General Surgery Fundamentals

Definition

Inflammatory mediators are biologically active substances derived from host cells or plasma that initiate, amplify, regulate, and resolve the inflammatory response following injury, infection, or noxious stimuli.

Classification

A. Cell-Derived Mediators

1. Preformed (released immediately):

• Histamine — mast cells, basophils, platelets → vasodilation, ↑ permeability.
• Serotonin — platelets → vasoconstriction, platelet aggregation.
• Lysosomal enzymes — leukocyte granules → tissue destruction.

2. Synthesised de novo:

• Arachidonic acid metabolites:
  • Prostaglandins (PGE₂, PGI₂) → vasodilation, pain, fever.
  • Thromboxane A₂ → vasoconstriction, platelet aggregation.
  • Leukotrienes (LTB₄ = chemotaxis; LTC₄, LTD₄ = bronchospasm, permeability).
• Lipoxins → resolution of inflammation.
• PAF (Platelet Activating Factor) — vasodilation, chemotaxis, ↑ permeability.
• Nitric Oxide (NO) — vasodilation, cytotoxic.
• Chemokines — leukocyte migration.
• Cytokines — IL-1, TNF-α, IL-6, IL-8 (pro-inflammatory); IL-4, IL-10, TGF-β (anti-inflammatory).

B. Plasma-Derived Mediators

• Complement system — C3a, C4a (anaphylatoxins), C5a (chemotaxis), C3b (opsonisation).
• Kinin system — Bradykinin → vasodilation, pain, ↑ permeability.
• Coagulation & fibrinolytic system — thrombin, fibrin degradation products.

Role of Cytokines in Inflammation

Definition

An integrated neuroendocrine, inflammatory, and metabolic reaction to tissue injury, aiming to restore homeostasis and initiate repair. SIRS and CARS occur simultaneously — the balance between them determines outcome.

Sequence of Events

Neuroendocrine Activation

Rapid activation of the hypothalamic–pituitary–adrenal (HPA) axis and sympathetic nervous system:

• Cortisol — gluconeogenesis, protein catabolism, immune modulation.
• Adrenaline (epinephrine) — glycogenolysis, lipolysis, ↑ cardiac output.
• Glucagon — hepatic glucose release.
• Growth hormone (GH) — lipolysis, insulin antagonism, pro-inflammatory effect.
• Net metabolic effect: ↑ glucose, ↑ free fatty acids, ↑ amino acids for repair.

High-Yield Summary Table

Definition

The sum of molecular, structural, metabolic, and functional changes within cells following noxious stimuli, aiming to restore homeostasis, initiate repair, or — if injury is severe — lead to cell death.

I. Classical Cellular Adaptations (Reversible)

• Hypertrophy — ↑ cell size.
• Hyperplasia — ↑ cell number.
• Atrophy — ↓ size/function.
• Metaplasia — replacement by another cell type.

II. Reversible vs Irreversible Injury

III. Cell Death — Necrosis vs Apoptosis

IV. Modern Immuno-Metabolic Response

Initial Danger Signals: DAMPs (HMGB1, HSPs, ATP, uric acid) from damaged cells activate PRRs (TLRs, NLRs) → innate immunity.

Innate Immune Activation: Macrophages, neutrophils, dendritic cells, NK cells release IL-1, TNF-α, IL-6, IL-8, interferons.

Adaptive Immune Modulation: SIRS coexists with CARS. ↑ IL-10 and IL-6, ↓ HLA-DR on monocytes, T-cell apoptosis, lymphopenia, Tregs suppress APCs and CD8&spplus; cells.

Metabolic reprioritisation: Skeletal muscle breakdown via ubiquitin–proteasome pathway → amino acids for acute-phase proteins; liver ↑ fibrinogen, CRP; peripheral insulin resistance → hyperglycaemia.

Definition & Historical Context

A non-specific, generalised inflammatory state affecting the whole body, triggered by infectious or non-infectious insults, diagnosed when ≥2 of 4 clinical criteria are met (ACCP/SCCM Consensus, Bone et al., 1992).

Diagnostic Criteria (≥2 required)

Aetiology

Infectious: bacterial (esp. Gram-negative), viral, fungal, parasitic.

Non-infectious: major trauma, burns, acute pancreatitis, ischaemia–reperfusion injury, massive transfusion, severe allergic reaction, autoimmune disorders.

Pathophysiology & Mediators

• Trigger: DAMPs (tissue injury) or PAMPs (microbes) recognised by PRRs.
• Cytokine release: TNF-α, IL-1, IL-6, IL-8 → cytokine storm.
• Endothelial activation → ↑ permeability, leukocyte extravasation, microvascular thrombosis.
• Systemic effects: ↓ SVR, ↑ cardiac index (hyperdynamic phase), pulmonary oedema, neuronal injury.
• Genomic storm: 3,700 leukocyte genes altered after endotoxin; 80% of leukocyte genome altered in 28 days after severe trauma.

Relationship with CARS & Clinical Progression

• SIRS — overactivation of innate immunity.
• CARS — suppression of adaptive immunity.
• Both occur simultaneously, not sequentially.
• Excess CARS → immunoparalysis → secondary infections, poor healing, MODS.

Progression: SIRS → Sepsis (if infection) → Severe Sepsis → Septic Shock → MODS.

Management

1. Treat underlying cause — infection: source control + antibiotics; non-infectious: condition-specific.
2. Supportive care — airway, oxygenation, ventilatory support; fluid resuscitation; vasopressors; temperature and glucose control; early enteral nutrition.
3. Prevent complications — DVT prophylaxis, stress ulcer prophylaxis, early mobilisation.

Definition

An acquired clinicopathological syndrome characterised by widespread activation of the coagulation cascade, leading to intravascular fibrin deposition and microvascular thrombosis, with subsequent consumption of platelets and coagulation factors, resulting in a bleeding tendency. DIC is always secondary to an underlying disorder.

Pathophysiology

1. Trigger — tissue factor release (trauma, endotoxin, tumour) → endothelial injury.
2. Coagulation activation — extrinsic pathway (TF–VIIa) → massive thrombin generation → fibrin clots throughout microvasculature.
3. Microvascular thrombosis — multi-organ ischaemia (MODS).
4. Consumption coagulopathy — platelets and clotting factors depleted.
5. Bleeding tendency — fibrinolytic system activated → ↑ FDPs → inhibit further coagulation.

Causes

• Sepsis — most common (especially Gram-negative).
• Severe trauma, burns.
• Malignancy — acute promyelocytic leukaemia, adenocarcinoma.
• Obstetric — abruptio placentae, amniotic fluid embolism, retained dead fetus.
• Massive transfusion reactions; liver failure.

Clinical Features

Thrombotic: Organ dysfunction (renal failure, respiratory distress, altered sensorium), skin necrosis, acral ischaemia.

Bleeding: Oozing from venepuncture/wound sites (classic), purpura, ecchymoses, mucosal bleeding, GI/GU haemorrhage.

Investigations

No single test is diagnostic — diagnosis is clinical + combined lab evidence.

Scoring: ISTH DIC Scoring System (≥5 = overt DIC).

Management

Definition

A severe form of acute lung injury characterised by non-cardiogenic pulmonary oedema and refractory hypoxaemia, resulting from diffuse alveolar damage.

Etiology

Direct lung injury: Aspiration, pneumonia, lung trauma, inhalational injury, near-drowning.

Indirect (systemic): Sepsis (most common), trauma, pancreatitis, burns, massive transfusion, fat embolism.

Pathophysiology

• Inflammation at alveoli → alveolar-capillary membrane damage.
• ↑ Permeability → protein-rich alveolar oedema.
• ↓ Surfactant activity → alveolar collapse (atelectasis).
• ↓ Lung compliance, ↓ gas exchange → hypoxaemia.
• Three phases: Exudative (0–7 days) → Proliferative (7–21 days) → Fibrotic (>21 days).

Berlin Definition & Severity Classification

Berlin Criteria (all 4 must be present):

1. Timing — within 1 week of known insult or new/worsening respiratory symptoms.
2. Imaging — bilateral opacities on CXR or CT not fully explained by effusions, collapse, or nodules.
3. Origin — respiratory failure not fully explained by cardiac failure or fluid overload.
4. Oxygenation — PaO₂/FiO₂ ratio with PEEP ≥5 cmH₂O.

Management

ARDSNet Ventilation Strategy:

1. Low tidal volume: 6 mL/kg IBW.
2. Plateau pressure: ≤30 cmH₂O.
3. PEEP: 10–12 cmH₂O (adjust as needed).
4. Sedation / neuromuscular blockade to improve compliance.
5. Prone positioning — improves oxygenation in severe ARDS.
6. If refractory: consider ECMO.

Supportive care: Treat underlying cause; conservative fluid management; nutritional support; avoid high FiO₂ and barotrauma.

Prognosis: Mortality 30–40%; better with early detection and lung-protective ventilation.

Definition

Acute Physiology and Chronic Health Evaluation II — introduced in 1985 to quantify disease severity in ICU patients and predict hospital mortality. Uses acute physiological variables, age, and chronic health status. Widely used for ICU audit, research, and outcome prediction.

APACHE II Score = Acute Physiology Score (APS) + Age Points + Chronic Health Points

1. Acute Physiology Score (APS) — worst values in first 24 h

2. Age Points & 3. Chronic Health

Chronic Health: +5 pts for nonoperative/emergency postoperative patients with severe organ insufficiency or immunosuppression; +2 pts for elective postoperative.

Mortality Prediction

Limitations: Requires accurate data within 24 h; not applicable in burns or coronary care; predicts group outcomes better than individual outcomes; not for individual treatment decisions.

Definition

A standardised system to grade the severity of postoperative complications based on the type of therapy required to correct them. Proposed by Clavien et al. (1992), revised by Dindo et al. (2004).

Core Principle: Severity = intervention required to correct the complication, not the complication itself.

Suffix “d” added if patient remains disabled at discharge (e.g. stroke → Grade IVa-d). Highest grade per patient = overall morbidity score.

Definition

Performance status scales quantify a patient's functional capacity. They correlate with survival and tolerance to therapy, and guide perioperative risk assessment and eligibility for systemic treatment.

ECOG Performance Status Scale

Karnofsky Performance Status (Selected Values)

Definitions (Sepsis-3, 2016)

• Sepsis — suspected/confirmed infection + acute organ dysfunction (↑ SOFA score ≥2).
• Septic Shock — sepsis + persistent hypotension requiring vasopressors to maintain MAP ≥65 mmHg + serum lactate >2 mmol/L after adequate fluid resuscitation.

First-Hour Bundle

1. Recognise sepsis (qSOFA/SOFA where appropriate).
2. Measure lactate immediately; repeat if elevated.
3. Obtain blood cultures before antibiotics — if this does not delay therapy.
4. Broad-spectrum antibiotics ≤1 hour for septic shock or high likelihood.
5. ~30 mL/kg IV crystalloids for sepsis-induced hypoperfusion within 3 h; reassess with dynamic measures.
6. Vasopressors if hypotension persists → norepinephrine first-line, target MAP ≥65 mmHg.
7. Source control as soon as feasible.

Key Targeted Recommendations

Definition

A structured tool introduced by WHO (2008) as part of the Safe Surgery Saves Lives campaign. Reduces surgical morbidity and mortality by ensuring adherence to essential perioperative safety practices.

Evidence of Impact

• Reduces perioperative mortality by up to 47%.
• Decreases complication rates by 36%.
• Improves team communication, cohesion, and accountability.

Definition

Temperature >38.5°C on ≥2 occasions at least 4 hours apart after surgery. Temporal pattern of onset is the key to diagnosis.

Differential Diagnosis — The “5 Ws”

Management

• Atelectasis: Chest physiotherapy, incentive spirometry, early ambulation.
• UTI: Remove/replace catheter, antibiotics per culture.
• Wound infection: Drain pus, wound care, antibiotics.
• DVT/PE: Anticoagulation (LMWH), compression stockings.
• Drug fever: Withdraw offending agent.

Definition

Temporary impairment of bowel motility after abdominal or other major surgery, in the absence of mechanical obstruction.

Normal Gut Motility Recovery

Pathophysiology

• Neurogenic inhibition: Peritoneal handling → activation of inhibitory spinal reflexes.
• Inflammatory: Macrophage activation in intestinal muscularis releases NO, prostaglandins, cytokines → smooth muscle suppression.
• Pharmacological: Opioids activate µ-opioid receptors in enteric nervous system → ↓ acetylcholine → ↓ peristalsis.

Prevention & Management

• Early enteral nutrition within 24 h.
• Multimodal opioid-sparing analgesia (NSAIDs, paracetamol, epidural, TAP blocks).
• Early mobilisation (POD 0–1).
• Minimally invasive surgery preferred.
• Avoid routine NG tubes and drains.
• Correct electrolytes (K&spplus;, Mg²&spplus;).
• Alvimopan — peripherally acting µ-opioid receptor antagonist; licensed for post-colectomy ileus.

Definition

Enhanced Recovery After Surgery (ERAS) is a multimodal, evidence-based perioperative care pathway designed to minimise surgical stress response, accelerate recovery, and reduce hospital stay without increasing readmission rates.

Outcomes: ↓ LOS by 2–4 days; ↓ complications (ileus, infections, pulmonary); no ↑ in readmission rates; cost-effective. ERAS Society Guidelines 2022 (colorectal) — >20 evidence-based recommendations.

Types of Ventilatory Support

Key Ventilator Settings

Weaning: FiO₂ ≤0.4, SpO₂ ≥92%, PF ratio >150–200, PEEP ≤5–8, haemodynamic stability, adequate spontaneous effort → Spontaneous Breathing Trial (SBT) 30–120 min → extubate if successful.

Definition

Intermittent inhalation of 100% oxygen at a pressure >1 ATA (usually 2–3 ATA) inside a pressurised chamber. Results in supraphysiological oxygen delivery by increasing dissolved O₂ in plasma (Henry's law).

Mechanisms of Action

Surgical Indications

• Diabetic foot ulcers (refractory to standard care)
• Osteoradionecrosis (Marx protocol)
• Necrotising soft tissue infections — adjunct to debridement + antibiotics
• Compromised skin flaps and grafts
• Chronic osteomyelitis (refractory)
• Carbon monoxide poisoning; gas gangrene

Protocol: 2–3 ATA; 60–120 min/session; 20–40 sessions for chronic conditions.

Four-Zone Layout (Least to Most Sterile)

Key OT Features

• Laminar airflow: Positive pressure with HEPA filtration; ≥20 air changes/hour.
• Temperature: 18–22°C; humidity 50–60%.
• Lighting: Shadowless; 100,000 lux at operative field.
• Flooring: Anti-static, seamless.
• Traffic flow: Unidirectional — clean to dirty; no cross-traffic.
• Doors: Sliding (reduces turbulence); kept closed during surgery.

Practical Protocol — Elective Left-Sided Colorectal Surgery

1. Low-residue diet 2–3 days before surgery.
2. Day before: PEG solution until clear effluent; Neomycin 1 g + Metronidazole 1 g at 1 PM, 2 PM, 11 PM.
3. Day of surgery: IV antibiotic prophylaxis 30–60 min before incision; clear fluids up to 2 h before anaesthesia (ERAS).

Normal Values

pH 7.35–7.45  |  PaCO₂ 35–45 mmHg  |  HCO₃⁻ 22–26 mmol/L  |  Base Excess ±2 mmol/L. Compensation never fully normalises pH.

Anion Gap in Metabolic Acidosis

AG = Na&spplus; − (Cl⁻ + HCO₃⁻). Normal = 8–12 mEq/L.

Definition

Infections developing ≥48 hours after hospital admission, not incubating at time of admission, or within 30 days of an operative procedure. (Bailey & Love, 28th ed.)

Occur in 5–10% of hospitalised patients; up to 30% in ICU. Most common sites: urinary tract > surgical wound > respiratory tract > bloodstream.

Prevention — “SHE IS CLEAN”

Definition

Staphylococcus aureus resistant to all β-lactam antibiotics via mecA gene → encodes PBP2a with low affinity for β-lactams. HA-MRSA = multidrug resistant (ICU, burns, postoperative). CA-MRSA = more virulent, less resistant; “spider-bite” lesions characteristic.

Treatment

Investigations: Culture + cefoxitin disc test; PCR for mecA gene = gold standard (same-day result).

Recent advances: Ceftaroline, ceftobiprole (anti-MRSA β-lactams); dalbavancin, oritavancin (long-acting lipoglycopeptides).

Definition & Classification

Infection at or near a surgical incision within 30 days (or 1 year if implant used) related to the surgery. Accounts for 20–30% of all HAIs.

• Superficial: Skin/subcutis
• Deep: Fascia/muscle
• Organ-space: Cavity or organ operated upon

Wound Classification & SSI Rates

Antibiotic Prophylaxis Principles

Management

Golden rule: Pus = Drain it. Remove sutures/clips → drain pus → debride necrotic tissue → antibiotics (empirical then per culture) → delayed primary closure (3–5 days) or secondary intention.

Definition

Pneumonia occurring ≥48 hours after endotracheal intubation. Most common HAI in ICU; mortality 30–50%. Pathogenesis: aspiration of oropharyngeal secretions around ETT cuff → lower respiratory tract inoculation.

Common organisms: Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, MRSA.

VAP Prevention Bundle

Treatment: Empirical carbapenem or pip-tazo + MRSA cover; de-escalate per BAL culture (≥10⁴ CFU/mL); 7–8 day course.

Risk of Transmission to Surgeon

HBV ~6–30% (without vaccination); HCV ~1.8%. Risk increases with: deep injury, visible blood on device, device used in artery/vein, high source viral load.

PEP Protocol

1. Wash wound with soap and water immediately. Do not suck. Irrigate mucous membranes with saline/water.
2. Report to occupational health immediately.
3. Assess exposure — type of injury; source HIV status.
4. Start PEP within 2 hours (max 72 hrs).
5. 3-drug ART for 28 days: Tenofovir + Lamivudine (or Emtricitabine) + Dolutegravir.
6. Baseline serology: HIV, HBV, HCV — both surgeon and source patient.
7. Follow-up HIV testing at 6 weeks, 3 months, 6 months.

Ethical Aspects