Allergic and autoimmune diseases Flashcards
1
Q
What is the difference between allergy and autoimmunity?
A
Allergy is a response to external antigens (e.g. pollen), whereas autoimmunity is a response to internal antigens (e.g. myelin, β cells in pancreas)
2
Q
What are the similarities between allergy and autoimmunity?
A
They are both hyperimmune responses with inflammatory responses and symptoms
3
Q
List three significant symptoms of anaphylaxis
A
- Rash/urticaria
- Throat constriction
- Low blood pressure
4
Q
At which point has anaphylaxis become anaphylactic shock?
A
When BP drops by 30% or more
5
Q
List some common causes of anaphylaxis
A
-
Food
- Peanuts, wheat, nuts, seafood, milk, eggs
- More common in children/young adults
-
Venom
- Insect bites/stings
- Bees, wasps
-
Medications
- β-lactam antibiotics, aspirin, NSAIDS
6
Q
Describe the pathophysiology of anapylaxis
A
- Triggered by the allergen binding to mast cells (direct effect) or by IgE antibodies binding to mast cells receptors (antibody mediated release)
- Mast cells and basophils release inflammatory mediators/cytokines (e.g. histamine)
- Mast cells overreact and quickly degranulate, promoting oedema and bronchoconstriction
7
Q
What is the function of antihistamines?
A
Antihistamines block the action of histamine. Note they don’t block histamine release, so other mechanisms to shut down the mast cell overresponse are required
8
Q
List four physiological effects of inflammatory mediators/cytokines and the symptoms that result
A
- Vasodilation (increased blood vessel diameter) — reduced BP
- Cardiac muscle depression — reduced cardiac output and BP
- Fluid leakage from blood vessels — oedema
- Smooth muscle contraction in bronchi — loss of airway patency
9
Q
List three less common symptoms of anaphylaxis
A
- Intestinal cramps — gut-associated lymphoid tissue (GALT)
- Pelvic pain — smooth muscle in bladder/uterus
- CNS depression — neurokinin mediates the CNS response to anaphylaxis/allergen, increasing GABA activity
10
Q
List the symptoms of anaphylaxis
A
- Urticaria
- Oedema
- Hypotension
- Lightheadedness
- Syncope
- LOC
- Tachycardia (compensatory response)
- SOB
- Wheezes (∵ bronchospasm)
- Stridor (∵ swelling)
- Hyperventilation (compensatory response)
11
Q
The biphasic response occurs in what percentage of all anaphylactic reactions?
A
~20%
12
Q
What is the biphasic response?
A
The recurrence of anaphylaxis after initial reaction and treatment, usually within 1 to 8 hours but can occur up to 24 hours post-exposure
13
Q
List the rx for anaphylaxis and the purpose of each
A
- Adrenaline — shock, bronchodilation
- O2 (if SpO2 <94%)
- IV fluid — BP, dehydration
- Hydrocortisone — prevention of secondary (biphasic) response
- Salbutamol (β2 adrenergic agonist) — bronchodilation, increases blood flow to the heart)
- Ipatropium bromide (antimuscarinic agent) — bronchodilation
14
Q
Describe the effects and dangers of adrenaline as anaphylaxis rx
A
- Activates sympathetic nervous system
- Increases cardiac output and BP
- Bronchodilation
- May cause arrhythmias/dysrhythmias; vasospasm can encourage thrombus formation, leading to MI
- May interact with MAO (monoamine oxidase) inhibitors
- Can increase the half-life of adrenaline
15
Q
Describe hydrocortisone and its function as anaphylaxis rx
A
- Adrenocortical steroid — anti-inflammatory
- Inhibits:
- Accumulation of inflammatory cells
- Phagocytosis
- Lysosomal enzyme release
- Cytokine synthesis
- Can also inhibit release of histamine from mast cells
- Potentially blocks biphasic reaction
16
Q
List some autoimmune diseases
A
- Type 1 diabetes (IDDM)
- Inflammatory bowel diseases
- Hashimoto’s thyroiditis
- Addison’s disease
- Grave’s disease
- Reactive arthritis
- Rheumatoid arthritis
- Sjögren’s syndrome
- Systemic lupus erythematosus
- Multiple sclerosis
- Guillain-Barre
- Celiac sprue disease
- Vitiligo
- Scleroderma
- Psoriasis
17
Q
Describe the trigger and symptoms of Guillain-Barre syndrome
A
- Begins with bacterial infection (e.g. Campylobacter jejuni [food poisoning commonly contracted from chicken])
- Bilateral muscle weakness in hands and feet
- Compromised ability to control breathing
18
Q
What test result is indicative of Guillain-Barre syndrome?
A
Absent/depressed tendon reflexes
19
Q
What occurs at a cellular level in Guillain-Barre syndrome?
A
Autoantibodies attack myelin or axons of the peripheral nervous system
Demyelinating variant: Schwann cells
20
Q
What is Babinski’s sign, and what does it indicate?
A
When a soft point is run up the middle of the sole of the foot from heel to toes, the normal response is flexion of the toes (bend down). An abnormal response is extension (fanning up and out); this is called the Babinski sign and is indicative of a problem in the CNS
21
Q
List the rx for Guillain-Barre syndrome
A
- Life support
- Plasmapheresis — filter out the antibodies from plasma
- Immunotherapy — neutralise the autoantibodies with IgG antibodies (polyclonal IgGs from donors)
22
Q
What is the prognosis for pts with Guillain-Barre syndrome?
A
- Peripheral nerves can recover in most cases
- 5% mortality
- 80% recover within a year
23
Q
What is the chronic form of Guillain-Barre syndrome?
A
Chronic inflammatory demyelinating polyneuropathy (CIDP)
24
Q
How is multiple sclerosis similar to Guillain-Barre syndrome?
A
Multiple sclerosis is the demyelination in the CNS, whereas Guillain-Barre occurs in the PNS
25
Crohn's disease and ulcerative colitis are both examples of what disease group?
Inflammatory bowel diseases
26
What areas of the body are affected by Crohn's disease?
Anywhere in the GIT, commonly the ileum of the small intestine; frequently transmutal
27
List three possible causes of Crohn's disease
* Genetic
* Immune
* Microbial
28
What areas of the body are affected by ulcerative colitis?
Large intestine (colon and rectum); extends only into the mucosa
29
What causes ulcerative colitis?
Autoimmune
30
In general terms, what are inflammatory bowel diseases?
Autoimmune diseases characterised by excessive T-cell infiltration in effected areas of the GIT
31
Which populations of T-cell are involved in a) Crohn's disease and b) ulcerative colitis?
Crohn's — TH1
Ulcerative — TH2
32
What is the source of IDDM in the majority of cases?
Autoimmune
33
What causes IDDM to arise?
* T-cells attack islets of Langerhans in the pancreas
* Possible connection with coxsackie B4 virus infection; not just genetic — triggered
34
When does IDDM occur?
Any time in life, though often juvenile
35
What is the basic role of the pancreas?
Blood glucose regulation
36
What function is stimulated by insulin?
Uptake of glucose
37
What function is stimulated by glucagon?
Release of glucose
38
What is the difference between type 1 and type 2 diabetes mellitus?
* Type 1 (IDDM)
* Little/no insulin
* Autoimmune
* Type 2 (NIDDM)
* Insulin resistance
* Acquired
39
What are metabolic syndromes?
A cluster of metabolic abnormalities that constitute a known risk for CVD
40
WHO defines metabolic syndromes as any three of five features — list them.
* **Central obesity** (waist circumference \>102cm in males and \>88cm in females)
* **Impaired fasting glucose** (\>6.1mmol/L)
* **Low HDL cholesterol** (\<1.0mmol/L in males and \<1.3mmol/L in females)
* **Hypertrigliceridaemia** (\>1.7mmol/L)
* **Hypertension** (BP \>135/85)
41
Explain how obesity puts people at risk of CVD
Obesity is a trigger for development of insulin resistance, leading to diabetes, hypertension, dislipaemia, and ∴ CVD
42
Explain how obesity leads to insulin resistance
Excess circulating lipids associaetd with obesity builds up in tissues such as liver and skeletal muscle (lipotoxicity) and interferes with signalling pathways such as insulin, leading to insulin resistance
43
What are adipokines?
Cytokines produced by adipose tissue
44
Name the 'good' adipokines
* **Adiponectin** - increases insulin sensitivity
* **Leptin** - decreases appetite
45
Name the 'bad' adipokines
* **Resistin** - induces insulin resistance
* **Growth factors** (such as vascular endothelial growth factor)
* Pro-inflammatory cytokines
46
Explain the connection between insulin and lipid accumulation leading to release of 'bad' cytokines
Insulin is a hormone that induces a biological response. If the cell is accumulating lipids, the responses aren't going to be properly commanded or carried out. The more adipose tissue in the body, the more likely the 'bad' cytokines are to be released.
47
Name the three primary fuel sources for the body
* Carbohydrates
* Lipids
* Proteins
48
List four features of carbohydrates as fuel sources for the body
* Glucose is the principle fuel in the short term
* Glucose energy yield is ~4kcal/g
* Stored as glycogen
* Humans can synthesis all the carbohydrates they need
49
List three features of lipids as fuel sources for the body
* Highest calorific values 9kcal/g
* Stored as triacylglycerols (fatty acids + glycerol)
* Used when fuel is scarce or during prolonged energy expenditure
50
List two features of proteins as fuel sources
* Polymers of amino acids (9 of 20 amino acids can't be synthesised by humans [essential amino acids])
* Not stored for energy but can be used as a fuel source in times of need
51
List the eight key metabolic pathways in fuel metabolism
* **Glycolysis** - main pathway of glucose metabolism, produces small amount of ATP
* **Lipolysis** - breakdown of triglyercides into fatty acids and glycerol
* **β-oxidation** - the 'burning' of fatty acids to create energy
* **KREBS/citric acid cycle** - uses acetyl-CoA to produce high energy yielding reduced hydrogen ion carriers which are used in the mitochondrial respiratory chain to generate ATP
* **Glycogenolysis** - breakdown of glycogen to glucose or glucose-1 phosphate
* **Gluconeogenesis** - generation of glucose from metabolic precursors
* **Lipogenesis** - synthesis of fats for storage from acetyl-CoA
* **Glycogenesis** - conversion of glucose to gycogen for storage
52
Intestinal blood supply flows directly to which organ?
Liver
53
Hepatic blood supply is closely linked to the pancreatic blood supply — what is the hormonal effect of this?
Insulin/glucagon hormones exert their effects on the liver first (although it does not effect glucose uptake)
54
The liver stores ____ as ____ in a process called glycogenesis
Glucose; glycogen
55
The liver can break down and release ____ when required in a process called \_\_\_\_.
Glycogen; glycogenolysis
56
What is the name of the process by which the liver can synthesis 'new glucose'?
Gluconeogenesis
57
The liver can synthesise ketones (small water soluble acids) from fatty acids and amino acids as an alternative energy source when carbohydrates are scarce — what is the term for this process?
Ketogenesis
58
The liver can synthesise fatty acids and triglyercides (lipids) from glucose and amino acids in a process called \_\_\_\_.
Lipogenesis
59
Skeletal muscle utilises ____ as an energy source during fed state and activity, and utilises ____ as an energy source during fasting.
Glucose; lipids
60
Skeletal muscle can store glucose as glycogen which will only be used by what cell type?
Muscle cells
61
Differentiate between type 1 and type 2 skeletal muscle fibres
* **Type 1 (red/slow twitch)**
* Glucose and lipids used as energy source
* **Type 2 (white/fast twitch)**
* More equipped for anaerobic glycolysis and use glycogen stores for energy
62
True or false: skeletal muscle has endocrine functions
63
True or false: skeletal muscle secretes myokines which signal to other metabolic tissues
64
True or false: adipose is a metabolic tissue
65
Which metabolic tissue stores fatty acids as triacyl-glycerol/triglyceride (esterified fatty acids)?
Adipose
66
Adipose tissue releases fatty acids as what substance?
Non-esterified fatty acids
67
What are the two key enzymes in the process of hormone-controlled fatty acid release?
**Lipoprotein lipase** (activated by insulin to promote lipid uptake) and **hormone sensitive lipase** (inhibited by insulin; promotes lipid breakdown and release)
68
Why was adipose often described as an inert tissue?
It has a low consumption of oxygen
69
How many grams of glucose down the brain oxidise per day? What percentage of whole body expenditure does this account for?
120g; 20%
70
To what level does BSL have to fall before impaired brain function becomes evident?
2mmol/L
71
Why does pyruvate bottleneck the mitochondria and is ∴ converted to lactic acid instead?
Because conversion to acetyl CoA by the mitochondria is aerobic respiration (i.e. requires O2), whereas the conversion to lactic acid is anaerobic and can take place without oxygen
72
List the names and examples of the three main fat types
* **Cholesterol**
* Cell structure
* Hormones
* **Phospholipids**
* Cell structure
* **Triglycerides** (glycerol + 3 fatty acids)
* Cell structure
* Energy (stored in fat cells)
73
What is the main fat storage molecule?
Triglycerides
74
What are the two main functions of dietary protein?
1. Replace tissue protein broken down during metabolism
2. Synthesise specialised molecules that contain nitrogen
75
Each tissue, including blood, has a large pool of ____ \_\_\_\_.
Amino acids
76
In the fed state, ____ \_\_\_\_ are taken up and used for protein synthesis
Amino acids
77
Amino acids can be used to make ____ when required.
Glucose
78
True or false: gluconeogenesis is a reversal of glycolysis.
No, though they do have some intermediate substrate steps in common
79
Where does gluconeogenesis occur?
80% in the liver, 20% in the kidneys
80
What are the three main substrates of gluconeogenesis?
* Amino acid **alanine**
* **Lactate** from anaerobic glycolysis
* **Glycerol** from lipid breakdown
