GI & Hepatology JC068: Abdominal Distension: Ascites And Cirrhosis Flashcards
Complications of Cirrhosis
- Ascites
- Spontaneous Bacterial Peritonitis (SBP)
- Hepatorenal syndrome (HRS)
- Variceal bleeding
- Hepatic Encephalopathy (late stage)
- HCC
***Pathogenesis of Complications
Cirrhosis
—> Portal hypertension
—> Splanchnic arterial vasodilation
—> ↓ Total systemic vascular resistance
—> Arterial underfilling
—> ↓ Effective arterial blood volume / BP
—> Stimulation of neurohormonal systems (RAAS, SNS, ***AVP (arginine vasopressin, same as vasopressin / ADH))
↑ RAAS / SNS:
↑ Renal tubular reabsorption of Na
—> ***Na retention
—> Ascites + Edema
AVP:
↑ Water reabsorption in distal renal tubules
—> **Water retention
—> **Dilutional hyponatraemia
↑↑ RAAS / SNS:
↓ Systemic / Local vasodilators +/- ↑ Local vasoconstrictors
—> ***Renal vasoconstriction
—> Perfusion of kidney jeopardised
—> Hepatorenal syndrome
Ascitic fluid
Physical properties:
1. Colour
- straw (normal, pale yellow)
- blood-stained (∵ traumatic tapping, if severe need to suspect rupture viscera)
- chylous (lymphoma, TB)
- ***Protein
- may be as high as 40 g/L without special clinical significance - ***Rate of reabsorption (of fluid back into systemic circulation)
- 900ml/day (in tense ascites, may ↑ to 1.5 L/day) -
WCC (helpful to diagnose SBP)
- <500 (<250 PMN) - Malignant cells
- <10% positive in malignant ascites (very low yield)
Investigations of Ascites
- ***Diagnostic paracentesis for WBC in every patient
- ∵ need to rule out SBP - Glucose level (not useful), Malignant cells (low yield)
-
Serum-ascites albumin gradient (SAAG)
- **Serum albumin - Ascitic fluid albumin
- normal <11, elevated in abnormal situations (more free fluid leaving circulation ∵ ↑ hydrostatic pressure —> concentrating serum albumin)
- >11 g/L (↑ Hydrostatic pressure) —> Portal hypertension
- <11 g/L (NO portal hypertension) —> need to consider other causes of ascites
—> **↑ Capillary permeability: e.g. malignancy, TB peritonitis, pancreatitis
—> ***↓ Oncotic pressure: e.g. nephrotic syndrome (although protein not move across to interstitial space —> protein in serum is already low in the beginning —> ∴ SAAG is still low)
Management of Ascites
- Bed rest (for in-hospital patients)
- ∵ better perfusion, better renal perfusion - ***Salt restriction
- 0.5-2 g/day - ***Fluid restriction
- 0.8-1 L/day
—> Effective for mild ascites
—> Difficult patient compliance
- ***Diuretics
- ***Therapeutic paracentesis
Diuretics
Aim at ***1kg weight loss / day
- Distal loop diuretics
- advantage: K sparing
- **Spironolactone (Aldactone A)
—> most physiological agent (∵ hyperaldosteronism in cirrhosis)
—> high incidence of painful gynaecomastia esp. in alcoholic cirrhosis
—> relative CI in male
- **Amiloride, Triamterine - Proximal loop diuretic
- to be added on if insufficient
- ***Bumetanide (Loop diuretic)
- Furosemide (absorption in GI tract unreliable in portal hypertension) -
**IV diuretics + **Albumin infusion (to ↑ oncotic pressure in IV volume)
- oral diuretic may not have satisfactory response ∵ poor absorption in GI tract due to edema
Therapeutic paracentesis
- for ***tense ascites
- reserved for symptomatic relief only
- avoid draining too rapidly / large volume
- complications
—> **shock
—> **electrolyte disturbance
—> ***renal impairment
—> infection
—> encephalopathy
Abdominal tap of **4-6L is safe
- with **albumin infusion (to top up oncotic pressure) +/- if patient has peripheral edema (more buffer to ***shift fluid into IV volume (rather than lose in tap))
—> can prevent IV volume depletion
Complications:
- bleeding from puncture site
- **sepsis
- **perforation of caecum with R-sided puncture (∵ caecum a fixed organ) (recommend in ***L-sided lower abdomen instead, sigmoid mesentery will make sigmoid float away)
(- shock
- electrolyte disturbance
- uraemia
- encephalopathy
- protein deletion (SpC Medicine))
Spontaneous Bacterial Peritonitis (SBP)
Other 2 forms of inflammation of peritoneal fluid:
1. Monomicrobial bacterascites (有細菌, 無PMN)
- **positive for a single organism in ascitic fluid —> antibiotics still indicated
- but **no ↑ PMN (<250)
- a ***mild form of infected ascites
- Culture negative neutrocytic ascites (CNNA) (無細菌, 有PMN)
- opposite to above
- **cannot identify bacteria —> **NO antibiotics indicated, only observe
- **PMN >=250 / 500 (i.e. system can mount inflammatory response to get rid of bacteria)
- no alternative cause of ↑ in PMN
- almost certainly an **early form of SBP
Pathogenesis:
**Deficient serum complement activity / **Poor endothelial system function / GI haemorrhage / Invasive procedures
—> Bacteraemia
—> **Monomicrobial bacterascites
1. —> Good ascitic fluid opsonic activity —> resolution by macrophages
2. —> Intermediate ascitic fluid opsonic activity —> **CNNA —> resolution
3. —> Poor ascitic fluid opsonic activity —> ***SBP
Clinical features (SpC Medicine):
1. **Asymptomatic
2. **PUO
3. Encephalopathy
4. ***Abdominal S/S (none to marked)
5. Diarrhoea
6. Hypothermia
7. May be fatal / recurrent
Risk factors (UpToDate):
1. Advanced cirrhosis
2. Ascitic fluid total protein concentration <1 g/dL (<10 g/L)
3. Prior episode of SBP
4. Serum total bilirubin concentration >2.5 mg/dL
5. Variceal hemorrhage
6. Possibly malnutrition
7. Use of proton pump inhibitors
Complications:
1. Hepatorenal syndrome
2. ***Liver failure
Diagnosis of SBP
- WCC
- >500 WBC: suspicious
- **>250 PMN in patients with S/S of SBP (e.g. **fever, ***abdominal pain) (more definite diagnosis)
- >500 PMN in asymptomatic patients
(vs CAPD peritonitis: >100 WBC / mm3) - Culture
- usually **Gram -ve / **Streptococci
- may be ***negative - pH (SpC Medicine)
- pH <7.3 suspicious (if blood pH not acidotic)
- pH <7.15 poor prognosis
- Arterial-ascitic fluid pH gradient of 0.1 (normal: 0.02-0.05)
Treatment of SBP
**Broad spectrum antibiotics
- **3rd gen Cephalosporin (SpC Medicine)
- exponential ↓ in PMN count after initiation
- duration of treatment: **~5 days, can stop antibiotics as soon as PMN **<=250
Prevention of Recurrence of SBP:
**Quinolones (Norfloxacin): Long-term **selective intestinal decontamination
- incompletely absorbed by gut
- highly active against **gram -ve bacilli
- **low activity against anaerobes (∵ do not want to wipe out flora)
- rarely causes bacterial resistance
- low SE
Renal failure in Liver diseases
Causes:
1. **Hepatorenal syndrome (∵ Renal vasoconstriction)
2. **Hypovolaemia (Diuretics, GI bleeding) —> IV Fluid depletion —> Renal impairment
3. Sepsis
4. Nephrotoxic drugs
5. Parenchymal renal disease
Rmb:
- Renal impairment in cirrhosis / ascites —> first DDx is NOT Hepatorenal syndrome, instead ***Overdiuresis most common
- consider 2-5 before 1
Hepatorenal syndrome
Renal failure that occurs in patients with severe liver disease
- in absence of any pathological causes for development of renal failure
Pathogenesis:
↑↑ RAAS / SNS
—> ↓ Systemic / Local vasodilators +/- ↑ Local vasoconstrictors
—> ***Renal vasoconstriction
—> Perfusion of kidney jeopardised
—> Hepatorenal syndrome
***Diagnostic criteria of Hepatorenal syndrome
- Urine volume <500 ml/day (***Oliguria)
- ***Urine Na <10
- Urine osmolality (i.e. ***concentrated urine) > Plasma osmolality
- ***Absence of Haematuria
- ***Serum Na <130 (Dilutional hypoNa)
Treatment of Hepatorenal syndrome
- Optimise BP
- **Terlipressin/Glypressin +/- **Albumin
Terlipressin:
- vasoconstrictors (**↑ systemic vascular resistance, ↑ mean arterial pressure)
—> suppresses activation of SNS
—> improves central blood volume (?)
—> **improves BP + renal perfusion pressure
—> ***↑ GFR + ↓ serum creatinine
Albumin:
- ↑ oncotic pressure —> ***↑ blood volume —> ↑ renal perfusion
Other drugs:
- Norepinephrine
- Octreotide
- Optimisation of renal haemodynamics
- ***Paracentesis
—> drainage of tense ascites (intraabdominal pressure physically pressing on renal system) may temporarily improve renal haemodynamics + renal function
—> but may be associated with modest fall in BP
Possible causes of bleeding in cirrhotic patients
- ***Varices (esophageal, gastric)
- Portal hypertensive gastropathy (SpC Medicine)
- Peptic ulceration
- ***Coagulopathy (generalised bleeding tendency) (∵ ↓ clotting factor synthesis + ↓ Plt due to splenomegaly)
- Others e.g. ***Mallory-Weiss syndrome
Variceal bleeding
- comes in column around lower end of esophagus
- extend from ***EG junction up to lower esophagus
When does variceal bleeding occur?
Probably associated with vessel wall-stress
1. **Portal BP (unlikely to bleed if portal pressure **<12 mmHg (but hard to measure))
—> if high portal pressure
—> wall becomes thinner
—> rupture
2. Large vessels with ***thin walls
***Management of Variceal bleeding
Management of cirrhotic patients with GI bleeding
1. **Shock treatment (fluid resuscitation, blood transfusion)
2. Monitor vital signs (Q1H)
3. **Endoscopic diagnosis of source of bleeding (ulcer / variceal)
4. **Prevention / Treatment of HE (GI bleeding a precipitating factor for HE)
- **Lactulose
5. **Correct coagulopathy: **Vit K1 therapy + Correction of clotting factor defects (in case there is any ***cholestatic elements —> ↓ Vit K absorption)
Management of Variceal bleeding:
Acute
1. Endoscopic treatment
- **Band ligation
- **Sclerotherapy
- Variceal obliteration by tissue adhesive (for gastric varices in fundus)
- Drug therapy
- Vasoconstrictors (Terlipressin, Octreotide)
—> ↓ SMA, Splenic arterial flow —> ↓ Portal pressure
—> ↓ Blood flow to gut - Balloon tamponade
- ***Sengstaken Blakemore tube
- seldomly done - Emergency surgery
- ***transect esophagus
- seldomly done
Long-term / Prophylaxis
1. **Propranolol / other β blockers (e.g. Nadolol, Carvedilol (SpC Medicine))
- Propranolol (TDS) vs Carvedilol, Nadolol (OD (preferred))
- **↓ CO —> ↓ portal blood flow
- effective in prevention of rebleeding
- can be combined with vasodilators e.g. Isosorbide mononitrate
- should be stopped in end-stage cirrhosis (decreased CO may cause hypotension + hepatorenal syndrome), sepsis (SpC Medicine)
- target HR: ***50-60 (SpC Medicine)
- Repeated band ligation
- better than long-term sclerotherapy - ***Transjugular Intrahepatic Portosystemic Shunt (TIPS)
Ultimate effect of treatment on patient survival
1. Liver transplantation
Revision: Liver failure and Coagulopathy
- ***↓ Hepatic synthetic function —> ↓ clotting factors, inhibitors
- ***Thrombocytopenia (∵ Portal hypertension —> increased splenic sequestration i.e. hypersplenism)
- ***Cholestasis —> ↓ Vit K absorption —> ↓ active Vit K dependent factor + inhibitors
- Acquired dysfibrinogenaemia
- Failure to clear activated intermediates of coagulation and fibrinolysis from bloodstream
Band ligation / Injection sclerotherapy
- Immediately done (effective but can be difficult)
- Need to ensure all remaining vessels should be sclerosed in the weeks after stopping of haemorrhage
- Generally band ligation > injection sclerotherapy (create another puncture in varices)
Complications (few):
- **transient esophageal pain
- esophageal ulcers (rarely bleed)
- **sloughing of bands during subsequent endoscopies (delay 7-10 days before next endoscopy (SpC Medicine))
- ***stricture (balloon dilatation to treat)
- mediastinitis (only for injection sclerotherapy)
- aspiration pneumonia
Disadvantage:
- cannot reach **gastric varices —> need **tissue adhesive
- stops acute bleeding in 80-90% but bleeding may recur in next few days —> overall success 60-70%
Octreotide / Somatostatin
- synthesised Octapeptide sharing 4 a.a. with Somatostatin —> longer t1/2, greater potency
- action not well-defined
—> **↓ Splanchnic blood flow in normal subjects
—> **Data in cirrhosis contradictory with variable effects on portal, variceal pressure
Advantages:
- very minimal SE
Disadvantages:
- efficacy 60-70%
- now out of favour (∵ not as good as Terlipressin)
Sengstaken-Blakemore tube
- requires careful handling
- need to connect tube to bedside for traction (扯住條tube) otherwise tube fall into stomach
Gastric balloon: anchor tube in place
Esophageal balloon: compress varices (tamponade effect)
Disadvantages:
- patient discomfort
- **esophageal ulceration / necrosis (keep in place <24 hours (SpC Medicine))
- **asphyxia due to balloons (obstruct airway)
- ***aspiration pneumonia
Transjugular Intrahepatic Portosystemic Shunt (TIPS)
- stenting between hepatic vein and portal vein
- portal vein —> shunt directly bypass liver sinusoids —> hepatic vein
- ***↓ portal pressure
Indications:
1. **Variceal bleeding
- resistant + recurrent
- acute uncontrolled
2. **Refractory ascites
3. Refractory cirrhotic hydrothorax
4. Budd-Chiari syndrome
5. Prophylactic portal decompression prior to transplant
Contraindications:
1. **RH failure (∵ ↑ venous return)
2. **Frequent HE
3. ***HCC
4. Liver abscess / cholangitis
5. DIC
6. Cavernous formation of portal vein
7. Thrombosis of R/L IJV, SVC / IVC
Acute complications:
1. Procedure-related
- Severe / fatal **intra-abdominal bleeding from perforation of liver capsule / stent at portal bifurcation
- Haemobilia
- Haematoma of liver
2. **Thromboembolism with clot in stent
3. ***Volume overload with heart failure
4. Renal failure (related to dye)
5. DIC
6. Sepsis
Chronic complications:
1. ***HE
2. Stent stenosis / occlusion
3. Recurrent bleeding (∵ non-portal hypertensive bleed / inadequate portal decompression (SpC Medicine))
Portal hypertensive gastropathy (SpC Medicine)
Congestive gastropathy:
- Portal hypertension causing mucosal vascular ectasia (NOT due to H. pylori)
- Occurrence common
- More frequent in patients with large varices, poor liver function
- ?↑ by sclerotherapy which ↑ gastric mucosal congestion
- Mostly causes occult bleeding
Treatment:
- Beta-blockers
Related condition (Wiki):
Gastric antral vascular ectasia (GAVE) / Watermelon stomach
- However, in GAVE, the ectatic blood vessels are more commonly found in the antrum or lower part of the stomach
