Case 15- Stress and nutrients

Question 1

Vitamin D deficiency (rickets)

Answer 1

Delay or failure of mineralisation of the cartilagious growth plates in the growing child. Growth plate becomes wide and irregular. ‘Bow legs’ or ‘knock knees.’ They usually have a height and weight below the 3rd percentile.

Question 2

Factors predisposing you to rickets

Answer 2

High latitude, lack of sunlight, infants whose mothers were vitamin D deficient in pregnancy, prolonged breast feeding without vitamin D supplementation, low dietary calcium intake, increased melanin pigmentation.

Question 3

Rickets treatment

Answer 3

• Oral: Aggressive treatment involving calcium and/or vitamin D supplements
• IM: having a vitamin D injection each 6 months/year (this is only necessary if the child cannot take the supplements by mouth or has intestinal or liver disease)

Question 4

Rickets prevention- babies

Answer 4

• If exclusively breast-feeding, must consume vitamin D supplement of 5ug/day (oral or drops)
• Formula feeds must have vitamin D added, calcium intake should be maintained

Question 5

Osteomalacia

Answer 5

Vitamin D deficiency. A failure of bone mineralisation and presents as an excess of poorly calcified osteoid. Osteoid is the bone protein matrix, composed primarily of type 1 collagen. Adult disease of vitamin D deficiency.

Question 6

Vitamin E deficiency

Answer 6

• Mild deficiencies affect the skin- dermatitis
• Sever deficiency causes neuropathy and haemorrhaging
• Selenium should be given with vitamin E, they work to prevent and repair cell damage in the body

Question 7

Vitamin C deficiency

Answer 7

Scurvy which is characterised by general weakness, anaemia, gingivitis and skin haemorrhaging

Question 8

Vitamin K deficiency

Answer 8

Increases prothrombin (clotting) time, in serious conditions this could cause a haemorrhagic event. Seen mostly in GI disorders like Cystic fibrosis, IBD (Crohns), chronic pancreatitis, liver disease, using warfarin.

Question 9

Why are newborn infants at risk of vit K deficiency

Answer 9

Poor placental transfer, hepatic immaturity, low vit K content in breast milk. Prevented by viamin K (oral or IM injection) within 6 hours of birth.

Question 10

Thiamin deficiency (vitamin B1)

Answer 10

Beri Beri, impaired muscle contractions. Impaired cardiac function, oedema and muscle twitches. Decreased neurological function and memory loss. Due to heavy alcohol consumption with inadequate food consumption. Alcohol interferes with absorption (Wernicke-Korsakoff syndrome), the poor and elderly are at risk for not eating sufficient energy

Question 11

Riboflan deficiency (vitamin B2)

Answer 11

Deficiencies are rare though people may take in marginal amounts. Drug and alcohol users and restricted calory intake. The collection of deficiencies is caused Ariboflavinosis which is inflammation of the mucous membranes of the oral cavity and pharynx.

Question 12

Niacin deficiency (vitamin B3)

Answer 12

Pellagra. Dermatitis symptoms include: red, flaky skin, areas of discoloration ranging from red to brown, thick, crusty, scaly or cracked skin. International health issue but rare. The rash forms on the face, lips, feet or hands. In some people it forms around the neck (casal neck).

Question 13

Vitamin B12 deficiency symptoms

Answer 13

Rare, bacterial synthesis in gut. Causes pernicious anaemia, bone marrow cells become abnormally large, neutrophils develop multi-lobed nuclei, megoblastic red blood cells. A form of megoblastic anaemia, causes chronic fatigue. There is demyelination of nerves causing progressive myopathy. There may be an increased risk of cancer (via methylation, dUMP metabolism and ROS).

Question 14

Folate deficiency (vitamin B9)

Answer 14

Megaloblastic anaemia. Megaloblastic enterocytes cause malabsorption and diarrhoea. No effect on myelination. Raised plasma homoCys levels – an important risk factor for CVD and stroke. Low plasma folate is associated with neural tube defects in babies. Increased risk of colo-rectal cancer.

Question 15

Stress

Answer 15

The bodys response to a disruption in equilibrium by an external demand. Stress encompasses: the input (stress stimuli), the processing system (i.e. areas of the brain) and output (stress response)

Question 16

The 2 major sub groups of stressors

Answer 16

• Physical/environmental stressors- put strain on the body i.e. cold, hot, injury, chronic illness
• Psychological stressors- events, situations, individuals or comments that we interpret as negative or threatening i.e. not finding a babysitter

Question 17

Selye’s General adaption syndrome

Answer 17

Stage 1- Acute stress- Alarm reaction- Fight or flight
Stage 2- Episodic stress- Resistance- Struggle to overcome
Stage 3- chronic stress- Exhaustion- Fatigue, irritability, vulnerable to illness

Question 18

Acute stress

Answer 18

Most common form of stress, a response to demands of the past or anticipated demands in the future. A physical response that prepares the individual to be alert and ready to escape danger. When the stressful situation ends, endocrine signals switch off the stress response and the body returns to normal.

Question 19

Episodic stress

Answer 19

Extended over arousal due to repeated acute stress. This may appear as hostility, potentially deteriorating interpersonal relationships. Particular environments may be associated with stress like the workplace

Question 20

Chronic stress

Answer 20

When an individuals fails to see a way out of a threatening or miserable situation. Due to unrelenting demands over a long period. May relate to a traumatic, early childhood experience

Question 21

Acute stress response

Answer 21

The activation of the sympathetic nervous system causes the release of Catecholamines (adrenaline) from the adrenal medulla. The tissue effect is mediated by activation of adrenergic receptors.

Question 22

Physiological MoA of acute stress

Answer 22

• Perceptions via the senses (e.g. olfaction, sight) or psychological threat (recalling a feels which previously caused stress)
• Amygdala interprets the information
• Communicates to hypothalamus – stimulating the SNS, which runs parallel down the intermediolateral tract of the spinal cord to T1 where it runs paravertebrally until L2
• SNS has multiple effects, including stimulation of the adrenal medulla
• Occurs before you are conscious of the threat
• The neurotransmitter is Noradrenaline and the receptors are adrenergic
The cortex of the brain synthesises sensory information to deduce a threat, this communicates via the Amygdala to the Hypothalamus.

Question 23

SNS effects due to acute stress

Answer 23

Tachycardia, increased cardiac contractility, vasoconstriction, cortisol secretion, glucagon secretion and insulin suppression. Due to noradrenaline binding to adrenergic receptors on target tissues.

Question 24

What is released from the adrenal medulla

Answer 24

The adrenal medulla is an extension of the SNS. Releases both adrenaline (80%) and noradrenaline (20%) into the blood circulation (Catecholamine endocrine response).

Question 25

The effect of catecholamines on glucose control

Answer 25

1) Both adrenaline and nor-adrenaline increase glucose levels inducing a hyperglycemic effect. Stimulation of glycogenolysis and gluconeogenesis in the liver by activation of β and α receptors of the hepatocytes and indirectly through enhancement of glucagon secretion by the α cells of the pancreatic islets of Langerhans.
2) Catecholamines inhibit glucose uptake by adipose tissue by blocking the GLUT4 transporters and through inhibition of insulin secretion (causes hyperglycaemia). Increases blood plasma glucose levels.
3) Adrenaline activates adipose tissue lipase which promotes lipolysis increasing the plasma free fatty acid levels which in turn produce energy in the form of ATP either through gluconeogenesis or βeta oxidation.

Question 26

How the Catecholamine changes help you deal with acute stress

Answer 26

• Tachycardia / Hypertension - increased cardiac contractility, increased vasoconstriction and bronchodilation will occur increasing oxygenation to the muscles and brain.
• Acute Hypoinsulinemia - Glycogenolysis & Gluconeogenesis = Hyperglycaemia - glucose delivery to the muscles & brain. Lipolysis – free fatty acids = muscle fuel (Heart)
• Splenic contraction and increased mobilisation of blood cells into the systemic circulation will occur further aiding oxygen delivery.
• Decreased clotting time helps minimise blood loss if injured.
• Decreased gastrointestinal activity (including dry mouth) diverts useful blood flow away from non-urgent functions.
• Sweating reduces the risk of hyperthermia with anticipated increased muscle usage.
Pupillary dilation provides better vision.

Question 27

What is released first cortisol or adrenaline

Answer 27

Adrenaline, cortisol mediates its affects through nuclear transcription so it takes longer

Question 28

Stress- how is cortisol released?

Answer 28

1) The cortex receives sensory or psychological (memory / emotion) information and communicates this threat to the hypothalamus.
2) The hypothalamus releases CRH into the hypohyseal portal tract, to cause the anterior pituitary gland, to secrete ACTH into the systemic circulation.
3) This in turn stimulates the adrenal cortex to secrete glucocorticoids such as cortisol. Cortisol acts via the glucocorticoid receptors a classical nuclear hormone receptor.

Question 29

Cortisol effects

Answer 29

• Liver- glucose production (gluconeogenesis) and prevents glycogen formation (glycogenesis)
• Skeletal muscle- increased protein degradation, increased amino acids for gluconeogenesis
• Adipose tissue- increased lipolysis, increased free fatty acids and glycerol for gluconeogenesis
• Bone- matrix protein breakdown, increased amino acid for gluconeogenesis
• Pancreas- inhibits insulin release, causes hyperglycaemia

Question 30

Chronic stress response

Answer 30

Hyper activation of SNS and HPA, causes sustained levels of catecholamines and glucocorticoids

Question 31

Effects of chronic stress

Answer 31

• Altered metabolism- increased breakdown of glycognen and fat leads to tissue wasting. Raised cholesterol can lead to vascular disease and atherosclerosis
• Kidney disease- due to chronic hypertension. Elevated sympathetic activity increases vascular tone and alters renal sodium and water homeostasis, causing excess fluid volume and raised BP
• Adrenaline- increases contractility, increases heart rate, increases vasoconstriction
• Cortisol- increases vasoconstriction and blood volume, by increasing production of angiotensin 2 and the sensitivity and number of adrenergic receptors (increasing adrenaline’s effects)

Question 32

Selye’s general adaption syndrome

Answer 32

• Alarm reaction- fight or flight response, prepares the body for physical activity
• Stage of resistance- body adapts to the stressor its exposed, Parasympathetic response. Attempt to return physiological function back to normal whilst the body remains on alert
• Exhaustion- stress continues beyond the bodies capacity, bodies recources are depleted. Susceptible to disease and death
General adaption syndrome rarely occurs in its pure form, better defined as a spectrum. This is controlled by the Hypothalamic-pituitary-adrenal axis. Continues access to stress weakens the HPA axis.

Question 33

Where does the Hypothalamus send signals to:

Answer 33

1) Brain stem- has roles in the autonomic nervous system (temperature control)
2) Anterior thalamus and parts of the cerebral cortex- emotional control
3) Pituitary gland- hormonal control

Question 34

Function of Hypothalamus

Answer 34

• Endocrine function
• Homeostasis- temperature control, thirst, hunger, cicadian rhythm
• Sexual behaviour

Question 35

What controls male and female sexual arousal in the Hypothalamus

Answer 35

Female sexual arousal- Ventromedial hypothalamus
Male sexual arousal- Preoptic region, within the preoprtic region is the sexual dimorphic nucleus, different shape in males and females. Linked to sexual orientation

Question 36

Hypothalamus- temperature regulation

Answer 36

There are temperature sensitive neurones in the preoptic area, which sense the temperature of the blood. Thermoregulation also occurs in the anterior and posterior nucleus. Measures core body temperature.
Response- Hormone production, activation of ANS, behavioural response (links to cortical and limbic acreas of the brain- makes you want to put a jumper on when cold).

Question 37

Hypothalamus- regulation of body water

Answer 37

• Creates sensation of thirst- in the thirst centre (lateral hypothalamic area)
• Control excretion of water into the urine- supra-optic nucleus

Question 38

Hypothalamus- GI and feeding regulation

Answer 38

• Hunger- lateral hypothalamic area, causes behavioural response like getting something to eat. Can affect limbic system and reward pathways
• Desire for food, Satiety centre- ventromedial nuclei, makes you feel full. Issues with these receptors can lead to obesity and never feel full.
• GI activity- mammillary bodies, part of the limbic system below the hypothalamus. Controls eating behaviour

Question 39

The Orexigenuc and Anirexigenic response

Answer 39

Oexigenic- desire to eat
Anorexigenic- desire not to eat
Increased GI stretch (after eating) increases the Anorexigenic response and decreases the Orexigenic response.

Question 40

Cicadian rhythm

Answer 40

Infleunces when you feel awake, can be influences by sleeping patterns. Hypothalamus control the sleep-wake cycle and associated behaviour.

Question 41

Glucocorticoid (cortisol) immunosuppresent effect

Answer 41

• Genomic- The Glucocorticoid receptor promotes IkBa synthesis, which prevents p50/p65 nuclear translocation. So, prevents the production of inflammatory cytokines
• Non-genomic- the Glucocorticoid receptor complex directly binds to the p65 subunit which prevents p50/p65 nuclear translocation.

Question 42

How glucocorticoids prevent the recruitment of leukocytes to inflamed or infected tissues

Answer 42

• They reduce vasodilation, vascular permeability and leukocyte extravasation. Increases risk of infection and cancer
• Preventing leukocyte extravasation into tissues – Mechanism unclear (thought to interfere with cell adhesion molecules both on target tissues and leukocytes)
• Vasoconstriction of endothelial smooth muscle cells – increased adrenergic receptor expression and increased production of angiotensin 2

Question 42

How glucocorticoids prevent the recruitment of leukocytes to inflamed or infected tissues

Answer 42

• They reduce vasodilation, vascular permeability and leukocyte extravasation. Increases risk of infection and cancer
• Preventing leukocyte extravasation into tissues – Mechanism unclear (thought to interfere with cell adhesion molecules both on target tissues and leukocytes)
• Vasoconstriction of endothelial smooth muscle cells – increased adrenergic receptor expression and increased production of angiotensin 2

Question 43

How altered stress leads to atherosclerosis

Answer 43

Altered metabolism cuases increased breaskdown of glycogen and fat which raises blood cholesterol

Question 44

How does chronic stress lead to hypertension

Answer 44

1) Adrenaline increases contractility, heart rate and vasoconstriction.
2) Cortisol increases vasoconstriction and blood volume through the increased production of angiotnensin 2 and the increased sensitivity and number of adrenergic receptors (increasing the vasoconstrictive abilities of adrenaline).
3) Increasing cardiovascular and renal disease.

Question 44

How does chronic stress lead to hypertension

Answer 44

Adrenaline increases contractility, heart rate and vasoconstriction. Cortisol increases vasoconstriction and blood volume through the increased production of angiotnensin 2 and the increased sensitivity and number of adrenergic receptors (increasing the vasoconstrictive abilities of adrenaline). Increasing cardiovascular and renal disease.

Question 45

Stress- The clinical consequences of chronic atherosclerosis and hypertension

Answer 45

• Coronary heart disease
• Stroke
• Heart failure
• Retinopathy
• Kidney failure
• Aneurysm

Question 46

How does chronic stress lead to type 2 diabetes or insulin resistance- altered metabolism

Answer 46

• Suppression of insulin secretion
• Hyperglycaemia
• Hyperinsulinaemia
• Increase in lipid metabolites
• Affects signalling pathways
• Antagonise insulin receptor pathways

Question 47

How does chronic stress lead to overeating

Answer 47

1. Excess cortisol stimulates the secretion of ghrelin = enhanced appetite + eating
2. Excess cortisol reduces the sensitivity of the hypothalamus to the hormone leptin that tells the brain to stop eating when full

Question 48

The clinical consequences of chronic stress

Answer 48

1. Atherosclerosis
2. Hypertension
3. Cancer (reduced immunity)
4. Back pain/headache- catecholamines promote change in muscle tension
5. Emotional + behavioural changes- cortisol shrinks prefrontal cortex + expands amygdala
6. Insomnia- catecholamines + cortisol promote alertness
7. Psychological= Eating disorders, anxiety + depression, panic attacks + PTSD

Question 49

Outcomes of acute stress

Answer 49

A primal response to anticipated demands
• Tachycardia and hypertension 
• Increased metabolic rate 
• Reduced gastrointestinal activity 
• Increased alertness 
• Increased levels of adrenaline and adrenal steroids

Question 50

Outcomes of episodic stress

Answer 50

Repeated episodes of acute stress without complete recovery
• Common to be short-tempered, irritable, anxious and tense
• This may appear as hostility, leading to deterioration in interpersonal relationships
• Workplace becomes a very stressful environment
• Persistent tension headaches and migraine
• Combination of sleeplessness and tiredness

Question 51

Outcomes of chronic stress

Answer 51

When a stressful situation becomes constant and the individual cannot see a way out:
• Emotional distress
• Muscular problems
• Stomach bowel and gut problems
• Constant tiredness
• Increased risk of coronary heart disease