Nutrition And Disorders Of The Liver

Question 1

Intestinal failure: definition and types

Answer 1

• definition: a reduction in the functioning gut mass below the minimal amount necessary for adequate digestion and absorption of food
• DAYS (acute): mechanical (intestinal obstruction), non-mechanical (post operative, critical illness paralytic ileus)
• WEEKS/MONTHS: post-surgery awaiting reconstruction, Crohn’s disease, mesenteric ischaemia, radiation, adhesions, fistulae
• MONTHS/YEARS: short bowel syndrome, intestinal dysmotility

Question 2

Causes of intestinal failure: mesenteric ischaemia

Answer 2

• inadequate blood supply to the intestines
• commonly through superior mesenteric artery (thrombosis/embolism)
• if not treated causes irreversible infarct of the bowel
• distal small bowel resection and hemi-colectomy

Question 3

Causes of intestinal failure: Crohn’s disease

Answer 3

• chronic inflammatory disease of the intestine
• can affect the full thickness of the intestinal wall and has skip lesions (meaning it can prop up everywhere)
• epidemiology is increasing, and could be attributable towards a Western diet
• risk factors include: smoking, genetics, variance in immunity, interactions with the gut microbiome

Question 4

Causes of intestinal failure: chronic intestinal pseudo-obstruction (CIPO)

Answer 4

• dysmotile bowel: where the bowel doesnt contract properly
• patients have a colic type pain, causes nausea and vomiting
• small bowel bacterial overgrowth: leads to production of gas and exacerbation of symptoms
• may require total parental nutrition

Question 5

Causes of intestinal failure: fistulae

Answer 5

• occurs post-operatively, crohn’s disease
• high fistulae may connect between segment of gut or abdomen, may result in functional small bowel syndrome and diversion of fecal contents

Question 6

Causes of intestinal failure: pancreatic insufficiency

Answer 6

• causes: alcohol, gallstones, autoimmune pancreatitis, cystic fibrosis
• clinical features: diabetes mellitus, fat/protein/CHO malabsorption, fat soluble vitamin insufficiency
• need to supplement with additional vitamins and creon
• pancreas has exocrine functions which help us absorb food, and endocrine functions that help us control blood glucose

Question 7

Causes of intestinal failure: liver failure

Answer 7

• acute liver failure: viral hepatitis, drug-induced (paracetamol)
• acute-on-chronic liver failure: such as acute illness with underlying cirrhosis (alcoholic hepatitis, NAFLD, viral hepatitis)
• this leads to reduction in tissue sensitivity and reduced hepatic glycogenolysis, reduced glycogen stores and increased fat oxidation and gluconeogenesis leading to malnutrition
• heightened REE (due to systemic inflammatory response, heightened cellular regeneration) which can even persist 1 year post-transplant
• impaired fat metabolism due to limited bile production
• vitamins which may be particularly affected by liver failure: vitamin A (usually stored in liver), vitamin K (concentrated and distributed by the liver), vit E (hepatic uptake and released in LDL cholesterol), vitamin D (liver hydroxylation), vit B12 (stored in liver), B6 (stored and converted in the liver), B9 (folate, stored in liver)
• thiamine deficiencies also common due to poor diets and reduced absorption, leading to WE and Korsakoff’s psychosis

Question 8

GI diseases where diet is linked to cause: coeliac disease

Answer 8

• gluten-sensitive enteropathy
• genetic predisposition (HLA-DQ2/8)
• immunological reaction against Gliadin fragment of gluten (anti-gliadin can be used in diagnosis), leading to villous atrophy
• malabsorption leads to weight loss and diarrhoea, leading to iron, vitamin D, folate deficiency

Question 9

GI diseases where diet is linked to cause: metabolic syndrome

Answer 9

• a high fat and sugar diet can lead to obesity which causes disturbances in the gut microbiota (dysbiosis) which perturbs the gut barrier integrity
• this leads to metabolic endotoxemia and low grade inflammation which causes NAFLD (NASH)
• NASH: non-alcoholic steatohepatitis
• dysbiosis means bacteria metabolise dietary choline which can be pathogenic and skew the production of SCFA
• this alters FA production and lipid transport to the liver

Question 10

GI diseases where diet is linked to cause: gall stones

Answer 10

• high fat intake and obesity are risk factors
• there are genetic links
• can cause short bowel syndrome

Question 11

GI diseases where diet is the cause: acute pancreatitis

Answer 11

• causes: caused by alcohol or gall stones

- study showed 17% risk reduction for every 2 portions of veg

Question 12

GI diseases where diet may be the cause: diverticulosis/appendicitis

Answer 12

• diverticulous: hernias, out-pouching of hernias in gut
• appendicitis
• may be caused by western diets of low dietary fibre, increased pressure
• may be reduced by wholegrains

Question 13

GI diseases where diet may be the cause: alcoholic liver disease

Answer 13

• accumulation of acetaldehyde as cytochrome P450 2E1 is upregulated but acetoaldhyde dehydrogenase doesnt get upregulated in times of high alcohol consumption
• increases intestinal permeability and causes bacterial endotoxins to leak out into bloodstream and cause inflammation
• carcinogenic effect

Question 14

World cancer research fund and most likely causes of cancer

Answer 14

• alcoholic drinks: mouth, pharynx, larynx, oesophagus, liver, colorectal, breast (postmenopause), stomach, breast (premenopause)
• adult body fatness: oesophagus, pancreas, liver, colorectum, breast (postmenopause), endometrium, kidney, mouth, pharynx, larynx, stomach, gallbladder, ovary, prostate
• adult weight gain: breast (postmenopause)
• food preserved by salting: stomach
• aflatoxins: liver
• processed meat: colorectal
• red meat and cantonese style fish: colorectal, nasopharynx
• arsenic in drinking water: lung, bladder, skin
• mate: oesophagus

Question 15

World cancer research fund: decreases risk of cancer

Answer 15

• alcoholic drinks: kidney
• adult body fatness: breast (premenopause)
• body fatness in young adulthood: breast pre and post menopause
• physical activity: colorectum, breast (pre and post menopause), endometrium
• wholegrains, high dietary fiber: colorectum
• non-starchy vegetables and fruit: aerodigestive cancer and some other cancers
• dairy products: colorectum
• coffee: liver, endometrium

Question 16

Mechanism for body fat causing cancer

Answer 16

• altered mitochondrial function, increased nutrient uptake in obesity- associated tumours
• oestrogen, MAPK, ERK causes evasion of growth suppression and sustains proliferation
• insulin, PI3K and mTOR causes resistance of cell death
• adipose tissue-associated inflammation, leptin and STAT causes genome instability and mutation, and tumour promoting inflammation
• adipose stromal cells cause vascularisation and inflammation

Question 17

The protective effect of fiber and cancer

Answer 17

• contributes to a healthy microbiota, which produce SCFA which maintain health of colon, causes cancer cell apoptosis and inhibits chronic inflammation
• fiber also reduced colon content transit time limiting the exposure to carcinogens

Question 18

Why does red/processed meat cause cancer?

Answer 18

• haem iron can contribute to nitric oxide production in the stomach
• leads to gut inflammation and ROS

Question 19

Protective effects of dairy and cancer

Answer 19

• may be due to calcium, lipids, vitamin D

- probiotic or symbiotic effects of lactobaccilli

Question 20

Dietary interventions to prevent cancer: folate

Answer 20

• folate fortification introduced in countries as data emerged from canada on decreased colorectal cancer risk
• however, after fortification in Chile, found increased incidence of colorectal cancer
• meta-analysis found no association between folate and cancer risk
• suggest that supplementation just for fertile women?

Question 21

Lifestyle and dietary recommendations from the world cancer research fund

Answer 21

• avoid alcohol
• maintain weight towards lower BMI range
• be at least moderately physically active (keeping HR in range of 60-75%)
• limit consumption of sugar sweetened drinks
• eat diet with at least 30g of fibre/day
• include in most meals: wholegrains, non-starchy vegetables, fruits, pulses
• eat diet high in all types of plant foods including at least 5 portions of non-starchy vegetables and fruit everyday
• limit red meat to no more than 3 portions per week (<500g)
• consume very little, if any, processed meats
• limit consumption of processed foods high in fat, starches or sugar

Question 22

Diseases associated with the gut microbiome: what is affect of diet and how could we establish a causal relationship?

Answer 22

• diseases related with dysbiosis: asthma, eczema, IBD, depression, colon cancer, heart disease, diabetes, obesity, NASH
• high fat diets decrease bacteriocetes and increase firmicutes, low fat diets have opposite effect
• could investigate this further using a systems biology approach