Portal Hypertension: Anatomy & Physiology

1. Anatomy of the Portal Venous System

Fig. 124.1 — Yamada's Textbook of Gastroenterology

• Left gastric vein (coronary vein) → drains at the SMV–splenic confluence
• Inferior mesenteric vein (IMV) → drains into the splenic vein
• Short gastric veins, gastro-epiploic veins → via the splenic vein
• Veins from pancreas, duodenum, jejunum, ileum, ascending and descending colon

CT angiogram: portal vein anatomy (★ = main portal vein, white arrow = splenic vein, white ★ = SMV, black arrowheads = right/left branches)

2. Normal Hepatic Hemodynamics

• Nitric oxide (NO) — produced by endothelial NOS (eNOS) in response to shear stress → vasodilation
• Endothelin-1 (ET-1) — produced by endothelial cells → binds ET-A receptors on HSCs → vasoconstriction; binds ET-B receptors on endothelium → vasodilation (via eNOS)
• Others: sympathetic NS, angiotensin, prostaglandins, CO, hydrogen sulfide

3. Pathophysiology of Portal Hypertension

Portal Pressure = Portal Flow × Vascular Resistance

Fig. 124.2 — Yamada's Textbook of Gastroenterology

3a. Increased Intrahepatic Resistance (in Cirrhosis)

• Architectural distortion from progressive collagen deposition and regenerative nodules
• Vascular obliteration and sinusoidal capillarization
• Activated HSCs deposit collagen in the space of Disse → loss of endothelial fenestrae → formation of a subendothelial basement membrane
• Increased resistance at all levels: intrahepatic portal vein branches, sinusoids, hepatic venules

• ↓ intrahepatic NO production (dysfunctional eNOS in cirrhotic liver)
• ↑ ET-1 → HSC contraction → active sinusoidal narrowing
• This component is pharmacologically modifiable

3b. Increased Portal Blood Flow (Hyperdynamic Circulation)

• Increases blood flow into the portal system
• Creates a hyperdynamic circulation: high cardiac output, low systemic vascular resistance
• Perpetuates and worsens portal hypertension despite collateral formation

3c. Classification by Site of Resistance

4. Portosystemic Collaterals

Fig. 124.3 — Yamada's Textbook of Gastroenterology: Sites of portosystemic collateral circulation

5. Downstream Consequences

Fig. 93.1 — Sleisenger & Fordtran's: Pathophysiology of ascites and renal dysfunction in cirrhosis

Ascites

• RAAS activation → aldosterone → sodium retention
• SNS activation → renal vasoconstriction
• ADH/vasopressin → water retention → dilutional hyponatremia

Variceal Hemorrhage

• HVPG ≥ 10 mmHg → clinically significant portal hypertension (risk of varices)
• HVPG ≥ 12 mmHg → threshold for variceal bleeding
• HVPG reduction ≥ 20% from baseline or to < 12 mmHg → significantly reduces bleeding risk

Hepatic Encephalopathy

Splenomegaly / Hypersplenism

Hepatopulmonary Syndrome / Portopulmonary Hypertension

• HPS: intrapulmonary vasodilation → V/Q mismatch → hypoxemia
• PoPH: pulmonary arterial hypertension, related to excess vasoconstrictors reaching the pulmonary bed

6. Measurement: HVPG

• Yamada's Textbook of Gastroenterology, 7th ed. — Ch. 124, "Pathophysiology of portal hypertension"
• Sleisenger and Fordtran's Gastrointestinal and Liver Disease — Ch. 93, "Portal hypertension"
• Medical Physiology (Boron & Boulpaep) — Ch. 24, "Portal Hypertension"

Symptoms & Signs of Portal Hypertension

1. Gastrointestinal Bleeding

• Hematemesis — often effortless, recurrent; vomit described as dark red
• Melena — black tarry stool from upper GI blood
• Hematochezia — if bleeding is brisk
• Sources:
  • Esophageal varices — most common (lower esophagus, where left gastric vein anastomoses with azygos)
  • Gastric varices — especially fundal; bleed more massively
  • Portal hypertensive gastropathy (PHG) — chronic insidious blood loss, iron-deficiency anemia
  • Ectopic varices — duodenal, rectal, stomal (less common)

Suspect variceal hemorrhage in any patient with upper GI bleed who has peripheral stigmata of liver disease.

2. Ascites

• Abdominal distension, bloating, early satiety
• Dyspnea (diaphragm elevation, hepatic hydrothorax)
• Discomfort or pain from abdominal fullness

• Bulging flanks
• Shifting dullness on percussion
• Fluid wave (large volumes)
• Everted umbilicus
• Hepatic hydrothorax — usually right-sided pleural effusion (diaphragmatic defect allows ascites to track into pleural space)

• SAAG ≥ 1.1 g/dL → portal hypertension as cause (cirrhosis, cardiac ascites)
• SAAG < 1.1 g/dL → non-portal cause (malignancy, infection, TB)
• Ascitic fluid protein < 1.5 g/dL → high risk for spontaneous bacterial peritonitis (SBP)

3. Splenomegaly & Hypersplenism

• Left upper quadrant fullness or dull ache
• Early satiety (from enlarged spleen)

• Palpable enlarged spleen (left upper quadrant)
• Hypersplenism → sequestration and destruction of blood cells:
  • Thrombocytopenia — most sensitive lab indicator of portal hypertension; also increases bleeding risk
  • Leukopenia
  • Anemia (hemolytic + nutritional)

Thrombocytopenia is often the first laboratory clue to underlying portal hypertension.

4. Hepatic Encephalopathy (HE)

• Asterixis ("flapping tremor") — involuntary jerking of outstretched hands; hallmark of early-to-moderate HE
• Fetor hepaticus — sweet, musty breath odor from sulfur compounds (dimethyl sulfide)
• Hyperreflexia, Babinski sign (in advanced cases)
• Slurred speech, ataxia

5. Peripheral Stigmata of Chronic Liver Disease

6. Spontaneous Bacterial Peritonitis (SBP)

• Fever, abdominal pain/tenderness
• Worsening encephalopathy
• May be asymptomatic — diagnosis requires paracentesis

7. Hepatorenal Syndrome (HRS)

• Oliguria, rising creatinine
• Dilutional hyponatremia (serum Na⁺ < 130 mEq/L)
• No proteinuria, no structural kidney disease

8. Cardiopulmonary Complications

Clinical Approach Summary

Portal Hypertension
        │
        ├── GI Bleeding ──── hematemesis, melena (varices, PHG)
        ├── Ascites ────────── distension, dyspnea, hydrothorax
        ├── Splenomegaly ──── LUQ fullness → thrombocytopenia
        ├── Encephalopathy ── confusion, asterixis, fetor hepaticus
        ├── SBP ─────────────  fever + ascites + AMS
        ├── HRS ─────────────  oliguria, hyponatremia, ↑ creatinine
        └── Pulmonary ───────  HPS (platypnea), PoPH (exertional dyspnea)

• Harrison's Principles of Internal Medicine, 22nd ed. — Ch. 355, "Portal Hypertension"
• Sleisenger & Fordtran's Gastrointestinal and Liver Disease — Ch. 92, "Clinical Assessment"
• Yamada's Textbook of Gastroenterology, 7th ed. — Ch. 124

Treatment of Portal Hypertension

1. Pharmacological Reduction of Portal Pressure

Nonselective Beta-Blockers (NSBBs)

• β₁ blockade → ↓ cardiac output → ↓ portal inflow
• β₂ blockade → unopposed α₁ vasoconstriction in mesenteric vessels → ↓ splanchnic blood flow → ↓ portal pressure

• ≥ 20% reduction from baseline, OR
• Absolute HVPG < 12 mmHg → substantially reduces variceal bleeding risk and mortality

Vasoactive Agents (Acute Bleeding Only)

Other Agents

• Statins (simvastatin): Upregulate eNOS → improve sinusoidal endothelial function → modest portal pressure reduction. Survival benefit in Child-Pugh A/B; unsafe at ≥ 40 mg/day in Child-Pugh B/C due to rhabdomyolysis risk.
• ACE inhibitors / ARBs: Reduce intrahepatic resistance via RAAS blockade; only safe in early (Child-Pugh A) disease — high risk of hypotension and renal failure in advanced cirrhosis.
• Nitrates: No longer routinely used.

2. Management of Variceal Hemorrhage

A. Primary Prophylaxis (Before First Bleed)

• At diagnosis of compensated cirrhosis
• Every 2 years (active disease) or every 3 years (inactive disease)
• Skip screening if liver stiffness < 20 kPa AND no thrombocytopenia (low-risk varices unlikely)

• NSBB (propranolol, nadolol, or carvedilol) — preferred when tolerated
• Endoscopic variceal ligation (EVL) — preferred if NSBBs contraindicated or not tolerated

B. Acute Variceal Hemorrhage (Medical Emergency)

1. Resuscitation
   • Restricted transfusion strategy: transfuse when Hgb < 7 g/dL, target Hgb 7–9 g/dL
   • Avoid over-transfusion (worsens portal pressure)
   • Do not routinely correct elevated PT with FFP unless active coagulopathy at other sites
2. Vasoactive drugs — start immediately (before endoscopy)
   • IV octreotide or terlipressin → reduces portal inflow, aids hemostasis
3. Prophylactic antibiotics — start before endoscopy
   • IV ceftriaxone → reduces infections, rebleeding, and mortality
   • (Quinolones as alternative; ceftriaxone preferred in advanced cirrhosis)
4. Endoscopy (EGD within 12 hours)
   • Endoscopic variceal ligation (EVL) — first-line for esophageal varices
   • Sclerotherapy — if EVL unavailable (higher complication rate)
   • Gastric varices extending into cardia/fundus → EVL often fails → consider TIPS
5. Balloon tamponade (Sengstaken-Blakemore / Minnesota tube)
   • Bridge to definitive therapy if endoscopic control fails
   • Self-expanding metal stents are an alternative bridge
6. Early TIPS (within 72 hours)
   • In high-risk patients: HVPG > 20 mmHg, or Child-Pugh B with active bleeding at endoscopy, or Child-Pugh C
   • Significantly reduces rebleeding and mortality in this group

C. Secondary Prophylaxis (After First Bleed)

• Repeated EVL until varices obliterated, plus
• NSBB (combination superior to either alone)

Fig. 355-3 — Harrison's Principles of Internal Medicine, 22nd ed.

3. TIPS (Transjugular Intrahepatic Portosystemic Shunt)

• Refractory/recurrent variceal hemorrhage (salvage or secondary prevention)
• Refractory ascites
• High-risk acute variceal bleed (early/pre-emptive TIPS)
• Bridge to liver transplantation

• Congestive heart failure / tricuspid regurgitation
• Moderate–severe pulmonary hypertension
• Uncontrolled hepatic encephalopathy
• Severe liver failure (relative)

• Hepatic encephalopathy — up to 20%, especially in elderly or those with pre-existing HE
• Intra-abdominal hemorrhage (~1–2%)
• Heart failure (sudden ↑ venous return)
• Stent stenosis (monitor with Doppler ultrasound periodically)
• Contrast nephropathy, hemolytic anemia, sepsis

All patients requiring TIPS should be evaluated for liver transplantation.

4. Surgical Shunts

5. Treatment of Ascites

6. Treatment of Hepatic Encephalopathy

7. Treatment Summary by Complication

Portal Hypertension Treatment
│
├── Reduce Portal Pressure (all patients with CSPH)
│     └── NSBB (carvedilol preferred) ± EVL
│
├── Variceal Hemorrhage
│     ├── Acute: octreotide + ceftriaxone + EVL ± early TIPS
│     └── Secondary prevention: EVL + NSBB → TIPS if fails
│
├── Ascites
│     ├── Na restriction → spironolactone ± furosemide
│     └── Refractory: LVP + albumin or TIPS
│
├── Hepatic Encephalopathy
│     └── Lactulose ± rifaximin; correct precipitants
│
├── SBP
│     └── Cefotaxime (treatment); norfloxacin (prophylaxis)
│
├── HRS
│     └── Terlipressin + albumin; TIPS as bridge; transplant
│
└── Definitive Therapy
      └── Liver transplantation (evaluate all decompensated patients)

• Harrison's Principles of Internal Medicine, 22nd ed. — Ch. 355
• Yamada's Textbook of Gastroenterology, 7th ed. — Ch. 124
• Sleisenger & Fordtran's Gastrointestinal and Liver Disease — Ch. 92
• Miller's Anesthesia, 10th ed. — Ch. 14 (TIPS)