Endocrine Physiology Flashcards
What does the adrenal medulla secrete?
Adrenaline
Small amount of noradrenaline
Where is ADH secreted and what is its function?
Released from Posterior pituitary
Promotes water reabsorption in the collecting ducts of the kidneys by the insertion of aquaporin-2 channels.
Where is ADH synthesised?
Supraoptic nuclei of the hypothalamus, released by the posterior pituitary
What factors cause increased secretion of ADH?
- Extracellular fluid osmolality increase
- Volume decrease
- Pressure decrease
- Angiotensin II
What factors cause decreased secretion of ADH?
- Extracellular fluid osmolality decrease
- volume increase
- temperature decrease
What are the two forms of diabetes insipidus?
Cranial diabetes insipidus
Nephrogenic diabetes insipidus
What is the pathophysiology of diabetes insipidius?
Characterised by either a deficiency of antidiuretic hormone, ADH, (cranial DI) or an insensitivity to antidiuretic hormone (nephrogenic DI)
How can cranial diabetes insipidius be treated?
Desmopressin
An analog of ADH
Where in the kidney of ADH work?
Collecting duct
What are the downstream metabolites of arachidonic acid metabolism?
Endoperioxidases:
Prostacyclin - decrease platelet aggregation
Thromboxane - increase platelets aggregation
Prostaglandin PGE2 - increases pain, temperature
Leukotrines:
- LTB4: Increased neutrophil chemotaxis
- LTA, LTC, LTD, LTE - bronchoconstriciton
What are leukotrienes?
A family of inflammatory mediators produced by leukocytes
What is the function of the leukotrienes LT A-E 4?
LTA4 - bronchoconstriction
LTB4 - Neutrophil chemotaxis
LTC4- bronchoconstriction
LTD4 - bronchoconstriction
LTE4 -bronchoconstriction
What antibiotics can you use when breast feeding?
Penicillins, cephalosporins, trimethoprim
What epilepsy medication can be used when breast feeding?
Sodium valproate
Carbamazepine
What anticoagulants can be used in breastfeeding?
Heparin
Warfarin
What drugs should be avoided in breast feeding?
Antibiotics: ciprofloxacin, tetracycline, Chloramphenicol, sulphonamides
Psychiatric drugs: lithium, Benzodiazepines
Aspirin
Carbimazole
Methotrexate
Sulfonylureas
Cytotoxic drugs
Amiodarone
What hormone co-ordinate calcium metabolism?
Main:
Parathyroid hormone (PTH)
1,25-dihydroxycholecalciferol (calcitriol, the active form of vitamin D)
Others:
Calcitonin
Thyroxine
Growth Hormone
What are the actions of PTH?
Increases plasma calcium, decreases plasma phosphate
Increases renal tubular reabsorption of calcium
Increases osteoclastic activity*
Increases renal conversion of 25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol
decreases renal phosphate reabsorption
What are the actions of 1,25-dihydroxycholecalciferol?
increases plasma calcium and plasma phosphate
increases renal tubular reabsorption and gut absorption of calcium
increases osteoclastic activity
increases renal phosphate reabsorption
Absorption from gut is > than kidneys
What is the action of calcitonin?
Secreted by C cells of thyroid
Inhibits osteoclast activity
Inhibits renal tubular absorption of calcium
What makes growth hormone?
secreted by the somatotroph cells of the anterior lobe of the pituitary gland.
What is the mechanism of action of growth hormone?
Acts on a transmembrane receptor for growth factor
binding of GH to the receptor leads to receptor dimerization
Acts directly on tissues and also indirectly via insulin-like growth factor 1 (IGF-1), primarily secreted by the liver
What increases secretion of growth hormone?
Growth hormone releasing hormone (GHRH): released in pulses by the hypothalamus
Fasting
Exercise
Sleep (particularly delta sleep)
What decreases secretion of growth hormone?
Glucose
Somatostatin (itself increased by somatomedins, circulating insulin-like growth factors, IGF-1 and IGF-2)
What are the causes of metabolic alkalosis?
vomiting / aspiration
vomiting may also lead to hypokalaemia
diuretics
liquorice, carbenoxolone
hypokalaemia
primary hyperaldosteronism
Cushing’s syndrome
Bartter’s syndrome
What is the mechanism of metabolic alkalosis?
activation of renin-angiotensin II-aldosterone (RAA) system is a key factor
aldosterone causes reabsorption of Na+ in exchange for H+ in the distal convoluted tubule
ECF depletion (vomiting, diuretics) → Na+ and Cl- loss → activation of RAA system → raised aldosterone levels
in hypokalaemia, K+ shift from cells → ECF, alkalosis is caused by shift of H+ into cells to maintain neutrality
What are features of primary hyperparathyroidism?
PTH (Elevated)
Ca2+ (Elevated)
Phosphate (Low)
Urine calcium : creatinine clearance ratio > 0.01
May be asymptomatic if mild
Recurrent abdominal pain (pancreatitis, renal colic)
Changes to emotional or cognitive state
Most cases due to solitary adenoma (80%),
What are features of secondary hyperparathyroidism?
PTH (Elevated)
Ca2+ (Low or normal)
Phosphate (Elevated)
Vitamin D levels (Low
May have few symptoms
Eventually may develop bone disease, osteitis fibrosa cystica and soft tissue calcifications
Parathyroid gland hyperplasia occurs as a result of low calcium, almost always in a setting of chronic renal failure
What are features of tertiary hyperparathyroidism?
Ca2+ (Normal or high)
PTH (Elevated)
Phosphate levels (Decreased or Normal)
Vitamin D (Normal or decreased)
Alkaline phosphatase (Elevated)
Occurs as a result of ongoing hyperplasia of the parathyroid glands after correction of underlying renal disorder, hyperplasia of all 4 glands is usually the cause
What secretes prolactin?
Anterior pituitary
What increases prolactin secretion?
thyrotropin releasing hormone
pregnancy
oestrogen
breastfeeding
sleep
stress
drugs e.g. metoclopramide, antipsychotics
What decreases prolactin secretion?
Decreases secretion
dopamine
dopaminergic agonists
What is the function of prolactin?
Stimulates breast development (both initially and further hyperplasia during pregnancy)
Stimulates milk production
It decreases GnRH pulsatility at the hypothalamic level and to a lesser extent, blocks the action of LH on the ovary or testis.
What secretes renin?
Renin is secreted by juxtaglomerular cells and hydrolyses angiotensinogen to produce angiotensin I
What factors cause secretion of renin?
hypotension causing reduced renal perfusion
hyponatraemia
sympathetic nerve stimulation
catecholamines
erect posture
What factors reduce secretion of renin?
Factors reducing renin secretion
drugs: beta-blockers, NSAIDs
What are the layers and secretions of the adrenal medulla?
Adrenal cortex (mnemonic GFR - ACD)
- zona glomerulosa (on outside): mineralocorticoids, mainly aldosterone
- zona fasciculata (middle): glucocorticoids, mainly cortisol
- zona reticularis (on inside): androgens, mainly dehydroepiandrosterone (DHEA)
What is the mechanism of angiotensin II?
angiotensin-converting enzyme (ACE) in the lungs converts angiotensin I → angiotensin II
What is the action of angiotensin II?
causes vasoconstriction of vascular smooth muscle leading to raised blood pressure and vasoconstriction of efferent arteriole of the glomerulus → increased filtration fraction (FF) to preserve GFR. Remember that FF = GFR / renal plasma flow
stimulates thirst (via the hypothalamus)
stimulates aldosterone and ADH release
increases proximal tubule Na+/H+ activity
What is the action of aldosterone?
released by the zona glomerulosa in response to raised angiotensin II, potassium, and ACTH levels
causes retention of Na+ in exchange for K+/H+ in distal tubule
What isthe chloride shift?
Chloride shift
CO2 diffuses into RBCs
CO2 + H20 —- carbonic anhydrase -→ HCO3- + H+
H+ combines with Hb
HCO3- diffuses out of cell,- Cl- replaces it
Allows HCO3 to move into systemic circulation
What is the Bohr effect?
Bohr effect
increasing acidity (or pCO2) means O2 binds less well to Hb
What is the haldane effect?
Haldane effect
increase pO2 means CO2 binds less well to Hb
What is the function of thiamine?
important in the catabolism of sugars and aminoacids. The clinical consequences of thiamine deficiency are therefore seen first in highly aerobic tissues such as the brain (Wenicke-Korsakoff syndrome) and the heart (wet beriberi).
Conditions associated with low thiamine?
Wernicke’s encephalopathy: nystagmus, ophthalmoplegia and ataxia
Korsakoff’s syndrome: amnesia, confabulation
dry beriberi: peripheral neuropathy
wet beriberi: dilated cardiomyopathy
Consequences of B2 deficiency?
Riboflavin
Consequences of riboflavin deficiency:
angular cheilitis
What is vitamin B3 used for?
Niacin
precursor to NAD+ and NADP+ and hence plays an essential metabolic role in cells.
Consequences of B3 deficiency?
Biiosynthesis of niacin issues:
Hartnup’s disease: hereditary disorder which reduces absorption of tryptophan
carcinoid syndrome: increased tryptophan metabolism to serotonin
Consequences of niacin deficiency:
pellagra: dermatitis, diarrhoea, dementia
What is the use of vitamin B6?
Pyridoxine
converted to pyridoxal phosphate (PLP) which is a cofactor for many reactions including transamination, deamination and decarboxylation.
Causes of vitamin B6 deficiency?
Causes of vitamin B6 deficiency
isoniazid therapy
Features of B6 deficiency?
Consequences of vitamin B6 deficiency
peripheral neuropathy
sideroblastic anemia
What clotting factors does vitamin K affect?
II, VII, IX, X
How long does it take vitamin K to have an effect on clotting?
4 hours
What is the function of vitamin C?
antioxidant
synthesis of collagen
facilitates iron absorption
cofactor for norepinephrine synthesis
Features of vitamin C deficiency ?
gingivitis, loose teeth
poor wound healing
bleeding from gums, haematuria, epistaxis
general malaise
What vitamin aids absorption of iron and why?
Vitamin C (ascorbic acid) supplementation can aid iron absorption from the gut by conversion of Fe3+ to Fe2+
