cirrhosis Flashcards
consequences of cirrhosis
1) block blood flow
2) impede hepatocyte perfusion
3) impair liver synthetic function (e.g. produce albumin)
aetiology of cirrhosis
1) alcohol
2) chronic Hep B & C
3) metabolic liver syndrome
- hemochromatomasis: body cannot process iron properly, accumulate
4) drug induced: isoniazid, methyldopa, amiodarone, diclofenac, methotrexate
progression of cirrhosis
1) compensated
- silent, asymptomatic, generally good QoL
2) decompensated
- 1st clinical symptoms: ascites, bleeding, encephalopathy, jaundice
- progression due to development of complications
- end stage: death or liver transplant
complications of cirrhosis
1) variceal bleeding
2) hepatic encephalopathy
3) cirrhotic cardiomyopathy
4) hepatopulmonary syndrome, portopulmonary syndrome
5) hepatorenal syndrome, AKI
6) ascites
general ascites
- accumulation of excess fluid in peritoneal cavity
- prone to complications: bacterial infection, nutrient & electrolyte imbalance, HRS
pathogenesis of ascites
structural component
- cirrhosis -> development of nodules surrounded by fibrotic material -> impede blood flow to liver
functional component
- increase in vascular tone (constriction) -> portal HTN -> sphlanic vasodilation (body detect increase in portal pressure)
- portal HTN -> increase in hydrostatic pressure
- lower albumin synthesis -> lesser albumin to maintain oncotic pressure -> lower intravascular oncotic pressure
- portal HTN + vasodilation -> underfilling & lesser aldosterone in liver -> further activation of RAAS -> further Na & H2O retention
- sphlanic vasodilation: lymph formation > lymph return
- end of day: fluid from portal circulation into peritoneal cavity
ascites related sypmtoms
1) dyspnoea: difficulty breathing cuz stomach distended
2) abdominal distention & pain
goals of therapy of ascites
1) control ascites
2) prevent/relieve ascites related symptoms
3) prevent life threatening conditions: SBP, HRS
treatment of ascites
1) abdominal paracentesis
- insert needle into abdominal cavity to aspirate ascitic fluid
- send ascitic fluid for analysis: cell count w differential, ascitic fluid total protein, signs for bacterial infection, serum ascitic albumin gradient (SAAG, SAAG >/= 11 means portal HTN)
2) dietary
- no alcohol
- Na retention (2000mg/day) to prevent further fluid retention
3) spironolactone (aldosterone agonist) 100mg + frusemide 40mg (loop) OM PO
- titrate every 3-5 days with 100:40 ratio until adequate natriuresis & weight loss
- frusemide lower risk of hyperkaliemia & prevent water retention
4) antibiotics for SBP: long term prophylaxis
5) tie rubber band/BP lowering meds to prevent bleeding
caution for treatment of ascites
1) no NSAIDs cuz worsen
2) no ACEi/ARB cuz risk of AKI and HRS
3) no need for fluid retention
- patient already in state of hypovolemia
- fluid retention further activate RAAS -> further water retention
general varices
- swelling of veins around stomach & oesophagus -> burst & bleed
- asymptomatic until burst
- diagnosis: endoscopy to find swollen veins around stomach & oesophagus
hepatic venous pressure gradient (HVPG)
. pressure difference between portal and central venin
. HVPG > 5 mmHg = portal HTN
. HVPG > 10 mmHg = variceal bleeding
coagulation defects
. decrease synthesis of procoagulation factors and naturally occurring anticoagulants, antithrombin, protein C & S
. increase in anticoagulant factor VII & von Willdebrand
- state of rebalanced hemostasis
- balance can be tipped anytime (risk of bleeding/thrombosis)
. thrombocytopenia common
diagnosis for cirrhosis - history taking
1) identifying symptoms
- asymptomatic: compensated
- initial symptoms (non-specific): fatigue, loss of appetite, weight loss
- signs of decompensated cirrhosis
2) determine cause of cirrhosis
- alcohol/drug abuse
- obesity, diabetes, NAFLD
- risk factors for Hep B & C
- personal/family history of immune/hepatic disease
- drugs that can cause cirrhosis
diagnosis for cirrhosis - history taking
1) identifying symptoms
- asymptomatic: compensated
- 1st clinical sypmtoms (non-specific): fatigue, weight loss, loss of appetitie
- signs of decompensated cirrhosis
2) determine cause of cirrhosis
- alcohol/drug abuse
- obesity, diabetes, NAFLD
- risk factor for Hep B & C
- personal/family history of immune/hepatic disease
- drug induced
diagnosis for cirrhosis - physical examination
1) jaundice: yellowing of skin/eyes
2) pruritus
3) plamar erythema
4) spider angiomata
5) hyperpigmentation
6) metabolic problems: gynaecomastia, testicular atrophy, axillary hair loss (lower oestrogen produced by liver)
diagnosis for cirrhosis - lab test
1) assessment
- LFT: hepatocellular/cholestatic
- coagulation test (PT, aPTT, INR): synthetic function of liver
- complete blood count + platelet
2) other causes of cirrhosis
- Hep B/C: serologic test for viral load
- autoimmune disease: antinuclear antibody titer
- haemochromasis: serum Fe & transferrin saturation, genotype testing (maybe)
- alpha-1 antitrypsin deficiency: alpha-1 antitrypsin levels & genotyping
diagnosis for cirrhosis - imaging test
1) ultrasound
- presence of varices, portal HTN, cirrhosis
2) elastography
- if ultrasound cmi
diagnosis for cirrhosis - tissue biopsy
if non-invasive cmi
general approach to treating cirrhosis
A) identify and eliminate (if possible) causes for cirrhosis
B) assess risk for variceal bleeding and benign pharmacological prophylaxis when indicated
. prophylactic endoscopic therapy
- for patients with high risk medium-large size varices
- for patients CI/intolerant of BB
- tie rubber band around varices
. variceal obliteration w endoscopic techniques
- for acute bleeding
C) monitor for patient for ascites + pharmacotherapy + paracentesis
- monitor for spontaneous bacterial peritonitis (SBP) & acute deterioration of clinical status
D) monitor for other causes of HE
- pharmacotherapy (diet, lactulose, ribavirin)
E) monitor for other liver complications
- HRS, pulmonary insufficiencies, endocrine dysfunction
levels of treatment of cirrhosis
1) primary prophylaxis
- compensated, HVPG >/= 10 mmHg
- presence of varices
- goal: prevent decompensation
2) treat acute variceal bleeding
- first blood, presence of variceal haemorrhage
- goal: control bleeding, prevent early rebleeding and death
3) secondary prophylaxis
- goal: prevent rebleeding
primary prophylaxis
. for high risk varices
- small + red wales + Child-Pugh score C
- medium/large irregardless of Child-Pugh
. BB
- MOA:
1) B1 blockade: lower cardiac output
2) B2 blockade: lower splanchnic blood flow
- carvedilol: alpha blockade as well to increase release of NO
- target HR: 55-60bpm
- caution
1) systolic BP needs to be > 90 mmHg
2) refractory/tense ascites
3) other complications (AKI, bleeding)
- SE: pulmonary bronchospasms, bradycardia
. endoscopy variceal ligation
- tie rubber band around varices
- goal: eradication (until no further ligation possible)
- dose: every 2-3 wks until eradication
treatment for acute variceal bleeding
1) stabilise patient
- ABC
- volume replacement: crystalloids, transfusion (Hb < 7)
2) drug therapy
. vasoactive drug
- splanchnic dilation -> lower blood flow -> reduce bleeding
- doesnt stop bleeding, still require ligation
- osteopresin: hyperglycemia, HTN, bradycardia
- vasopressin, somatostatin
. antibiotics
- prevent risk of infection
3) endoscopic techniques
- within 12 hrs of bleed
- confirm site of bleed, ligation
4) continue drug therapy
- vasoactive: 3-5 days
- antibiotics: 5-7 days
5) after continuing drug therapy
. controlled: secondary prophylaxis
. bleeding
- transjugular intrahepatic portosystemic shunt (TIPS): insert stent between portal and hepatic vein to relieve pressure off varices, don’t need secondary prophylaxis but refer for transplant
- balloon tamponade: insert & inflate balloon tamponade, last 24 hrs
secondary prophylaxis
. BB + EVL
. TIPS if above cmi
what is hepatic encephalopathy + symptoms
. functional disturbance of brain
. wide spectrum of symptom severity
1) lowest: alteration in attention, memory, psychomotor skills
2) higher: behavioural changes (irritation, disinhibition)
3) worst: affect consciousness (coma)
pathogenesis of hepatic encephalopathy
. resistance in liver -> blood shunted to other organs (varices around stomach, brain)
. decrease liver function & shunting of blood through portosystemic collaterals bypassing liver -> accumulation of N substances -> go straight to brain
. entry of N substances into brain -> alter neurotransmission -> affect consciousness & behaviour
approach to treatment of hepatic encephalopathy
1) Care for patient with altered mental state
2) identify & treat other causes for altered mental state
3) identify & treat precipitating factors
4) begin empiric therapy
5) focus on lowering blood NH3 concentration (lab values)
therapy for hepatic encephalopathy
1) dietary measures
- lower protein intake (1.2g/kg/day - 1.6g/kg/day)
- veg & diary sources preferred
- supplement with Zn
2) lactulose
- lower oncotic pH, promote conversion of ammonia to ammonium for excretion, increase bowel movement for excretion
- initiate high dose to achieve catharsis (increased bowel movement), titrate to achieve 2-3 soft stools/day
3) rifaximin
- target anaerobic bacteria in gut that produce urease (convert urea to ammonia)
- 550mg BD
- + lactulose for recurrent HE
- low systemic absorption = low AE profile, preferred antibiotics
