ns 1150: final

reasons for poor nutrition in a hospital: physical

• generally feeling of unwellness

• decreased conciousness

• pain, nausea, vomiting

• mouth pathology, e.g. oral thrush

• physical disability, e.g. unable to swallow, cannot move arms/hand

• abdominal/gastrointestinal pathology, e.g. obstruction

reasons for poor nutrition in a hospital: iatrogenic (health-care related)

• nil by mouth

• medication side effects causing nausea, drowsiness, etc.

• interference during meal times

• ineptness by worker that places food in an inaccessible place

reasons for poor nutrition in a hospital: non-physical

• mental health: anxiety, fear, depression, ED

• cultural factors: language (not being able to communicate what they want), food preference

• hospital food quality

role of a dietician

• performs clinical nutritional assessment

• tailored to-made eating and diet plans for the individual

• often in tandem with speech and language therapist (SALT) to assess swallowing ability

refeeding syndrome

• intake of food after a prolonged period of starvation that causes insulin spike

• insulin spike causes ↑ absorption of electrolytes from neighboring bloodstream and causes ↓ [electrolytes] in blood that can cause seizures and cardiac failure

• to prevent: (1) monitor patients at high risk of refeeding syndrome (2) provide electrolyte replacements (3) provide vit. B supplements

alternative to oral feeding: nastrogenic feeding (NG)

• tube inserted via the nostril to the stomach

• liquid feed applied through the tube

  • bypasses upper mouth and esophagus

• useful for supplementing nutrition when oral intake is not possible or sufficient due to (1) reduced level of consciousness (2) reduced swallowing ability (3) upper gastrointestinal obstruction

• easily taken out so ideal for SHORT-TERM usage

• can be unsafe if implanted into the lung by accident

alternative to oral feeding: PEG

• tube inserted through the skin and into the stomach

• lower risk of tube coming out compared to NG tube and more safe

• can be hidden from view

• better tolerated by patients and preferred for LONG-TERM feeding

alternatives to oral feeding: TPN

• used when patients have problems absorbing food (bowel issues, side effects of chemotherapy)

• provides nutrition directly into blood stream via intravenous line (IV)

  • water and lipid emulsion that contains glucose, AA, lipids and essential micronutrients

• ideally for SHORT-TERM, can cause infections, blood clots and fatty liver disease when used long-term

nutritional health of the healthcare worker

• inadequate food and water intake

• ↑ risk of alcohol liver disease, smoking related health issues, kidney stones

• disruption of circadian rhythm

evolution of milk production

all mammalian species lactate to support postnatal offspring development

• development is specialized to suit offspring needs

hormones involved in mammary gland development

in puberty: oestrogen, progesterone

during pregnancy: oestrogen, progesterone, prolactin and placental lactogen

hormones involved in lactation

prolactin, oxytocin

progesterone levels decline, NO oestrogen

hormones involved in involution

oestrogen

benefits of breast milk: infants

1. nourish child with nutrients, fatty acids and amino acids

2. provide communication factors like stem cells and hormones, growth factors, enzymes

3. protect the infant with antibodies and urea

4. offer long term protection from obesity, asthma and diabetes

FDA milk formula

30 nutrients must be included, but there are maximum amounts for 10 nutrients

mature milk composition

• primarily water

• mostly carbohydrates (80g/L)

  • lactose (70g/L)

  • human milk oligosaccarides (hMOs) (5-15g/L)

  • 3rd most abundant component in human milk, functions to support infant gut health

  • maternal genes will determine the hMOs composition, specifically FUT2 and FUT3

• moderate fats (40g/L)

• little protein (8g/L)

breastfeeding with COVID-19

safe: baby will receive protection from SIgA antibodies in breastmilk and stay safe as long as viral load is maintained

breastfeeding suggested timeline

AAP & WHO recommends exclusive breastfeeding for 6 months after birth

however, it is still recommended to do so afterwards for 2 years and beyond with complementary foods

benefits of breastfeeding: mothers

• reduced risk for breast and ovarian cancer

• reduced risk for type 2 diabetes (for mothers with gestational diabetes)

• reduced risk for postpartum depression

contraindications to breastfeeding

medical contraindications to breastfeeding are rare but may occur when mother has

1. untreated HIV infection

   1. may be combatted through shortened duration (~6months), preventative medication, and maintained an undetectable viral load

2. leukemia-lymphoma virus infection

3. ongoing usage of illicit drugs

4. receiving chemotherapy

alternatives to maternal breastfeeding

• pasteurized donor milk

  • for premature or medically fragile infants

• infant formula

  • less health benefits

lactation critical window

first 14 days postpartum is a critical window to establish lactation

biological factors affecting early, unplanned lactation cessation

• impaired breast development

• hormonal dysregulation

• obesity and diabetes

• genetic disorders i.e. maternal mutation in ZnT2/SLC30A2, lowered Zn in breast milk that must be fortified

DNA

• double helix with sugar & phosphate backbone

  • AG - purines (agricultural)

  • CT - pyrimidine (sharp corner)

  • GC - 3 bonds

  • AT - 2 bonds

• stores genetic information, template for central dogma

organization of the human genome

• ~3 billion base pairs for 20k genes

• arranged into 46 chromosomes

  • 22 pairs of autosomes, 1 pair of sex chromosomes

  • can undergo mutations over time

genetic mutations

• can be used by DNA damage

  • exogenous causes: UV, tobacco, irradiation, pollutants

  • endogenous causes: ROS, errors during DNA replication

• causes changes in genetic codes

  • silent: does not impact encoded protein sequence

  • nonsense: pre-mature stop codon, truncates amino acid sequence

  • missense: changes encoded amino acid through replacement of nucleotides

  • frameshift: indel of nucleotide that will significant change the amino acid sequence downstream

consequences of mutations

• duplication (increased expression of genes)

• deletion (loss of genes)

• inversion (disruption of gene code)

• translocation (creates fusion protein from two different genes)

monogenic human disorders in absorption

• cystic fibrosis

  • autosomal recessive

  • loss of CFTR function causes thickened mucus in both lungs and pancreatic ducts that make it hard to breathe and also cause inflammation in pancreas

    • causes decreased absorption of fats and nutrients

    • common in European descent, suspected as a defense mechanism against cholera for mutant carriers

  • treatment: patients will require nutrient supplementation or pancreases

• hereditary hemochromatosis (excessive heptocorrin, ↑ iron in blood)

  • autosomal recessive

  • increased absorption and release of iron in body

    • cannot use hepcidin to downregulate iron levels

    • causes bronze appearance and permanent damage to heart, liver, pancreas and brain

    • possible evolved to counteract menstruation iron loss

  • treatment: regular phlebotomy (removal of blood) or iron chelators

monogenic human disorders in metabolism

• phenylketonuria

  • autosomal recessive

  • loss of PAH enzymatic activity

    • toxic accumulation of phenylalanine that interferes with newborn development of brain and nervous system

  • prevention starts with early detection using blood test in mothers

  • treatment: avoid high-protein diet and regular blood tests

monogenic human disorders in energy generation

• mitochondrial defects

  • causes insufficiency in ATP

  • two types:

    • 1) mutation in nuclear genome (which can still code for mitochondrial function even though mitochondria has its own genome)

      • autosomal dominant/recessive or x-linked

    • 2) mutation in mitochondrial genome

      • passed down from mother

      • severity depends on the number of mutant mitochondria passed down from mother

non-Mendelian inheritance patterns

• polygenic, where the phenotype is determined by a combination of multiple genes

  • greater # of genes = ↑ complexity in inheritance pattern

• can be influenced by gene-environment interactions

• do NOT exhibit inheritance pattern

research methods to uncover genetic contribution to diseases

1. check family history inheritance

2. conduct twin studies

   1. monozygotic » dizygotic

3. conduct adoption studies

   1. adoptees still has trait despite being adopted

4. genome-wide association studies (GWAS)

   1. observational case-control study of cohorts with and without the disease

   2. look for mutations that are more frequently present in the disease population compared to the control population

   3. done on a large scale

principles of GWAS

• whole genome sequencing to find mutations

  • expensive and inefficient

• therefore, use single nucleotide polymorphism database (SNPs)

  • examine single nucleotide location to check for point mutation (SNPs)

    • most are found in non-gene coding regions of DNA

    • therefore it is highly unlikely that it is the sole mutation that causes the disease

    • used instead as a genetic bookmark to highlight a region that may be associated with disease causing gene or another mutation

      • next steps: examine local sequence surrounding SNP allele

      • if there are more SNPs in the database (Human Genome Project) we can pinpoint what SNP is associated with the disease

• advantage lies in that it can use a very large sample size to identify a diverse # of genetic variations that contribute to the phenotype

  • also able to identify rare genetic variants

obesity: monogenic disease

• early-onset, no environmental influence

• disruption along the leptin-melanocortin pathway will cause increased food intake and decreased energy expenditure

  • ex: congenital leptin deficiency

obesity: polygenic disease

• common obesity, affected by environment

• SNPs in intron of FTO that are associated with obesity/type 2 diabetes but unclear the mechanism it plays

  • suggested that obesity association is because of how it alters the regulation of the neighboring IRX3 gene

nutrigenomics

• study of nutrients’ impact on gene expression

• bioactive components in food affecting gene expression

  • ex: S-Adenosyl-Methionine Deficiency, where folate (B₁₂) deficiency can limit methionine and subsequently SAM synthesis → hypomethylation of DNA, inappropriate expression of genes

nutrigenetics

• study of genes’ impact on nutrient metabolism/requirements

  • ** nutrigenetics

• ex: hereditary hemochromatosis, phenylketonuria, lactose intolerance, alcohol flushing syndrome

cancer

• abnormal growth and spread of cells due to failure to control cell growth and migration

• caused by mutations, epigenetic change and viruses

benign tumor

• cannot undergo metastasis

• has clearly defined and intact boundaries

• resemble normal cells

• NOT cancer, but can acquire further mutations to become malignant

malignant tumor

• tumor with the ability and POTENTIAL to spread to distant organs/tissues

• poorly defined boundaries

• often contain large nucleus, loss of normal cellular structures and normal organization with neighboring cells

• aka. cancer

common cancer types

men: prostate, lung, colorectal

women: breast, lung, colorectal

different types of DNA damage

• DNA breaks

  • single/double strand breakage

• base modification through oncogenes

  • simple/bulky

• crosslinks from protein

  • inter-/intra-

methods used to discover causes of cancer

• epidemiology: observation studies that identify an ASSOCIATION between environmental factors and specific factors

• experimental methods: bacteria for DNA mutations and animal models for cancer formation

  • may not reflect human cancer disease/physiology

how does nutrition contribute to causes of cancer

1. direct voluntary consumption of carcinogen (e.g. alcohol)

   1. injures epithelial cells in GI tract

   2. ethanol in alcohol is metabolized to acetaldehyde which can cause DNA to undergo mutations

      1. usually detoxified BUT in East Asian populations may have ALDH2 polymorphism that causes Alcohol Flushing Syndrome and cannot detoxify acetaldehyde

2. contamination of consumed food (e.g. alfatoxin B1)

   1. produced by fungus Aspergillus flavus

   2. found in corn, peanuts, cereal grains

   3. CANNOT be destroyed by drying, storage and processing

3. food-borne infectious pathogens (e.g. H. pylori)

   1. bacterium that is transmitted via contaminated food/water

   2. neutralizes acid in stomach and burrows into mucus of stomach

   3. injures gastric epithelium → gastritis, gastric ulcers, inflammation

      1. promotes ROS and cell proliferation rates

      2. early antibiotic treatment reduces risk of cancer development

4. deficiency in specific nutrients

   1. folate deficiency

      1. S-Adenosyl-Methionine Deficiency: affects SAM cycle → hypomethylation

      2. Uracil Misincorporation: limits dT synthesis and instead uses dU which is unstable and excised by DNA repair enzymes

5. clear epidemiological association between obesity and cancer, but mechanism not well understood

   1. possible mechanisms:

      1. inflammation

      2. increased circulation of lipids as nutrients for cancer cells

      3. increased insulin/IGF-1 as growth factors for cancer cells

      4. fat cells secrete adipokines which can stimulate growth of cancer cells

how does cancer impact diet and nutrition?

1. obstruction of various pathways

   1. airway → reduced energy for eating, discomfort

   2. oral-pharynx/esophagus → dysphagia, difficulty swallowing

   3. lower GI obstruction → reduced GI absorption capacity, reduced appetite

   4. urinary tract → discomfort, vomiting

2. compression from tumor or inflammation

   1. GI tract: obstruction

   2. brain and nerves: impacts muscles involved in mastication

3. pain

   1. reduces appetite

   2. compression of nerves

   3. bone fractures

4. bleeding

   1. chronic GI bleed → iron deficiency

5. inappropriate secretion of hormones

   1. insulin in pancreatic tumors: persistent hypoglycemia

   2. PTHrp in lung cancer: hypercalcemia

   3. ADH in lung cancer: hyponatremia, excess water reabsorption or SIADH

6. cachexia

   1. metabolic wasting disorder people with advanced cancer

   2. cannot be reversed by dietary intake

7. side effects of cancer treatment

   1. discomfort from chemotherapy

   2. mucositis (reduction of GI function) from chemotherapy and radiotherapy

   3. SIADH from chemotherapy

how does cancer hijack and rewire metabolism?

• sustained growth even in absence of growth hormone

• induced angiogenesis

• dysregulated cellular energetics to sustain its cells

  • Warburg effect: increased glucose uptake for synthesis of its essential macronutrients

  • alternative nutrient utilization when glucose is unavailable i.e. uridine

  • induced secretion of metabolites from neighboring cells

  • production of ROS

cancer treatments

1. surgery

   1. usually used for smaller cancers

   2. may cause lymphoedema (lymph accumulation in arms) or usage of stoma (external bag as the drainage of fecal contents)

2. radiotherapy

   1. targeted ionizing radiation (e.g. x-rays) to cancer cells

   2. may cause anemia, vomiting, hair loss, fatigue, cell damage

3. chemotherapy

   1. targeted delivery of cytotoxic agents

      1. cause DNA damage (cisplatin)

      2. inhibit synthesis of DNA nucleotides (methotrexate)

      3. disrupting mitosis (taxols)

   2. may be unhelpful for invisible cancer cells or complex cancers

targeting cancer metabolism in ALL: usage of anti-folates

aminopterin and methotrexate deplete cell of tetahydrofolate which therefore cancer cells cannot use folate to synthesize nucleotides for growth

targeting cancer metabolism in ALL: usage of asparaginase

• non-essential amino acid not expressed in ALL; cancer cells require external source of asparagine

• depletion of asparagine from blood to starve cancer cells

  • normal cells can synthesize their own

supportive role of nutrient in cancer treatment

• maintain general health

• avoid food/beverages that can interact with bioactivity of cancer drugs

  • e.g. alcohol can alter liver metabolism of chemotherapy drugs

• avoid food that can ↑ risk of food-borne infections

foodborne diseases

• caused by eating contaminated food

  • from bacteria, viruses, parasites, fungi, chemical/toxins

• majority causes diarrhea

• closely linked to poverty in low- and middle- income countries

bacterial foodborne diseases

• bacteria are 1) prokaryotic 2) unicellular 3) lack nuclei and membrane-bound organelles 4) divide rapidly by binary fission, an asexual reproduction that duplicates its circular chromosome into two daughter bacterium

• contains cell wall that adds additional structural support

  • made of peptidoglycan (protein/carb polymer)

  • can be detected using Gram’s stain

    • stain detected in Gram-positive cells. i.e. interacts with thick cell wall

    • stain NOT detected in Gram-negative cells i.e. have cell membrane that prevents interaction of stain with cell wall

• can be combatted using penicillin which inhibits peptidoglycan crosslinking (cell wall synthesis), killing the bacteria cell

• are tough due to the polysaccharide capsule that protects it from immune responses and harsh environmental conditions

• may also adapt to their environment by 1) switching on transcription of genes 2) ↑ mutation rate to speed up evolution 3) transfer parts of their genome to neighboring bacteria to spread resistance genes

• causes damage by

  • 1) DIRECT: secretion of toxins and infecting GI tract

    • gastroenteritis, salmonella

  • 2) DIRECT: ingestion of toxins from contaminated food, does NOT require bacterial infection of host

    • botulism

  • 3) INDIRECT: triggering immune response to destroy nearby tissue

    • acute sepsis

salmonella: transmission

• found in wild/farm animals as natural reservoirs

• contaminated food, direct contact, contaminated water from animal feces or between humans from fecal-oral route

• can also grow on food surfaces

salmonella: pathology & symptoms

1. non-typhoidal salmonellosis (S. Enteritidis)

   • onset soon after exposure

   • characterized by fever, diarrhea, stomach pains, nausea & vomiting, headache

   • low mortality

   • localized in GI tract

   • easily treated

2. typhoidal fever (S. Thyphimurium)

   1. onset weeks to months after exposure

   2. characterized by symptoms of non-typhoidal salmonellosis AND high fever, chills, rose spots, muscle aches

   3. spreads to other parts of body

   4. high morality rates

   5. can have mild symptoms in humans but act as reservoirs when the bacteria in feces is consumed by other humans

salmonella: treatment

1. rehydration therapy: correcting dehydration and loss of electrolytes from diarrhea

2. antiemetic & analgesia: for nausea and pain relief

3. antibiotics: used if prolonged/severe symptoms to kill bacterium

salmonella: prevention

• washing hands

• safe food preparation

botulism

• caused by poorly canned foods contaminated with Clostridium botulinum under anaerobic conditions

  • produces BoNT that prevents neurons from releasing acetylcholine

  • causes flaccid paralysis of skeletal muscles as early as 6 hours after ingestion

  • HIGH mortality rate due to inability to breathe

• treatment: 1) anti-toxin 2) early admission for mechanical ventilation (substitution for breathing)

acute sepsis

• lipopolysaccharide (LPS) in the dead bacteria cell membrane toxin in bloodstream recognized by macrophages, calls upon inflammatory cytokines

  • triggers inflammation all throughout body

  • will cause widespread blood vessel vasodilation, causing drop in blood pressure (hypotension) and multi-organ failure

h. pylori

• inflammation in the gastric epithelium

  • leads to gastric cancer

foodborne parasite infections

tapeworm from undercooked food or fecal matter can be ingested, causing nerve damage (holes in brain tissue) and nutrient competition

viruses

• DNA/RNA surrounded by protein shell

• nonliving, requires binding to human cell

  • penetrates then undergoes replication, transcription before assembling to be released

caliciviruses

• norovirus

  • caused by shellfish, uncooked foods, ready to eat foods (contaminated by food worker), liquid items

  • outbreaks may occur in healthcare facilities, restaurants, schools, cruise ships

viral infection detection

• electron microscope

• virus isolation in cell culture

  • plaque assays

  • immunofluorescence

• virus antigen ELISAs

• PCR

  • PROS: fast, sensitive and easy to use

  • CONS: not able to do at home, does not measure infectious virus

infection control measures

• stay home when sick

• avoid touching food with bare hands

• wash your hands

• rinse fruits and vegetables

• clean surfaces and utensils

• cook shellfish thoroughly

outbreak investigation timeline

1. diagnosis using PCR

2. gather information using epidemiological survey

3. identify likely cause using questionnaires

4. implement control measures

picornaviruses

• hepatitis A

  • jaundice

  • fever

  • dark urine, pale poop

  • NO CHRONIC INFECTION

• hepatitis E

  • YES CHRONIC INFECTION

hepatitis A

• spread by not washing hands, sex with infected partners, eating/drinking contaminated food, recreational drug usage

• wash hands, get vaccinated!

hepatitis E

• spread by contaminated water, undercooked meat, transfusion, organ transplants

• wash hands, use boiled/bottled/purified water, avoid raw meat

bovine spongiform encephalopathy (BSE)

• prion (misfolded protein that has >40% beta-sheet instead of >40 alpha-helix) that is transmissible from animals

  • occurs when animal is fed ground meat of its own kind and then killed to be served to humans (vCJD)

• causes spongiosis neuron loss in the brain