VIVA: Physiology - Endocrinology Flashcards
Name the endogenous catecholamines. Where are they produced?
Adrenal medulla *: adrenaline *, noradrenaline *, dopamine
Intrinsic cardiac adrenergic cells: adrenaline
Sympathetic nervous system cells: dopamine
*needed to pass
What are the physiological effects of adrenaline and noradrenaline?
Metabolic *:
- Glycogenolysis
- Increased metabolic rate
- Mobilisation of free fatty acids
- Increased lactic acid
Cardiovascular:
- Vasoconstriction and dilation *
- Increased heart rate and contractility *
By receptor:
- a1: constriction of blood vessels and smooth muscle (especially noradrenaline)
- a2: mixed smooth muscle effects (especially adrenaline)
- B1: cardiac inotropy and chronotropy, irritability (noradrenaline and adrenaline)
- B2: vasodilation in liver and skeletal muscle, other smooth muscle relaxation (adrenaline)
- B3: lipolysis, detrusor relaxation (especially adrenaline)
*one metabolic + one other to pass
What are the physiological effects of glucocorticoids?
Permissive action for catecholamine effects *:
- Pressor effect / vascular reactivity
Metabolic:
- Increased protein catabolism
- Increased hepatic glycogenolysis and gluconeogenesis, increased glucose-6-phosphatase (increased plasma glucose)
- Anti-insulin effects on peripheral tissues
- Increased lipolysis
- Free water excretion (decreased vasopressin)
- Inhibit ACTH secretion
Immunological:
- Decreased inflammation/allergic response
- Decreased lymphocyte activity
Haematological:
- Increased neutrophils, platelets, and red blood cells
- Decreased eosinophils, lymphocytes, and basophils
CNS:
- EEG slowing
- Personality changes
*needed to pass + 2 metabolic + 1 other
How is glucocorticoid secretion regulated?
Glucocorticoids (cortisol) secreted from adrenal cortex* in response to ACTH secretion* from the anterior pituitary*
ACTH secretion is regulated by CRH released from the hypothalamus in response to low cortisol levels or stress
Glucocorticoids provide negative feedback loop on the hypothalamus and anterior pituitary* to reduce ACTH secretion*
*needed to pass
What are the vascular effects of abruptly stopping long term glucocorticoids?
Vascular smooth muscle becomes unresponsive to noradrenaline and adrenaline*
Capillaries dilate and increase permeability
Failure to respond to noradrenaline impairs vascular compensation* for hypovolaemia and promotes vascular collapse*
What is the benefit of elevated glucocorticoid levels in stress?
Effect on vascular reactivity to catecholamines, plus necessary for catecholamines to mobilise free fatty acids for emergency energy source
Where in the body is calcium stored?
Bone (99%) * as hydroxyapatite
Plasma: bound to protein and unbound (free/ionised) * forms, important second messenger and is required for coagulation, nerve function, and muscle contraction
*needed to pass
How is plasma Ca2+ level regulated?
- Parathyroid hormone*:
- Increases plasma Ca2+ by mobilising Ca2+ from bone, increasing Ca2+ reabsorption in the kidney, and increasing formation of 1,25-dihydroxycolecalciferol in the kidney - 1,25-dihydroxycolecalciferol*:
- Increases Ca2+ absorption from intestine and kidneys - Calcitonin (from thyroid)*:
- Lowers circulating Ca2+ levels
- Effect mediated by inhibition of bone reabsorption
- Also increases Ca2+ excretion in urine - Glucocorticoids:
- Decrease plasma Ca2+ by inhibition of osteoclast formation - Oestrogens:
- Inhibit stimulatory effects of cytokines on osteoclasts - Growth hormone:
- Increases Ca2+ excretion in urine and absorption in intestine (net balance may be positive) - Hypercalcaemia is a complication of cancer, where it may be mediated either by bone erosion from osteolytic metastases, or release of parathyroid hormone related peptide by cancer cells
*needed to pass + their effects on plasma Ca2+ levels
How does bone resorption occur?
Osteoclasts* are monocytes that develop from stromal cells under the influence of RANKL (receptor activator of nuclear factor kappa B ligand):
- Attach to bone via integrins in sealing zone of the membrane
- Hydrogen dependent proton pumps move into cell and acidify the area
- Acid dissolves hydroxyapatite and acid proteases break down collagen
- Products move across osteoclast into interstitial fluid
*needed to pass + one other
What factors affect glucose homeostasis?
3 to pass:
- Glucose absorption from intestine
- Glucose uptake in the periphery (by muscle, brain, fat, red cells and hepatocytes)
- Reabsorption in the kidney
- Gluconeogenesis in the liver
- Under hormonal control by insulin and glucagon
What happens to glucose homeostasis in the absence of insulin?
Hyperglycaemia occurs due to (2/3 to pass):
- Decreased peripheral uptake of glucose into muscle and fat (direct effect)
- Decreased glucose uptake by liver (indirect effect)
- Increased glucose output by the liver and lack of glycogen synthesis
GIT, renal, brain and red cell uptake unaffected
What effect does glucagon have on blood glucose?
Increases BSL by increasing glycogenolysis and gluconeogenesis in the liver
What factors affect insulin secretion?
Stimulators*:
- Glucose
- Amino acids
- Intestinal hormones (GIP, GLP-1, gastrin, secretin, CCK)
- B-keto acids
- ACh
- Glucagon
- cAMP
- B-agonists
- Theophylline
- Sulfonylureas
Inhibitors*:
- Somatostatin
- Insulin
- Diazoxide
- Thiazide diuretics
- B-blockers
- a-agonists (adrenaline, noradrenaline)
- K+ depletion
- Phenytoin
- 2-deoxyglucose
- Mennoheptulose
- Galanin
- Alloxan
*two from each to pass
Describe the principal actions of insulin
Rapid (within secs):
- Increased transport of glucose, amino acids and potassium into insulin-sensitive cells
Intermediate (within mins):
- Stimulation of protein synthesis and inhibition of protein degradation
- Activation of glycolytic enzymes and glycogen synthase
- Inhibition of phosphorylase and gluconeogenic enzymes
Delayed (hours):
- Increase in mRNAs for lipogenic and other enzymes
*two actions from two different phases to pass
What are the effects of insulin on carbohydrate regulation and metabolism in different tissues?
Adipose*:
- Increased glucose and K+ entry
- Increased fatty acid synthesis
- Increased glycerol phosphate synthesis
- Increased triglyceride deposition
- Activates lipoprotein lipase
- Inhibits hormone-sensitive lipase
Muscles*:
- Increased glucose, amino acid, K+ and ketone uptake
- Increased glycogen synthesis
- Increased protein synthesis in ribosomes and decreased protein catabolism
- Decreased release of gluconeogenic amino acids
Liver*:
- Decreased ketogenesis
- Increased protein and lipid synthesis
- Decreased glucose output (decreases gluconeogenesis, increases glycogen synthesis and glycoclysis)
General*:
- Increased cell growth
*2 effects in 2 different tissues to pass
How are thyroid hormones regulated?
TRH from hypothalamus -> TSH from anterior pituitary -> T4 (and small amount of T3) -> T3 in periphery
Negative feedback on TSH by free T3 and T4 *:
- In hypothalamus and pituitary
- Effect of T3>T4 *
- Both secretion and synthesis of TSH affected
Thyroid hormone secretion:
- Increased by cold, decreased by warmth (especially in infants; effect in adults not clear)
- Decreased by stress (TRH)
- Decreased by glucocorticoids (TSH)
- Decreased by dopamine and somatostatin (TSH)
*needed to pass + concept
Other than cardiovascular, what are the physiological effects of thyroid hormones?
Calorigenic*:
- Increased metabolic rate and stimulation of O2 consumption
Adipose:
- Catabolic (stimulate lipolysis)
Muscle:
- Catabolic (increase protein breakdown)
Bone:
- Developmental (promote normal growth and skeletal development; deficiency in childhood/infancy causes cretinism)
Nervous system:
- Promotes normal brain development and mentation
Gut:
- Increased carbohydrate absorption
Cholesterol:
- Increased LDL receptors and removal of circulating cholesterol
*needed to pass + one other system effect
How do the effects of noradrenaline and adrenaline differ on the cardiovascular system?
Noradrenaline:
- BP: (SBP, DBP)
- HR:
- CO:
- TPR:
Adrenaline:
- BP (SBP, DBP)
- HR
- CO
- TPR:
