TRANSPLANTATION - Comprehensive Exam Notes

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1. APNEA TEST FOR DIAGNOSING BRAIN DEATH [5 marks]

Definition of Brain Death

Prerequisites Before Apnea Testing

1. Depressant drugs - narcotics, hypnotics, benzodiazepines must have been excluded
2. Primary hypothermia must be excluded (core temperature >36°C)
3. Metabolic/endocrine disturbances - no profound abnormality of electrolytes, acid-base, blood glucose
4. Neuromuscular blocking drugs - excluded by eliciting spinal reflexes or nerve stimulator
5. The condition must be due to irremediable structural brain damage

Clinical Tests for Brainstem Death (all must be absent)

• Pupils fixed and non-reactive to light
• No corneal reflex
• Vestibulo-ocular reflexes absent (no eye movement with 20 mL ice-cold water in each external meatus - caloric test)
• No motor response within cranial nerve distribution to somatic stimulation
• No gag reflex or response to bronchial suction
• No respiratory effort on ventilator disconnect = the Apnea Test

Apnea Test - Step by Step

1. Pre-oxygenate with 100% O2 for 10 minutes
2. Ensure baseline PaCO2 is 40-45 mmHg (normocarbia); adjust ventilator to target PaCO2 of 5.3-6.0 kPa (40-45 mmHg) as starting point
3. Disconnect ventilator - deliver 100% O2 via catheter at 6 L/min to prevent hypoxia
4. Observe closely for any respiratory effort (diaphragmatic or chest movements) for 8-10 minutes
5. Draw ABG at end of test
6. Apnea confirmed if no respiratory effort with PaCO2 ≥ 6.7 kPa (50 mmHg) - above the threshold that should stimulate respiration
7. CO2 rises at ~0.3-0.4 kPa/min (2-3 mmHg/min) during apnea

Stopping the Test

• Stop if cardiovascular instability occurs (SpO2 <85%, arrhythmia, hypotension)
• In such cases, use ancillary/confirmatory tests

Ancillary Confirmatory Tests (optional)

• EEG: isoelectric (electrocerebral silence)
• Radionuclide brain scanning: absence of cerebral blood flow
• Cerebral angiography: no intracranial filling
• Transcranial Doppler: absence of flow

Who Performs and How Many Times

• Two doctors (consultants) must independently confirm brain death
• At least one must be a neurologist/neurosurgeon; neither should be part of a transplant team
• Tests repeated after an appropriate interval

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2. TYPES OF ORGAN TRANSPLANT

By Source of Graft (Type of Donor)

By Type of Donor

• Living donor: Related (living related donor - LRD) or unrelated (living unrelated donor - LURD)
• Deceased donor (Brain Death Donor / DBD): Donation after Brain Death
• Donation after Circulatory Death (DCD): formerly called non-heart-beating donor

By Anatomical Position of Graft

• Orthotopic: Graft placed in same anatomical site (liver transplant - native liver removed and replaced)
• Heterotopic: Graft placed in a different site (kidney transplant in iliac fossa)
• Auxiliary: Native organ kept, graft added alongside (auxiliary liver transplant)

By Organ

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3. WARM AND COLD ISCHEMIC TIME [5 marks]

Between Donor Nephrectomy and Reperfusion - Three Time Periods

(A) First Warm Ischemia Time (Donor WIT / Extraction Time)

• Period from aortic cross-clamping or cardiac arrest to establishment of cold preservation
• This is the most damaging period
• For DBD donors: begins at cross-clamp
• For DCD donors: begins at cardiac arrest (withdrawal of life support)
• Acceptable: < 30 minutes for DBD; < 15-20 minutes for DCD kidneys

(B) Cold Ischemia Time (CIT)

• Period the organ spends in cold preservation solution (0-4°C); sandwiched between the two warm ischemia periods
• Begins when cold flush is established (organ flushed with cold preservative - e.g., UW solution, HTK solution)
• Ends when organ is removed from cold storage
• Organs slow down all metabolic activity at low temperature (reducing but not eliminating ischemic injury)
• Acceptable CIT limits (approximate):
  • Kidney: up to 24-36 hours (optimal <12 hours)
  • Liver: 8-12 hours (optimal <8 hours; >8 hours is associated with decreased graft survival)
  • Heart: 4-6 hours
  • Lung: 6-8 hours
  • Pancreas: 12-18 hours

(C) Second Warm Ischemia Time (Graft WIT / Implantation WIT)

• Period from removal of organ from cold storage to reperfusion in the recipient
• Begins when organ removed from ice at back-table (or disconnected from machine perfusion)
• Ends when arterial clamp released and reperfusion occurs
• Implantation WIT in kidney transplant should be < 30-45 minutes

Consequences of Prolonged Ischemia

• Delayed Graft Function (DGF): need for dialysis in first post-transplant week - commonest consequence of prolonged ischemia
• Primary Non-Function (PNF): irreversible graft non-function
• Ischemia-reperfusion injury: cell swelling, free radical generation, complement activation
• Increased risk of acute rejection (due to increased immunogenicity)
• Reduced long-term graft survival

Organ Preservation Solutions

• University of Wisconsin (UW) Solution: gold standard - contains lactobionate, raffinose, hydroxyethyl starch
• Histidine-Tryptophan-Ketoglutarate (HTK): low viscosity, used for flush
• Custodiol: another HTK-based solution

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4. RENAL TRANSPLANTATION - Indications, Patient Selection, Donor and Recipient Surgery [3+2+5]

Indications for Renal Transplantation

• Diabetic nephropathy (most common in Western countries)
• Hypertensive nephrosclerosis
• Chronic glomerulonephritis (IgA nephropathy, FSGS, membranous GN)
• Polycystic kidney disease (ADPKD)
• Reflux nephropathy / chronic pyelonephritis
• Lupus nephritis / SLE
• Alport syndrome
• Renal tubular disorders

Absolute Contraindications

• Active malignancy (except non-melanoma skin cancer, adequately treated cancer with appropriate disease-free interval)
• Active untreated infection (tuberculosis, HIV not well controlled)
• Active substance abuse
• Severe uncontrollable psychiatric disease
• Irreversible major organ dysfunction (severe cardiac disease, severe COPD)
• Patient non-compliance
• Short life expectancy (<1-2 years from non-renal cause)
• Active vasculitis or recent MI (relative)

Patient Selection / Pre-Transplant Evaluation

• Full history, examination
• Cardiac: ECG, echocardiography, stress testing (especially diabetics)
• Pulmonary: PFTs if indicated
• Malignancy screening: colonoscopy, mammography, PAP smear, PSA
• Infection screening: HIV, hepatitis B/C, CMV, EBV, TB (Mantoux), syphilis
• Urological: bladder capacity and voiding dynamics (urodynamics), voiding cystourethrogram if lower urinary tract abnormality suspected; ensure bladder is adequate for anastomosis

• Blood group (ABO compatibility mandatory)
• HLA typing (A, B, DR)
• Panel Reactive Antibody (PRA) - measures pre-formed antibodies
• Cross-match (donor-specific - mix recipient serum with donor lymphocytes)
• A negative cross-match is essential before transplant

• Peripheral vascular assessment (iliac vessels - Doppler, CT angiography)
• Exclude severe aorto-iliac disease that would preclude anastomosis

Surgery - Living Donor Nephrectomy

• Left kidney preferred (longer renal vein) unless right kidney needed for special reasons
• Hand-port in iliac fossa; ports in flank
• Vascular control: renal artery and vein clipped; ureter divided with surrounding periureteral fat preserved (to protect blood supply)
• Kidney extracted intact, immediately flushed with cold UW or HTK solution on back-table
• Donor stays one night; low morbidity

Surgery - Recipient (Heterotopic Renal Transplant)

1. Expose external iliac artery and vein (retroperitoneal dissection)
2. Venous anastomosis first: End-to-side anastomosis of renal vein to external iliac vein (or IVC if needed)
3. Arterial anastomosis: End-to-side anastomosis of renal artery (on Carrel patch if deceased donor) to external iliac artery; or end-to-end to internal iliac artery
4. Reperfusion: Release clamps - kidney reperfuses and usually turns pink immediately; brisk urine output expected
5. Ureteric anastomosis (ureteroneocystostomy): Modified Lich-Gregoir extravesical technique; double-J ureteric stent placed routinely
6. Native kidneys are NOT removed unless they cause problems (hypertension, recurrent UTI, polycythemia)
7. Wound closure in layers

• Hourly urine output
• CVP monitoring (keep well hydrated)
• Renal function (serum creatinine, urea) - should halve each day in well-functioning graft
• Doppler ultrasound on day 1 (assess blood flow)
• Immunosuppression: calcineurin inhibitor (tacrolimus/cyclosporine) + mycophenolate + prednisolone ± induction agent

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5. LIVER TRANSPLANTATION - Indications, Contraindications, Extended Donor Criteria [3+3+4]

Indications for Liver Transplantation

• Noncholestatic cirrhosis:
  • Alcoholic liver disease (~39% of all listings in USA) - requires sobriety criterion
  • Metabolic-associated steatohepatitis (MASH/NASH cirrhosis) - growing rapidly
  • Hepatitis C cirrhosis (reduced by DAA therapy, still listed)
  • Hepatitis B cirrhosis
  • Autoimmune hepatitis cirrhosis
  • Cryptogenic cirrhosis
  • Drug-induced cirrhosis
• Cholestatic cirrhosis:
  • Primary biliary cholangitis (PBC)
  • Primary sclerosing cholangitis (PSC) - complications of portal hypertension, recurrent cholangitis
  • Caroli disease, biliary atresia (pediatric)
  • Choledochal cyst

• Acetaminophen overdose (most common cause of ALF)
• Hepatitis B (fulminant)
• Drug-induced (non-acetaminophen)
• Wilson disease (acute decompensation)
• Autoimmune hepatitis
• Indeterminate ALF
• King's College Criteria used for listing:
  • Acetaminophen: arterial pH <7.3 after resuscitation; OR all three: PT >100 seconds + creatinine >300 umol/L + grade III-IV encephalopathy
  • Non-acetaminophen: PT >100 seconds alone; OR any three of: age <10 or >40 years, etiology (non-A non-B hepatitis, drug), jaundice >7 days before encephalopathy, PT >50 seconds, bilirubin >300 umol/L

• Milan Criteria (standard): 1 lesion ≤5 cm; or up to 3 lesions each ≤3 cm; no vascular invasion; no extrahepatic disease
• UCSF Criteria (extended): 1 lesion ≤6.5 cm; or up to 3 lesions largest ≤4.5 cm, total ≤8 cm
• Neoadjuvant therapy (TACE, ablation) used as bridge to transplant

• Wilson disease
• Hemochromatosis
• Alpha-1 antitrypsin deficiency
• Glycogen storage disease
• Familial amyloid polyneuropathy (neurological disease, liver is source of abnormal TTR protein)
• Primary hyperoxaluria type 1

• Hepatopulmonary syndrome (exception points for MELD)
• Portopulmonary hypertension (if mean PAP <35 mmHg with treatment)
• Budd-Chiari syndrome
• Hilar cholangiocarcinoma (selected cases, with neoadjuvant chemoradiation)

Contraindications to Liver Transplantation

1. Active extrahepatic malignancy (cancer outside liver not amenable to curative treatment)
2. Cholangiocarcinoma outside accepted protocols (intrahepatic CCA, perihilar CCA without neoadjuvant protocol)
3. Active uncontrolled sepsis or systemic infection
4. Active substance abuse (active alcohol/drug use without commitment to sobriety)
5. Severe cardiopulmonary disease incompatible with surgery (severe COPD, severe irreversible pulmonary hypertension mPAP >50 mmHg)
6. AIDS (not HIV alone - AIDS-defining illness with poor prognosis)
7. Anatomical impossibility of transplant (complete portal/hepatic vein thrombosis without options for reconstruction)
8. Non-compliance/inability to comply with post-transplant management

1. Age >70 years (case by case)
2. Portal vein thrombosis (technical challenge, not absolute)
3. Prior complex hepatobiliary surgery
4. Obesity (BMI >40)
5. Renal failure requiring dialysis (combined liver-kidney transplant now considered)
6. HIV infection (HIV alone - now successfully transplanted in many centers)
7. HCC outside Milan criteria (can be bridged, downsized)
8. Psychiatric illness (if treatable)
9. Marginal cardiac/pulmonary reserve
10. Portopulmonary hypertension if mPAP 35-50 mmHg (medically manage first)

Extended Donor Criteria (EDC) for Liver Transplant

1. Age > 60-65 years: Higher rates of PNF and initial poor function; acceptable in stable non-urgent recipients
2. Donation after Circulatory Death (DCD): Additional warm ischemia time incurred; higher rates of ischemic cholangiopathy ("biliary cast syndrome"), PNF, and DGF; used selectively
3. Macrovesicular steatosis:
   • <30%: acceptable
   • 30-60%: relative contraindication, selective use

   • 60%: near-absolute contraindication (high PNF risk); biopsy assessment mandatory

4. Prolonged cold ischemia time (>12 hours): Avoid in DCD, elderly, or fatty livers
5. Hypernatremia (Na >155 mmol/L): Correct before procurement; associated with worse outcome
6. Split liver grafts: Left lateral segment (segments II/III) for pediatric recipient; right lobe (segments V-VIII) for adult; requires expert hepatobiliary team
7. Living donor liver transplant (LDLT): Right lobe (65% of liver volume) for adult-to-adult; requires donor remnant >30% estimated liver volume; donor risk of major complications 0.5%, mortality 0.1-0.5%
8. Hepatitis C positive donor: Previously contraindicated; now successfully transplanted with post-transplant DAA therapy
9. Hepatitis B core antibody positive (anti-HBc+): Acceptable with prophylaxis (HBIG + antiviral); risk of de novo HBV in recipient
10. Marginal hemodynamics: Liver from donor with cardiac arrest history or prolonged hypotension - assess by functional tests, perfusion

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6. GRAFT VERSUS HOST DISEASE (GvHD) [5 marks]

Definition

Conditions Required (Billingham's Criteria, 1966)

1. Graft must contain immunologically competent cells (T lymphocytes)
2. Recipient must be immunologically unable to reject the graft (immunocompromised)
3. Recipient must express antigens absent from the donor (HLA mismatch)

Occurs in

• Bone marrow / hematopoietic stem cell transplant (HSCT) - most common and important
• Transfusion of non-irradiated blood products to immunocompromised patients
• Solid organ transplants containing significant lymphoid tissue (liver, small bowel)
• Thymus transplantation

Classification

Acute GvHD (within 100 days of transplant)

• Target organs: Skin, liver, gastrointestinal tract
• Clinical features:
  • Skin: maculopapular rash (palms, soles, ears), erythroderma, blistering
  • GI: watery/bloody diarrhea (>1 L/day), nausea, vomiting, abdominal cramping
  • Liver: cholestatic jaundice, elevated bilirubin and alkaline phosphatase

• Grade I: Skin only, mild
• Grade II: Skin + mild liver/gut involvement
• Grade III: Severe skin + moderate gut/liver
• Grade IV: Life-threatening, severe multiorgan

Chronic GvHD (after 100 days)

• Resembles autoimmune disorders (Sjogren syndrome, scleroderma, lichen planus)
• Organs: Skin (lichenoid changes, sclerosis), eyes (keratoconjunctivitis sicca), mouth (sicca syndrome, ulceration), liver (cholestasis), lungs (bronchiolitis obliterans), musculoskeletal (fasciitis, myositis)
• Can occur de novo or evolve from acute GvHD

Pathophysiology

• Donor T cells recognize recipient MHC + peptides via direct or indirect allorecognition
• IL-2, IFN-gamma, TNF-alpha drive inflammatory cascade
• Cytokine storm damages epithelial targets

Prevention

• HLA-matched donor selection (10/10 HLA match)
• T-cell depletion of graft (ex vivo purging)
• Immunosuppressive prophylaxis: Methotrexate + cyclosporine (or tacrolimus); mycophenolate
• Irradiation of blood products (to prevent transfusion-associated GvHD)

Treatment

• Acute GvHD: High-dose methylprednisolone (1-2 mg/kg/day) is first-line; second-line: anti-TNF (infliximab), extracorporeal photopheresis, ruxolitinib (JAK inhibitor - now approved)
• Chronic GvHD: Prolonged immunosuppression (steroids ± sirolimus); supportive care; ruxolitinib for steroid-refractory cGvHD

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7. GRAFT REJECTION - Types and Immunological Basis [5+5 marks]

Immunological Basis of Allograft Rejection

1. Direct pathway: Recipient T cells recognize intact donor MHC on donor APCs (dendritic cells)
   • Major mechanism for acute rejection
   • Very potent; many T-cell clones involved
2. Indirect pathway: Recipient T cells recognize processed donor peptides presented on SELF MHC by recipient APCs
   • More important in chronic rejection
   • Slower, more sustained

• Signal 1: TCR + Antigen (MHC-peptide) - recognized by tacrolimus/cyclosporine
• Signal 2: Costimulatory signal (B7-CD28 interaction) - recognized by belatacept (CTLA4-Ig)
• Signal 3: Cytokine-driven proliferation (IL-2) - recognized by mTOR inhibitors (sirolimus, everolimus) and anti-IL-2R (basiliximab)

• B cells produce donor-specific antibodies (DSA) against HLA antigens
• Antibody-mediated rejection (AMR) is increasingly recognized as distinct entity
• Complement activation (C4d deposition) is marker of AMR

Types of Graft Rejection

• Grade I: Tubulitis ± interstitial infiltrate
• Grade II: Arteritis (intimal)
• Grade III: Transmural arteritis/fibrinoid necrosis

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8. IMMUNOSUPPRESSION IN TRANSPLANTATION [5 marks]

Goals

• Prevent rejection
• Minimize drug toxicity
• Avoid over-immunosuppression (infection, malignancy)

Classification and Drugs

A. Induction Agents (peri-operative)

1. Anti-thymocyte globulin (ATG, Thymoglobulin): Polyclonal antibody depleting T cells; potent, non-specific; risk = cytokine release syndrome, over-immunosuppression
2. Basiliximab (Simulect): Monoclonal anti-IL-2 receptor (CD25) antibody; blocks T-cell proliferation; less immunosuppressive; fewer side effects
3. Alemtuzumab (Campath): Anti-CD52; depletes all lymphocytes; very potent

B. Maintenance Immunosuppression (triple therapy standard)

• Cyclosporine: Binds cyclophilin → inhibits calcineurin → blocks IL-2 gene transcription → prevents T-cell activation. Side effects: nephrotoxicity (dose-dependent), hypertension, hirsutism, gingival hyperplasia, neurotoxicity, PTDM (post-transplant diabetes mellitus). Narrow therapeutic window; trough levels monitored.
• Tacrolimus (FK506): Binds FKBP12 → same mechanism; 100x more potent. Preferred over cyclosporine (>90% liver transplants). Side effects: nephrotoxicity, neurotoxicity, PTDM (more than CSA), alopecia, GI upset. No gingival hyperplasia/hirsutism.

• Mycophenolate Mofetil (MMF): Inhibits inosine monophosphate dehydrogenase → blocks de novo purine synthesis → prevents lymphocyte proliferation. Side effects: GI (diarrhea, nausea), leukopenia, teratogenic.
• Azathioprine (older, still used): Pro-drug of 6-mercaptopurine; inhibits purine synthesis. Side effects: myelosuppression, hepatotoxicity.

• Sirolimus (Rapamycin): Binds FKBP12 → inhibits mTOR → blocks IL-2-driven lymphocyte proliferation (Signal 3). Side effects: hyperlipidemia, impaired wound healing, proteinuria, interstitial pneumonitis. CNI-sparing. Anti-tumor properties useful in HCC recipients.
• Everolimus: Similar to sirolimus; shorter half-life.

• Prednisolone/Methylprednisolone: Inhibit cytokine gene transcription (IL-1, IL-2, TNF-alpha), reduce T-cell migration, anti-inflammatory. Used for maintenance and treatment of acute rejection (pulse therapy). Side effects: DM, hypertension, osteoporosis, Cushingoid, cataracts, peptic ulcer, growth retardation in children.

• Belatacept: CTLA4-Ig fusion protein; blocks B7-CD28 signal 2; IV monthly; approved for kidney transplant; better renal function but higher acute rejection risk vs CNIs.

C. Treatment of Acute Rejection

• Cellular: IV methylprednisolone pulse (3 days); ATG for steroid-resistant
• Antibody-mediated: Plasmapheresis + IVIG + rituximab (anti-CD20) + eculizumab

Triple Therapy Standard Regimen

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9. DONATION AFTER CIRCULATORY DEATH (DCD) [5 marks]

Definition

Maastricht Classification

Warm Ischemia Time in DCD

• Functional warm ischemia begins when systolic BP drops <50 mmHg or SpO2 <70% (functional agonal phase)
• Total warm ischemia = agonal phase + no-touch period (5 min) + time to cold perfusion
• Acceptable total functional WIT for DCD: kidney <30 min, liver <15 min

Considerations

• Higher rates of Delayed Graft Function (DGF) in kidneys (2-3x vs DBD)
• Higher risk of ischemic cholangiopathy (biliary cast syndrome) in DCD liver grafts due to dual blood supply damage
• DCD kidneys: excellent long-term outcomes; preferred over dialysis
• Normothermic regional perfusion (NRP): re-perfuse abdominal organs in situ after death declaration to reduce ischemic injury - increasingly used
• Machine perfusion (hypothermic or normothermic) used to assess and recondition DCD organs

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10. LIVING DONOR vs DECEASED DONOR KIDNEY TRANSPLANTATION [5 marks]

• Single kidney
• Significant proteinuria (>500 mg/day)
• GFR <80 mL/min (or reduced eGFR)
• Diabetes mellitus
• Hypertension requiring >1 medication (or uncontrolled)
• Active malignancy
• Active systemic illness (autoimmune, HIV)
• Obesity (BMI >35)
• Urological abnormalities in remaining kidney
• Pregnancy (absolute at time of donation)

• Young age (long residual lifetime at increased risk)
• Mild hypertension on single agent
• Borderline GFR
• Nephrolithiasis (solitary stone, metabolic risk)
• History of psychiatric illness
• Moderate obesity (BMI 30-35)
• Family history of renal disease
• Abnormal anatomy requiring complex surgery

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11. EVALUATION OF POTENTIAL RECIPIENTS FOR ORGAN TRANSPLANTATION [5 marks]

Components:

• Establish etiology and irreversibility of organ failure
• Confirm ESRD, ESLD, or other indication
• Assess severity: MELD (liver), GFR/dialysis status (kidney), cardiac index (heart)

• ECG, 2D echocardiography
• Stress testing (nuclear/dobutamine echo) in diabetics, older patients
• Coronary angiography if indicated
• Peripheral vascular assessment (for kidney - iliac vessels)
• Cardiology clearance

• Chest X-ray
• PFTs (for lung recipients; for liver: exclude hepatopulmonary syndrome/portopulmonary HTN)
• CT chest if abnormal

• Age-appropriate cancer screening
• Colonoscopy (>50 years)
• Mammography, pap smear (women)
• PSA (men >50)
• Skin check (dermatology)
• CT chest/abdomen/pelvis if history of malignancy
• Cancer-free period required (typically 2-5 years depending on tumor type)

• Serology: HIV, Hepatitis B (HBsAg, anti-HBc, anti-HBs), Hepatitis C, CMV, EBV, HSV, VZV, HTLV I/II, Toxoplasma
• TB: Mantoux / IGRA
• Urinalysis and urine culture
• Dental evaluation

• ABO blood group
• HLA typing (A, B, C, DR, DQ, DP)
• Panel Reactive Antibody (PRA) - screen for pre-formed antibodies
• Donor-specific antibody (DSA) testing

• Psychiatric evaluation
• Substance use history (alcohol, drugs)
• Compliance assessment
• Social support (caregiver available post-transplant)
• Financial/insurance planning

• BMI, albumin, nutritional status
• Obesity (BMI >35 relative contraindication)
• Malnutrition treatment pre-transplant

• Urological evaluation (kidney): voiding history, urodynamics if lower tract dysfunction
• Native liver assessment (hepatology): coagulation, portal HTN complications
• Ophthalmology (diabetes)
• Bone density (liver - osteoporosis common in cholestatic disease)

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12. CRITERIA FOR DECLARING BRAIN STEM DEATH (for organ donation) [5 marks]

Who Performs

• Two registered medical practitioners, each of appropriate experience
• At least one a consultant; neither may be part of the transplant team
• Both must independently confirm; tests may be done simultaneously or serially

Preconditions (Must ALL be fulfilled)

1. Cause established: Irremediable structural brain damage - head injury, intracerebral hemorrhage, post-cardiac arrest hypoxic injury
2. Deeply comatose: GCS 3, on ventilator
3. Drug exclusion: No depressant drugs (narcotics, benzodiazepines, barbiturates); adequate time elapsed
4. Hypothermia excluded: Core temperature >35°C
5. Metabolic causes excluded: No severe electrolyte/acid-base/glucose disturbances; no endocrine crisis

Seven Brainstem Reflex Tests (all must be ABSENT):

1. Pupillary light reflex: Fixed, dilated pupils; no response to bright light
2. Corneal reflex: No blink to cotton wool touching cornea
3. Oculo-cephalic reflex (Doll's eyes): No eye movement when head rotated (not applicable in C-spine injury)
4. Vestibulo-ocular reflex (Caloric test): No eye movement after 20 mL ice-cold water instilled into each ear (with confirmed intact tympanic membrane)
5. Response to pain in cranial nerve territory: No grimacing or response to supraorbital pressure
6. Gag reflex: No response to pharyngeal stimulation
7. Cough reflex: No response to tracheal suction

Apnea Test (as above - 8th test):

• PaCO2 must rise to ≥ 50 mmHg (6.7 kPa) with NO respiratory effort

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13. ISLET (PANCREATIC) TRANSPLANTATION [5 marks]

Background

• Insulin-producing beta cells from the islets of Langerhans of a deceased pancreas are isolated and transplanted into the portal vein of the recipient
• Settles in the liver sinusoids and produces insulin
• Aim: insulin independence and prevention of hypoglycemic unawareness in Type 1 DM

Types of Pancreatic Transplant

1. Simultaneous Pancreas-Kidney (SPK): Most common; pancreas + kidney transplanted simultaneously in ESRD diabetic patient. Best outcomes.
2. Pancreas After Kidney (PAK): Pancreas transplant after prior successful kidney transplant
3. Pancreas Transplant Alone (PTA): For brittle Type 1 DM without ESRD; controversial (requires lifelong immunosuppression)
4. Islet cell transplantation: Less invasive; multiple donors usually needed; Edmonton protocol (2000)

Edmonton Protocol (Islet Transplant)

• Steroid-free immunosuppression: sirolimus + tacrolimus + daclizumab

• 70% achieved insulin independence at 1 year

• At 5 years, only ~10-20% maintain insulin independence (progressive islet loss)
• Improved results with better islet isolation and immunosuppression protocols

Indications for Islet Transplant

• Type 1 DM with severe hypoglycemic unawareness
• Brittle DM with life-threatening hypoglycemia
• Progressive diabetic complications despite optimal insulin therapy
• Prior/concurrent kidney transplant (already requires immunosuppression)

Limitations

• Need 2-3 donors per recipient
• Progressive function loss over years
• Risk of portal hypertension (from infusion), bleeding
• Lifelong immunosuppression required
• Shortage of suitable donors

Current Status

• Whole pancreas transplant (SPK) remains gold standard for combined type 1 DM + ESRD (insulin independence rates >80% at 1 year)
• Islet transplant is still considered investigational in many countries but increasingly accepted for selected indications

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14. COMPLICATIONS OF RENAL TRANSPLANT

Surgical Complications

• Vascular: Renal artery/vein thrombosis (early graft loss), renal artery stenosis (late hypertension, graft dysfunction)
• Urological: Urinary leak (early, from anastomosis), ureteral stenosis (late), lymphocele (most common perigraft fluid collection)
• Wound: Hematoma, seroma, infection, hernia

Medical Complications

• Delayed Graft Function (DGF): Temporary requirement for dialysis; managed with fluid balance, avoidance of nephrotoxic drugs
• Acute Rejection: Rising creatinine, treated with steroids/ATG
• Chronic Rejection (Chronic Allograft Nephropathy): Gradual decline, managed by optimizing immunosuppression
• Calcineurin inhibitor toxicity: Nephrotoxicity, hypertension
• Infections: Bacterial (UTI, pneumonia); viral (CMV - months 1-6, BK virus nephropathy, EBV-related PTLD); fungal (Aspergillus, Candida, PCP)
• Metabolic: PTDM, hyperlipidemia, hypertension, gout
• Malignancy: PTLD (post-transplant lymphoproliferative disease - EBV-related), skin cancers (50x increased risk), Kaposi sarcoma

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SUMMARY TABLE: Ischemia Time Limits

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TRAUMA, UGIB, URETHRA, UROLOGY, VASCULAR & VENOUS - Comprehensive Exam Notes

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TRAUMA

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1. 20-Year-Old Male: RTA with Scalp CLW + GCS 13/15 - Initial Management & Scalp Bleeding Control [5+5]

PART A: INITIAL MANAGEMENT AND EVALUATION

Primary Survey - ABCDE

• GCS 13 - patient likely maintaining airway, but monitor
• Assume cervical spine injury until proven otherwise - apply hard collar, manual in-line stabilization
• Suction blood/secretions if any
• If GCS drops to ≤8 - immediate RSI intubation

• Inspect chest for equal air entry, paradoxical movement, sucking wounds
• Pulse oximetry - target SpO2 ≥95%
• Supplemental O2 via non-rebreather mask (15 L/min)
• CXR to exclude pneumothorax/hemothorax

• Scalp wounds BLEED PROFUSELY due to rich vascular supply and inability of scalp vessels to contract (attached to fibrous septa)
• Two large-bore IV lines (16G antecubital) - send bloods: FBC, coagulation, cross-match, renal/liver/glucose, ABG
• IV fluid resuscitation if hypotensive (0.9% NS or Hartmann's)
• BP, HR, pulse oximetry monitoring
• Control scalp bleeding immediately (see Part B)
• Assess for shock (scalp alone can cause significant blood loss especially in children)

• Glasgow Coma Scale - score currently 13/15; record baseline and re-check every 15-30 minutes
• Pupils: size, equality, reactivity
• Assess: best eye, verbal, motor response
• Assess for lateralizing signs (hemiparesis)
• Blood glucose (exclude hypoglycaemia as cause of confusion)
• GCS 13 = mild-moderate head injury (13-14 = moderate; 15 = mild; ≤8 = severe)

• Full head-to-toe secondary survey
• Remove clothing, log roll (C-spine maintained)
• Keep patient warm (prevent hypothermia)

GCS Scoring Table

Secondary Survey - Head Evaluation

• Scalp: palpate for boggy swelling (subgaleal hematoma), step deformity (depressed fracture)
• Skull: examine CLW - depth, contamination, pulsatile bleeding
• Periorbital: bruising (raccoon eyes = anterior fossa base fracture)
• Mastoid: Battle's sign = middle fossa base fracture
• Ears/nose: CSF leakage (CSF otorrhoea/rhinorrhoea - halo sign on gauze)
• Cranial nerve exam

Investigations

• CT head (non-contrast): MANDATORY - indications in mild-moderate TBI:
  • Any loss of consciousness
  • Post-traumatic amnesia
  • Vomiting
  • Seizure
  • GCS <15
  • Skull fracture suspected
  • Anticoagulant use
  • Age >65
• CT findings to look for: extradural haematoma (biconvex), subdural haematoma (concave), intracerebral contusion/haemorrhage, skull fracture, pneumocephalus, cerebral oedema, midline shift
• CT cervical spine: if C-spine injury suspected
• Skull X-ray (if CT not available): look for vault fractures
• FBC, coagulation, cross-match, U&E, glucose, toxicology

Monitoring and Ongoing Care

• Neurological observations every 15-30 minutes
• Indications for ICU/neurosurgical referral: deteriorating GCS, pupil changes, CT findings, GCS ≤8
• Keep MAP ≥70 mmHg (avoid secondary hypotension)
• Avoid hypoxia (SpO2 ≥95%), hypercapnia
• Elevate head 30°
• Anti-emetics (vomiting raises ICP)
• Tetanus prophylaxis (contaminated scalp wound)
• Antibiotics (contaminated/compound wounds)
• Seizure prophylaxis: phenytoin/levetiracetam if penetrating injury or cortical contusion

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PART B: CONTROL OF SCALP BLEEDING

Why Scalp Bleeds Severely

• Scalp has 5 layers: Skin - Connective tissue (dense) - Aponeurosis (Galea) - Loose connective tissue - Pericranium (mnemonic: SCALP)
• Blood vessels run in the dense connective tissue layer, tethered to fibrous septa - they CANNOT retract/constrict when cut
• Blood supply: superficial temporal, posterior auricular, occipital (ECA branches); supraorbital, supratrochlear (ICA branches)
• Blood loss can be 500-1500 mL from a large scalp laceration

Methods of Scalp Bleeding Control

• Direct pressure: firm continuous pressure with gauze for 5-10 minutes (mainstay of initial control)
• Pressure dressing: tight bandage or wound padding
• Skin/galea staples: rapid deployment in Emergency - multiple staples rapidly placed along wound edges - most effective quick measure
• Raney clips (neurosurgical scalp clips): metal clips applied to wound edges - traditional neurosurgical method; clamp vessels in the galea edge

• Clean wound with saline irrigation
• Debride devitalized tissue
• Galea closure first (interrupted absorbable suture, e.g. 0 Vicryl) - closes dead space, stops galeal bleeding
• Then skin closure: interrupted nylon sutures (3/0) or staples
• Suturing the full-thickness wound provides compression of scalp vessels and is the definitive method

• For large named vessels in the wound - formal ligation with absorbable ties
• Figure-of-8 absorbable sutures can compress deeply bleeding points in the wound bed

• Infiltration of wound edges with 1:200,000 adrenaline (in lidocaine) causes vasoconstriction
• Reduces operative blood loss significantly
• NOT for definitive use but very useful preoperatively / during wound repair

• Coagulate identified bleeding points
• Essential in the operating theatre for persisting bleeders

• Oxidized cellulose (Surgicel), bone wax (for diploic bone bleeding), gelatin foam (Gelfoam)
• Useful adjuncts for wound bed or bony bleeding

• Interventional radiology: selective embolization of scalp arterial branches (e.g., superficial temporal artery)
• Reserved for uncontrolled major scalp bleeding not amenable to direct surgery

• Circumferential compression of scalp with wide bandage proximal to injury
• Only as temporizing measure; risk of pressure injury

Wound Management Summary

1. Immediate: Direct pressure / wound staples / Raney clips
2. Thorough irrigation, debridement
3. Galea closure (dead space elimination + haemostasis)
4. Skin closure (sutures or staples)
5. Tetanus prophylaxis + antibiotics if contaminated
6. Dressing

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2. TENSION PNEUMOTHORAX [5 marks]

Definition

Pathophysiology

• One-way valve: air enters on inspiration, cannot exit on expiration
• Progressive pressure rise in affected hemithorax
• Ipsilateral lung collapse + mediastinal shift to OPPOSITE side
• Compression of contralateral lung and great veins (SVC/IVC)
• Reduced venous return → reduced cardiac output → obstructive shock → cardiac arrest
• Causes: rib fracture with pleural tear, penetrating chest wound, barotrauma (ventilated patient), central line insertion

Clinical Features (Classic Triad + Signs)

• Respiratory distress, tachypnoea, hypoxia
• Tachycardia, hypotension (shock)
• Decreased/absent breath sounds on AFFECTED side
• Hyperresonance (tympanic) on percussion of AFFECTED side
• Distended neck veins (JVD) - due to impaired venous return
• Tracheal deviation AWAY from the affected side (LATE sign - unreliable)

• Severe hypotension, cyanosis
• Pulseless electrical activity (PEA) arrest

Diagnosis

• CLINICAL diagnosis - do NOT wait for CXR before treating
• CXR (if time allows and patient stable): hyperexpanded hemithorax, absent lung markings, contralateral mediastinal shift, ipsilateral diaphragm depression

Management - IMMEDIATELY TREAT ON CLINICAL SUSPICION

• Large-bore needle (14-16G angiocatheter)
• 2nd intercostal space, midclavicular line, upper border of 3rd rib (avoids neurovascular bundle)
• In obese patients: 5th ICS, anterior axillary line
• A hiss of escaping air confirms diagnosis
• Converts tension to simple pneumothorax - immediate haemodynamic improvement expected
• This is a temporizing measure only

• 5th intercostal space, anterior/mid-axillary line (safe triangle: anterior border of latissimus dorsi, lateral border of pectoralis major, above horizontal nipple line)
• 28-32 F drain connected to underwater seal drain
• Remove needle after chest tube placed
• CXR post-insertion to confirm position and lung re-expansion

• Sudden desaturation, rising airway pressures, haemodynamic collapse
• Immediate needle decompression without delay

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3. FLAIL CHEST - Presentation, Management + Fracture of Upper 3 Ribs [6+4]

PART A: FLAIL CHEST

Definition

1. Anterior flail: bilateral fracture near sternum (sternal fracture involved) - most serious
2. Lateral flail: fractures along lateral chest wall
3. Posterior flail: posterolateral fractures; relatively protected by paraspinal muscles, less paradoxical movement

Mechanism

• Significant high-energy trauma (motor vehicle crash, crush injury)
• Energy required for flail chest is substantial; always associated with pulmonary contusion (PC)

Pathophysiology

• Paradoxical chest wall movement: flail segment moves IN during inspiration (when rest of chest expands) and OUT during expiration
• Previously thought paradoxical movement caused respiratory failure ("Pendelluft" theory)
• Modern understanding: the respiratory failure and hypoxemia are caused by the underlying pulmonary contusion, not the paradoxical movement itself
• Pulmonary contusion → interstitial and alveolar oedema → V/Q mismatch → hypoxemia

Clinical Presentation

• Severe chest pain (fracture site)
• Paradoxical chest wall movement (visible on inspection - segment moves in opposite direction to rest of chest)
• Respiratory distress, tachypnoea, hypoxia (SpO2 low)
• Shallow breathing (splinting due to pain)
• Tachycardia
• Subcutaneous emphysema if pneumothorax co-exists
• Haemoptysis (pulmonary contusion)
• Mortality: up to 40% due to associated injuries and pulmonary complications (ARDS, pneumonia)

Investigations

• CXR: multiple rib fractures (may underestimate if costochondral - cartilage not visible)
• CT chest: gold standard - shows rib fractures, extent of pulmonary contusion, pneumo/haemothorax
• ABG: hypoxemia (PaO2 <60 mmHg), hypercarbia (late)

Management

• Thoracic Epidural Analgesia (TEA): preferred - EAST guideline recommended; reduces need for intubation; 0.25% bupivacaine ± fentanyl
• Thoracic Paravertebral Block (TPVB): if epidural contraindicated
• IV opioids, NSAIDs
• Intercostal nerve blocks (shorter duration)
• IV Ketamine infusion (opioid-sparing)
• Serratus anterior plane block (ultrasound-guided)

• O2 supplementation
• Non-invasive ventilation (CPAP/BiPAP): for mild-moderate respiratory compromise; trial before intubation
• Mechanical ventilation (ETT): indications:
  • PaO2 <60 mmHg on O2
  • PaCO2 >50 mmHg
  • Respiratory rate >35/min
  • Failed CPAP trial
  • Other injuries requiring intubation (TBI, haemodynamic instability)
• Positive pressure ventilation provides internal pneumatic stabilisation of flail segment

• Indications:
  • Chest wall instability with paradoxical movement
  • Failed weaning from ventilator
  • Chest wall deformity/severe pain refractory to analgesia
  • Open chest wounds
  • Thoracotomy required for other reasons (haemothorax, lung injury)
• Technique: titanium rib plates/locking plates or intramedullary splints (e.g., STRATOS system)
• Reduces ICU stay, ventilator days; improves long-term outcome
• Increasingly recommended over purely conservative management

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PART B: FRACTURE OF UPPERMOST 3 RIBS AND ASSOCIATED INJURIES

• These ribs are SHORT, STRONG, and WELL PROTECTED by the shoulder girdle, clavicle, and scapula
• Enormous force required to fracture upper 3 ribs = marker of high-energy trauma
• Historically associated with high mortality due to associated injuries

• Pulse inequality (absent radial pulse) → subclavian artery injury
• Brachial plexus palsy (Erb's / Klumpke's)
• Mediastinal widening on CXR → aortic injury
• Pneumomediastinum → tracheobronchial tear
• Absent breath sounds → haemopneumothorax

• CXR: mediastinal width, rib fractures, haemothorax, pneumothorax
• CT Angiography of chest (aorta and great vessels): mandatory if mediastinal widening
• Doppler/Angiography if subclavian injury suspected
• CT/MRI brachial plexus if neurological deficit

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4. TRIAGE AND GOLDEN HOUR IN POLYTRAUMA + DAMAGE CONTROL SURGERY [(3+3)+4]

A. TRIAGE (3 marks)

B. GOLDEN HOUR (3 marks)

• In major trauma with haemorrhage, progressive haemodynamic deterioration leads to the Lethal Triad:
  1. Acidosis (lactic acidosis from hypoperfusion)
  2. Hypothermia (heat loss from exposure + blood loss)
  3. Coagulopathy (dilutional, consumptive, hypothermia-induced)
• This triad becomes self-reinforcing (a "downward spiral") and can be irreversible
• Intervention within the golden hour interrupts this cycle before it becomes irretrievable

• Pre-hospital: rapid extraction, haemorrhage control, basic airway, rapid transport
• "Scoop and run" vs "stay and play" debate
• Hospital: immediate trauma team activation; primary survey and life-saving interventions within minutes
• Direct to OR without delay for haemodynamically unstable patients

C. DAMAGE CONTROL SURGERY (DCS) [4 marks]

1. Stop active surgical bleeding
2. Control contamination (seal bowel perforations, limit soilage)
3. Restore normal physiology (not full anatomical repair at this stage)

• Damage Control Resuscitation (DCR): begins pre-operatively
• Permissive hypotension (target systolic 80-90 mmHg; 50-60 mmHg if TBI avoided)
• Avoid excessive crystalloids (dilutional coagulopathy)
• Haemostatic resuscitation: balanced transfusion of packed red cells : FFP : platelets in ratio 1:1:1 (simulates whole blood)
• Tranexamic acid (TXA) within 3 hours of injury (CRASH-2 trial)
• Point-of-care testing: thromboelastography (TEG) to guide clotting product use
• Minimize time in ED - get to OR early

• Brief operation (<90 minutes target)
• Haemorrhage control: packing, vessel ligation, vascular shunts (temporary intraluminal shunts for major arteries)
• Contamination control: bowel stapling (not anastomosis), damage control colostomy
• Temporary abdominal closure: "Open abdomen" technique using:
  • Bogota bag (sterile IV bag)
  • "Vac-Pac" / OPSITE sandwich technique: plastic over bowel + suction drain + adhesive drape
  • Negative Pressure Wound Therapy (NPWT) devices (ABThera)

• Correct hypothermia (warming blankets, warm IV fluids)
• Correct coagulopathy (FFP, platelets, cryoprecipitate, Vitamin K)
• Correct acidosis (adequate resuscitation, ventilation)
• Organ support (vasopressors, ventilation)
• Reassess, plan definitive surgery

• After 24-72 hours when physiology is normalized
• Full anatomical reconstruction: bowel anastomosis, vascular repair, fracture fixation
• Abdominal closure (fascial closure preferred; if impossible - planned hernia repair later)

• Haemodynamic instability despite initial resuscitation
• Lethal triad (hypothermia <35°C, pH <7.2, coagulopathy PT >19 sec)
• Predicted massive transfusion requirement
• Multiple life-threatening injuries
• Extended or complex reconstruction that would exceed patient's physiological reserve

• Early Total Care (ETC): definitive repair of all injuries in one operation - appropriate for stable patient (good physiological reserve, no lethal triad)
• DCS: for the physiologically depleted patient - "stop the clock, buy time"

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5. RETROPERITONEAL HEMATOMA (RPH) - Management [5 marks]

Classification (Zone-Based - Mattox Classification)

General Principles

• Most RPH discovered at laparotomy for trauma or on CT
• Decision to explore depends on: mechanism (blunt vs penetrating), zone, haemodynamic stability, expanding vs stable haematoma

Management of Pelvic RPH (Most Common - From Pelvic Fracture)

• Haemodynamic stability: observation, pelvic binder application (closes pelvic ring, reduces volume, tamponades venous bleeding)
• NPO, monitor, serial Hb

1. Pelvic binder / external fixator: reduces pelvic volume; pre-peritoneal pelvic packing (PPP) if haemodynamically unstable
2. Pre-peritoneal Pelvic Packing (PPP): midline incision, dissection to pre-peritoneal space, pack all four pelvic quadrants; rapidly controls venous bleeding; combination with external fixation
3. Angioembolization: for arterial bleeding (identified on CT angiography); selective embolization of internal iliac artery branches (inferior gluteal, superior gluteal, internal pudendal)
4. REBOA (Resuscitative Endovascular Balloon Occlusion of the Aorta): aortic Zone 3 balloon occlusion for refractory haemorrhage; bridge to definitive control
5. Exploratory laparotomy with packing for Zone I haematoma

Management of Zone I (Central RPH)

• Always open - life-threatening major vessel injury common
• Proximal aortic control (supracoeliac aorta at diaphragmatic hiatus first)
• Aortic/IVC repair or ligation depending on injury and stability
• Pancreatic/duodenal injuries addressed simultaneously

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6. PERICARDIAL TAMPONADE (Blunt Chest Trauma) [5 marks]

Pathophysiology

• Blood accumulates in pericardial sac (inelastic)
• Pericardium cannot stretch acutely; even 150-200 mL can cause tamponade
• Rising intrapericardial pressure → compresses all four chambers → reduced filling → reduced CO → obstructive shock

Causes in Trauma

• Blunt cardiac injury (steering wheel impact) → myocardial rupture (especially RV - most anterior)
• Penetrating injury (stab wound to anterior chest "cardiac box")
• Aortic root tear

Clinical Features - BECK'S TRIAD (Classic but insensitive)

1. Hypotension (low cardiac output)
2. Muffled/distant heart sounds (blood insulating sounds)
3. Distended neck veins (JVD - impaired venous return to heart)

• Tachycardia
• Pulsus paradoxus: abnormal drop in systolic BP >10 mmHg on inspiration (IVS shift compresses LV during RV filling)
• Kussmaul's sign: JVP rises on inspiration (more for constrictive pericarditis)
• ECG: sinus tachycardia; low voltage QRS; electrical alternans (alternating QRS amplitude due to swinging heart) - pathognomonic

Diagnosis

• FAST (Focused Assessment Sonography in Trauma): most rapid and accurate bedside tool
  • Pericardial effusion: echo-free space between myocardium and pericardium (particularly in the subxiphoid view)
  • Signs of tamponade: RV diastolic collapse, RA systolic collapse, plethoric IVC
• CXR: globular ("water bottle") enlarged cardiac silhouette - not sensitive in acute setting
• Echo (formal): if time permits in stable patient

Management

• Emergency resuscitative thoracotomy (ER thoracotomy):
  • Left anterolateral thoracotomy in 5th ICS
  • Open pericardium (vertical incision anterior to phrenic nerve)
  • Evacuate clot, temporary cardiac repair (digital occlusion, skin staples over cardiac wound)
  • Internal cardiac massage, cross-clamp descending aorta

• Pericardiocentesis (needle aspiration):
  • Subxiphoid/parasternal route under ultrasound guidance
  • 18G spinal needle, 60 mL syringe, ECG monitoring (ST elevation if touches myocardium)
  • Even 10-20 mL removal can dramatically improve haemodynamics
  • Temporizing measure - definitive surgery still required

• Formal thoracotomy (usually median sternotomy): cardiorraphy (repair of cardiac laceration), pericardial decompression, associated injuries addressed

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7. GCS COMPONENTS AND HEAD INJURY WITH GCS 8 [2+3]

GCS Components (2 marks)

• Mild TBI: GCS 13-15
• Moderate TBI: GCS 9-12
• Severe TBI: GCS ≤8 (intubation threshold)

Medical Management - GCS 8 (Severe TBI) (3 marks)

• GCS ≤8 = intubate (airway protection, controlled ventilation)
• Rapid Sequence Intubation (RSI): ketamine or propofol + suxamethonium or rocuronium; C-spine precautions
• Target: normoventilation initially (PaCO2 35-40 mmHg); hyperventilation (PaCO2 30-35) only if herniation suspected - short-term bridging

• Target SpO2 ≥95%, PaO2 ≥60 mmHg
• Avoid hypoxia at all costs (hypoxia doubles mortality in TBI)

• Target CPP (Cerebral Perfusion Pressure) = MAP - ICP ≥60 mmHg
• Maintain MAP ≥70-80 mmHg (target SBP ≥90-100 mmHg)
• Avoid hypotension (increases secondary injury)
• Isotonic fluids (0.9% NS); avoid hypotonic fluids (worsen cerebral oedema)

• First-tier: Head elevation 30°, adequate sedation (propofol + fentanyl), aim normocarbia, normothermia, CSF drainage (if EVD placed)
• Osmotherapy: Mannitol 0.25-1 g/kg IV bolus (raises osmolarity, reduces cerebral oedema) or hypertonic saline (3% NaCl)
• Seizure prophylaxis: levetiracetam or phenytoin (prophylaxis for 7 days in severe TBI)
• Avoid: hyperthermia, anaemia, hyponatraemia, hyperglycaemia

• Emergent CT head (non-contrast)
• If extradural/subdural with significant midline shift - emergency evacuation

• EDH >30 mL or >15 mm thickness or >5 mm midline shift
• SDH >10 mm thickness or >5 mm midline shift, or GCS drop ≥2
• ICH with elevated ICP refractory to medical treatment
• Depressed skull fracture >1 cm
• Decompressive craniectomy for refractory intracranial hypertension

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8. ATLS CONCEPTS AND SPLENIC INJURY [3+7]

ATLS Basic Concepts (3 marks)

• A - Airway + C-spine control
• B - Breathing + ventilation
• C - Circulation + haemorrhage control
• D - Disability (neurological - GCS, pupils, gross motor)
• E - Exposure + Environment (undress, prevent hypothermia)

• IV access × 2, fluids, blood products
• Monitoring: ECG, SpO2, ETCO2, urinary catheter (output target 0.5-1 mL/kg/hr)

• History (AMPLE: Allergies, Medications, Past history, Last ate, Events)
• Complete physical exam head to toe
• Investigations: X-rays (CXR, pelvis), FAST, CT as indicated

Management of Splenic Injury - Blunt Abdominal Trauma (7 marks)

• Left upper quadrant pain/tenderness
• Kehr's sign: referred left shoulder tip pain (blood irritating left hemidiaphragm)
• Haemodynamic compromise if major injury
• Abdominal guarding/rigidity

• FAST ultrasound: free fluid in abdomen (LUQ, Morrison's pouch)
• CT abdomen+pelvis (contrast): gold standard for grading; "contrast blush" indicates active extravasation
• FBC, coagulation, cross-match
• DPL (Diagnostic peritoneal lavage) - rarely used now (replaced by CT)

• Resuscitate (DCR principles)
• If haemodynamics do not improve with 2L fluid/blood: Emergency splenectomy
• Midline laparotomy; early proximal splenic artery control at splenic hilum
• Packing and splenorrhaphy (suture repair) for lower-grade injuries if feasible
• Damage control if needed

• ICU/HDU monitoring (vital signs, serial abdominal exams, serial Hb)
• Absolute bed rest initially; no oral intake
• Serial CT at 24-48 hours if concerns
• No eating for 24-72 hours, graduated mobility thereafter
• Success rate: Grade I-II >95%; Grade III ~85%; Grade IV ~70%

• For CT "contrast blush" or Grade III-IV with stable haemodynamics
• Selective splenic artery embolization (distal) or main splenic artery embolization (proximal)
• Reduces failure rate of NOM in Grade IV-V

• NOM failure (haemodynamic deterioration, transfusion requirement >4 units/24h)
• Grade V
• Splenorrhaphy techniques: mattress sutures, argon beam coagulator, haemostatic agents (Surgicel, fibrin glue), mesh wrapping
• Splenectomy: if not salvageable or haemodynamically unstable

• OPSI (Overwhelming Post-Splenectomy Infection): Encapsulated organisms - Pneumococcus, Meningococcus, Haemophilus influenzae
• Vaccinations: pneumococcal, meningococcal, Hib (ideally 2 weeks pre-op, but give post-op if emergency)
• Penicillin V prophylaxis (daily for 2-5 years; lifelong in some guidelines for high-risk)

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9. CRUSH SYNDROME [5 marks]

1. Prolonged external pressure → muscle ischaemia → cell membrane failure
2. Massive release of: myoglobin, K+, phosphate, urate, creatine kinase, lactic acid
3. On reperfusion: local oedema (fluid shifts into muscle - "third spacing"), hypovolaemia
4. Myoglobin → filtered by kidney → tubular precipitation (especially in acid urine) → acute tubular necrosis (ATN) → Acute Kidney Injury (AKI)
5. Hyperkalemia → cardiac arrhythmias
6. DIC (from tissue thromboplastin release)
7. Compartment syndrome in affected limbs

• History: prolonged entrapment (earthquake, building collapse, deliberate crush)
• Injured limbs: swollen, tense, paraesthetic or paralysed (compartment syndrome)
• Dark/tea-coloured urine (myoglobinuria)
• Haemodynamic shock (hypovolaemia from third-spacing)
• Cardiac arrhythmias (from hyperkalaemia, hypocalcaemia)
• Oliguria/anuria (AKI developing over hours to days)

• Serum CK: markedly elevated (>1000 IU/L diagnostic; often >10,000)
• Serum creatinine, BUN: rising
• Serum K+: hyperkalaemia
• Serum Ca2+: hypocalcaemia (Ca binds to damaged muscle)
• Serum phosphate: hyperphosphataemia
• Urine: myoglobinuria (dipstick shows blood but no RBCs on microscopy), oliguria
• ABG: metabolic acidosis
• ECG: hyperkalaemia changes (peaked T waves, wide QRS)
• Coagulation screen (DIC screen)

1. Aggressive IV fluid resuscitation (cornerstone):
   • Start BEFORE extrication if possible (pre-hospital)
   • Target: 1-1.5 L/hr initially (Hartmann's or 0.9% NS; avoid lactated Ringer's in severe hyperK)
   • Target urine output 200-300 mL/hr
   • Monitor closely for pulmonary oedema
2. Urinary alkalinization (controversial but used):
   • IV sodium bicarbonate (1-2 mEq/kg): alkalinizes urine (pH >6.5) → prevents myoglobin precipitation in tubules
   • Avoid if metabolic alkalosis or hypocalcaemia worsens
3. Diuretics (with adequate fluid):
   • Mannitol: osmotic diuretic, free radical scavenger; 1 g/kg IV
   • Furosemide: only after adequate volume resuscitation
4. Hyperkalaemia management:
   • Calcium gluconate (cardiac membrane stabilization)
   • IV dextrose + insulin (shifts K intracellularly)
   • Sodium bicarbonate
   • Salbutamol nebulizer
   • Kayexalate (binds K in gut)
   • Dialysis (RRT) if severe or refractory
5. Compartment syndrome:
   • Measure compartment pressure (>30 mmHg or within 30 mmHg of diastolic = fasciotomy)
   • Emergency fasciotomy of all compartments of affected limb
6. Renal replacement therapy (RRT): for AKI with uraemia, fluid overload, refractory hyperK/acidosis
7. DIC: FFP, cryoprecipitate, platelets as needed

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UGIB

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10. LEFT-SIDED PORTAL HYPERTENSION [5 marks]

• Splenic vein occlusion → increased splenic venous pressure
• Splenic outflow diverts through short gastric veins → gastric fundal varices
• Portal vein and liver are normal (HVPG and hepatic function normal)
• Oesophageal varices typically absent (gastro-oesophageal junction veins normal)
• Isolated gastric fundal varices = hallmark

• Pancreatitis (most common - acute and chronic): peripancreatic inflammation causes splenic vein thrombosis
• Pancreatic carcinoma: compression/invasion of splenic vein
• Pancreatic pseudocyst: compresses splenic vein
• Post-surgical: after pancreatectomy
• Other: retroperitoneal fibrosis, trauma, lymphoma

• Splenomegaly (almost universal)
• Gastric fundal varices (risk of severe haemorrhage)
• Gastrointestinal bleeding (haematemesis, melena) - typically more severe than oesophageal variceal bleeding
• Normal liver function tests
• Normal hepatic venous pressure gradient (HVPG) - distinguishes from cirrhotic portal HTN
• Pancreatic symptoms (pain, weight loss, steatorrhoea depending on underlying cause)

• Duplex Doppler ultrasound: first-line; shows splenic vein occlusion, splenomegaly, gastric varices
• CT angiography (CTAP): defines splenic vein anatomy, identifies underlying pancreatic pathology
• MRI/MRCP: pancreatic disease characterization
• Endoscopy (OGD): isolated gastric fundal varices, no oesophageal varices - characteristic pattern; fundal varices bleed profusely
• LFTs: normal (unless concurrent liver disease)
• HVPG: normal

• Splenectomy: definitive treatment - removes the "pump" driving the gastric varices; highly effective; bleeding stops and varices regress
• Elective splenectomy for patients with symptomatic/bleeding gastric varices
• Emergency management of acute bleed:
  • Resuscitation (IV access, blood, vasoconstrictors)
  • Endoscopic therapy: cyanoacrylate (histoacryl) glue injection for gastric varices (band ligation less effective for fundal varices)
  • Balloon tamponade (Linton-Nachlas tube for gastric varices; or Sengstaken-Blakemore)
  • TIPSS: effective but may be technically difficult if splenic vein thrombosed
  • Splenectomy: definitive even in emergency if bleeding not controllable
• Treat underlying cause (pancreatic pathology)

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11. MASSIVE UPPER GI BLEED IN CHRONIC ALCOHOLIC WITH MELENA AND SHOCK [3+7]

Evaluation (3 marks)

• Resuscitate simultaneously with evaluation (ABCDE)
• History: amount of blood loss, prior variceal bleeds, known cirrhosis, alcohol intake, medications (NSAIDs, anticoagulants), prior abdominal surgery
• Signs of chronic liver disease: spider naevi, palmar erythema, gynaecomastia, leukonychia, jaundice, ascites, splenomegaly, asterixis

1. Oesophageal varices (most likely in alcoholic with portal hypertension) - accounts for ~70% of UGIB in cirrhotics
2. Portal hypertensive gastropathy
3. Gastric varices
4. Peptic ulcer disease (NSAIDs or stress ulcer)
5. Mallory-Weiss tear (vomiting-induced)
6. Gastric erosions

• FBC (Hb, WBC, platelets), coagulation (PT prolonged in liver disease), LFTs, albumin, U&E, creatinine, serum ammonia
• Child-Pugh / MELD score
• ABG (metabolic alkalosis + anaemia)
• Blood group and cross-match (4-6 units)
• Chest X-ray
• OGD (Oesophago-gastro-duodenoscopy): most important investigation AND therapeutic tool; perform within 12-24 hours (within 12 hours if haemodynamically unstable after resuscitation)
• Ultrasound abdomen: liver size/texture, splenomegaly, ascites, portal vein diameter

Management (7 marks)

• Large-bore IV access × 2 (or central line)
• Fluid resuscitation: crystalloids initially; switch to blood products early
• Target: Hb 7-8 g/dL (restrictive transfusion strategy - over-transfusion increases portal pressure and re-bleeding risk; TRIGGER transfusion study)
• FFP and platelets if coagulopathy (INR >1.5, platelets <50,000)
• Correct hypovolaemic shock
• Airway: if hematemesis with encephalopathy - intubate to protect airway before endoscopy

• Vasoconstrictors: Terlipressin (1-2 mg IV 4-6 hourly; synthetic vasopressin analogue) - reduces portal pressure; reduces splanchnic blood flow; reduces early re-bleeding and 5-day mortality
  • Alternative: Octreotide (50 mcg IV bolus then 50 mcg/hr infusion) or Somatostatin
  • Continue for 3-5 days
• Broad-spectrum antibiotics (mandatory in cirrhotics with UGIB):
  • Norfloxacin 400 mg bd orally OR IV ceftriaxone 1 g daily
  • Reduces SBP risk, reduces re-bleeding, improves survival
  • Give for 5-7 days
• IV PPI (omeprazole/pantoprazole): if peptic ulcer possible; also useful pre-endoscopy

• Oesophageal varices: Endoscopic Band Ligation (EBL) - first-choice; rubber bands placed on varices
  • Alternative: Endoscopic Sclerotherapy (1-3% polidocanol, sodium tetradecyl sulphate) if ligation not feasible
  • Repeat sessions every 2-4 weeks until variceal obliteration
• Gastric varices: Cyanoacrylate glue injection (N-butyl-2-cyanoacrylate) - preferred for fundal varices
  • Thrombin injection or TIPSS alternatives

• Sengstaken-Blakemore (SB) tube: oesophageal + gastric balloon; controls oesophageal variceal bleeding in 80-90%
• Linton-Nachlas tube: single large gastric balloon; for gastric varices
• Self-expanding metal stents (SEMS) are replacing SB tube in some centres
• Risks: oesophageal rupture, aspiration; only bridge to definitive therapy

• Interventional radiology: creates porto-systemic shunt within liver (portal vein to hepatic vein through liver parenchyma) using expandable metal stent
• Reduces portal pressure immediately
• Indications in acute UGIB:
  • Failure of endoscopic haemostasis (2 failed sessions)
  • "Pre-emptive" or rescue TIPSS in high-risk bleeders (Child-Pugh B/C with HVPG >20 mmHg) - improves survival
• Contraindications: hepatic encephalopathy (worsens), severe hepatic failure (Child-Pugh C >13), portal vein thrombosis (relative), severe cardiopulmonary disease
• Complications: hepatic encephalopathy (20-30%), stent stenosis/thrombosis, heart failure (from increased preload)

• Non-selective beta-blockers (propranolol/carvedilol): reduce portal pressure; start once haemodynamically stable
• Repeat EBL sessions (every 2-4 weeks)
• TIPSS for recurrent bleeders or those with refractory ascites

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12. TIPSS IN VARICEAL HAEMORRHAGE [5 marks]

• Transjugular approach: catheter from right internal jugular vein → right hepatic vein → needle puncture through hepatic parenchyma to portal vein → deploy covered metal stent → creates shunt bypassing liver sinusoids
• Reduces portal pressure by 50-60%; target HVPG <12 mmHg

1. Acute variceal bleeding: failure of 2 sessions of endoscopic treatment (rescue TIPSS)
2. Early TIPSS (pre-emptive): Child-Pugh B/C with HVPG >20 mmHg or active bleeding at endoscopy - evidence shows improved survival
3. Secondary prophylaxis: recurrent variceal bleeding despite optimal pharmacotherapy + EBL
4. Refractory ascites: improves diuretic response, reduces ascites
5. Hepatic hydrothorax
6. Budd-Chiari syndrome
7. Portal hypertensive gastropathy refractory to medical therapy
8. Hepatorenal syndrome (bridge to transplant)

• Absolute: severe hepatic failure (Child-Pugh >13/15), severe encephalopathy, severe pulmonary hypertension (mPAP >45 mmHg), uncontrolled sepsis, biliary obstruction
• Relative: hepatocellular carcinoma (central), portal vein thrombosis (relative - technical challenge)

• Hepatic encephalopathy (most common - 20-30%): use polytetrafluoroethylene (PTFE)-covered stents (Viatorr) to reduce risk
• Stent dysfunction (stenosis/occlusion): monitor with Doppler; re-intervention
• Intra-abdominal haemorrhage
• Bilhaemia
• Contrast nephropathy
• Heart failure (increased venous return to right heart)

• Controls acute variceal bleeding in >90%
• Re-bleeding rate: 10-20%
• 1-year stent patency: >80% with covered stents

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URETHRA

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13. STRADDLE INJURY WITH URETHRAL INJURY (Male, 38 years) - Evaluation & Management [5+5]

Presentation Analysis

• Straddle injury: perineum strikes hard surface (bicycle bar, fence, beam)
• Classic mechanism for anterior urethral (bulbar urethral) injury - most commonly the bulbar urethra (fixed, least mobile portion)
• Key triad: Blood at meatus + Perineal hematoma + Hematuria

Anatomy of Male Urethra

Evaluation (5 marks)

• Mechanism, time of injury
• Ability to void (can they urinate? partial vs complete disruption)
• Blood at meatus, haematuria, perineal pain

• Vital signs
• Inspect: blood at urethral meatus (DO NOT insert catheter until urethrogram done)
• Perineal butterfly hematoma (blood tracks in Colles' fascia → perineum, scrotum, penile shaft - "butterfly pattern" limited by Colles' fascia attachments)
• Rectal exam: rule out rectal injury; assess anal sphincter tone
• Pelvic exam: assess for pelvic fracture (posterior urethral injury less likely here but check)
• Rule out scrotal/testicular injury

• Retrograde Urethrogram (RUG): First and most important investigation
  • Method: 14 Fr Foley catheter in fossa navicularis, inject 20-30 mL water-soluble contrast (diluted)
  • Shows: site, extent, and type of injury (extravasation pattern)
  • Partial tear: contrast extravasates but also passes through to bladder
  • Complete tear: no contrast reaches bladder
• Cystogram / CT cystogram: if bladder injury suspected
• Urine dipstick/microscopy
• FBC, coagulation, cross-match (if haemodynamically compromised)
• FAST/CT abdomen-pelvis (if polytrauma)

• Type I: Contusion (urethrogram normal, blood at meatus)
• Type II: Partial disruption (extravasation AND contrast in bladder)
• Type III: Complete disruption (no contrast in bladder)

Management (5 marks)

• Attempt gentle urethral catheterisation OR suprapubic catheter
• Most heal with 2-4 weeks of catheterisation
• Monitor for stricture formation (urethrogram before catheter removal)
• Follow up urethrogram at 6 months (stricture surveillance)

1. Suprapubic catheter (SPC) insertion: immediate urinary diversion; avoids further urethral manipulation; allows haematoma to resolve
2. Perineal hematoma management: usually managed conservatively; surgical drainage if secondary infection develops
3. Definitive repair after 3-6 months when scarring matures:
   • Excision and Primary Anastomosis (EPA): gold standard for bulbar urethral stricture/complete disruption; scar excised, healthy urethral ends spatulated and anastomosed; success rate >90% for short strictures
   • Pedicled skin flap urethroplasty (buccal mucosal graft): for longer strictures (>3 cm); onlay or augmented anastomotic; BMG from cheek

• Urethral stricture (most common long-term - months to years)
• Urinary fistula
• Erectile dysfunction (pudendal nerve/vessel damage)
• Perineal abscess
• Retrograde ejaculation

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14. PELVIC FRACTURE WITH URETHRAL INJURY (Posterior Urethral Injury) [2+3+5]

• RUG (as above) - most important
• Pelvic X-ray / CT pelvis: type of pelvic fracture (straddle fracture - both pubic rami bilaterally most associated)
• CT cystogram if bladder injury
• NEVER pass urethral catheter until RUG done

• Haemodynamic stabilisation (pelvic fracture = major haemorrhage risk; binder/external fixator)
• Suprapubic catheter (SPC): immediate urinary diversion
• Immediate primary repair vs delayed:
  • Primary endoscopic realignment (within 2 weeks): retrograde railroading of catheter; reduces stricture rate
  • Delayed urethroplasty (3-6 months): EPA posteriorly (perineal or perineal + abdominal approach); high success rates
  • Open primary repair at time of pelvic surgery: increasingly performed with fixation

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UROLOGY

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15. BILATERAL HYDRONEPHROSIS - Causes and Management [4+6]

Causes of Bilateral Hydronephrosis (4 marks)

• Benign prostatic hyperplasia (BPH) - most common in males >50
• Carcinoma of prostate
• Urethral stricture
• Posterior urethral valves (children)
• Neurogenic bladder (spinal cord injury, diabetes, MS)
• Bladder neck dysfunction

• Retroperitoneal fibrosis (bilateral ureteric encasement)
• Bilateral ureteric calculi
• Bilateral PUJ (pelvi-ureteric junction) obstruction
• Bilateral ureteric strictures
• Retroperitoneal tumour/lymphadenopathy
• Aortic aneurysm

• Cervical carcinoma (compression of both ureters)
• Rectal carcinoma
• Ovarian carcinoma (bilateral)
• Pregnancy (physiological bilateral mild hydronephrosis)

• Large bladder tumour obstructing both ureteric orifices
• Bilateral ureteroceles

• Diabetes insipidus (massive diuresis - non-obstructive)
• Primary megaureter

Management - Bilateral Ureteric Calculi with AKI (S.Creatinine 4.5) (6 marks)

• IV access, fluid resuscitation (but cautious with AKI)
• Strict I/O monitoring, urine output
• Serum electrolytes: check K+ (hyperkalaemia in AKI - dangerous)
• ABG: metabolic acidosis
• Nephrology consultation

1. JJ Stenting (Bilateral Double-J Ureteric Stents): cystoscopy + retrograde ureteroscopy + stent insertion past stones → immediate drainage. Most rapid; both ureters stented in one session.
2. Percutaneous Nephrostomy (PCN - bilateral): if stenting not possible (impacted stones, failed retrograde access); ultrasound-guided nephrostomy tube; also allows antegrade ureteric access later.

• IV fluids (once renal function starts recovering, avoid fluid overload)
• Treat hyperkalaemia: calcium gluconate, dextrose-insulin, bicarbonate, salbutamol, dialysis if needed
• Post-obstructive diuresis: after decompression, can have massive diuresis - replace 50% of urine output hourly to prevent hypovolaemia
• Analgesia (morphine cautious in AKI; ketorolac/NSAIDs avoided - nephrotoxic)
• Antibiotics if infected urine (obstructed system + infection = emergency)

• 13 mm right lower ureteric stone: likely amenable to Ureteroscopy + Laser Lithotripsy (URSL) or Shock Wave Lithotripsy (ESWL) (15-20 mm threshold; lower ureter - ureteroscopy preferred)
• 15 mm left ureteric stone: Ureteroscopy + Laser Lithotripsy (left lower ureter; >10 mm = ureteroscopy over ESWL)
• ESWL less effective for stones >10 mm or lower ureter stones
• Allow 4-6 weeks for renal function recovery before definitive intervention
• Metabolic work-up for stone disease (24-h urine citrate, calcium, oxalate, uric acid)

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16. PUJ OBSTRUCTION - Treatment Options [5 marks]

1. Pyeloplasty (Anderson-Hynes dismembered pyeloplasty): gold standard; excise stenotic segment, spatulate and anastomose renal pelvis to ureter over stent; open, laparoscopic, or robotic; success 90-95%; preferred when crossing vessel present or large redundant pelvis
2. Endopyelotomy: incise PUJ under vision; retrograde (ureteroscopic) or antegrade (percutaneous); success 70-80%; less for crossing vessels; outpatient procedure
3. Percutaneous nephrostomy: only if emergency decompression needed (infection, AKI)
4. ESWL: not effective for PUJ obstruction per se
5. Nephrectomy: only if non-functioning kidney (split function <10%)
6. Balloon dilation: poor results; not recommended
7. Robotic pyeloplasty: increasing use; same principles as laparoscopic; excellent outcomes with shorter hospital stay

• Symptomatic (flank pain, recurrent UTI)
• Deteriorating renal function
• Stones secondary to obstruction
• Split function <40% (relative)

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VENOUS

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17. DEEP VEIN THROMBOSIS (DVT) [5 marks]

Pathophysiology - Virchow's Triad

1. Endothelial injury: surgery, trauma, central lines, inflammation
2. Stasis of blood flow: immobility, heart failure, varicose veins, pregnancy, obesity
3. Hypercoagulability: inherited (Factor V Leiden, Protein C/S deficiency, Antithrombin III deficiency, Prothrombin gene mutation) or acquired (malignancy, OCP, pregnancy, antiphospholipid syndrome, SLE)

Risk Factors

• Recent surgery (especially orthopaedic - hip/knee replacement)
• Prolonged immobility, long-haul flights
• Previous DVT/PE
• Malignancy (especially pancreatic, GI, lung)
• Pregnancy and postpartum period
• OCP/HRT
• Obesity (BMI >30)
• Age >60
• Thrombophilia

Clinical Features

• Calf/leg pain (usually unilateral)
• Swelling: unilateral oedema of affected leg
• Erythema, warmth of affected limb
• Homans' sign (calf pain on passive dorsiflexion) - not reliable (50% sensitive, many false positives)
• Cord-like tenderness along deep venous course
• Phlegmasia alba dolens: severe DVT with lymphoedema ("white painful leg") - superficial veins spared
• Phlegmasia cerulea dolens: massive DVT with venous gangrene threatening - profound congestion ("blue painful leg") - limb-threatening emergency

Diagnosis

• Negative D-dimer + low Wells score = DVT excluded (high negative predictive value)
• Positive D-dimer has low specificity (raised in surgery, cancer, infection, pregnancy)

Management

• DOAC (Direct Oral Anticoagulants): now first-line for most patients
  • Rivaroxaban: 15 mg bd × 21 days, then 20 mg od
  • Apixaban: 10 mg bd × 7 days, then 5 mg bd
  • Dabigatran: after initial parenteral (5 days LMWH first)
  • Advantages: fixed dose, no monitoring, oral, comparable or superior efficacy to LMWH/warfarin
• LMWH (Low Molecular Weight Heparin): enoxaparin 1 mg/kg BD SC; used in cancer-associated DVT (superior to warfarin, increasingly replaced by edoxaban/rivaroxaban)
• UFH (Unfractionated Heparin): IV infusion; for severe renal failure (eGFR <15), when reversal needed; monitored by APTT
• Warfarin: target INR 2.0-3.0; requires bridging with LMWH/UFH until therapeutic; increasingly replaced by DOACs
• Duration: 3 months for provoked DVT; 6 months - indefinite for unprovoked or cancer-associated

• Phlegmasia cerulea dolens (limb-threatening venous gangrene): catheter-directed thrombolysis (CDT) or pharmacomechanical thrombectomy
• Massive ileo-femoral DVT (<14 days): CDT can restore venous patency, reduce post-thrombotic syndrome
• Not for routine DVT

• When anticoagulation absolutely contraindicated (recent CNS surgery, active haemorrhage)
• Recurrent DVT/PE despite adequate anticoagulation
• Retrievable filters preferred (remove when anticoagulation possible)

• Mechanical: compression stockings (TEDS), intermittent pneumatic compression (IPC)
• Pharmacological: LMWH (enoxaparin 40 mg od), UFH 5000 units tds, fondaparinux, DOACs (extended prophylaxis after hip/knee arthroplasty: rivaroxaban 10 mg od × 35 days)

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18. VARICOSE VEINS - CEAP, Classification, and Endovenous Treatment [4+6]

CEAP Classification (4 marks)

Pathophysiology

• Incompetence of valves in great saphenous vein (GSV) system → superficial venous hypertension
• Elevated venous pressure → vessel wall changes → varicosities
• Inflammatory mediators → skin changes, lipodermatosclerosis, ulceration (malleolar region)
• Saphenofemoral junction (SFJ) incompetence most common source

Endovenous Treatment Techniques [6 marks]

• Endovenous Laser Ablation (EVLA/EVLT): laser fibre (1470 nm wavelength) inserted via catheter under tumescent anaesthesia; thermal energy applied as catheter withdrawn → steam bubbles damage vein wall → fibrosis and occlusion
  • Tumescent anaesthesia: 0.1% lidocaine + adrenaline injected around vein under ultrasound guidance - anaesthesia + compression to avoid perforations + heat sink
  • Advantages: day procedure, no GA, quick recovery
  • Disadvantages: post-procedure bruising, EHIT risk (endovenous heat-induced thrombus), post-ablation pain
  • Success: 90-95% occlusion at 5 years
• Radiofrequency Ablation (RFA/VNUS ClosureFast): radiofrequency energy via catheter (120°C) → thermal wall injury → fibrosis; similar to EVLA but often less post-procedure pain and bruising
  • Most commonly used: 7 cm segmental heating, 20-second cycles
  • Success: comparable to EVLA

• Foam Sclerotherapy (Ultrasound-Guided Foam Sclerotherapy - UGFS): sclerosant (sodium tetradecyl sulphate - STS 1-3%, or polidocanol) mixed with air/CO2 to create foam (Tessari technique) → injected under ultrasound guidance → denudes endothelium → thrombosis and fibrosis
  • Foam has greater contact with vessel wall than liquid
  • Multiple sessions often needed
  • Cheap, outpatient, no anaesthesia
  • Risk: visual disturbance (foam tracking), skin staining, DVT (rare), pigmentation
• Liquid Sclerotherapy: for telangiectasias/spider veins (C1); fine needle injection

• Mechanochemical Ablation (MOCA - ClariVein): rotating wire (friction) + simultaneous sclerosant injection; no tumescent needed; less pain
• Cyanoacrylate Adhesive (VenaSeal): medical-grade glue injected via catheter → seals vein; no tumescent, no compression stocking needed; good short-term results
• Steam Ablation: steam injected via catheter; limited evidence; used in Europe

• Small stab incisions along varicose tributary veins; vein hooked and avulsed using phlebectomy hook
• Usually done alongside thermal ablation or as standalone for tributaries
• Day procedure, local anaesthetic

• Trendelenburg procedure: flush ligation of SFJ (junction of GSV and femoral vein) + stripping of GSV
• SEPS (Subfascial Endoscopic Perforator Surgery): for incompetent perforators in chronic venous disease with ulcers
• Now reserved for recurrent varicose veins, complex anatomy

• Day-case procedure under LA
• Faster recovery and return to work
• Lower complication rates (haematoma, nerve injury, wound infection)
• Comparable or superior long-term recurrence rates
• Less post-procedure pain
• No general anaesthesia required

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19. VENOUS THROMBOEMBOLISM (VTE) - RISK FACTORS AND PROPHYLAXIS [2+3]

Risk Factors (2 marks)

• Factor V Leiden mutation (most common; activated protein C resistance)
• Prothrombin G20210A mutation
• Protein C deficiency
• Protein S deficiency
• Antithrombin III deficiency

• Surgery (especially hip/knee replacement, gynaecological, vascular)
• Immobilisation (hospital admission, long-haul flights)
• Pregnancy and puerperium
• Combined oral contraceptive pill / HRT
• Malignancy (especially pancreatic, brain, lymphoma)
• Previous VTE (strongest risk factor)
• Obesity (BMI >30)
• Age >60
• Heart failure
• Inflammatory conditions (IBD, SLE, antiphospholipid syndrome)
• Central venous catheters
• Polycythaemia, essential thrombocythaemia

Prophylaxis (3 marks)

• All hospitalised patients should have VTE risk assessment on admission
• Caprini score: 0-1 = low; 2 = moderate; 3-4 = high; >5 = very high

• Graduated compression stockings (GCS/TEDS): reduce venous stasis; apply before surgery; contraindicated in arterial insufficiency (ABI <0.5), acute stroke (until DVT excluded), severe leg deformity
• Intermittent Pneumatic Compression (IPC) devices: sequential pneumatic compression; very effective; used intraoperatively and post-op; especially when anticoagulation contraindicated

• LMWH (Low Molecular Weight Heparin): enoxaparin 20-40 mg SC od; most widely used; start 12 hours pre-op or 12 hours post-op
• UFH 5000 IU SC tds: for renal failure (eGFR <30) or morbid obesity
• DOACs:
  • Rivaroxaban 10 mg od: hip (35 days), knee (14 days) replacement
  • Apixaban 2.5 mg bd: similar indications
• Fondaparinux 2.5 mg SC od: Factor Xa inhibitor; for patients with HIT
• Aspirin: inferior to LMWH/DOACs; not recommended as sole prophylaxis in surgical patients
• Duration: general surgery 7-10 days; hip arthroplasty 35 days; knee arthroplasty 14 days; medical patients 6-14 days; cancer surgery 4 weeks

• Active bleeding
• Recent CNS surgery
• Severe thrombocytopaenia (<50,000)
• Recent haemorrhagic stroke
• In these cases - mechanical prophylaxis only

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20. CHRONIC VENOUS INSUFFICIENCY (CVI) AND VENOUS ULCER [5 marks]

• Incompetent venous valves (superficial, deep, or perforator) → sustained ambulatory venous hypertension → capillary hypertension → extravasation of red cells → haemosiderin deposition (pigmentation) → fibrin cuffs → pericapillary leukocyte trapping → local tissue hypoxia → venous ulceration

• Oedema (dependent, pitting, worst at end of day)
• Pigmentation (haemosiderin - brownish-purple discolouration)
• Lipodermatosclerosis: induration and fibrosis of dermis and subcutaneous fat (feels woody); classic "inverted champagne bottle" deformity of leg
• Atrophie blanche: white stellate scars surrounded by telangiectasias
• Corona phlebectatica: prominent superficial veins at ankle
• Varicose eczema: weeping, itchy dermatitis
• Venous ulcer (C6): see below

• Duplex Doppler ultrasound: assess for reflux and obstruction; map incompetent veins
• ABPI (Ankle-Brachial Pressure Index): mandatory before compression; if <0.8, compression may be harmful
• Venography: if deep venous reconstruction considered

• Compression therapy: graduated compression stockings (class II - 23-32 mmHg); reduces venous pressure; cornerstone of CVI management
• Treat superficial venous incompetence (EVLA/RFA/sclerotherapy): removes high-pressure source
• SEPS for incompetent perforators
• Skin care (emollients, topical corticosteroids for eczema)

Venous Ulcer Treatment (C6)

• Site: typically gaiter area (medial malleolus - perforating veins most numerous here)
• Distinguishing features: irregular margin, shallow, sloping edges, granulation base, surrounding pigmentation/lipodermatosclerosis; relatively painless compared to arterial ulcer

1. Exclude arterial disease: ABPI; if ABPI <0.8 → mixed arterial-venous; modified/reduced compression
2. Wound care: appropriate dressing (hydrofibre - Aquacel, foam dressing); debridement (sharp, enzymatic, larval/maggot therapy for sloughy wound)
3. Compression therapy (most important): four-layer compression bandage (e.g., Profore system) or two-layer compression; maintains 40 mmHg pressure at ankle; heals 70% within 3 months
4. Treat superficial incompetence: EVLA/surgery of GSV - reduces recurrence (ESCHAR trial)
5. Pentoxifylline: oral drug - improves capillary blood flow; adjunct to compression
6. Venous ulcer skin grafting: split-skin grafting for large/non-healing ulcers; reduces healing time; high re-ulceration without compression
7. Biological agents: becaplermin (PDGF) not routinely used
8. Treat infection: systemic antibiotics only if clinically infected (erythema, pus, fever) - not for colonization; topical antibiotics generally discouraged (resistance)
9. Preventing recurrence: lifelong compression stockings; treat underlying venous disease

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