DISEASE OF THE LIVER AND GALLBLADDER nausea

							                             UNIVERSITY OF THE WESTERN CAPE

                             Therapeutic Nutrition 311
                                           &
                             Nutritional Medicine 312

                           Lecturer: Dr. A. van Graan
                      Acknowledgements: Mrs Hilary Woodley


                           Disease of the liver
Learning objectives:
The student must be able to:

Describe the function of the liver, as well as the liver function test

Discuss all the different abnormalities in liver function in terms of:
           Aetiology
           Pathophysiology
           Complications
           Signs / Symptoms
           Medical and Dietary Treatment

Define the following:
           Ascites
           Cholecystitis
           Cholecystitis
           Choledocholithiasis
           Cholelithiasis
           Whipple procedure
           Paracentesis

Identify and describe the clinical signs and other manifestations of liver
disease

Plan and implement the Nutritional support of a patient with liver disease




                                                                             1
Physiology and functions of the liver structure:
The liver is the major organ in the control of the nutritional and metabolic
homeostasis
Weight 1.5kg
Right and left lobes
Blood supply – 2 sources:
            hepatic artery 1/3 blood from aorta
            portal vein other 2/3 of blood and collects blood drained from
               digestive tract
            1.5L circulates through the liver per minute
System of bile ducts

Liver functions:
Able to regenerate itself
Require 10-20% functional to sustain life
No liver function – death within 24hours
Integral to most metabolic functions
Performs > 500 tasks
            Metabolism (Recap physiology notes)
                   CHO
                   Protein
                   Fats
            Storage and activation of vitamins and minerals
            Formation and excretion of bile
            Conversion of ammonia to urea
            Metabolism of steroids
            Filter can flood chamber

Carbohydrates



Protein


Lipids



Vitamins and minerals


Bile

Steroids and other


Filter



                                                                               2
Liver function tests:
NB Table 31.1 pg 741-742 Krause 11th ED



Disease of the liver (acute / chronic):
A. Acute viral hepatitis
B. Fulminant hepatitis
C. Chronic hepatitis
D. Alcoholic liver disease
E. Cholestatic liver disease
F. Inherited disease
G. Other liver diseases
H. Cirrhosis

A. Acute viral hepatitis
Widespread inflammation of liver
Causes:
          Hepatitis viruses A,B,C,D,E
          Epstein-Barr virus
          Cytomegalovirus
          Herpes simplex
          Yellow fever
          Rubella

Classification   Transmission               Note         Prognosis
                                                         complete
                                                         recovery
HAV              Faecal-oral                             95%
                 (contamination drinking
                 water & food) and
                 sewerage
HBV              Blood (contaminated        Can become   90%
                 needles, blood             chronic
                 transfusion, open
                 cuts/wounds, splashes
                 into mouth/ eyes or
                 sexual contact), saliva,
                 semen
HCV              Blood, saliva, semen       Can become   Acute HCV
                                            chronic      15-30%
HDV              Blood                      Usually
                                            becomes
                                            chronic
                                            Dependant
                                            on HBV
HEV              Faecal-oral via            Generally    Liver function
                 contaminated water         acute        test normal
                                                         within 6
                                                         weeks


                                                                          3
Symptoms:
Anorexia, nausea, vomiting, right upper quadrant abdominal pain, dark urine,
and jaundice.

Four Phases of Acute Viral Hepatitis:
Early Production phase:
fever, arthralgia, arthritis, rash, angioedema
25% pt affected
Pre-icteric phase:
malaise, fatigue, myalgia, anorexia, nausea, vomiting, dysgeusia (taste
change), dysomia (partial loss of speech), abdominal pain
Icteric phase:
jaundice (see definition pg 739 Krause 11th ED)
Convalescent phase:
jaundice begins to subside

B. Fulminant hepatitis
DEF: absence of pre-existing liver disease and development of hepatic
encephalopathy within 8 weeks of onset of illness

Causes:
             Viral hepatitis (75%)
             Chemical toxicity
             Wilson’s disease
             Fatty liver (pregnancy)
             Reye’s syndrome
             Hepatic ischemia
             Hepatic vein obstruction
             Dissemination malignancies

Extrahepatic complications:
         Cerebral oedema
         Co-agulopathy and bleeding
         Cardiovascular abnormalities
         Renal failure
         Pulmonary complications
         Acid-base disturbances
         Electrolyte imbalances
         Sepsis
         Pancreatitis

C. Chronic hepatitis
Defined as chronic when at least 6 month of hepatitis or biochemical & clinical
evidence of liver disease (biopsy findings – un-resolving hepatic inflammation)
Aetiology:
            Autoimmune
            Viral eg HCV
            Metabolic eg Wilson’s disease, hemochromatosis
            Toxic eg some drugs

D. Alcoholic liver disease

                                                                               4
Pathogenesis:
         Metabolic derangements caused by the toxic effects on
           mitochondrial structure and function produced by acetaldehyde a
           by product of alcohol metabolism
         Several variables may predispose certain individuals ( genetic,
           gender, infections with viruses, immunological factors and poor
           nutritional status)

See:
           Focus on metabolic consequences of alcohol consumption pg
            743 Krause 11th ED (self study)
                                         th
           Figure 31.3 pg 745 Krause 11 ED

3 stages of progression of alcohol disease:

Hepatic steatosis / fatty infiltration (reversible with abstinence from alcohol)
           Increased FA mobilisation
           Increased hepatic synthesis FA
           Decreased fatty acid oxidation
           Increased TG production
           Trapping TG in liver
Alcohol Hepatitis
           Hepatomegaly (discontinue alcohol use can resolve)
           Modest raised transaminase
           Increased serum billirubin concentration
           Anemia
           Thrombocytopenia

             Patient may have:
                  Abdominal pain
                  Anorexia
                  Nausea
                  Vomiting
                  Weakness
                  Diarrhea
                  Weight loss
                  Fever
Cirrhosis
Mimic alcohol hepatitis
+Ascites
Portal HPT
Hepatic encephalopathy
GI bleeding


E. Cholestatic liver disease
Primary Biliary Cirrhosis
          Immune mediated disease
          Chronic – progressive destruction of small intermediate sized
             intra-hepatic bile ducts
          90% of patients are women

                                                                                   5
              Slow progression – cirrhosis and portal hypertension - transplant
               or death

Nutrition complications:
            Osteopenia
            Hypercholesterolemia
            Fat soluble vitamin deficiency




Sclerosing Cholangitis
          Maybe immune disorder
          Fibrosing inflammation of segments of extrahepatic bile ducts
          Intra-hepatic duct might be involved
          Progression – portal HPT – hepatic failure – cholangio
            carcinoma
          50-75% also have IBD (ulcerative colitis)
          60-70% of patients are men
          Increased fat soluble vitamin deficiency due to steatorrhea
          Hepatic osteodystrophy may occur due to vitamin D and calcium
            malabsorption
                Resulting in secondary hyperparathyroidism and
                   osteomalacia or rickets


F. Inherited disease (self study pg 746 Krause 11th ED)
Hemochromatosis:
     20 – 40 g of iron stored compared to 0.3 – 0.8 g
     May develop: hepatomegaly, oesophageal varices. ascites, impaired
       hepatic synthetic function, abnormal skin pigmentation, glucose
       intolerance, hypogonondism, arthropathy and hepatocellular
       carcinoma
     Rx- phlebotomy

Wilson’s disease:
    Autosomal recessive disorder
    Associated with impaired copper excretion
    Copper accumulates in liver, brain, cornea, kidneys
    Low s- ceruloplasmin levels and Keyser-Fleischer ring – Dx
    Rx- copper chelating agent and zinc supplementation and low copper-
      diet if other Rx fail



α1-antitrypsin deficiency:(self study pg 747 Krause 11th ED)

G. Other liver diseases



H. Cirrhosis

                                                                               6
      Chronic liver disease due to diffuse necrosis and regeneration l
      Leading to an increase in fibrous tissue formation disrupting the normal
       liver structure
      Has many clinical manifestations:
      Icteric sclera, alopecia, asterixis, palmer ertythema, gynecomastia,
       ascites, testicular atrophy, spider angioma, jaundice, bruising and
       muscle wasting


Complictions
Major complications of end-stage liver disease (ESLD) include:
          Malnutrition
          Ascites
          Hyponatremia
          Hepatic encephalopathy
          Glucose alterations
          Fat malabsorption
          Hepatorenal syndrome
          Osteopenia

Nutrition assessment:

      Appropriate MNT can reverse malnutrition and clinical outcomes
       improved
      Including ascites, encephalopathy, infection and decreased mortality
      Before appropriate nutrition therapy can be implemented a nutrition
       assessment must be performed
      To determine the extent and cause of malnutrition.
      Traditional markers are affected by liver disease making it difficult.

Objective parameters:

      anthropometry
      diet

See:
             Table 31.3 pg 749 Krause 11th ED
             Box 31.1 pg 749 Krause 11th ED



Malnutrition:

See:
             Figure31.7 pg 750 Krause 11th ED


      Moderate to severe malnutrition common in advanced liver disease
      Plays role in the pathogenesis of disease and has negative impact on
       prognosis
      Factors: inadequate intake, caused by anorexia, dysgeusia, early
       satiety, nausea, vomiting, medication
                                                                                7
         Maldigestion and absorption: Steatorrhea
         Altered metabolism
         Micronutrient function affected by storage in liver, decreased transport
          due to reduction is liver-synthesized proteins and renal losses




Medical nutrition therapy (MNT)
          GIT symptoms and ascites (early satiety frequent complaint)
          Small frequent meals
          Evidence – frequent feedings improve nitrogen balance and
              prevent hypoglycaemia
          Oral liquid supplementation
          Enteral nutrition support if:
                   Intake is < 0.8g protein / kg
                   Intake is < 30 cal/kg
                   Patient is at risk

Energy:
                ESLD without ascites 120-140% of REE
                ESLD with ascites, infection, malabsorption 150-175% of REE
                25-35 cal/kg dry body weight
                Estimated dry body weight should be used to prevent over
                 feeding

CHO:
                Preference for lipid and amino acids for energy
                Liver's primary role is CHO metabolism
                Glucose production and utilization is reduced
                Gluconeogenesis is decreased with
                Amino acids and lipids preferred for energy
                Alterations in hormones: insulin, glucogon, cortisol, end
                 epinephrine

Lipids:
                FFA, glycerol and ketones are increased
                Body prefers lipids as energy substrate
                Lipolysis is increased with active mobilazation of lipid deposits
                25-40% of energy

Protein:
             
              Controversial
              Cirrhosis seen as catabolic disease
              Increased protein breakdown and inadequate re-synthesis
              Resulting in depletion of visceral protein stores and muscle
               wasting
              Uncomplicated hepatitis or cirrhosis without encephalopathy
                    0.8 – 1g/kg dry weight / day to achieve nitrogen balance
                    1.2 – 1.3g/kg dry weight / day to promote nitrogen
                      accumulation or positive nitrogen balance
                                                                                     8
             During stress:
                  alcoholic hepatitis
                  decompensated disease (sepsis, infection, GI bleeding,
                     severe ascites)
                  1.5g/kg/day

Vitamin and minerals: (self study)
           Supplement needed for all ESLD
           Due to liver and medication
           Water and fat soluble Vit
           Vit K intramuscular or IV
           Water-soluble vit associated with alcoholic liver disease: B6,
            B12, folate, Niacin
           Fe may be depleted in GIT bleeding, avoid in hemacromatosis,
            hemosiderosis
           Elevated S-copper and manganese – in cholestatic liver disease
           Cu and manganese are excreted via bile – no supplementation
           Zn, Mg low in alcoholic liver and diuretic therapy
           Ca, Mg and Zn – malabsorbed in steatorrhoea
           Meet DRI
                                              th
           See table 31.4 pg 752 Krause 11 ED

Portal Hypertension (HPT)
           Increase in collateral blood flow – can result in varices in GIT
           Often leads to bleeding

             MNT:
                 Acute bleeding cannot feed enterally
                 If the person will be NPO >5 days TPN

Ascites
             Accumulation of abnormal amounts of fluid in the abdomen
             May develop as a consequence of:
                  Portal vein hypertension: pressure in the portal vein helps
                    to force fluids out of the blood into the abdominal cavity
                  Plasma osmotic pressure due to impaired albumin
                    synthesis (hypoalbuminemia)
                  Lymphatic obstruction
                  Renal retention of sodium and fluid
                  Due to increased release of catecholamine, rennin,
                    angiotensin, aldosterone, ADH

             Medical Treatment:
               Paracentesis
               Diuretics:
                     Furosemide
                     Spironolactone (Potassium-sparing)

                 Monitor:
                     weight
                     abdominal girth
                     urinary sodium concentration
                                                                               9
                       serum urea nitrogen
                       creatinine
                       albumin
                       uric acid
                       electrolytes

            MNT:
                       Sodium restriction: 2000mg/d
                       Adequate protein if regular paracentesis

            Complications of Ascites:
                   Pleural Effusion
                   Anorexia
                   Renal failure
                   GIT – oedema
                   Increase Portal venous pressure
                   Hernia

Hyponatremia
          Occurs because of decreased ability to excrete water
          Sodium loss with paracentesis
          Excessive diuretic use
          Overly aggressive sodium restriction

            MNT:
                Restrict fluid 1-1.5L/day depending on oedema and
                  ascites
                If hyponatremia severe and persistent 500-750ml plus
                  urine loss
                Moderate sodium intake (excessive intake worsen fluid
                  retension)

Hepatic encephalopathy

            Causes and aetiology
            Many conditions can cause HE : GIT bleeding, fluid and
             electrolyte abnormalities, uraemia, infection, sedatives,
             hyperglycaemia, constipation and acidosis can precipitate HE
         



          Stages see box 31.2 pg 753 Krause 11th ED
          Stage I – Mild confusion, agitation, irritability, sleep disturbance,
           decreases attention
          Stage II – Lethargy, disorientation, inappropriate behaviour,
           drowsiness
          Stage III – Somnolent but arousable, incomprehensible speech,
           aggressive when awake
          Stage IV - Coma




                                                                               10
           Medical treatment
           Lactulose – non-absorbable disaccharide which acidifies the
            colonic contents and retaining ammonia as ammonium ion
           Neomycin – non-absorbable – helps decrease colonic ammonia



           MNT
           Unnecessary protein restriction may worsen body protein losses
            and must be avoided
           Mixed protein diets up to 1.5 g/g can be tolerated
           Experts suggests BCAA-enriched are indicated in pt's who don't
            tolerate standard protein and have not responded to lactulose
            and neomycin
           Theory based on vegetable protein- low in methionine and rich in
            BCAA


Glucose alterations
          Glucose intolerance in 2/3 of patients with cirrhosis
          10-37% develop diabetes mellitus
          GI due to Insulin resistance in peripheral tissue
          Hyperinsulinemia occurs:
                  increase insulin production
                  hepatic clearance reduced
                  defect in insulin-binding action at receptor site
                  post-receptor defect
                  portasystemic shunting occurs
          Fasting hypoglycaemia occurs
                  decrease ability of glucose from glycogen + failing
                    gluconeogenic capacity in ESLD
                  more common in acute or fulminant liver failure
                  can also occur after alcohol consumption


Fat malabsorption due to:
          Decreased bile acid secretion
          Administration of neomycin + cholestyaramine
          Pancreatic enzyme deficiency
          Stools appear greasy, floating, light or clay colour

             MNT:
                 Significant steatorrhoea- replace some LCT with MCT
                   (15ml x 4/day)
                 Trial low fat diet (40g) if it does not resolve discontinue
                   diet


Hepatorenal syndrome
          Renal failure associated with severe liver disease without
            intrinsic kidney abnormalities
          Characterised by reductions in:
                  Renal blood flow
                                                                                11
                   Cortical perfusion
                   Glomerular filtration rate

            Treatment:
                 Discontinuation of Nephrotoxic drugs
                 Optimise intravascular volume status
                 Treat infection / other complications
                 Monitor input and output
                 Dialysis

            MNT:
                May require alteration in fluid, sodium, potasium,
                  phosphorus

Osteopenia
            Problem in:
                 Primary biliary cirrhosis
                 Sclerosing cholongitis
                 Alcohol liver disease
                 Hemochromatosis
                 Long term corticosteroid treatment eads to
                 increase bone resorption, suppressed osteoblastic
                   function
                 affects sex hormone secretion, intestinal absorption of
                   dietary Ca, and renal excretion of Ca, Po, and Vit D

            MNT:
                   Weight maintenance
                   Well balanced diet
                   Protein: adequate to maintain muscle mass
                   Calcium: 1500 mg/d
                   Adequate vitamin D from diet or supplement
                   Avoid alcohol
                   Monitor for steatorrhea




Liver resection and transplant
         Increased protein and energy needs due to surgery
         Also to promote liver cell regeneration
         Small frequent nutrient-dense meals
         Oral supplements
         Tube feed if intake is poor
         TPN when inadequate GIT function
         Acute post-transplant needs are increased to promote healing,
          infection, recover and to replenish body stores
         N2 requirements are elevated can be met with early postop tube
          feeding
         Multiple medications have nutritional side effects have to be
          taken into consideration

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              Post-transplant: nutrient needs are adjusted to Rx problems of
               obesity, hyperlipideamia, hypertension , DM and osteopenia



Nutrition Care Guidelines for liver Transplantation
Nutrient     Pretransplant           Acute                 Long-term
                                     posttransplant        posttransplant
Calories       High                  Moderate              Wt maintanance
               (basal + > 20% )      (basal + 15 - 30%)    (basal + 10 - 20%)
Prot           Mod (1 – 1.5 g/kg)    High (1.2 -           Mod (1g/kg)
                                     1.75g/kg)
Fat            As needed              20 -30 % of E        low (≲30 % of E)
CHO            High (simple &        70 % of E             Reduced simple
               complex)
Na             2 - 4g                2 - 4g                2 - 4g
Fluid          1000- 1500 ml         As need               As needed
Ca             800 – 1200 mg         800 – 1200 mg         1200 – 1500 mg
Vitamins       to DRI levels          to DRI levels        to DRI levels
               additional water & fat additional water &   additional water & fat
               soluble                fat soluble          soluble




                                                                                13
Case study 1 (15 marks)
36 year old women
dranks 3-4 alcohol units per day > than 17 years (stoped last week)
Weight: 42kg
Height: 1.6m
Temperature: 39 oC
Clinical: Jaundice, hepatomegally, UTI
Biochem: AST 214, ALT 60, conjugated bilirubin 17, blood glucose 8.8, urea
2.8
Medication: prednizone > 4 weeks

             Interpret biochemistry (5)
             What is the cause of the hepatomegaly? (1)
             What dietary treatment would you give her? (9)

Case study 2 (15 marks)
Male patient with bad ascities and cirrhosis secondary to alcohol abuse
Weight 58kg (and gaining)
Height 1.76m
Biochem: S-Na 120mmol/L, S-K 3mmol/L; blood glucose normal
Medication: none
Diet: 8800kJ, 85g protein, free fluid, low salt

What is his ideal weight (1)
What is his current BMI (1)
Explain his biochem (2)
How would the use of a diuretic influence his needs (4)
Would you make any dietary changes? (3)
Do you agree with the use of a low salt diet? Motivate (1)
Should he be fluid restricted? Motivate (1)
How much weight should the patient lose per day? Motivate (1)
Is the use of waist circumference any good? Motivate (1)

Case study 3 (22 marks)
A women with stage III hepatic encephalopathy, esophageal varices, bad
ascities and constipation.
Weight 62kg
Height 160cm
Biochem:
       Albumin 28g/L
       K 2,7mmol/L
       Urea 2.7mmol/L
       Creatinine 91 mcmol/L
       Sodium 128 mmol/L
       GGT 320
       AST 90
       ALT 82
Medication:
       Lactulose
                                                                             14
      Thiamin
      KCl

Interpret the patients biochem (10)
Give this patients nutritional diagnosis (4)
Briefly discuss the using the following parameters in evaluating the patients
nutritional status (8):
        Weight
        CHI
        Skin folds
        Serum proteins
        Nitrogen balance
        Lymphocyte count and delayed hypersensitivity reaction




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