physiology + pathology Flashcards
function of endocrine glands
endocrine glands secrete chemical substances (hormones) which travel through the bloodstream to effect changes in distant cells or organs
types of hormones
peptides and proteins (bind to cell surface receptors), amino acid derivatives, steroid derivatives (diffuse through plasma membrane and bind to intracellular receptors)
hypothalamic hormones (6)
• thyrotropin releasing hormone
• gonadotropin releasing hormone
• corticotropin releasing hormone
• growth hormone releasing hormone
• growth hormone inhibitory hormone
• prolactin inhibiting hormone
growth hormone actions
promotes linear growth of skeleton in childhood, promotes growth of body tissues and intermediary metabolism, inhibits actions of insulin on carbs and lipids, increased protein synthesis and decreased catabolism of proteins and amino acids
regulation of growth hormone secretion
hypothalamic control: GH releasing hormone stimulates production of GH by somatotrophs –> GH stimulates secretion of IGF-1 by liver, somatostatin inhibits production of GH
thyroid and sex hormone stimulation of GH
negative feedback: IGF-1 inhibits GH and GnRH and stimulates somatostatin
factors affecting GH secretion
diurnal variation, age, body weight, stress, exercise, blood glucose, amino acids
tests for GH
exercise GH stimulation test, glucose tolerance test, IGF-1 blood conc test
NOTE: random blood glucose test for GH is not indicative because GH secretion is episodic
GH deficiency syndromes (3)
- dwarfism: all physical parts of body develop in the appropriate proportions but rate of development decreased
- panhypothyroidism: tumour compressing pituitary gland –> ant pit cells destroyed –> hypothyroidism, decreased production of glucocorticoids by adrenal glands, suppressed secretion of GH
- Kallmann syndrome: congenital hypogonadotropic hypogonadism
GH excess syndromes
- gigantism: excess GH before adolescence (and fusion of growth plates) leading to height increase and excessive growth of long bones, usually caused by pit gland tumour
- acromegaly: excess GH after adolescence, bones become thicker and soft tissues continue to grow –> lower jaw protrusion, forward slant of forehead, large nose feet hands, enlargement of soft tissue organs
antidiuretic hormone (ADH) actions
collecting ducts of renal tubules becomes permeable to water due to fusion of aquaporins into the collecting duct membrane, causing water to be reabsorbed into the blood –> urine is concentrated and in small volume
regulation of ADH secretion
- real decrease in ECF volume
- baroreceptors detecting change in ECF volume
low ECF volume causes ADH to be released from the posterior pituitary
causes of polydipsia (thirst) and polyuria (high urine output)
- diabetes mellitus causing osmotic diuresis
- diabetes insipidus causing ADH deficiency (central) or ADH resistance (nephrogenic)
- psychiatric cause (primary polydipsia)
T3 and T4 actions
- brain development in fetal and postfetal life
- growth (GH production)
- regulation of growth metabolism: increases basal metabolic rate, has thermogenic actions
tests for thyroid hormones
free T4 levels
NOT T3: can come from thyroid gland or other tissues, most serum T3 comes from the peripheral conversion of T4 to T3
NOT total T4: only free T4 is physiologically active and bound T4 doesn’t contribute to hyperthyroidism
hypothyroidism causes
primary hypothyroidism: disease affecting thyroid gland, T4 is low but TSH is high (eg Hashimoto Thyroiditis, dietary iodine deficiency)
secondary hypothyroidism: disease affecting pituitary gland, T4 is low and TSH is low/normal
symptoms of hypothyroidism
cretinism (in childhood cases), slow thinking, cold intolerance, slow HR, sluggishness, (may have a goiter)
hyperthyroidism causes
primary hyperthyroidism: disease affecting thyroid gland, T4 is high, TSH is low (eg Grave’s disease, subacute thyroiditis)
secondary hyperthyroidism: disease affecting pituitary gland, T4 is low, TSH is high/normal (eg TSH producing tumour in pituitary gland)
pathophysiology of Grave’s disease
• autoimmune condition where thyroid stimulating immunoglobulins stimulate thyroid gland to be overactive
• GRAVES SPECIFIC: exothalmos, proptosis, upper eyelid retraction, dryness and irritation of eyes
pathophysiology of subacute thyroiditis
• viral infection affecting thyroid gland, causing inflammation
• dying thyroid cells leak out preformed thyroid hormones into circulation
• disease subsides after a few weeks or months
symptoms of hyperthyroidism
heat intolerance, weight loss, increased HR, heart palpitations, fatigue and insomnia, hands tremor, nervousness, increased sweating, thyroid gland hyperplasia
pathophysiology of pheochromocytoma
tumour of adrenal medulla producing adrenaline and/or norepinephrine, resulting in increased BP, HF, pulmonary edema, stroke, sudden death
aldosterone actions
increases Na+ reabsorption in collecting ducts, increases ECF volume, enhances K+ secretion in collecting ducts
regulation of aldosterone secretion
RAAS regulation: angiotensinogen –> angiotensin I by renin –> angiotensin II by ACE, angiotensin II stimulates aldosterone release
[K+] in blood: acts directly on aldosterone producing cells when [K+] is high (above 3.5-5mmol/L) to produce more aldosterone
adrenocorticotropic hormone (ACTH): released from anterior pituitary to stimulate aldosterone production
symptoms of aldosterone excess
hypokalemia (muscle weakness and paralysis), hypertension (increase in ECF volume), mild metabolic alkalosis
NOTE aldosterone escape: increase in ECF volume can lead to renal perfusion pressure increase and excretion of Na+ and H2O (pressure natriuresis and diuresis)
symptoms of aldosterone deficiency
hyperkalemia, cardiac toxicity, severe ECF dehydration and low blood volume, natriuresis and diuresis
actions of cortisol
survival during stress, intermediary metabolism, vascular reactivity of catecholamines (adrenaline and norepinephrine)
pharmacological effects: anti-inflammatory effects, suppression of immune system
regulation of cortisol secretion
corticotropin releasing hormone (CRH): released by hypothalamus, carried to ant pit to induce ACTH secretion, ACTH stimulates cortisol secretion in the adrenal cortex
physical, mental or emotional stress: enhances ACTH –> cortisol secretion
negative feedback from cortisol: decreases formation of CRH and ACTH (but stress can override this inhibition)
tests for cortisol
- plasma/urine cortisol (measure over 24h due to circadian variation)
- dexamethasone suppression test: can suppress CRH and ACTH to distinguish between pituitary gland disorder (will still have high ACTH) and primary adrenal disorder (low ACTH)
- ACTH levels in blood: low ACTH indicates adrenal gland overproduction (negative feedback to ant pit), normal/high ACTH indicates ant pit overproduction
- ACTH injection for adrenal insufficiency: measure cortisol response - if low, adrenal gland failure
pathophysiology of Cushing’s syndrome
excess amounts of cortisol caused by: ACTH producing pituitary tumour, abnormal hypothalamus, ectopic ACTH syndrome, adrenal cortex adenoma, iatrogenic corticosteroid medication
leading to: buffalo torsal, truncal obesity, moon face and red cheeks, hypertension, increased blood glucose concentration, decreased tissue proteins, muscle weakness, suppressed immune system, osteoporosis
types of adrenal failure
primary: Addison’s disease (failure of adrenal cortices to produce adrenocortical hormones)
secondary: due to ACTH deficiency (aldosterone levels remain normal)
concentration of calcium in the body
50%: ionised/free, diffusible through capillary membrane
41%: combined with plasma proteins, non-diffusible through capillary membrane
9%: complexed with anions of plasma and interstitial fluids, non ionised, diffusible through capillary membrane
more calcium is bound to proteins in alkaline pH
composition of bone (6)
hydroxyapatite, osteoid, osteoblasts, osteocytes, osteoclasts, chondrocytes
process of vit D formation
7 - dehydrocholesterol –> (UV rays) vitamin D3 –> (liver) 25-hydroxycholecalciferol –> (kidneys) 1,25-dihydroxycholecalciferol aka active form of vit D
vit D can also be obtained from the diet (eg fatty fish)
regulation of vit D formation in the kidneys
positive feedback by parathyroid hormone, negative feedback by increased concentrations of phosphate (PO4-)
vitamin D actions
promotes PTH effect on bone resorption, increases kidney calcium and phosphate reabsorption, increases GIT calcium and phosphate absorption for bone mineralisation
regulation of parathyroid hormone
decrease in ECF [Ca2+] detected by calcium sensing receptors on parathyroid gland cells –> PTH secretion –> increase in ECF [Ca2+] –> PTH secretion suppressed
parathyroid hormone actions
activation of existing osteocytes to promote calcium and phosphate absorption, proliferation of osteoclasts and increased osteoclastic reabsorption of bone, decreased phosphate reabsorption in PCT, increased calcium reabsorption in DCT and activation of vitamin D
regulation of calcitonin secretion
secreted by C/parafollicular cells in thyroid gland as stimulated by high [Ca2+]
action of calcitonin
decreases resorption of bone (opposes PTH and vit D actions), decreases calcium resorption in kidney
fibroblast growth factor 23 regulation
secretion stimulated by high [PO42-], formed by osteoblasts and osteocytes
fibroblast growth factor 23 action
decreases PCT and gut phosphate reabsorption, decreases concentration of active vit D
pathophysiology of hypocalcemia
- hypoparathyroidism leading to PTH deficiency
- vitamin D deficiency
increased excitability of nervous system leading to tetany and musculopathies, neuropathies, cardiopathies, poor dentition, nail and hair issues
pathophysiology of hypercalcemia
- hyperparathyroidism leading to overproduction of PTH
- vitamin D intoxication
- malignancy: certain lung cancers can secrete PTH
vitamin D deficiency syndromes
- rickets: lack of vitamin D in children causing bone to be undermineralised, low phosphate levels and extreme osteoclastic resorption of bone
- osteomalacia: usually steatorrhea in adults leading to vitamin D deficiency
pathophysiology of osteoporosis
resorption of bones > formation of bones, osteoblastic activity decreased and/or osteoclastic activity increased
causes: postmenopausal decrease in estrogen, inactivity and lack of physical stress on bones, lack of vitamin C, malnutrition, old age, Cushing’s syndrome
actions of insulin
increase glucose uptake, glycogen synthesis, fat synthesis, protein synthesis, glycolysis
actions of glucagon
glycogenolysis, lipolysis, gluconeogenesis, ketogenesis
hormones regulating the fasted state
epinephrine (glycogenolysis, lipolysis, gluconeogenesis), cortisol (lipolysis, proteolysis, gluconeogenesis, ketogenesis), growth hormone (lipolysis)
types of diabetes mellitus
type 1: absolute insulin deficiency causing disordered metabolism, autoimmune disease usually presenting in youth
type 2: relative insulin deficiency with insulin resistance causing disordered metabolism, multifactorial causes including genetics
normal blood glucose levels
random: 4-7.8mmol/L
fasting: 4-6mmol/L
post-prandial: 4-7.7mmol/L
indicators of metabolic syndrome
- waist circumference: ≥90cm (men), ≥80cm (women)
- high triglyceride ≥1.7mmol/L
- high fasting glucose ≥6.1mmol/L
- high blood pressure ≥130/85 mmHg
- low HDL cholesterol ≤1.0mmol/L (men) or ≤1.3mmol/L (women)
effects of metabolic syndrome
adipose tissue dysfunction
persistent low-grade inflammation (M2 macrophages become M1 macrophages)
insulin resistance
physical indicators: apple body shape and high amounts of abdominal fat
diagnosis of diabetes mellitus
- fasting blood glucose ≥7.0 mmol/L
- oral glucose tolerance test ≥11.1 mmol/L
- HbA1C > 6.9%
effects of diabetes mellitus
high plasma glucose, accumulation of ketone bodies (type 1, ketoacidosis), retinopathy, nephropathy and nephrotic syndrome, vascular damage, neuropathy, osmotic diuresis
diagnosis of hypoglycemia (Whipple’s triad)
- low blood sugar
level 1: 3.0-3.9mM
level 2: 2.2-2.9mM
level 3: <2.2mM - symptoms of hypoglycemia
- relief of symptoms upon eating
symptoms of hypoglycemia
cold sweats, palpitations, shakiness, headache
severe: weakness, blurred vision, slurred speech, confusion and abnormal behaviour, seizures
causes of hypoglycemia
- insulin excess
- medications
- insulinomas
Conn’s syndrome pathogenesis and presentation
pathogenesis: aldosterone-secreting tumour of zona glomerulosa cells / hyperplastic adrenal cortices secrete aldosterone instead of cortisol
presentation: low renin levels (RAAS negative feedback), hypokalemia, hypertension, mild metabolic alkalosis ± pressure natriuresis and diuresis
