Week 11 Flashcards
1
Q
What is the origin of the adrenal medulla?
A
Neural crest
2
Q
What is the origin of the adrenal cortex?
A
Mesodermal
3
Q
What is the physiology/function of mineralocorticoids?
A
- Regulate salt/electrolyte & water balance
- Na+ retention in kidney to maintain BP
4
Q
What is the main mineralocorticoid?
A
Aldosterone
5
Q
What is the physiology/function of glucocorticoid?
A
- Affect carbohydrate & protein metabolism
- Potent effects on host defence mechanisms (immunosuppressive & anti-inflammatory)
6
Q
What is the main glucocorticoid in humans?
A
Hydrocortisone (also called cortisol)
7
Q
Why are hydrocortisone actions not completely separate from mineralocorticoid actions?
A
Because hydrocortisone has equal potency for the mineralocorticoid & glucocorticoid receptors so can have effects on water & electrolyte balance
8
Q
What 3 things are glucocorticoids used most commonly for?
A
- Replacement therapy
- Anti-inflammatory
- Immunosuppressive
9
Q
What does ACTH (from anterior pituitary) stimulate?
A
Synthesis & secretion of glucocorticoids & mineralocorticoids from adrenal cortex
10
Q
What does the renin-angiotensin system aid ACTH to promote?
A
Mineralocorticoid secretion
11
Q
What synthetic analogue is used instead of recombinant ACTH?
A
Tetracosactide
12
Q
What drug is used to mimic the mineralocorticoid effect?
A
Fludrocortisone
13
Q
What drug is used to mimic the glucocorticoid effect?
A
Prednisolone
14
Q
What is the rate limiting step in the biosynthesis of corticosteroids, mineralocorticoids & sex hormones?
A
Conversion of cholesterol to pregnenolone (regulated by ACTH)
15
Q
What drug inhibits the conversion to pregnenolone (rate limiting step)?
A
Aminoglutethimide
16
Q
What does the drug Trilostane do?
A
Blocks 3 beta-dehydrogenase
17
Q
What is Trilostane used to treat?
A
Cushing’s & primary hyperaldosteronism
18
Q
What does the drug Metapyrone do?
A
Prevents the beta-hydroxylation of C11
19
Q
What does the drug Carbenoxolone do?
A
Inhibits the conversion of hydrocortisone to cortisone in the kidney
20
Q
What is the mechanism of action of Glucocorticoids?
A
- Bind intracellular receptors migrate to nucleus, dimerize & regulate gene transcription
- Rapid non-genomic effects mediated through signalling systems in cytosol
21
Q
What are the 3 common glucocorticoids drugs used systematically?
A
- Hydrocortisone
- Prednisolone
- Dexamethasone
22
Q
What are the metabolic effects of glucocorticoids mediated by?
A
By enzymes such as cAMP-dependent protein kinase (PKA) but not all the target genes are known
23
Q
Describe glucocorticoids regulatory actions on the hypothalamus & pituitary?
A
Negative feedback on CRF & ACTH leading to reduced release of endogenous glucocorticoids
24
Q
Describe glucocorticoids regulatory actions of the cardiovascular system?
A
Reduced vasodilation & fluid exudation
25
Describe glucocorticoids regulatory actions of the musculoskeletal system?
Decreased osteoblast & increasing osteoclast activity to give a tendency for osteoporosis
26
Describe glucocorticoids metabolic actions on carbohydrates?
- Decreased uptake & utilisation of glucose accompanied by increased gluconeogenesis to cause hyperglycaemia
- Increased glycogen storage
27
Describe glucocorticoids metabolic actions on proteins?
Increased catabolism & reduced anabolism particularly in muscle, leading to muscle waste
28
Describe glucocorticoids metabolic actions on lipids?
Permissive effect on lipolytic hormones & redistribution of fat
29
Describe glucocorticoids acute inflammatory effect?
Decreased influx & activity of leukocytes
30
Describe glucocorticoids chronic inflammatory effects?
Decreased activity of mononuclear cells, decreased angiogenesis & fibrosis
31
Describe glucocorticoids effects on lymphoid tissue?
- Decreased clonal expansion of T & B cells & decreased activation of cytokine-secreting T cells
- Switch from Th-1 & Th-2 responses
32
Describe/List glucocorticoids actions on mediators of inflammatory & immune responses?
- Decreased production & action of cytokines (interleukins, TNF-α, cell adhesion factors & induced nitric oxide)
- Reduced eicosanoids due to decreased COX-2
- Reduced IgG & complement components in blood
- Increased anti-inflammatory factors (IL-10 & Annexin-1)
33
Describe the overall action of glucocorticoids on immune systems?
Reduction in activity of innate & acquired immune systems
34
When would you use glucocorticoids for replacement therapy?
Adrenal failure (Addison's disease)
35
When would you use glucocorticoids for anti-inflammatory/ immunosuppressive therapy?
- Hypersensitivity & Asthma
- Topically in inflammatory conditions of skin, eye, ear & throat
- Rheumatoid arthritis, IBD, haemolytic anaemias, idiopathic thrombocytopenia
- Prevent graft-versus host disease
36
When would you use glucocorticoids for treating cancer?
- Combination with cytotoxic drugs for Hodgkin’s disease & acute lymphocytic leukaemia
- Reduce oedema in tumours (Dexamethasone)
37
List the adverse/unwanted effects of glucocorticoid therapy?
- Suppress response to infection & injury
- Opportunistic infections can be problematic
- Oral fungal/yeast infections can occur
- Wound healing is impaired
- Osteoporosis
- Hazard of fractures
- Hyperglycaemia
- Muscle wasting & weakness
- Inhibition of growth in children
- Euphoria, depression & psychosis
- Glaucoma
38
When are adverse/unwanted effects of glucocorticoid therapy commonly found?
Mainly after prolonged systemic use but not following replacement therapy
39
Describe the potential causes of Cushing's syndrome?
- Excessive exposure to glucocorticoids
| - Disease (tumour) or prolonged administration of glucocorticoid drugs
40
How common is a pituitary tumour the cause of Cushing's syndrome?
70% of endogenous cases
41
How common is an adrenal tumour the cause of Cushing's syndrome?
15% of endogenous cases
42
What are the physical signs/symptoms of Cushing's syndrome?
- Euphoria/ depression
- Buffalo hump
- Thinning of skin
- Thin arms & legs (muscle wasting)
- Osteoporosis
- Hyperglycaemia
- Easy bruising
- Poor wound healing
- Increased abdominal fat
- Moon face, red cheeks
- Cataracts
- Benign intracranial hypertension
43
What is the main treatment for iatrogenic Cushing's syndrome?
Decrease/ withdraw use of corticosteroids gradually
44
What is the main treatment for endogenous Cushing's syndrome?
- Surgery to remove tumour
- If surgery unsuccessful, or not possible to remove the tumour safely, medication can be used to counter the effects of the high cortisol levels
45
What happens if Cushing's syndrome is left untreated?
High blood pressure which increases risk of heart attack & stroke
46
What is the main clinical use of mineralocorticoids?
Replacement therapy as in Addison’s disease where there is decreased aldosterone secretion
47
What is the most common mineralocorticoid drug?
Fludrocortisone (oral)
48
What is the mechanism of action of Fludrocortisone?
- Increases Na+ reabsorption in distal tubules & increases K+ & H+ efflux
- Acts on intracellular receptors that modulate DNA transcription
49
What is spironolactone?
Competitive antagonist of mineralocorticoids & is a potassium-sparing diuretic
50
What 4 things is Spironolactone used for?
1. Hyperaldosteronism
2. Resistant hypertension
3. Heart failure
4. Oedema
51
What is Addison's disease?
Adrenal glands are dysfunctional & lead to cortical insufficiency
52
Describe the epidemiology of Addison's disease?
- Rare
- Most 30-50yrs old
- Can occur at any age
- 7 in 10 cases due to autoimmune disease
53
Describe autoimmune Addison's disease?
Antibodies destroy adrenal cortex cells which make cortisol & aldosterone
54
How can TB cause Addison's disease?
Can spread to & gradually destroy adrenals
55
What are 4 other causes of Addison's disease?
1. Metastatic cancers
2. Atrophy due to prolonged steroid therapy
3. Hemochromatosis
4. Amyloidosis
56
List the symptoms of Addison's disease?
- Anorexia
- Nausea/vomiting
- Weakness
- Hypotension
- Skin pigmentation (due to ACTH)
- Low sodium/high potassium
- Chronic dehydration
- Sexual dysfunction.
57
What is the treatment for Addison's disease?
- Corticosteroid (steroid) replacement therapy for life
- Hydrocortisone used to replace cortisol (tablet 2-3x day)
- Prednisolone/ Dexamethasone
58
What treatment should you give in Addison's disease if greater mineralocorticoid effects are needed?
Aldosterone is replaced with fludrocortisone, a more selective analogue
59
What is a cause of primary hyperaldosteronism?
Adrenal adenoma / Conn's syndrome (80%+)
60
Describe the treatment for Adrenal adenoma / Conn's syndrome causing hyperaldosteronism?
- Prior to surgery use aldosterone antagonists (Spironolactone) usually for 4 weeks
- Surgical adrenalectomy, laparoscopic surgery is preferred
61
Why might hypertension persist after removal of the adenoma in hyperaldosteronism?
Due to effects of previous hypertension on vasculature
62
Describe how an Adrenal hyperplasia can cause primary hyperaldosteronism?
In bilateral adrenal hyperplasia (BAH) adrenal cells become hyperplastic, resulting in excessive secretion of aldosterone (15%)
63
How is the rare unilateral adrenal hyperplasia treated?
Adrenalectomy
64
Describe adrenal carcinoma causing primary hyperaldosteronism?
- Rare
| - Only diagnosed once adrenal adenoma removers & examined histologically
65
Describe congenital adrenal hyperplasia?
- Genetic disorder where C-21 hydroxylase enzyme is missing
| - Non-hydroxylated versions of cortisol, corticosterone & aldosterone are made
66
Why are non-hydroxylated versions of cortisol, corticosterone & aldosterone bad?
Lack normal activity & do not negatively feedback on HPA axis
67
What does high levels of ACTH cause?
Constant stimulation of production of C-19 androgens
68
How do you treat congenital adrenal hyperplasia?
- Cortisol to replace missing cortisol & cause negative feedback
- Replace mineralocorticoid
69
How many different types of arthritis & rheumatic disease are there?
Over 200
70
What is Rheumatoid arthritis?
- Chronic, systemic autoimmune disease
| - Inflammation of lining/synovium of the joints
71
What may rheumatoid arthritis lead to?
Long-term joint damage resulting in chronic pain, loss of function & disability
72
Describe the epidemiology of rheumatoid arthritis?
- 3x more common in women
- 30-50yrs, can also affect young
- All ethnic groups & parts of the world
73
Describe the symptoms of rheumatoid arthritis?
- Inflamed joints are warm, tender, swollen, red & painful & difficult to move
- Fatigue
- Loss of appetite, weight loss, flu-like symptoms, depression, anemia
- Vasculitis
- Sjogren’s syndrome
- Inflammation surrounding heart & lungs
74
Describe the foot, knee & ankle when affected by rheumatoid arthritis?
Effusions & synovial thickening of knee usually detected easily
75
How commonly is the hip affected by rheumatoid arthritis?
Common, but early manifestations are not apparent
76
How commonly are the hands & wrists affected by rheumatoid arthritis?
Affected in virtually all people with RA
77
Describe the elbow when affected by rheumatoid arthritis?
- Effusion difficult to detect on physical exam
| - Only objective finding is loss of motion
78
Describe the shoulders when affected by rheumatoid arthritis?
Neck stiffness & general loss of motion
79
Describe how blood is affected by rheumatoid arthritis?
Hypochromatic-microcytic anemia with low serum ferritin & low/normal iron-binding capacity almost universal
in patients with active RA
80
Describe how nerves are affected by rheumatoid arthritis?
Results from cervical spine instability, peripheral nerve entrapment & vasculitis resulting in mononeuritis multiplex
81
Describe how the heart is affected by rheumatoid arthritis?
Pericardial effusion present in ~50%, but clinical symptoms are rare
82
Describe how the lungs are effected by rheumatoid arthritis?
Interstitial lung disease common, but may be asymptomatic
83
Describe how the eyes are affected by rheumatoid arthritis?
Keratoconjunctivitis sicca, episcleritis, scleritis
84
Describe how the skin is affected by rheumatoid arthritis?
Rheumatoid nodules in 50%, dermal vasculitic lesions
85
What are Major histocompatibility complex (MHC)?
Membrane glycoproteins on the cell surface that display peptide antigens to T cells
86
What is the function of MHC II?
Bind peptides derived from proteins from extracellular sources that have been internalised into intracellular vesicles (DC, macrophage/ phagocytic cells & B cells)
87
What does class II MHC present?
Peptides to CD4+ T helper cells
88
What does Th1 produce in general?
Cell mediated immunity
89
What does Th2 produce in general?
Antibody responses
90
What do the Th1 cytokines activate?
Macrophages
91
What do the Th2 cytokines activate?
B cells
92
What have been found to be associated with rheumatoid arthritis?
Specific human leukocyte antigen (HLA)-DR genes
93
What is present in 2/3's of caucasians with rheumatoid arthritis?
HLA-DR4
94
Where are Specific human leukocyte antigen (HLA)-DR genes located?
Reside in the MHC & participate in antigen presentation
95
What are the 3 potential roles of HLA-DR genes?
1. Binds to arthritogenic peptides
2. Serves as target for auto reactive T cells
3. Closely linked to other genes in MHC
96
What help mediate autoimmunity?
Regulatory T (Treg) cells by suppressing autoreactive T cells by secreting inhibitory cytokines (IL-10 & TGF-Beta)
97
What is tolerance?
Process that keeps the immune system from attacking “self”
98
Describe deletional tolerance (recessive)?
- Self-reactive T cells are deleted in thymus.
| - Occasionally, may escape deletion and in periphery can cause tissue damage
99
Describe regulatory tolerance (dominant)?
- T cell specific for self antigen becomes a regulatory T cell
- Cytokines (IL-10 & TGF-beta) produced by Treg inhibit other self-reactive T cells
100
What are cytokines?
Proteins made by cells that affect the behavior of other cells (i.e. interleukins)
101
What are chemokines?
Small chemoattractant proteins that stimulate the migration & activation of cells
102
What are synovial fibroblasts activated by?
- IL-1
- TNF-alpha
- IL-15, 16, 17, 18, 22, 23
103
What can synovial fibroblasts do?
Invade cartilage & bone & regulate monocyte differentiation into osteoclasts
104
How do you diagnose rheumatoid arthritis?
- Medical history
- Physical examination
- Lab tests
105
List 3 different types of lab tests for rheumatoid arthritis?
1. Imaging studies- Erythrocyte Sedimation Rate
2. Blood tests- (CRP)
3. Rheumatoid factor- Antinuclear Antibodies (ANA)
106
What 4 factors does the treatment of rheumatoid arthritis focus on?
1. Relieving pain
2. Reducing inflammation
3. Stopping/ slowing joint damage
4. Improving functioning & sense of well-being
107
What are the 3 symptomatic medications for rheumatoid arthritis?
1. NSAIDs
2. Analgesics
3. Corticosteroids
108
What are the 4 disease modifying drugs for rheumatoid arthritis?
1. Methotrexate
2. Sulfasalazine, Azathioprine
3. Cyclosporine, Hydroxychloroquine
4. Minocycline
109
What are the 3 biologic modifiers for rheumatoid arthritis?
1. Infliximab (anti-TNF)
2. Rituximab (anti-CD20)
3. Combination DMARD Therapy
110
How are people with rheumatoid arthritis likely to be affected?
- 75% joint pain, swelling & flare-ups
- 20% always have mild rheumatoid arthritis
- 5% develop severe disease with extensive disability
111
What is Ankylosing Spondylitis (AS)?
Chronic inflammatory arthritis predominantly affecting the joints of the spine
112
Describe the epidemiology of Ankylosing Spondylitis (AS)?
3 Males: 1 Females
113
Describe the treatment for Ankylosing Spondylitis (AS)?
- 1st usually NSAID
- Aspirin, ibuprofen,
indomethacin,
Diclofenac, ketoprofen (COX-2 inhibitors)
- Anti-TNF mAb (infliximab) proved very effective
114
What is Ankylosing Spondylitis (AS) associated with?
Human class I MHC molecule HLA- B27 (90% of patients)
115
Describe the symptoms/signs of Ankylosing Spondylitis (AS)?
- Back pain
- Bone grows out from both sides of vertebrae & may join them together
- "Bamboo spine"/ locked spine
116
What is B27 also linked to?
Reactive Arthritis (ReA), but at lower level (~50%)
117
What is Reactive Arthritis triggered by?
Bacterial infection, usually of gut/urinary tract (salmonella, campylobacter, chlamydia)
118
List signs of reactive arthritis?
- Eye inflammation
- Diarrhoea
- Lower back pain
- Scaly skin patches on genitalia
- Flaky skin patches on sole
- "Sausage" toes
- Swelling in knee, heel or ball of foot
119
What are the theories for B27 peptide and Ankylosing Spondylitis (AS)?
- Peptide from bacteria presented by B27, looks like host peptide in spine
- Autoreactive T cells target joint (however, you can remove CD8 T cells & still get disease)
120
What is the theory for B27 misfolds & Ankylosing Spondylitis (AS)?
- Misfolds insides cells & causes cells to be stressed & secrete cytokines
- Or, misfolded at cell surface & recognised incorrectly by Natural Killer cells
121
What is coeliac disease?
Gut condition where small intestines become inflamed losing the villi (diarrhoea, abdo pain & bloating)
122
What are the complications associated with Coeliac disease?
- Osteoporosis
- Iron, vit B12, folate deficiency anaemia
- Bowel cancer
123
Describe the epidemiology of coeliac disease?
- 2-3x higher in females
- 1 in 100 in UK
- Onset within 1st year but diagnosis may take longer
- Adulthood 40-60yrs
- 1st degree relatives should be tested
124
What is gluten made up of?
Long strings of gliadin molecules which contain glutamine
125
What bit of gluten is coeliac disease reactive to?
33-mer peptide
126
What is the function of the parathyroid gland chief cells & oxyphilic cells?
- CHIEF CELLS: parathyroid hormone (PTH)
| - OXYPHILIC CELLS: unknown
127
What is the primary action of the parathyroid hormone?
Maintenance of plasma [Ca2+]
128
What is the action of PTH + Vit D3?
Increase plasma Ca2+
129
What is the action of calcitonin?
Decreases plasma Ca2+
130
Where is the Ca2+ located in the body?
- 99% bone/teeth
| - 1% mainly intracellular
131
What is CaPO4 converted to?
Hydroxyapatite
132
Describe the breakdown of Ca2+ in plasma 2.3-2.6mM (0.1% of body calcium)?
- 50% free
- 45% bound to protein
- 5% chelated to dicarboxylic acids ie. citrate/lactate
133
Describe the 6 physiological functions of Ca2+?
1. Prosthetic group for many enzymes & structural proteins
2. Structure of plasma membrane
3. Excitation-contraction coupling in muscle
4. Excitation-secretion coupling at axonal terminals & endocrine & exocrine glands
5. Blood coagulation
6. Major intracellular second messenger
134
How much calcium is in our extracellular fluid?
1000mg
135
How much ECF phosphorus pool is there?
500mg
136
What regulates parathyroid hormone (PTH) secretion?
Increased [Ca2+]o causes stimulation of PKC, increased PKC & [Ca2+]i inhibits PTH synthesis & release
137
What is the Pre-proparathyroid 115 residue made up of?
- Signal sequence
- Pro-sequence
- Biologically active sequence
- C-terminal fragment sequence
138
Describe the processing of pre-proparathyroid hormones?
- It enters the endoplasmic reticulum and signal sequence is cleaved off = Proparathyroid 90 residues
- Enters Vesicle secretion and pro sequence is cleaved off = parathyroid (secreted) 84 residues
139
Describe the processing of pro-calcitonin in the parafollicular C cells within the thyroid?
- Primary transcript undergoes RNA processing & losses CGRP = mature mRNA
- mRNA translation causes loss of A or B
- Proteolytic processing splits it up into N terminal peptide, Calcitonin & CCP (mature peptides)
140
Describe the processing of pro-calcitonin in the brain neurones?
- Primary transcript undergoes RNA processing & losses Calcitonin & CCP
- mRNA translation causes loss of A or B, C & D
- Proteolytic processing splits it up into N terminal peptide, CGRP & C-terminal peptide
141
Describe how osteocytes are stimulated/produced to cause bones resorption?
- PTH & Vit D act on osteoblasts to secrete growth factors (macrophage colony-stimulating factor & IL-6)
- M-CSF causes stem cells to become osteoclast precursors --> mononuclear osteoclast
- IL-6 RANK ligand stimulates osteoclasts (multi nucleated) to reabsorb bone
142
Describe how osteoblasts cause bone formation?
They secrete Ca2+ and phosphate to cause nucleation and lay down new bone
143
What do interns on the osteoclast mate with?
Vitronectins on the bone to seal off the area
144
Describe the metabolism of vitamin D?
7-dehydrocholesterol --> Cholecalciferol (Vit D3) --> 25-Hydroxycholecalciferol (25-OHD3) --> 1,25-(OH)2D3
145
What is the active form of Vitamin D which stimulates osteoblasts?
1,25-(OH)2D3
146
What is Ergocalciferol (vit D isoform) also known as?
Vitamin D2
147
Describe the intestinal absorption of Ca2+?
- Vit D allows Ca2+ from intestinal lumen to move into epithelial cell & bind to calbindin
- Ca2+ moves into interstitial space & allows H+ to enter
- Ca2+ moves into interstitial space & allows 2 Na+ to enter
148
Describe the intestinal absorption of phosphate?
- 2 Na+ & NaPi enter epithelial cell from intestinal lumen
- Protein synthesis allows for HPO4 or H2PO4- to leave into interstitial space
- It also allows for 3 Na+/2 K+ ATP channel to be activated
149
Describe what chief cell of parathyroid releasing PTH does to control plasma [Ca+]?
1. Increases bone Ca reabsorption
2. Inhibits tubule Pi reabsorption
3. Increases conversion of 25-OH-vitamin D to active form 1,25(OH)2-vit D
4. Increases kidney tubule Ca reabsorption
150
What is the definition of long term conditions?
Condition that requires ongoing medical care, limits what one can do & is likely to last longer than 1 year
151
What how much do long term conditions use up NHS resource, GP consultations & hospital bed days (%)?
- NHS resource: 78%
- GP consultations: 80%
- Hospital bed days: 60%
152
Describe the epidemiology of Long term conditions?
- ~2million Scots have atleast 1 LTC
- 1/3 of households
- 61% of 75-84yrs have 1 LTC
- 22% of 75-84yrs have 2+ LTC
153
Describe the 3 points to Scotland's mutual care model for LTC?
1. Culture which supports people with LTC & their carers to be lead partners in decisions about health
2. Workforce with awareness, environment, knowledge & capability to enable LTC living well
3. Health, housing, social services, community & voluntary partners work together with people & families with LTC
154
What help does the lower risk people with LTC get?
- Supporter self-care (70-80%)
| - Professional care
155
What help does the high risk people with LTC get?
- Disease management (15-20%)
| - MIU, A&E, emergency
156
What help does the individuals with complex LTC needs get?
Case management (3-5%)
157
What does SPARRA stand for?
Scottish Patients at Risk of Readmission & Admission
158
What does SPARRA do?
- Identify patients aged over 65 most at risk of emergency admission in the coming year
- Feedback probabilities & details of patients to front-line teams
159
What does SPARRA act as a basis for?
Further assessment to identify those patients who will benefit most from preventive interventions ie. intensive case management
160
What is Shared Medical appointments (SMA) & what does it aim to do?
- 1:1 patient-centred consultation (60mins) with a clinician-provider in presence of other patients & other healthcare providers
- Aim to improve health & wellbeing
161
What are the possible benefits of group consultations/shared medical appointments (SMA)?
- People living with diabetes improved HbA1c up to 1 year
- Less complications for baby & mother in group antenatal care
- Older people improved continence
- Improved patient knowledge
- Improved quality of life in COPD
- Improved patient satisfaction
162
What are the whole system benefits of group consultations/shared medical appointments (SMA)?
- Efficiency gains (clinician time) 40% productivity gain
- Reduced A&E use & emergency admissions
- Reduced bed days
- 50% reduction psychiatric bed days
- Lower care & societal costs
- Reduced waiting times 3 months to 3 weeks
- Improved patient & staff satisfaction
163
Describe the epidemiology of diabetes in Scotland?
- Prevalence 5%
- 88% have type 2
- 88% of those are overweight/obese
- 10,000 new cases per year
164
At 40yrs of age, what are the years lost due to a BMI>30 compared to a BMI<25 in men and women?
- MEN: 5.8yrs lost
| - WOMEN: 7.1yrs lost
165
Describe the relationship between insulin resistance and obesity?
- Insulin resistance closely linked to abdominal obesity
| - Weight increases, insulin resistance increases
166
What is a 5% (4.5kg) weight loss equal to?
22% of excess weight = 40% of excess abdominal fat
167
What does weight loss do among obese diabetic patients?
- Reduced Blood pressure
- Improves lipid profile
- Glycaemic control
168
What do we tell our obese patients to do for weight maintenance?
Reduce intake by 50-100kcal per day for weight maintenance
169
What are the 3 successes associated with weight monitoring?
1. Sustained weight, no increase
2. Minor weight loss with dietary change to reduce risk of complications
3. Weight normalisation- rare
170
How much body fat is there in a caucasian compared to south asian with both BMI 22.3?
- Caucasian: 9.1%
| - South Asian: 21.2%
171
What is an obesogenic environment?
- Imbalance calories consumed & burned
| - Static leisure, transport, employment
172
Describe the Healthy Weight Communities (EPODE)?
- Cut childhood obesity by 1/4
- All sectors: breastfeeding, walking clubs, gala days, community centres, parks, schools, shops etc.
- Total environment approach
173
What else can be used as a tool to facilitate healthier lifestyles & prevent obesity?
Law to regulate harms
174
Describe the changes in rules for marketing & labelling foods?
- 24 Oct 2012: consistent from of pack labelling, voluntary but food industry on board
- 11 Oct 2012: food choices not fully conscious "Impulse marketing"
175
What 4 things should we encourage to try decrease levels of obesity in society?
1. Greater personal responsibility
2. Greater personal & societal responsibility without legislation
3. Greater persoanl & societal responsibility including legislation
4. Societal responsibility & legislation
176
What are 3 ideas for compulsory improvements in food & drink labelling?
1. Regulation to ban marketing of foods high in sugar, salt & fat before 9pm watershed on TV to protect children
2. Creation of a 20% per L sugar sweetened beverages
3. Prioritise & fund health services to address weight in obese patients, in a similar way to smoking cessation
177
What are the 4 different pathologies causing adrenal hyperfunction?
1. Cushing's syndrome
2. Conn's syndrome
3. Adrenogenital syndrome & Congenital adrenal hyperplasia
4. Adrenocortical neoplasms
178
Describe Cushing's syndrome?
- Excessive secretion of cortisone
- Also mineralocorticoid effectds
- Female>Male
179
Describe the features of Cushing's syndrome?
- Muscle catabolism
- Abdominal Fat
- Abnormal collagen maturation
- Hypertension
- Osteoporosis
- Impaired glucose tolerance
- Hirsutism
- Buffalo hump (fat neck)
- Depression/psychosis
180
What causes approx 2/3 of Cushing's syndrome?
Pituitary adenoma producing ACTH --> adrenal hyperplasia
181
What causes approx 1/6 of Cushing's syndrome?
Primary adrenal neoplasm- benign & malignant 50:50
182
What causes approx 1/6 of Cushing's syndrome?
- Ectopic ACTH or related peptides --> adrenal hyperplasia
| - Iatrogenic --> adrenal atrophy
183
What is Conn's disease?
Primary hyperaldosteronism
184
Describe the sign's of Conn's disease?
- Hypokalaemia
- Muscle weakness & cramps
- Metabolic alkalosis
- High aldosterone
- Low renin
185
What is the gender ratio for Conn's?
Females 4 : Males 1
186
What do 80% of Conn's have?
Adrenal adenoma (tends to be benign)
187
What do 20% of Conn's have?
Bilateral hyperplasia of zona glomerulosa but unknown cause
188
What can cause secondary hyperaldosteronism?
Increased renin-angiotensin activity ie. as a result of renal ischaemia (associated with renal artery stenosis)
189
How common is Congenital adrenal hyperplasia?
- Uncommon but not impossible
| - 1 in 15,000
190
What are 2 causes of Congenital adrenal hyperplasia?
1. 21 hydroxylase deficiency (CYP21)
| 2. 11-beta hydroxylase deficiency
191
List the 3 different types of adrenal neoplasia?
1. Benign
2. Primary malignant (cortex, medulla)
3. Secondary malignant (lung, breast, kidney, colon, melanoma, lymphoma)
192
Describe an Adenoma?
- Not infrequent at autopsy but only diagnosed in life if functional
- Low malignant potential so treat conservatively (do nothing)
- Most adenomas non-functional!
193
Describe an Adrenal carcinoma?
- Rare
- Poor outlook as aggressive with necrosis & rapid growth
- More often secrete sex steroids
- Surgery is only hope
194
What are the 2 purposes of monitoring molecular changes in adrenal pathology?
1. Possible use in distinguishing adenoma from carcinoma (limited)
2. Identification of familial syndromes
195
Describe a Phaeochromocytoma?
- Chromaffin cells
- Intermittent production of catecholamines
- Not easy to say if benign or malignant (10% benign, 10% malignant)
196
Describe the episodic/stress induced presentation of Phaeochromocytoma?
- Hypertension
- Sweating
- Collapse
- Glycosuria
197
What can cause Phaeochromocytoma?
20% familial, may be part of MEN (genetic predisposition)
198
Describe a neuroblastoma?
- Very rare
- Commonest malignant tumour in children
- N-myc (oncogene) amplification or adrenal site worse prognosis
199
What is a cause of acute adrenal hypofunction?
Meningococcal septicaemia
200
What are 4 causes of chronic adrenal hypofunction?
1. Addison's disease
2. Amyloid
3. Tuberculosis
4. Metastasis
201
What is the cause of Addison's disease 75% of the time?
Autoimmune adrenalitis
202
What are the 2 illnesses associated with Addison's disease?
1. Vitiligo
| 2. Diabetes
203
What is the ratio of type 1 & type 2 diabetes mellitus?
DM2 10: DM1 1
204
What is the usual cause of type 1 diabetes mellitus?
Insulitis (may be triggered by viral infection)
205
What is the usual association of type 2 diabetes mellitus?
Beta-cell failure correlates with the formation of pancreatic islet amyloid deposits
206
Describe type 1 diabetes mellitus?
- Under 40, childhood
- Thin
- 1 in 500
- Danger of ketosis
- 40% concordance in monozygous twins
- Destruction of beta cells
207
Describe type 2 diabetes mellitus?
- Over 40y
- Obese
- 1:50
- Hyperosmolar not ketosis
- No MHCII linkage
- Not autoantibodies to islets
- Beta cells persist
208
What are 3 other causes of diabetes?
1. Pancreatitis (destroy islets)
2. Cystic fibrosis (scarring, inflammation)
3. Tumour
209
What are the 4 theories of the placebo effect?
1. Endogenous opiates- Naloxone-sensitive results
2. Conditioning- Pavlov's dog
3. Expectancy- wine & placebo alcohol, dopamine & money
4. Motivation- more compliant patient?
210
What are the 2 examples of blinding & acupuncture?
1. Sham acupuncture locations- variation anyway, could hit meridians "by chance", practitioner blinding
2. Sham acupuncture needles- practitioner/patient blinding
211
What are 3 orthodox explanations for acupuncture?
1. Gate control theory of pain
2. Opioid release
3. Placebo effect
212
How can we test the claims of complementary alternative medicine (CAM)?
Emily Rosa & therapeutic touch
213
Describe chiropractic on trial?
- Comparative treatments ie. physiotherapy
| - Massage often part of chiropractic assessment
214
What 3 things are not possible to confirm/refute for treatment in lower back pain?
1. Painkillers
2. Exercise
3. Physiotherapy
215
What did Simon Singh say about the British Chiropractic Association (BCA) & what happened?
- Said chiropractic treatment "happily promotes bogus treatment"
- BCA sued him for libel (false information) in June 2008, case was dropped in April 2010
216
What did the Cochrane review conclude for Acupuncture & osteoarthritis?
- Sham-controlled trials show statistically significant benefits but don't meet thresholds
- Atleast partially due to placebo effects from incomplete blinding
- Waiting list-controlled trials of acupuncture suggests statistically significant, much of which due to expectation/placebo
217
What did the Cochrane review conclude for Chiropractic interventions for low-back pain?
- Combined chiropractic interventions slightly improve pain & disability in short/med-term for acute & subacute LBP
- Future research is very likely to change estimate of effect & confidence in results
218
What are the 4 questions we ask regarding if CAM interventions work?
1. Is there a placebo effect?
2. Something within the body that explains how a placebo effect occurs?
3. CAM effect over & above what can be attributed to the placebo effect?
4. Something within the body that could explain how 1+ CAM effects occurs?
219
List the reasons why people use CAM?
- Health promotion/disease prevention
- Exhausted conventional options
- Conventional option side effects/risks
- No conventional therapy
- Conventional approach emotionally/spiritually bereft
- Do they know its CAM?
220
Why can/can't CAM appear effective?
- Some MAY be effective: herbal remedies could contain active ingredients
- Some CAM clearly have NO plausible scientific explanation/inherent efficacy
221
What are the 3 factors that can make CAM treatment appear effective?
1. Disease-associated
2. Patient-focussed
3. CAM-based
222
List the natural impediments to making valid inferences/conclusions?
- Placebo effect
- Natural history of disease
- Causal inferences
- Reluctance to admit when wrong
- Simple optimism
- Respect for authority
- Conspiracy-orientated view of the world
223
What are the 2 ethical issues around CAM's working?
1. It it’s nothing more than a placebo, is that a bad thing?
| 2. Do we need to know how a treatment works?
224
What are the 2 ethical issues around CAM's being safe?
1. Regulation of practitioners/ substances
| 2. Direct vs indirect harm
225
How can you balance patient choice against the 1st duty of a doctor?
- Make the care of your patients your first concern
- Patient autonomy
- Informed choice
226
What are the 2 ethical questions regarding if CAM should be researched?
1. Worthwhile finding active ingredient in herbal meds?
| 2. As worthwhile researching homeopathy?
227
What is the ethical question for if there is a fair allocation of money regarding CAM?
Diversion of funds from science-based therapies?
228
What are the 2 ethical questions for CAM being a fair exploration of choice?
1. Or weakening commitment to the scientific method?
| 2. Undermining or enhancing public trust?
