
• Cleveland Clinic (Wexner) score or Fecal Incontinence Severity Index for quantification
• Anorectal manometry: Resting (IAS) and squeeze (EAS) pressures
• Endoanal ultrasound (EAUS): Gold standard for sphincter defect identification
• MRI: Pudendal neuropathy assessment, sphincter anatomy
• Pudendal nerve terminal motor latency (PNTML): Neuropathy assessment
• Defecography/proctography: Dynamic assessment; rectal prolapse

Treatment

• Dietary modification (fibre, bulking agents); avoid loose stools and trigger foods
• Loperamide or codeine (slows transit, increases IAS tone)
• Perineal exercises (pelvic floor physiotherapy)
• Biofeedback: Trains voluntary sphincter control; significant improvement in 50-70%
• Anal plugs, incontinence pads

• Topical phenylephrine 10% (increases IAS tone)
• Amitriptyline (reduces rectal sensitivity and colonic motility)

• Sphincter repair (Sphincteroplasty): Direct overlapping repair for discrete sphincter defect; 50-80% short-term improvement; deteriorates over time (60% failure at 10 years)
• Sacral Nerve Stimulation (SNS): Permanent lead implanted at S3 foramen; modulates sphincter and pelvic floor neuromuscular function; 50-75% significant improvement; effective even without structural defect; gold-standard for idiopathic, neurogenic, and failed repair incontinence
• Sphincter augmentation:
  • Artificial Bowel Sphincter (ABS): Silastic device; good results but high infection/explantation rate
  • Magnetic sphincter augmentation
• Injection therapy: Bulking agents (carbon-coated microspheres, NASHA/Dx) into IAS for minor passive incontinence
• PTNS (Posterior Tibial Nerve Stimulation): Peripheral neuromodulation; less invasive than SNS
• Colostomy: Last resort; improves quality of life when all else fails

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15. Management of High Fistula-in-Ano [5]

Definition

Principles

Step-wise Approach

• If acute sepsis: drainage + insertion of loose draining seton
• Allow 3-6 months for resolution of acute inflammation before definitive repair

• MRI fistula protocol: Define tract, sphincter involvement, secondary extensions

• Crohn's disease, TB, malignancy

• Loose seton → advancement flap or LIFT

• Full-thickness rectal flap raised above internal opening; internal opening closed; flap advanced and sutured over defect
• Success 65-80%; can be repeated; relatively safe for sphincter
• Best results: No active sepsis; experienced surgeon

• Via intersphincteric approach; identify fistula in intersphincteric plane; ligate + divide; close both IAS side and EAS side
• Success 57-94%; no sphincter division; low incontinence risk
• Suitable for trans-sphincteric fistulas

• Staged division of sphincter with simultaneous fibrosis
• Acceptable incontinence rates; prolonged treatment

• Sphincter-preserving; modest success for high complex fistulas

• VAAFT ablates tract + flap closes internal opening

• Temporary defunctioning loop colostomy in selected complex/multiply-recurrent cases
• Reduces fecal contamination; allows healing

• Last resort; intractable disease; permanent stoma

Key Decision Points

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16. Management of Strangulated Haemorrhoids [5]

Definition

Clinical Features

• Severe, constant anal pain
• Prolapsed, edematous, purple-black mucocutaneous masses at anal verge
• Inability to reduce
• Mucus discharge, bleeding
• Urinary retention (reflex)
• May progress to gangrenous haemorrhoids (rare)

Initial Assessment

• Examine under good light; document extent
• Distinguish from full-thickness rectal prolapse (concentric mucosal folds)
• Check for gangrene (black/necrotic tissue)

Treatment

• Administer adequate analgesia (oral/IV)
• Ice pack application: Reduces edema and pain (20-30 min, repeated)
• Elevate foot end of bed
• Osmotic agents applied topically: Hypertonic saline-soaked gauze, sugar (sucrose granules) applied to reduce edema
• Manual reduction: After adequate analgesia/sedation; gentle sustained pressure on prolapsed tissue; often successful if attempted promptly; GA/spinal may be needed if severe spasm
• Once edema reduces, patient can be taken for elective hemorrhoidectomy (6-8 weeks later)

• Emergency hemorrhoidectomy - traditionally controversial; now increasingly accepted as safe
• Indications: Failed manual reduction; gangrene; patient preference
• Technique: Milligan-Morgan (open) hemorrhoidectomy under GA/spinal
  • Can perform 3-column hemorrhoidectomy safely
  • Must preserve adequate anoderm bridges to prevent stenosis
• Advantages of early surgery: Definitive treatment; shorter overall recovery; patient preference
• Meta-analyses show emergency haemorrhoidectomy has acceptable complication rates and good outcomes

• Into the edematous tissue to reduce swelling and facilitate reduction (anecdotal evidence)

• Emergency haemorrhoidectomy mandatory
• Prophylactic antibiotics
• Ensure adequate anoderm preservation

Complications

• Post-op bleeding
• Urinary retention
• Infection/sepsis
• Anal stenosis (if anoderm bridges not preserved)

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17. Endoscopic Ultrasound [5]

Definition

Equipment

• Radial EUS: 360° cross-sectional image; mainly diagnostic
• Linear EUS (curvilinear array): Allows real-time needle guidance; used for EUS-FNA/FNB

Indications

• Esophageal carcinoma: T and N staging; EUS most accurate for T-staging (T1-T3)
• Gastric carcinoma: T-staging; linitis plastica assessment
• Pancreatic cancer/IPMN: Superior to CT for small tumors; local staging; vascular invasion assessment; celiac axis involvement
• Rectal carcinoma: uT and uN staging; sphincter involvement; mucosal vs. full-thickness; guides endoscopic vs. surgical resection
• Lung cancer: Mediastinal lymph node staging via EUS-B (EBUS - endobronchial US)
• Cholangiocarcinoma: Hilary staging

• Submucosal lesions: GISTs, carcinoids, lipomas, varices - assess size, origin (mucosal vs. muscularis propria)
• Chronic pancreatitis: Parenchymal and ductal changes; better than CT for early changes
• Choledocholithiasis: Most sensitive imaging (>95%) for common bile duct stones; more accurate than MRCP for small stones
• Mediastinal masses
• Anal sphincter anatomy (endoanal ultrasound - separate probe)

• EUS-guided FNA/FNB: Tissue diagnosis of pancreatic masses, lymph nodes, submucosal lesions
• EUS-guided cystogastrostomy / LAMS (lumen-apposing metal stent): Pancreatic pseudocyst/walled-off necrosis drainage
• EUS-guided biliary drainage (EUS-BD): When ERCP fails; hepaticogastrostomy, choledochoduodenostomy
• EUS-guided celiac plexus neurolysis (CPN): Pancreatic cancer pain palliation
• EUS-guided FNI (fine needle injection): Ethanol ablation of cysts/tumors; radiofrequency ablation

TNM Staging by EUS (Key)

• EUS adds "u" (ultrasound) prefix: uT1N0
• Accuracy: ~80-90% for T-staging; ~70-80% for N-staging
• EUS + CT + PET-CT = most complete staging workup for GI malignancies

Limitations

• Operator-dependent
• Cannot assess beyond 5-10 cm distance
• Cannot stage distant metastases (use CT/PET-CT)
• Not useful if lumen is obstructed

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18. Surgical Safety Checklist [5]

Three Phases ("Pause Points")

1. Patient has confirmed: identity, site, procedure, consent
2. Site marked? (Yes/Not applicable)
3. Anesthesia machine and medication check complete?
4. Pulse oximeter on and functioning?
5. Known allergies? Any reaction to anesthesia?
6. Difficult airway or aspiration risk? Equipment/assistance available?
7. Risk of >500 mL blood loss? IV access, fluids, blood products available?

1. All team members have introduced themselves by name and role
2. Surgeon, anesthesia professional, and nurse verbally confirm patient, site, procedure
3. Anticipated critical events:
   • Surgeon: Key steps, operative time, anticipated blood loss
   • Anesthetist: Patient-specific concerns
   • Nursing team: Sterility confirmed, equipment issues, concerns
4. Antibiotic prophylaxis given within last 60 minutes?
5. DVT prophylaxis given?
6. Essential imaging displayed?

1. Nurse verbally confirms procedure recorded
2. Instrument, sponge, and needle count correct?
3. Specimen labeled correctly (including patient name)?
4. Any equipment problems to address?
5. Surgeon, anesthesia professional, nurse review key concerns for recovery and management of patient

Impact

• Reduces surgical site infections, unplanned returns to OR, anastomotic leaks
• Improves communication; identifies potential errors before they occur
• Mandated by hospitals worldwide; now part of regulatory requirements in most countries

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19. Enhanced Recovery After Surgery (ERAS) Protocol [5]

Definition

Key Elements (Organized by Phase)

1. Patient education and counseling: Expectations, analgesia plan, early mobilization
2. Nutritional assessment: Treat malnutrition before surgery; avoid prolonged fasting
3. Carbohydrate loading: 400 mL carbohydrate drink 2h before surgery (reduces insulin resistance, catabolism)
4. Fasting: Solids - 6 hours; clear fluids - 2 hours (abandons traditional "NPO from midnight")
5. Bowel preparation: NOT routinely used for colorectal surgery (no evidence of benefit; increases dehydration)
6. Prehabilitation: Exercise, smoking cessation, alcohol reduction
7. Thromboprophylaxis: LMWH + TED stockings commenced
8. Antibiotic prophylaxis: Single dose 30-60 min before incision

1. Minimally invasive surgery: Laparoscopic preferred over open
2. Goal-directed fluid therapy (GDFT): Avoid over- and under-hydration; use cardiac output monitoring (LiDCO, oesophageal Doppler)
3. Normothermia: Forced air warming blankets; warmed IV fluids; maintain >36°C
4. Minimizing drains/nasogastric tubes: Avoid routine NGT; remove drains early
5. Epidural analgesia / TAP block / spinal: Reduces opioid requirements; improves pain control; facilitates mobilization
6. Short-acting anesthetic agents: Desflurane, propofol TIVA - rapid awakening

1. Early oral feeding: Fluids within 6 hours; soft diet within 24 hours; avoid prolonged IV fluids
2. Multimodal analgesia: Paracetamol + NSAIDs + regional block + opioid-sparing approach
3. Early mobilization: Sit out of bed day 0; walk day 1
4. Urinary catheter removal: Within 24-48 hours
5. Early removal of all drains and lines: Reduces infection risk
6. PONV prophylaxis: Dexamethasone + ondansetron; reduces nausea limiting mobilization
7. Glycemic control: Target glucose 6-10 mmol/L; avoid hypo and hyperglycemia
8. Discharge criteria: Tolerating oral diet, adequate pain control on oral analgesia, independently mobile

Outcomes

• Reduces hospital stay by 30-50% (colorectal surgery: 9 days → 4-5 days)
• Reduces complications by 20-30%
• Reduces costs
• No increase in readmissions

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20. SIRS, Metabolic Response to Injury, and Neuroendocrine Pathway [2+3+5]

SIRS (Systemic Inflammatory Response Syndrome) [2]

• SIRS → Sepsis (SIRS + suspected/confirmed infection)
• Sepsis → Severe Sepsis (+ organ dysfunction)
• Severe Sepsis → Septic Shock (+ refractory hypotension despite fluid)
• (Note: Sepsis-3 [2016] replaced these with new definitions based on Sequential Organ Failure Assessment [SOFA] scores)

Metabolic Response to Injury [3]

• Hypoperfusion, hypometabolism
• Reduced cardiac output, reduced O₂ consumption
• Core body temperature falls
• Reduced oxygen delivery to tissues
• Priority: Maintain perfusion

• Hypermetabolism: BMR increased 20-150% (burns, sepsis worst)
• Pyrexia
• Nitrogen wasting: Muscle catabolism; negative nitrogen balance; urinary nitrogen >20 g/day
• Muscle proteolysis → gluconeogenesis
• Lipolysis: Free fatty acids mobilized
• Hyperglycemia ("diabetes of injury"): Insulin resistance + increased gluconeogenesis
• Protein synthesis redistributed to acute-phase proteins (CRP, fibrinogen, complement)
• Reduced albumin, transferrin (negative acute-phase)
• Sodium and water retention (aldosterone + ADH)

• Positive nitrogen balance
• Lean mass recovery
• Return to metabolic baseline

Neuroendocrine Pathway [5]

1. Hypovolemia/hemorrhage: Detected by:
   • Baroreceptors (carotid sinus, aortic arch) - decreased stretch → activate sympathetic nervous system
   • Atrial volume receptors
   • Renal juxtaglomerular apparatus → renin release
2. Pain and emotion: Via somatosensory afferents to hypothalamus and limbic system
3. Tissue hypoxia/inflammation: Cytokines (IL-1, IL-6, TNF-α) from injured tissue act on hypothalamus
4. Hypoglycemia: Detected by hypothalamic glucose sensors

• Hypothalamus integrates all signals
• Releases CRH (Corticotropin-Releasing Hormone)
• Activates the HPA axis (Hypothalamic-Pituitary-Adrenal axis)
• Also activates sympathoadrenal axis via locus coeruleus

• Released from adrenal medulla and sympathetic nerve endings
• Epinephrine + Norepinephrine
• Effects: Tachycardia, vasoconstriction (↑ SVR), ↑ cardiac output, glycogenolysis, gluconeogenesis, lipolysis, renin release, bronchodilation

• CRH → pituitary ACTH → adrenal cortex → cortisol
• Effects: Gluconeogenesis, protein catabolism (muscle), lipolysis, anti-inflammatory (at physiological levels), sodium retention, suppression of immune function, mineralocorticoid activity

• Paradox: ↑ GH but ↓ IGF-1 (insulin-like growth factor) - peripheral GH resistance
• Anti-insulin effects; lipolysis; protein synthesis in healing tissues

• Released by pancreatic alpha cells (in response to sympathetics + low insulin)
• Promotes glycogenolysis and gluconeogenesis
• Catabolic; opposes insulin

• Reduced secretion initially (sympathetic inhibition)
• Insulin resistance in peripheral tissues
• Later, may be elevated with ongoing hyperglycemia

• Via renin-angiotensin-aldosterone system (RAAS)
• Renin from juxtaglomerular cells (renal hypoperfusion + sympathetics)
• Angiotensin I → II → aldosterone
• Effects: Na⁺ and H₂O retention; K⁺ excretion

• Released from posterior pituitary (osmoreceptors + volume receptors)
• Promotes water reabsorption from renal collecting duct
• Peripheral vasoconstriction at high doses

• Maintain BP and tissue perfusion
• Mobilize energy substrates (glucose, FFA)
• Prioritize vital organs (heart, brain)
• Prepare for repair (at expense of non-essential tissue catabolism)

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21. CDC Classification of Wounds [5]

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22. Classification of Hemorrhagic Shock [5]

• Class I-II: Compensated shock; body maintains BP through ↑HR + vasoconstriction
• Class III: Decompensating; requires blood transfusion; immediate surgical control often needed
• Class IV: Life-threatening; immediate surgery/IR; activate MTP (massive transfusion protocol)
• Base deficit correlates with severity; BD < -6 = significant shock
• Lactate >4 mmol/L = inadequate tissue perfusion; poor prognosis
• ATLS 10th edition (2018): Added "Class 0" concept and updated resuscitation to damage-control approach (1:1:1 pRBC:FFP:platelets)

1. Baroreceptor activation → ↑ SNS → tachycardia + vasoconstriction
2. RAAS → aldosterone → Na⁺/H₂O retention
3. ADH → renal water retention
4. Capillary refill from interstitium (transcapillary refill)
5. Increased O₂ extraction from blood (↑ a-vO₂ difference)

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23. Necrotising Enterocolitis (NEC) [10]

Definition

Epidemiology

• Incidence: 1-3/1000 live births; 5-10% of VLBW infants (<1500 g)
• Mortality: 15-30% overall; 40-50% in those requiring surgery
• Higher risk: Prematurity (<32 weeks) > formula feeding > intrauterine growth restriction

Pathogenesis

1. Prematurity: Immature gut (abnormal motility, poor barrier function, immature immune response, decreased sIgA)
2. Microbial colonization/dysbiosis: Pathological colonization with gram-negative organisms (E.coli, Klebsiella, Enterobacter, Clostridia) instead of normal commensal flora
3. Enteral feeding: Formula feeding (vs. breast milk) - substrate for pathological bacteria; rapid feed advancement

• Pathological TLR-4 (Toll-like receptor 4) activation in immature enterocytes by bacteria/LPS
• Excessive NF-κB activation → pro-inflammatory cytokine cascade (IL-8, TNF-α, IL-1β, PAF)
• Impaired intestinal blood flow (mesenteric vasoconstriction)
• Intestinal ischemia → transmural necrosis → bacterial translocation → systemic sepsis
• Gut mucosal injury → loss of barrier → perforation

Bell's Staging Criteria

Clinical Features

• Abdominal distension
• Bloody stools ("red currant jelly")
• Feeding intolerance, increased gastric residuals
• Apnea, bradycardia
• Temperature instability
• Lethargy
• Systemic signs of sepsis (poor perfusion, mottling, pallor)

Investigations

• Abdominal X-ray (AXR): Most used; shows:
  • Dilated bowel loops
  • Pneumatosis intestinalis (intramural gas - PATHOGNOMONIC)
  • Portal venous gas (ominous sign)
  • Pneumoperitoneum (perforation - surgical emergency)
• Abdominal ultrasound: Better for portal venous gas, ascites, perforation

• FBC: Thrombocytopenia, neutropenia (poor prognosis), left shift
• CRP, blood cultures
• Blood gas: Metabolic acidosis, lactate
• Electrolytes: Hyponatremia, hypokalemia
• Coagulation: DIC in severe cases

Treatment

1. Nil by mouth: Stop all enteral feeds immediately
2. Nasogastric decompression
3. IV fluids: Maintain perfusion; correct electrolyte imbalances
4. Broad-spectrum antibiotics: Typically 7-14 days
   • Ampicillin + Gentamicin + Metronidazole (covers gram-negative, anaerobic)
   • Vancomycin if MRSA risk
5. Parenteral nutrition (TPN): Total via central line for duration of nil by mouth
6. Serial AXR: Every 6-8 hours for deteriorating patients
7. Thrombocytopenia: Platelet transfusion if <50,000
8. Vasopressors if septic shock
9. Monitor for 24-72 hours; most Stage I-II respond to medical management

1. Primary Peritoneal Drainage (PPD):
   • Local anesthesia; bedside drain insertion (RIF or both flanks)
   • For extremely premature/unstable infants (<1000 g, too sick for laparotomy)
   • Controls peritoneal contamination; may allow stabilization
   • ~30-40% will still require laparotomy
2. Laparotomy + Resection:
   • Standard surgical approach
   • Resect clearly necrotic bowel; preserve as much bowel as possible
   • Primary anastomosis: Only if well infant, no peritonitis, good bowel ends
   • Proximal stoma (ileostomy/colostomy): Safer option in most cases; second-stage anastomosis at 6-8 weeks
   • Pan-involvement ("Bell's toll"): Patch-drain-wait approach vs. staged second-look laparotomy
3. Second-look laparotomy: 24-48 hours after initial procedure; reassess bowel viability

Complications

• Short Bowel Syndrome: Most feared; if >50% small bowel resected; TPN-dependent
• Intestinal stricture: Post-NEC; colonic (esp. left colon); presents with obstruction weeks-months later; requires resection
• Neurodevelopmental impairment: In survivors; white matter injury from systemic inflammation
• Cholestatic liver disease: Prolonged TPN
• Recurrent NEC; anastomotic leak; intraabdominal abscess

Prevention

• Human breast milk (most protective - sIgA, lactoferrin, oligosaccharides)
• Probiotic supplementation (Lactobacillus, Bifidobacterium): Strong evidence for reduction in NEC incidence
• Slow, careful feed advancement protocols
• Antenatal steroids for threatened preterm labor
• Minimize antibiotic exposure to preserve commensal flora

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24. Compartment Syndrome [5]

Definition

Pathophysiology

Causes

• Tight cast/dressing/splint
• Escharotomy not performed in burns
• Circumferential tight bandage

• Bleeding: Fractures (tibia, radius, humerus), vascular injury
• Reperfusion injury: After vascular reconstruction, embolectomy
• Crush injury: Myonecrosis + edema
• Burns: Especially circumferential
• Exercise-induced
• Envenomation (snake bite)
• IV fluid extravasation

Commonly Affected Compartments

• Leg (4 compartments): Anterior (most common), lateral, deep posterior, superficial posterior
• Forearm: Volar, dorsal, mobile wad
• Hand
• Thigh
• Foot
• Gluteal (rare)
• Abdominal compartment syndrome (ACS) - separate entity

Clinical Features - The 6 P's (and beyond)

1. Pain - most reliable early sign; out of proportion to injury; severe; worsened by passive stretch of muscles in that compartment
2. Pressure - tense, woody feeling on palpation of the compartment
3. Paresthesia - earliest objective finding (nerve ischemia)
4. Paralysis - late sign; muscle weakness/inability to move
5. Pallor - capillary insufficiency
6. Pulselessness - very LATE sign; distal pulse may be present with severe compartment syndrome (pulse does NOT exclude diagnosis)
7. Poikilothermia (coolness)

• Pain on passive stretch of muscles in the compartment is the most sensitive clinical sign
• In unconscious/sedated patients, always measure compartment pressure
• Do NOT wait for all 6 P's - they are late signs

Diagnosis

• Clinical (in awake, alert patients): Classic 6 P's sufficient
• Compartment pressure measurement:
  • Stryker STIC device or arterial line manometer technique
  • Normal: <10 mmHg
  • Indication for fasciotomy: >30 mmHg, or delta P (diastolic BP - compartment pressure) <30 mmHg
• Urine myoglobin (rhabdomyolysis)
• CK >5000 U/L suggests rhabdomyolysis/muscle necrosis

Treatment

• Two-incision technique:
  • Lateral incision (6-8 cm, between tibia and fibula): Decompresses anterior and lateral compartments
  • Medial incision (2 cm posterior to tibial border): Decompresses superficial and deep posterior compartments
• Incisions ~15 cm long; all fascia incised; wounds left open

• Volar decompression (Henry incision) + carpal tunnel release
• Dorsal incision if needed

• Wounds left open; moist dressings
• Reassess viability at 48-72 hours (second-look)
• Close wounds when swelling resolves (delayed primary closure or split skin graft)

Abdominal Compartment Syndrome

• Intra-abdominal pressure (IAP) >20 mmHg + new organ failure
• Diagnosed by bladder pressure measurement
• Treatment: Medical measures first (NG decompression, diuretics, neuromuscular block); if fails → emergency decompressive laparotomy + open abdomen management

Reperfusion Injury After Fasciotomy

• On fasciotomy: Reperfusion of ischemic muscle
• Releases: Potassium, hydrogen ions, myoglobin, oxygen free radicals
• Can cause: Cardiac arrhythmias, AKI (myoglobin pigment nephropathy), ARDS
• Management: Aggressive IV hydration to force myoglobin excretion (urine output >200 mL/h); sodium bicarbonate to alkalinize urine

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25. Perioperative Measures to Prevent Surgical Site Infection (SSI) [4]

Definition

CDC SSI Classification

• Superficial incisional: Involves only skin/subcutaneous tissue
• Deep incisional: Involves deep soft tissue (fascia, muscle)
• Organ/space: Involves any anatomical area opened/manipulated during surgery

Perioperative Bundle Measures

1. Identify and treat remote infections before elective surgery
2. MRSA screening and decolonization: Nasal mupirocin + chlorhexidine skin wash for high-risk patients (joint replacement, cardiac surgery)
3. Optimize diabetes: HbA1c < 7% (69 mmol/mol); peri-op glucose 6-10 mmol/L
4. Smoking cessation: At least 4 weeks before surgery
5. Reduce BMI in morbidly obese before elective surgery
6. Shower with antiseptic soap (chlorhexidine) night before and morning of surgery
7. Hair removal: Electric clippers (NOT razor - micro-abrasions) immediately before surgery; NOT the night before

1. Antibiotic prophylaxis:
   • Given within 60 minutes before incision (30 min for fluoroquinolones/vancomycin)
   • Re-dose every 2 half-lives during prolonged surgery (e.g., re-dose cefazolin at 4h)
   • Drug choice based on wound class and organism profile (cephalosporin most common)
2. Sterile technique: Strict hand scrubbing; sterile gown/gloves; minimizing OR traffic
3. Skin preparation: Chlorhexidine-alcohol superior to povidone-iodine (NICE/WHO recommendation)
4. Maintain normothermia: Forced-air warming; warm IV fluids; temperature >36°C (hypothermia impairs neutrophil function)
5. Maintain normovolemia/normoxia: Goal-directed fluid therapy; FiO₂ 0.8 peri-op (evidence mixed but often used)
6. Minimize dead space and hematoma: Good surgical technique; adequate hemostasis
7. Irrigation of wound: With saline (or dilute betadine for contaminated wounds)
8. Appropriate wound closure: Primary closure for clean wounds; delayed for contaminated

1. Wound care: Sterile dressing for 24-48 hours; then keep clean and dry
2. Glycemic control: Continuous insulin infusion if needed; avoid hyperglycemia
3. Drain management: Remove drains at earliest opportunity; closed suction drainage; avoid open drains
4. Surveillance: Daily wound inspection; recognize SSI early

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26. Aetiology of Leg Ulcers [5]

Classification by Cause

• Chronic venous insufficiency (deep vein thrombosis, varicose veins)
• Venous hypertension → fibrin cuffing → "Chronic Lipodermatosclerosis" → ulceration
• Location: Gaiter area (around malleolus), typically medial
• Appearance: Shallow, irregular edges, sloping edges, granulation tissue base, exudate
• Associated: Varicose veins, lipodermatosclerosis, hemosiderin pigmentation, atrophie blanche

• Peripheral arterial disease (atherosclerosis, Buerger's disease)
• Risk factors: Diabetes, smoking, hypertension, dyslipidemia
• Location: Toe tips, heel, pressure points, lateral malleolus
• Appearance: Well-defined "punched out" edges; deep; pale base; no granulation; painful (classically worse at night/elevation)
• ABPI <0.5 in severe ischemia

• Diabetic neuropathy (most common cause), leprosy, tabes dorsalis, syringomyelia, spinal cord injury
• Location: Pressure points - metatarsal heads (plantar surface), heel; painless
• Appearance: Callused margin (hyperkeratotic rim); "punched-out"; surrounded by thick callus; deep
• Mechanism: Loss of protective sensation → repeated pressure → ulceration without patient awareness

• Both venous and arterial components; ABPI 0.5-0.8
• Common in elderly with multiple comorbidities

• Prolonged pressure over bony prominences
• Sacrum, heels, trochanters, ischial tuberosities
• Staged by EPUAP/NPIAP classification (Stage I-IV)

• Rheumatoid arthritis (most common systemic cause)
• SLE, polyarteritis nodosa, Wegener's/GPA, cryoglobulinemia
• Small vessel vasculitis → skin ischemia → ulceration
• Multiple small ulcers; atypical location; treatment targets underlying disease

• Pyoderma gangrenosum: Rapidly enlarging, painful, purple undermined edges; associated with IBD, RA, hematological malignancy
• Calciphylaxis: Renal failure patients; vascular calcification
• Necrobiosis lipoidica: Diabetes; shins; waxy yellow plaques breaking down

• Tropical: Leishmaniasis, tropical ulcer (Fusobacterium + Borrelia vincentii)
• Syphilis (tertiary gummatous ulcer)
• Tuberculosis (lupus vulgaris)
• Ecthyma (streptococcal)

• Marjolin's ulcer: Squamous cell carcinoma arising in chronic wound/burn scar/venous ulcer
• Basal cell carcinoma (rodent ulcer): Rolled, pearly edges; telangiectasia
• Malignant melanoma
• Lymphoma
• Kaposi's sarcoma

• Sickle cell disease: Medial malleolus; recurrent
• Thalassemia, polycythemia

• Post-radiation ulcer
• Factitious ulcer (self-inflicted)

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27. Avoidable Factors that Compound the Response to Injury [5]

• Inadequate fluid replacement perpetuates the ebb phase
• Ongoing tissue ischemia → amplified inflammatory cascade
• Prevention: Aggressive resuscitation to endpoints (MAP >65, urine output >0.5 mL/kg/h, lactate clearance)

• Core temperature <36°C causes:
  • Coagulopathy (impaired platelet function, clotting enzyme dysfunction)
  • ↑ Metabolic demand on rewarming
  • Impaired immune function (↑ SSI risk)
  • Cardiac arrhythmias
• Prevention: Forced-air warming, warm IV fluids, warm irrigants, warm operating room

• Metabolic acidosis from hypoperfusion/lactic acidosis worsens coagulopathy ("lethal triad")
• Prevention: Restore perfusion; damage-control surgery; bicarbonate if pH <7.1

• Uncontrolled pain amplifies the neuroendocrine response
• ↑ Catecholamine release → prolonged catabolic state
• Immobility → DVT, PE, respiratory complications
• Prevention: Multimodal analgesia; epidural; nerve blocks

• Inadequate nutritional support → accelerated muscle wasting during the catabolic phase
• Depletes glutamine stores (essential for gut mucosa and immune cells)
• Prevention: Early enteral nutrition (within 24-48 hours of ICU admission); TPN if enteral not feasible

• Promotes muscle wasting, DVT, PE, pressure sores, respiratory complications, insulin resistance
• Prevention: Early mobilization; physiotherapy; sequential compression devices

• Secondary infection dramatically amplifies inflammatory response
• Prevention: Antibiotic prophylaxis; aseptic technique; urinary catheter care bundles; VAP prevention

• Tissue hypoxia prolongs anaerobic metabolism and lactic acidosis
• Impairs wound healing
• Prevention: Supplemental O₂; adequate ventilation; treat pneumothorax/haemothorax

• Activates HPA axis and sympathoadrenal system
• Prevention: Pre-operative counseling; explanation; anxiolytic medication

• Impairs hormonal regulation (↓ GH, ↑ cortisol, impaired insulin sensitivity)
• ICU environment: Night-time noise, light, interruptions
• Prevention: ICU sleep protocols; earplugs; minimize nighttime interventions

• Impairs neutrophil function → ↑ infection risk
• Prolongs inflammatory response
• Prevention: Insulin infusion; target glucose 6-10 mmol/L

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28. Audit Cycle [5]

Definition

The Audit Cycle (5 Stages)

• Based on high volume, high risk, or high cost areas
• Can arise from critical incidents, complaints, national guidelines, or clinical questions
• Topic should be relevant, measurable, and improvable

• Criterion: A specific and measurable statement about an aspect of care (e.g., "All patients with hip fracture should receive DVT prophylaxis")
• Standard: The expected level of compliance (e.g., "100% of patients should receive DVT prophylaxis within 12 hours")
• Standards derived from: NICE guidelines, SIGN, Royal College guidelines, published evidence, expert consensus

• Prospective or retrospective data collection
• Representative sample
• Data recorded against agreed criteria
• Tools: Case notes review, patient questionnaires, electronic records

• Identify gaps between actual practice and the standard
• Identify causes of variance (system, process, individual)
• Present findings to relevant stakeholders

• Develop an action plan to address identified deficiencies
• Changes may include: Education, protocol revision, equipment procurement, staffing changes
• Assign responsibility and timeline

• After implementing changes, repeat data collection
• Compare against previous results and the standard
• Demonstrates whether change has improved care
• Cycle continues until standards are consistently met

Types of Audit

• Structure audit: Resources, equipment, staffing
• Process audit: What is done (adherence to protocols)
• Outcome audit: What happens to patients (mortality, complication rates)
• National audits: NCEPOD (National Confidential Enquiry into Patient Outcomes and Death), National Bowel Cancer Audit (NBOCA)

Audit vs. Research

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29. Gompertzian Growth [5]

Definition

The Gompertz Model

Characteristics of Gompertzian Growth

1. Early phase (small tumor): Rapid exponential growth; short doubling time; cells proliferating maximally
2. Intermediate phase: Exponential growth slows; doubling time increases
3. Plateau phase (large tumor): Growth approaches zero; cell birth rate ≈ cell death rate
4. Sigmoidal (S-shaped) curve when tumor volume is plotted against time on linear scale

Why Growth Slows (Biological Reasons)

• Inadequate vascular supply (outstripping angiogenesis)
• Nutrient and oxygen limitation (hypoxic necrotic core)
• Accumulation of metabolic waste
• Contact inhibition
• Immune surveillance
• Autocrine growth inhibitors
• Increased differentiation; reduced stem cell proportion

Clinical Significance in Oncology

• A 1 cm tumor (~10⁹ cells, ~30 doublings from first cell) is in the SLOW growth phase
• Most growth occurred BEFORE clinical detectability
• A tumor is clinically detectable at 1 cm but has already been growing for years (estimated ~10 years for many solid tumors)

• When a large tumor is resected, residual cells are released from growth inhibition (smaller mass) → move to the steeper part of the curve → faster growth
• Theoretical basis for early adjuvant chemotherapy (treat when residual tumor burden is small)

• A fixed dose of chemotherapy kills a FIXED PROPORTION (not a fixed number) of cells
• Tumors in the steep growth phase (smaller tumors, early disease) are more chemosensitive
• Tumors in plateau phase are relatively chemoresistant (fewer cycling cells)
• This supports: dose-dense chemotherapy; early adjuvant treatment

• Rapidly cycling cells (steep Gompertz phase) are more susceptible to cell-cycle-active drugs
• Slow-growing (plateau) tumors: More dependent on non-cell-cycle-active (alkylating) agents

• Metastatic deposits are smaller → on steeper part of their Gompertz curve → faster doubling time than primary

Practical Applications

• Screening programs: Targeting early detection when growth rate is high
• Neoadjuvant therapy: Shrinks tumor before surgery; may convert unresectable to resectable
• Adjuvant chemotherapy: Most effective when disease burden is minimal (steep growth phase)

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30. Complications of Blood Transfusion [5]

Immunological (Immune-Mediated)

1. Acute Haemolytic Transfusion Reaction (AHTR):
   • ABO incompatibility (clerical error most common cause)
   • IgM anti-A/B → complement activation → intravascular hemolysis
   • Features: Fever, rigors, chest/loin pain, hemoglobinuria (pink/red urine), hypotension, DIC
   • Life-threatening; can be fatal
   • Management: STOP transfusion immediately; IV fluids; maintain urine output; treat DIC; check samples
2. Febrile Non-Haemolytic Transfusion Reaction (FNHTR):
   • Most common reaction; antibodies to donor WBC antigens
   • Fever ≥1°C rise, chills; no hemolysis
   • Management: Slow/stop transfusion; paracetamol; restart after exclusion of AHTR
3. Allergic/Anaphylactic Reaction:
   • IgE-mediated reaction to plasma proteins
   • Urticaria (mild) to anaphylaxis (severe)
   • Management: Antihistamines; epinephrine for anaphylaxis; steroids
4. TRALI (Transfusion-Related Acute Lung Injury):
   • Severe acute lung injury within 6 hours of transfusion
   • Donor antibodies (HLA/HNA) activate recipient neutrophils → pulmonary capillary endothelial damage → non-cardiogenic pulmonary edema
   • Presents: Acute dyspnea, hypoxia, bilateral infiltrates on CXR, no cardiogenic cause
   • Most common cause of transfusion-related death
   • Management: Supportive; O₂/ventilation; no diuretics

1. Delayed Haemolytic Transfusion Reaction (DHTR):
   • Anamnestic (memory) antibody response to minor RBC antigens (Kidd, Duffy, Kell)
   • Extravascular hemolysis (splenic macrophages)
   • Days 3-10: Falling hemoglobin, jaundice, positive DAT
   • Usually mild and self-limiting
2. Transfusion-Associated Graft vs. Host Disease (TA-GvHD):
   • Donor T lymphocytes engraft and attack host
   • Almost universally fatal; 90% mortality
   • Prevention: Irradiation of blood products for immunocompromised patients
3. Post-Transfusion Purpura (PTP):
   • Severe thrombocytopenia 5-12 days post-transfusion
   • Antibodies to platelet antigens (HPA-1a) destroy both donor and patient platelets
   • Treatment: IVIG; plasmapheresis

Non-Immunological

1. Transfusion-Transmitted Infections (TTI):
   • Bacterial contamination: Platelets most at risk (room temp storage); gram-positive organisms; gram-negative in RBCs (Yersinia enterocolitica)
   • Viral: HIV (1:8 million per unit UK), HCV (1:28 million), HBV (1:1.7 million), CMV, EBV, parvovirus B19
   • Parasitic: Malaria, Chagas' disease, leishmaniasis (rare in UK)
   • Prion: vCJD theoretical risk (now screen by leucodepletion)
2. Fluid Overload (TACO - Transfusion-Associated Circulatory Overload):
   • Acute pulmonary edema, hypertension, raised JVP
   • High-risk: elderly, cardiac disease, renal failure
   • Management: Slow infusion; diuretics; oxygen
3. Metabolic Complications (Massive Transfusion - >10 units in 24h):
   • Hypocalcemia: Citrate (anticoagulant) chelates calcium; particularly with liver disease; treat with IV calcium gluconate
   • Hyperkalemia: Stored RBCs leak potassium; risk of arrhythmia
   • Hypothermia: Cold stored blood; use blood warmers
   • Coagulopathy/Dilutional: Depletion of clotting factors and platelets by packed RBC administration; use 1:1:1 protocol
   • Metabolic alkalosis: Citrate conversion to bicarbonate
4. Haemosiderosis (Iron Overload):
   • Repeated transfusions; thalassemia patients
   • Iron deposits in liver, heart, endocrine organs
   • Treatment: Chelation therapy (deferasirox, deferoxamine)
5. Immunosuppression:
   • Transfusion-related immunomodulation (TRIM)
   • Theoretical risk of cancer recurrence with perioperative blood transfusion

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31. Classification of Shock [5]

Definition

Classification

• Reduced circulating volume
• Haemorrhagic: Trauma, GI bleed, ruptured aortic aneurysm, ectopic pregnancy
• Non-haemorrhagic: Burns (plasma loss), diarrhea/vomiting (GI losses), third-space (pancreatitis, bowel obstruction)
• Pathophysiology: ↓ preload → ↓ CO → ↑ SVR (compensatory vasoconstriction) → ↑HR

• Maldistribution of blood flow; total blood volume may be normal but effective perfusion reduced
• Septic shock (most common): Vasodilation + myocardial depression (gram-negative LPS → cytokines → NO production)
• Anaphylactic shock: IgE-mediated massive vasodilation + bronchospasm + increased vascular permeability
• Neurogenic shock: Spinal cord injury (T6 and above) → loss of sympathetic tone → vasodilation + bradycardia
• Toxic shock
• Hemodynamics: ↓ SVR (warm extremities initially - "warm shock"), ↑HR, normal/high CO (early septic shock)

• Failure of the heart as a pump
• Myocardial: Acute MI (large territory - >40% LV loss), myocarditis, cardiomyopathy
• Mechanical: Acute MR, VSD, papillary muscle rupture
• Arrhythmic: VT, VF, complete heart block
• Hemodynamics: ↓ CO, ↑SVR (compensatory), ↑ PCWP, cold extremities, ↓ urine output
• Management: Inotropes (dobutamine), IABP, ECMO

• Obstruction to blood flow through the cardiovascular system
• Cardiac tamponade: Beck's triad (hypotension, raised JVP, muffled heart sounds); pulsus paradoxus; pericardiocentesis
• Massive pulmonary embolism: Acute RV failure; raised JVP; ECG changes (S1Q3T3); thrombolysis
• Tension pneumothorax: Mediastinal shift; absent breath sounds; needle decompression
• Aortic coarctation / aortic dissection (Type A)

• Addisonian crisis: Adrenocortical insufficiency; hypoglycemia, hyponatremia; refractory hypotension
• Hypothyroid crisis (myxedema coma)
• Treatment: Hydrocortisone + T4

Common Features (All Types)

• Hypotension (SBP <90 or MAP <65 mmHg)
• Tachycardia
• Tachypnea
• Oliguria (<0.5 mL/kg/h)
• Altered consciousness
• Cold, clammy peripheries (except distributive early)
• Metabolic lactic acidosis

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32. Discharge Criteria for Day Case Surgery [5]

Post-Anaesthetic Discharge Scoring System (PADSS) or Aldrete Score

Criteria (Modified PADSS - each scored 0-2; total ≥9 required for discharge)

1. Vital signs: BP and HR within 20% of preoperative values
2. Ambulation: Able to walk without dizziness or IV assistance (for appropriate procedure)
3. Nausea/vomiting: Minimal; controlled with oral medication
4. Pain: Controlled with oral analgesia; acceptable level (VAS <3/10)
5. Surgical bleeding: Minimal; not requiring dressing change

SNAP Criteria (UK - NHS)

• Stable vital signs
• Nausea controlled (oral fluids tolerated)
• Adequate pain control on oral analgesia
• Patient fit to mobilize to appropriate level for procedure

Full Discharge Criteria

• Observations (BP, HR, RR, SpO₂, temperature) within normal range / pre-op baseline for ≥1 hour
• Conscious and orientated
• No respiratory distress; SpO₂ >94% on room air
• Nausea and vomiting controlled (can take oral fluids)
• Pain controlled with oral analgesics (VAS ≤3)
• No excessive bleeding at wound/drain site
• Passed urine (important after spinal anesthesia/pelvic surgery)

• Able to mobilize safely to the level appropriate for the procedure
• An escort (responsible adult) present to accompany home
• Responsible adult to care for patient overnight
• Patient lives within reasonable distance of the hospital (usually <1 hour)

• Written and verbal discharge instructions given and understood
• Discharge medications dispensed with clear instructions
• Emergency contact numbers provided
• Follow-up appointment arranged (if needed)
• Patient aware of wound care and activity restrictions

• Uncontrolled pain
• Persistent nausea/vomiting
• Hemodynamic instability
• Active bleeding
• Inability to tolerate oral fluids
• No escort/carer available
• Procedure-specific: Spinal - must have passed urine; upper limb block - must have regained sensation/motor function

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33. Principles of Energized Surgical Dissection and Coagulation [5]

Types of Energy Sources

• Current passes from active electrode (surgical instrument) through patient's body to dispersive pad (grounding pad) and back to generator
• Cutting mode: High-frequency, continuous alternating current; rapid intracellular heating → cell vaporization; thin, precise cut
• Coagulation mode: Interrupted/damped waveform; lower frequency; slower cell desiccation → coagulum formation
• Blend mode: Combination
• Risks: Burns at incorrect return electrode site; interference with pacemakers; capacitive coupling in laparoscopic trocar sites; direct coupling
• Lateral thermal spread: 1-5 mm (varies by technique)

• Current flows between two tips of the instrument (e.g., bipolar forceps); does NOT pass through the patient's body
• Precise coagulation of small vessels; less lateral spread
• Safer near nerves and in confined spaces
• Limitation: Cannot cut; inferior hemostasis for large vessels

• LigaSure (Medtronic): Uses bipolar energy + mechanical pressure to fuse vessel walls by denaturing collagen and elastin; seals vessels up to 7 mm; minimal lateral thermal spread (2-3 mm); audible feedback when seal complete
• EnSeal (Johnson & Johnson): Similar tissue fusion; integrated cutting blade; self-limiting temperature
• Applications: Major vessel sealing; thyroidectomy, colectomy, hepatectomy

• Piezoelectric transducer converts electrical energy to mechanical vibration at 55,000 Hz (Harmonic; Ethicon)
• Blade vibrates longitudinally; denaturing proteins by vibration → "hydrogen bond cleavage"
• Temperature reached: 80-100°C (much lower than diathermy)
• Advantages:
  • No electrical current passes through patient
  • No smoke plume
  • Less lateral thermal damage (1-3 mm)
  • Simultaneous cut and coagulation
  • Safe near metallic clips, pacemakers, nerve monitoring
  • Less desiccation = less char
• Disadvantage: Fragile blade; slower for large vessels; still accumulates heat on blade

• Argon gas conducts monopolar current; creates plasma arc
• Superficial, broad-area hemostasis; ideal for parenchymal bleeding (liver, spleen)
• Very superficial char layer; minimal depth penetration
• Risk of gas embolism if used on raw vascular surface

• Light amplification by stimulated emission of radiation
• CO₂ laser: Precise tissue vaporization; used in gynecology, ENT, ophthalmology
• Nd:YAG: Deeper penetration; tumor coagulation/ablation
• KTP laser: Vascular lesions

Principles Governing Use

1. Minimum effective power setting - reduces collateral thermal injury
2. Short bursts - allows tissue to cool between applications
3. Dry tissue contact preferred for coagulation; moisture disperses current
4. Zone of thermal injury must be respected near bile ducts, ureters, bowel
5. Avoid touching metallic clips (arc → metal heats → burns adjacent structure)
6. Smoke evacuation in laparoscopy - electrosurgical smoke contains carcinogens
7. Pacemaker/ICD awareness: Use bipolar or ultrasonic; place grounding pad to minimize current path through device

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34. Vasodilatory Shock: Causes, Pathophysiology, Diagnosis, and Treatment [5]

Definition

Causes

1. Septic shock (most common) - gram-negative bacteria (LPS), gram-positive (exotoxins/PAMP), fungi, viruses
2. Anaphylaxis - IgE-mediated (drugs, foods, venom, latex)
3. Neurogenic shock - spinal cord injury (T6 and above); sympathetic denervation; bradycardia + vasodilation
4. Post-cardiac surgery vasoplegia - prolonged bypass; heparin; ACE inhibitor use
5. Drug-induced vasodilation - overdose of calcium channel blockers, beta-blockers, nitrates, phosphodiesterase inhibitors, phenothiazines
6. Adrenocortical insufficiency (Addisonian crisis) - relative lack of cortisol → loss of vasomotor tone
7. Toxic Shock Syndrome - exotoxin-mediated; TSST-1 (Staphylococcus aureus), streptococcal toxin
8. Systemic inflammatory conditions - SIRS, pancreatitis, burns (massive cytokine release)
9. Liver failure (hepatorenal syndrome)
10. Cyanide toxicity / carbon monoxide poisoning - histotoxic (not true vasodilatory but distributive features)

Pathophysiology

• LPS, PAMPs, DAMPs activate TLR4, TLR2 (pattern recognition receptors on endothelium, macrophages)

• NF-κB activation → TNF-α, IL-1β, IL-6, IL-8, PAF (platelet-activating factor)

• Cytokines (especially TNF-α, IL-1β) induce inducible NOS (iNOS) in vascular smooth muscle
• Massive, unregulated NO production → cGMP → smooth muscle relaxation → pathological vasodilation

• ↓ SVR → ↓ MAP
• Compensatory: ↑ HR, ↑ CO (early "warm" shock)
• Maldistribution: Some capillary beds perfused in excess; others ischemic (microvascular dysfunction)
• AV shunting: Blood bypasses capillary beds

• Excessive NO inhibits cytochrome c oxidase (Complex IV of respiratory chain)
• Cellular inability to utilize O₂ ("cytopathic hypoxia" or "histotoxic hypoxia")
• Lactate accumulates despite normal/high cardiac output

• Cytokines damage endothelium → ↑ capillary permeability → fluid extravasation → relative hypovolemia
• Glycocalyx destruction

• Kidneys: AKI (reduced afferent flow despite systemic vasodilation)
• Lungs: ARDS
• Gut: Mucosal ischemia → bacterial translocation → further sepsis
• Adrenal: Relative adrenal insufficiency (critical illness-related corticosteroid insufficiency - CIRCI)

Diagnosis

• Hemodynamic: SBP <90 mmHg or MAP <65 mmHg; tachycardia; wide pulse pressure
• Warm peripheries (initially - skin flushing, bounding pulse): Due to ↓SVR and ↑ skin perfusion (distinguishes from cardiogenic/hypovolaemic shock)
• Oliguria (<0.5 mL/kg/h)
• Confusion/altered consciousness
• Fever or hypothermia (in sepsis)

• Lactate >2 mmol/L (sepsis-3 criterion for septic shock)
• Metabolic lactic acidosis on ABG
• ↑ WBC or leucopenia; ↑ CRP; ↑ procalcitonin (sepsis)
• ↑ creatinine (AKI), ↑ bilirubin (liver dysfunction), ↑ troponin (myocardial injury)
• Blood, urine, sputum cultures (before antibiotics if possible)
• Coagulation screen (DIC if severe)

• ↓ SVR (<800 dyn·s·cm⁻⁵)
• ↑ or normal CO / cardiac index
• ↑ heart rate
• Low or normal CVP, low PCWP (before fluid loading)
• ECHO: Normal/hyperdynamic LV function (distinguishes from cardiogenic)

• Serum tryptase (elevated within 1-3 hours; confirms mast cell degranulation)
• Specific IgE testing after recovery

Treatment

• Septic shock: Source control (drain abscess, remove infected device, surgery for perforated viscus) + broad-spectrum antibiotics within 1 hour (Surviving Sepsis Campaign)
• Anaphylaxis: Remove allergen; epinephrine IM (0.5 mg, 1:1000)
• Drug overdose: Specific antidotes

• High-flow O₂; early intubation + mechanical ventilation if hemodynamically unstable or deteriorating

• Large-bore IV access; central line + arterial line (ICU)
• Crystalloid bolus: 30 mL/kg in first 3 hours (Surviving Sepsis) - but reassess frequently
• Balance: Avoid fluid overload (worsens ARDS and AKI)
• Target: MAP ≥65 mmHg, urine output >0.5 mL/kg/h, lactate clearance

• Norepinephrine (noradrenaline): First-line vasopressor; α1-agonist + β1 (to maintain CO); target MAP ≥65
• Vasopressin (ADH analog): Added as second agent when norepinephrine doses escalate (>0.25 mcg/kg/min); directly vasoconstricts via V1 receptors; bypasses NO pathway
• Epinephrine: Second-line; especially anaphylaxis
• Phenylephrine: Pure α1-agonist; useful in neurogenic shock (when ↑HR is undesirable)
• Methylene blue: Inhibits guanylyl cyclase → reduces cGMP → reduces NO-mediated vasodilation; rescue therapy for refractory vasoplegia (post-bypass, severe sepsis)
• Hydroxocobalamin: Scavenges NO; used in cyanide poisoning + refractory vasoplegia

• Dobutamine: β1+β2 agonist; adds inotropic support to norepinephrine when septic cardiomyopathy present

• Hydrocortisone 200 mg/day IV (in divided doses or continuous infusion)
• Indicated: Septic shock not responsive to fluids and vasopressors (CIRCI)
• Mechanism: Upregulates α1-adrenergic receptors; anti-inflammatory; supports adrenal axis
• Evidence: ADRENAL trial (2018) - hydrocortisone reduces vasopressor dependence and ICU stay but not 90-day mortality
• Anaphylaxis: High-dose hydrocortisone 200 mg IV to prevent biphasic reaction

• Cultures before antibiotics
• Broad-spectrum within 1 hour (beta-lactam ± aminoglycoside ± antifungal if at risk)
• De-escalate after 48-72 hours based on culture/sensitivity
• Surgical source control: Drainage, debridement, resection within 6-12 hours

• Renal: RRT (continuous hemofiltration/dialysis) for AKI with fluid overload or refractory acidosis
• Respiratory: Lung protective ventilation (tidal volume 6 mL/kg ideal body weight; plateau pressure <30 cmH₂O; PEEP individualized)
• Glycemic control: Target 6-10 mmol/L

• Epinephrine 0.5 mg IM (1:1000) - FIRST and most important
• H1 antihistamine (chlorphenamine 10 mg IV)
• H2 antihistamine (ranitidine)
• Hydrocortisone 200 mg IV
• IV fluid bolus (crystalloid 500-1000 mL)
• Bronchodilators (salbutamol nebulizer) if bronchospasm
• Patient observation ≥4 hours (biphasic reaction); ≥12 hours if severe

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