Endo Physiology Flashcards
Location of the hypothalamus
Forebrain
Floor of third ventricle
Hypophyseal stalk
Communication between hypothalamus and pituitary gland
Development of anterior pituitary
Outpouching of tissue from oral cavity - ectoderm
rathke’s pouch
Linked to hypothalamus by hypophyseal portal circulation
Development of posterior pituitary
Dwongrowth of neural tissue
Continuous with hypothalamus
Paraventricular and supraoptic nuclei lie in hypothalamus and project neurons down to posterior pituitary
Production of ACTH
Released with MSH and B-endorphin in response to CRH
What is growth hormone stimulated by?
GHRH, inhibited by GHIH or somatostatin
Dopamine control of prolactin
Dopamine inhibits prolactin release
If dopamine levels are lowered (or it can’t access the anterior pituitary) prolactin levels will increase
Paraventricular nucleus
Produce oxytocin, stimulated by mechanoreceptors on breast and stimulates uterine contractions
Supraoptic nucleus
Produces ADH, in response to osmoreceptors and cardiac stretch receptors
Prolactin inibits…
GnRH
–> reduction in andogens and oestrogens
Urinary sodium in SIADH
ADH –> reabsorption of water in collection ducts
There is increased urinary osmolarity
Volume expansion has occured –> there will be salt wasting and hence Urinary Na >30
What is the main components of thyroid colloid?
Thyroglobulin
Production of triiodothyronine and thyroxine
Iodide ions pumped from ECM to follicular cells
Iodide ions converted to iodine
Iodine paired with tyrosine in colloid
Forms monoiodotyrosine
Diiodotyrosine
Coupled to form T3 and T4
Causes of Primary Hyperthyroidism
Graves: IgG autoantibodies binding to receptors
Plummer disease: Singular toxic adenoma / nodules
Toxic multiodular goitre
Acute phase of thyroid cell injury
Drugs e.g. amiodarone
Causes of secondary hyperthyroidism
Pituitary / Hypothalamic tumour secreting TRH / TSH
Metastatic thyroid cancer
Choriocarcinoma (can produce substance similar to TSH)
Ovarian teratoma - struma ovarii
Thionamides
Competively compete for the thyroid peroxidase enzyme that converts iodide to iodine
Also inhibits coupling of iodotyrosine molecules
Carbimazole
Propylthiourcail
- Propylthiouracil also inhibits the peripheral deiodination of T4
Lugol’s solution
Iodide
iodide is thought to work by blocking the binding of iodine with tyrosine residues
+ reduces vascularity of thyroid gland
Pendred syndrome
Hypothyroidism + Deafness
Causes of primary and secondary hypothyroidism
Autoimmune e.g. Hashimoto’s (fibrosis, atrophy and hurthle cells)
Iodine deficiency
Congenital - Pendred’s syndrome
Iatrogenic
Drugs e.g. Lithium
Neoplasmia
secondary: Hypopituitarism, TSH deficiency
Actions of hydroxylated Vitamin D3
Increase calcium and phosphate absorption from gut
Increase calcium and phosphate absorption from kidney
Activates osteoclast bone resorption
Promotes mineralisation of osteoid
Actions of PTH
Stimulates osteocyte mobilisation of Ca from bone and longer term osteoclast resorption from bone
increase in Ca resorption from kidney
increased phosphate excretion
stimulates conversion of vitamin D to active form
Actions of Vitamin D
Increases phosphate and Ca resorption from gut and kidney
Stimulates osteoclastic bone resorption
Promotes mineralization of osteoid
Actions of calcitonin
Produced by parafollicular C-cells
Decreases Ca2+ and phosphate reabsorption
from the renal tubules
Stimulates osteoblasts to mineralise bone and
thus take Ca2+ from the circulation.
Causes of Hypoparathyroidism
Congenital e.g. DiGeorge
Autoimmune
Iatrogenic
HypoMag
Causes of Hyperparathyroidism
Primary (most common due to single adenoma) (low phosphate)
Secondary (calcium normal or low)
Tertiary (Ca, PTH and phosphate high)
Ectopic PTH
SQUAMOUS CELL lung cancer
ECG in Hypercalcaemia and Hypocalcaemia
Hyper: Short QT interval
Hypo: Long QT interval
Causes of hypocalcaemia
HypoAlb
HypoMg
HypoPhos
Acute Pancreatitis
Rhabdomyolysis
Sepsis
Causes of hypercalcaemia
Excess PTH
Excess Vit D
Sarcoidosis
Excess Calcium intake
Drugs e.g. thiazide
Malignancy
Causes of hypophosphataemia
Refeeding
TPN
Diabetic ketoacidosis
Hyperparathyroidism
Paracetamol overdose
Acute liver failure
Causes of hyperphosphataemia
Chronic renal failure
Tumour lysis syndrome
myeloma
Vitmain D-resistant Rickets
Famlilial condition
Hypophosphataemia
Phosphoturia
Rcikets
Adrenal medulla produces
Epinephrine (adrenaline)
Norepinephrine (noradrenaline)
Dopamine
β-hydroxylase (enzyme involved in catecholamine
synthesis)
ATP
Opioid peptides (metenkephalin and leuenkephalin).
Adrenal cortex
Cholesterol converted to pregnenolone in mitochondria
adrenal steroids are broken down by liver and excreted via kidneys and faeces
Aldosterone
Mineralocorticoid stimulated by:
RAS
Increase in potassium
ACTH
Actions:
Resorption of Na from DCT
Secretes K into DCT
Secretes H into DCT
Protein-binding of cortisol
Transcortin ~ 75%
Albumin 15%
= 10% active
Cortisol
Released by ZF of adrenals
Stimulated by:
ACTH
Circadian rhythm
Stress
Burns
Trauma
Infection
Exercise
Hypoglycaemia
Actions: gluconeogenesis, glycogenesis, lipolysis, Vasopressor effect, Euphoria,
Immune effects of Cortisol
Anti-inflammatory:
lowers immunocompetent cells and macrophages
Stimulates the synthesis of lipocortin in leukocytes (inhibits phospholipase A2 and prevents the formation of inflammatory mediators such as prostaglandins, leukotrienes and platelet activating factor)
Immunosuppressive effects:
decreases t cell number and function
decreases b cel clonal expansion
decreases basophils and eosinophils
inhibits complement
Secretion of androgens in the zona reticularis
Stimulated by ACTH
NOT LH
Causes of Addison’s
Autoimmune 80%
TB 20%
Waterhouse-Friderichsen: meningococcal septicaemia –> haemorrhage
malignant infiltration
drugs
Effects of Addison’s disease
decreased blood sodium
decreased BP
metabolic acidosis
weight loss
anorexia
lethargy
Primary causes of Conn’s
most commonly due to adrenal adenoma (60-70%)
BAH in 20-30%
Secondary causes of Hyperaldosertonism
Due to increased renin production
Causes:
Renal artery stenosis
CCF
Cirrhosis
–> Hypokalaemia
–> Fluid overload
–> Metabolic alkalosis as H+ secretion in DCT
Cushing’s
ACTH dependent: (either pituitary or ectopic secretion from tumour)
ACTH independent (Adrenal adenoma, carcinoma, exogenous steroid)
Features of Cushing’s
Hyperglycaemia
muscle wasting
stretch marks
osteoporosis
moon face
buffalo hump
high BP
hirsutism and acne
Congenital adrenal hyperplasia
Commonest deficiency: 21-Hydroxylase
–> decreased cortisol production
–> Increased ACTH
Vast steroid pre-cursors converted to androgens which causes:
Male - rapid growth and early development of sexual characteristics
Female- Masculinisation of external genitalia + male body shape
Phaeo rule of 10s
10% are malignant
10% are multiple
10% from medulla
Growth hormone stimulators
GHRH
Hypoglycaemia
high during deep sleep
anxiety
pain
hypothermia
haemorrhage
fever
trauma
exercise
Gigantism
GH excess in children
aided by IGF-1
stimulates mitosis in cartilage cells in epiphyseal plates at end of long bones
Acromegaly
GH excess in adults
increases glycogenolysis
decreased glucose uptake by cells
promotes amino acid uptake
promotes protein synthesis
increases lipolysis
decreases ldl cholesterol
Half life of insulin
10 - 15 minutes
Stimulation of insulin
Most things stimulate insulin include all of the mediators released in response to food
Inhibitors:
-Sympathetic input
-Somatostatin
-Serotonin
-Dopamine
-Cortisol (reduces sensitivity)
Effects of glucagon
Increases glycogenolysis
Increases gluconeogenesis
stimulates lipase
Necrolytic migratory erythema
Sign of glucagonoma
-75% malugnant
Somatostatin
stimulated by:
increased plasma glucose, increased amino acids, increased glycerol
effects:
inhibits glucagon and insulin, decreases GI motility secretion and absorption .
Gastrinoma
seen in Zollinger-Ellinson syndrome
arise from G cells
gastric hypersecretion, diarrhoea and widespread peptic ulceration
VIPoma
excess VIP
severe watery diarrhoea
decrease in potassium
Achlorhydria
Somatostatinoma
from D cells
causes DM, cholelithiasis and steatorrhoea
Platelet activating factor
Produced in response to IL-1 and TNF-a
Stimulates platelet aggregation and vasoconstriction
Ebb anf Flow Phase
Ebb phase
-Initial response to injury
-Phase of reduced energy expenditure and metabolic rate that lasts for approximately 24 h
Flow phase
-Follows = catabolic phase
-Increased metabolic rate, hyperglycaemia,
-Negative nitrogen balance
-Increased O2 consumption.
The flow phase has significant
What do norepinephrine and epinephrine bind to?
alpha receptors and beta receptors respectively
deactivated by COMT and MAO in liver and kidney
