Y2 Endocrinology Revision Flashcards
What are the subtypes of CD4+ cells?
Effector subsets: fight pathogens
- Th1: IFN-gamma
- Th2: IL-4 & IL-5
- Th17: IL-17
Regulatory subsets: regulate the effectors
- Tr1: IL-10
- Th3: TGF-beta
- CD25: IL-10 & TGF-beta
What are Th1 cells responsible for?
- Fight intracellular pathogens, release IFN-gamma
What are Th2 cells responsible for?
Fight extracellular pathogens, secrete IL-4&5
What are Th17 cells responsible for?
Fighting extracellular bacteria and fungi, secrete IL-17
What are microfold (M) cells?
- Specialised antigen uptake cells found in mucosa
- Take up antigens by phagocytosis
- M cells release antigens which are picked up by APCs which activate T-cells in GALT
What is the dominant antibody class in the mucosal immune system?
IgA
- IgA is dimeric
- sits on the luminal surface where is neutralizes pathogens
- we produce 5g of IgA everyday
- binds to receptor via J chain and transports across the cell, it uses J chain to stop getting washed away
- coats membrane and stops pathogens binding
- IgA doesn’t produce inflammation or activate compliment
What can take over if IgA is not present?
IgM – pentameric, also has a J chain
What is NOD2?
- Protein encoded by the NOD2 gene on chromosome 16
- recognises bacterial molecules and stimulates an immune reaction
- expressed in Paneth cells, leads to expression of anti-microbial peptides
- mutation in NOD2 linked to Crohn’s
What are aminosalicylates?
Drugs that dampen inflammation, mech. not well understood
- Mesalamine is the active ingredient
examples:
- Sulfasalazine
- Mesalazine
What is methotrexate?
Immunosuppressor
- inhibits DNA synthesis and cellular replication
What is infliximab?
MAB – binds to TNF-alpha and stops it working
Discuss gastroenteritis
Infectious diarrheoa, inflammation of gut
- antibiotics not recommended
usually viral:
- norovirus
- rotavirus
bacteria:
- campylobacter
- E.coli
- salmonella
parasites:
- giardia lambila
What is the role of the appendix
GALT – storage area of flora
people without an appendix often get recurrent bouts of c.diff because they don’t have their flora In storage
What is absorbed in the duodenum?
Iron
What do goblet cells secrete?
Mucins
What is absorbed in the jejunum?
Sugars
Amino acids
Fatty acids
What is absorbed in the ileum?
B12
Bile salts
What are the 4 zones of the adrenal glands?
- Glomerulosa: Mineralocorticoids
- Fasciculata: Glucocorticoids
- Reticulans: Androgens
- Medulla: Catecholamines (80% adrenaline, 20% noradrenaline)
What are steroid hormones derived from?
Cholesterol
Discuss the HPA axis
- Hypothalamus (corticotropin releasing H)
- Pituitary (adrenocorticotropic H)
- Adrenal glands (cortisol)
Where is aldosterone released from?
Adrenal glands
Discuss adrenal insufficiency
Primary: problem with gland not releasing cortisol
Secondary: problem with anterior pituitary not releasing ACTH
Tertiary: hypothalamus not releasing CRH
Discuss Addison’s disease
- Primary adrenal insufficiency
- Usually autoimmune
- Diagnosed when cortisol <100mmol/L
- check cortisol, inject ACTH and check again
What is fludrocortisone?
Synthetic adrenocortical steroid – mineralocorticoid and glucocorticoid properties
1) Increases ion and water transport
2) Raises extracellular fluid volume and blood pressure
3) Lowers potassium levels.
What are the consequences of prolonged steroid use?
Adrenal atrophy, lack of ACTH production
Discuss Cushing’s syndrome
- Prolonged exposure to elevated levels of glucocorticoids
- most common cause is use of exogenous steroids e.g. for COPD
*test for urine cortisol – has to be 2x normal
What is the difference between Cushing’s syndrome and disease?
Syndrome = symptoms associated with hypercortisolism
Disease = ACTH producing adenoma in pituitary
What is the dexamethasone suppression test?
Dexamethasone = synthetic cortisol
Given to patient, should cause cortisol levels to drop below 50nmol/L
*If not – Cushing’s
What is the function of mineralocorticoids?
Salt and water balance
What is a glucocorticoid?
*Cortisol is a glucocorticoid
Corticosteroids involved in the metabolism of carbs, proteins, fats
Have anti inflammatory properties e.g. hydrocortisone
What is intrinsic clearance?
Theoretical max clearance of unbound drug by an eliminating organ
What are the consequences of a lack of mineralocorticoids?
Fatal shock due to diminished cardiac output
What converts corticosterone to aldosterone?
18-hydroxylase
What are the actions of cortisol?
- Increases gluconeogenesis
- Induces glucagon activity to increase blood sugar
- increases protein catabolism
What is congenital adrenal hyperplasia?
- Most commonly due to 21-Hydroxylase deficiency
- Results in decreased cortisol and aldosterone
- Excessive androgen production leading to masculinisation of female genitals
Other cause = 11B-Hydroxylase deficiency which causes increased androgens and increased mineralocorticoids
What is the role of angiotensin II in the production of mineralocorticoids?
Converts cholesterol to pregnenolone
Converts corticosterone to aldosterone
Which drugs have high glucocorticoid activity?
Dexamethasone
Betamethasone
Which drugs have moderate glucocortioid activity?
Hydrocortisone, Triamcinolone, Prednisolone
What is fludrocortisone?
Synthetic adrenocortical steroid possessing very potent mineralocorticoid properties and high glucocorticoid activity
