Nutrition and immunity Flashcards
What causes malnutrition?
Severe undernutrition is the of two interacting and often concurrent processes
- the quantitive change is a reduction in total food intake, so that the energy provided by the food is inadequate to meet the needs of the body –> quantity of food
- the qualitative change is deficiencies of specific nutrients, with the pattern and extent of these deficiencies being variable –> quality of nutrient intake
How can malnutrition link to immunity?
Infection links to nutrition and immune response.
Infection –> Activation of inflammatory response
- Increased metabolic rate
- Redistribution of nutrients
- Increased nutrient requirement
Infection
- Anorexia –> can be physiological which can help to trigger/ up-regulate some physiological responses which can help to activate the immune cells and improve the immune response
- Malabsorption
- Intestinal damage
- Diarrhoea
Which can lead to
- Nutrient loss
- Decreased nutrient absorption
- Decreased nutrient intake
e.g. Gastrointestinal infection –> causing intestinal damage which affect nutrient absorption, and diarrhoea which can lead to nutrient loss. Can challenge recovery due to not meeting the nutrient requirements
How do gastrointestinal infections affect nutrient absorption?
Inflammation from GI infections/ damage can compromise the absorption of nutrients.
Depending on the location of damage will depend on what nutrients are at risk of malabsorption
e.g. Duodenum –> iron, calcium magnesium, cl-
Ileum –> protein, fat, cholesterol, bile salts and vitamin B12, Vitamins A and D
How does malnutrition affect barrier function?
Malnutrition alters the quantity of mucus maintained on epithelial surfaces and can also affect its structure –> lower ability to synthesise mucus
- affect first line of defence
Salivary flow and production is also reduced as the chemical composition of saliva is altered in undernourished children. Decreased secretory IgA has been observed in undernutrition
- affects type of enzymes and proteins
- e.g. Vitamin B deficiency can reduce the amount of IgA in saliva –> especially B12 and B9 has been found to be important in improving the amount of IgA in saliva
Lower gastric acid secretion which increases the likelihood of significant numbers of bacteria reaching the small intestine. This, together with a slowing in intestinal transit, contributes to the increased risk of bacterial overgrowth in the small intestine and further impairs the ability to digest and absorb food normally
- first line barrier which reduces risk of infections
- gastric juice, which provides a low pH aids in the conversion of nitrate to nitric oxide, important in mucus production. Not producing enough gastric juice compromises this process
What can cause lack of mucus secretion in malnutrition?
Malnutrition can reduced the amount of gastric acid secretion. Gastric juices provide a low pH which the body relies on in order to convert nitrate into nitric oxide.
Nitric oxide is a key contributor in mucus production. So by compromising gastric juices, leads to reduces nitric oxide conversion and overall a decreases secretion on mucus.
This affects the first line of defence as mucus is a key element in trapping and preventing entry on pathogens into the body.
Compromising mucus secretion means there is an easier access for pathogens to enter the body and cause harm
What is the second line of defence also known as?
Cell mediated immunity
Innate immunity
What is the third line of defence also known as?
Humoural immunity –> antibody respose
Adaptive
How does malnutrition affect the second line of defence?
Does it affect 3rd?
Affects 2nd more than 3rd
- 3rd line has some antibodies which can fight some infections
Severe undernutrition causes atrophy of the lymphoid organs (thymus, spleen, lymph nodes, tonsils). There is also a loss of bone marrow reserves of leukocytes.
The lymphatic system links the 2nd line of defence to the 3rd line (up-regulate)
Atrophy in these organs reduces the numbers of T and B cells in the lymph organs which compromises immune responses to immune challenges.
How does malnutrition impair the leukocyte respiratory burst?
What is this?
Leukocyte respiratory burst is the ability of immune cells to form free radicals.
Under normal circumstances, the respiratory burst leads to an increased generation of potentially toxic oxidant damage caused by unbalanced generation of free radicals
Usually, the integrity of the system is maintained by cellular antioxidant systems and processes
One of the more important changes in cellular function that limits the ability of undernourished children to cope with infection is impaired antioxidant defences.
Macrophages produce free radicals which is important in the first stage of infection/ immune response as it is an effective mechanism in killing pathogens.
Require a balance of antioxidants to reduce harm of free radicals to the organs/ tissues that are infected or damaged.
During malnutrition the ability to form free radicals is reduced, this also reduces the number of endogenous antioxidants. This can cause an imbalance, which induces oxidative stress and lead to organ damage.
This is related to activation of inflammatory cytokines, which activate macrophages and T cells, which forms free radicals. When this happens chronically (several days) along with not getting enough nutrients in diet, it is likely the levels of the endogenous antioxidants will be eradicated.
What are GTX and SOD?
What does it do?
Endogenous antioxidant
Produced in mitochondria
If there are enough levels
SOD can reduce O2 to H2O2 and then GTX reduces it to H20 which is less reactive.
During malnutrition, the amount of endogenous antioxidants are reduced, along with the ability to form free radicals. This causes an imbalance which increases the amount of oxidative stress which can lead to organ damage.
This is related to activation of inflammatory cytokines, which activate macrophages and T cells, which forms free radicals. When this happens chronically (several days) along with not getting enough nutrients in diet, it is likely the levels of the endogenous antioxidants will be eradicated. Despite the lower production of free radicals oxidative stress is still induced.
What is a cytokine storm?
Creating of a pro-oxidant and pro-inflammatory environment
Systemic inflammatory response system (triggered by pathogen/ infection) –> activates 2nd and 3rd line of defence without being able to down-regulate.
Over response to the immune challenge can cause multiple organ dysfunction syndrome (MODS)
MODS can occur early or late after SIRS.
This is related to activation of inflammatory cytokines, which activate macrophages and T cells, which forms free radicals. When this happens chronically (several days) along with not getting enough nutrients in diet, it is likely the levels of the endogenous antioxidants will be eradicated.
e.g. COVID-19 –> lungs where the first organ to be damage by the virus (primary), some patients also suffered heart disease which was related to the lack of resolution to the inflammatory response.
Why is it not always easy to know someone has a deficit in nutrients?
Best way to measure?
Blood levels doesn’t alway give accurate deficit levels due to there being some being stored. So there level in blood isn’t representative of the amount as a whole.
e.g V A and D are lipid soluble and can found in adipose tissue
Blood test can be used to identify potential deficit, but isn’t 100% accurate.
Sometimes the best way is to look at some biomarkers related to vitamin metabolism, such as B12 can be measured by Haemoglobin, Haematocrit, RBC, Intrinsic factor. B9 (folate) is also related to these other measure. So deficit in theres biomakers could relate to either.
Vitamin D in blood is pretty accurate to true levels, however can be stored in the adipose tissue
How can malnutrition and inflammation be identified?
Assess nutritional status
- Blood biomarkers
- Muscle loss –> measuring urinary nitrogen excretion
- Muscle mass –> bioimpedance, CT or MRI
- Water –> both intra and extracellular water, useful to assess hydration status of patient who may have issues affecting body water such as burns.
Inflammation
- No consensus to which inflammatory markers are the best to differentiate between chronic and acute inflammation or between various phases of inflammatory responses
- Measuring the concentration of inflammatory markers in the bloodstream under basal conditions is probably less informative compared with data related to the concentration change in response to a challenge
- CRP (non specific inflammatory marker) –> must then look at symptoms and potential other diagnostic methods to identify location
- ESR (non specific inflammatory marker) –> measure rate of blood cell sedimentation within an hour, the faster the sedimentation the more inflammation. General marker for screening cancer
- TNFa
- IL-6
Cytokines often measured after surgery
Tissue damage markers
- Transaminases –> Reflects liver damage and function. Some infections affect liver function which can increase levels of transaminases in blood
- Creatine Kinase –> Reflects the recovery process. Intracellular enzymes found in muscle. Used commonly after surgery
Antibodies
- IgE –> Food allergies
- IgA and IgG –> Coeliac disease
How can loss of appetite or anorexia be managed?
- Small, high energy meals frequently
- Eat most when feeling hungry
- Add locally available herbs or spices to meals
- Exercise
Response often differently between chronic and acute.
How can infection affect energy requirements?
Critically ill patients are usually highly catabolic, losing significant amounts of protein and muscle. Proteolysis may induce a loss of 20% of muscle mass in 10 days of hospitalisation.
Energy requirements are very individual to the patient and their circumstances. Important to look at body composition.
Losing muscle mass can compromise energy metabolism.
Energy requirement may increase BMR by x 1.3
Severe damage/ immune challenge - trauma
- The initial recommendation is to wait for the haemodynamic stability of the patient. Glycaemic control is important and, therefore at the beginning of calories should no exceed 25kcal/kg/day. In contrast the protein must be high from 1.5-2g/kg/day.
- Have inflammatory markers under control, may not be in range, but to see a decline
- Lack of appetite makes meeting these increased energy requirements even harder
