CLD Flashcards
Definition of CLD
Disease of the liver lasting 6 months or more
Consists of a spectrum of liver disease which includes chronic hepatitis, liver cirrhosis and hepatocellular carcinoma
The prototype is liver cirrhosis
This is the final common pathway of all chronic liver diseases
Term was 1st coined by Laennec in 1826
Histologically, it is characterized by diffuse fibrosis and nodular regeneration which lack the well organized zonal structure of normal liver lobules/acini.
There is distortion of the portal and biliary tracts with haphazard blood perfusion and oxygenation of hepatic parenchyma
Hepatocyte extinction, micro- and macro-vascular remodeling, neoangiogenesis and nodule formation ensues
Liver function is ultimately compromised resulting in liver failure.
Epidemiology
Globally, 1.5 billion persons had CLD in 2017
Most commonly resulting from Non-alcoholic fatty liver disease (60%), Hepatitis B virus (29%), Hepatitis C virus (9%), and alcoholic liver disease (2%).
Cirrhosis represents the fourth cause of death due to non-communicable diseases worldwide
In a Nigerian study, cirrhosis constituted 28% of all liver biopsies over a ten year period
Aetiology
Viral hepatitis (B D, C), i.e. post-necrotic cirrhosis
Alcoholic (Laënnec’s) cirrhosis
Metabolic
-haemochromatosis
- NAFLD
- Wilson’s disease
- 1-antitrypsin deficiency
Hepatic venous outflow obstruction
- veno-occlusive disease
- Budd-Chiari syndrome
- cardiac cirrhosis
Toxins & drugs
- Alcohol
- methotrexate
-amiodarone
Disturbed immunity
- autoimmune hepatitis
- Primary biliary cirrhosis
- Primary sclerosing cholangitis
Etiology of cirrhosis
Etiology: triad
• 1. necrosis
• 2. regenerating nodules
• 3. fibrosis
> Categories:
• Major
Alcoholic (#1 cause in western world)
Post necrotic
• Minor
Wilson’s disease
Haemochromatosis
Biliary
Chronic hepatic congestion
• Budd-Chiari syndrome
• uncommon condition
Healthy
Induced by thrombotic or nonthrombotic
obstruction to hepatic venous outflow.
• Cardiac
• Right sided heart failure
• Tricuspid insufficiency
Pathology
Histologically, cirrhosis can be classified into two types:-
Micronodular cirrhosis defined by small nodules of about 1mm. Usually associated with alcohol
Macronodular cirrhosis defined by larger nodules >3mm. Usually associated with viral hepatitis
Pathophysiology
Primary event is injury to hepatocellular elements
-hepatocytes
- kupffer cells
- bile ducts
Initiates inflammatory response with cytokine release and activation of stellate cells
These cells transform into contractile myofibroblast producing cells with destruction of hepatocytes, bile duct cells, vascular endothelial cells
Repair through cellular proliferation and nodular regeneration and fibrosis
Prevents normal flow of nutrients to hepatocytes and increases hepatic vascular resistance
Initially, fibrosis may be reversible if inciting events are removed
With sustained injury, process of fibrosis becomes irreversible and leads to cirrhosis
Portal hypertension is the major driver in the transition from the compensated to the ‘decompensated’ stage of cirrhosis defined by the presence of clinical complications
Sequence if pathological events in liver cirrhosis
Diffuse liver cell injury leading to hepatocyte necrosis
↑↑ Fibrous tissue formation
Nodular regeneration
Progressive distortion of the liver vascular bed
Portal hypertension
Diagnosis
Liver biopsy
Stigmata of chronic liver disease
Abdominal findings
Other investigations
Liver function tests
Clotting profile
Abdominal ultrasound
Transient elastography
Complications
Ascites
Spontaneous bacterial peritonitis
Variceal bleeding
Cirrhotic cardiomyopathy
Hepatorenal syndrome
Hepatic encephalopathy
Hepatic hydrothorax
Hepato-pulmonary syndrome
Hepatocellular carcinoma
Impaired coagulation
Prognosis-Child-Pugh Classification
1 2 3
Encephalopathy (Grade) None 1 & 2 3 & 4
Ascites Absent Mild Moderate
Serum bilirubin (mg/dl) 1 – 2(<34)* 2 – 3(34-50) > 3(>50)*
Serum albumin (g/dl) 3.5 2.8 – 3.5 < 2.8
PT (seconds prolonged) 1 – 4 4 – 6 > 6
INR <1.7 1.7-2.3 >2.3
Class A: 5 – 6 Class B: 7 – 9 Class C: 10 – 15
*umol/l
MELD-Score
The Model for End-stage Liver Disease (MELD) was initially created to predict survival in patients with complications of portal hypertension undergoing elective TIPSS
The MELD uses only objective variables-Bilirubin, INR, Creatinine
Presently used to predict organ allocation for orthotopic liver transplantation
Ascites
Defined as free fluid in the peritoneal cavity
Mechanism of ascites
Underfilling theory
Overflow theory
Peripheral artery vasodilatation
Hypoalbuminemia
Reduced aldosterone metabolism
Lymphatic weep
Grading of ascites
Grading of ascites.
Grade 1.
Mild ascites: it is only detectable by ultrasound examination
Grade 2.
Moderate ascites: it is manifest by moderate symmetrical distension of abdomen
Grade 3.
Large or gross ascites: it provokes marked abdominal distension
Investigations of ascites
Investigations- SAAG, neutrophil count, cytology, culture, protein
Treatment
Low salt diet(80–120 mmol or 4.6–6.9 g /day)
Diuretics (spironolactone, canrenone or K-canrenoate)/frusemide
LV Paracentesis + Albumin
TIPS(polytetrafluoroethylene (PTFE)-covered stent grafts
Automated low-flow ascites pump (Alfapump)
SPONTANEOUS BACTERIAL PERITONITIS(SPB)
Usually results from translocation of bacteria from gut to peritoneal cavity or from hematogenous transmission.
Risk factors- portosystemic shunting, gut dysbiosis , low complement/protein levels (serum/ascitic fluid), impaired immunity and genetic factors(NOD2)
Clinical features
- asymptomatic abdominal pain, fever, absent bowel sounds, worsening of ascites.
TREATMENT
Broad spectrum antibiotics ± albumin infusion
Third-generation cephalosporins or quinolones are recommended as first-line antibiotic treatment
Amoxicillin/clavulanic acid maybe assoc with drug induced liver injury
Piperacillin/tazobactam or carbapenem should be given in cases of multi-drug resistance
Tx for 5-7 days
Repeat diagnostic paracentesis after 48hours
Hepatorenal syndrome
HRS is traditionally defined as “a functional renal failure caused by intra-renal vasoconstriction
Pathophysiology of HRS
Hypoperfusion due to macrocirculatory dysfunction
Increased circulating levels of pro-inflammatory cytokines and chemokines
There is mitochondria-mediated metabolic downregulation which increases sodium chloride delivery to the macula densa
This triggers further intrarenal activation of the RAAS and thus lowers GFR.
Finally, severe cholestasis further impair renal function by worsening inflammation and bile salt-related direct tubular damage.
Treatment of HRS
Terlipressin plus albumin is
Telipressin initial dose of 1 mg every 4–6 h or continuous i.v. infusion at 2 mg/day to maximum of 12 mg/day
Albumin solution (20%) should be used at the dose 20–40 g/day
Continous renal replacement therapy
Molecular adsorbent replacement systems
Liver transplantation
What is Hepatic encephalopathy?
Neuropsychiatric syndrome associated with liver failure and portosystemic shunting leading to cognitive, behavioral/motor dysfunction.
Precipitants of Hepatic encephalopathy
Dehydration
Hypokalemia
High protein diet
Constipation
Infection
UGI bleeding
Drugs
Grading of Hepatic encephalopathy
Grade 1- altered sleep pattern, poor concentration
Grade 2- lethargic, drowsy or euphoric
Grade 3- somnolence, marked confusion and disorientation
Grade 4- coma
Pathogenesis of HE
Astrocyte dysfunction
Neurotoxin hypothesis
Ammonia hypothesis
GABA hypothesis
Role of neurosteroids
