ENCDOCRINOLOGY Flashcards
Location of the hypothalamus:
Location of the third ventricle
What do magnocellular neurons secrete in the posterior pituitary?
- Secrete ADH and oxytocin (from either supraoptic nucleus OR paraventricular nucleus
What is the blood supply of the ANTERIOR PITUITARY
Internal carotid artery which goes into the hypophyseal arteries–> form median eminence –> divides into veins (portal veins) –> come down and supply anterior pit.
What is the blood supply of the posterior pituitary?
- MIddle hypopyseal artery
- Inferior hypophyseal arteries
Where does the pituitary gland sit?
- In pituitary fossa
What is the pituitary gland surrounded by?
- Carnevous sinus (contains carotid arteries), cranial nerves, Sphenoid sinus
What will a tumor in the pituitary gland affect?
- The surrounding structures, puts pressure on the optic chiasm–> double vision
What does a tumor in the pituitary gland putting pressure on the canernous sinuses cause?
Bad headaches
What can a pituitary tumor that presses LATERALLY on the cranial nerve (oculomotor) cause?
- Transmission can be affected (lesions)
- Eye muscles don’t work properly
Where does the posterior pituitary develop from?
- Develops from BRAIN (buds off and moves down)
Where does the anterior pituitary develop from?
- Develops from roof of mouth and moves UP during development
What are the 5 cell types from the anterior pituitary and what do they secrete?
SOMATOTROPHS--> Growth Hormone (GH) LACTOTROPHS--> Prolactin (PRL) THYROTROPHS--> TSH (thyroid stimulating hormone) GONADOTROPHS-->FSH AND LH CORTICOTROPHS--> ACTH
Where are the parvocellular neurones and where do their nerve terminals go?
- Within paraventricular nucleus area of hypothalamus
- Nerve terminals go TO median eminence
Is the posterior pituitary a gland?
- NO! It is an extension of the hypothalamus (embryo-buds off from brain)
When are ADH or oxytocin released in terms of APs?
- If the nerves ARE electrically stimulated (AP)
Where are oxytocin and ADH made?
- Paraventricular nucleus and supraoptic nucleus clusters
- WIthin cell bodies of neurones
- Then transported DOWN axon and stored in axon terminal
What is oxytocin (what type of structure) and what is it inoolved in?
- 9aa peptide
- Involved in lactation
- Involved in suckling (positive feedback via mechanoreceptors) –> oxytocine released
- Labour (positive feedback) -stretch recepotrs–> signals to brain and hypothalamus
What does prolactin cause?
- Milk production
What does oxytocin casue in terms of feeding?
- Milk let down
Which two things is ADH most sensitive to?
- Change in plasma osmolarity (1% changes it is sensitive to)
- Change in BP (10-15% changes it is sensitive to) –> baroreceptors in aortic arch and carotid bodies + low pressure vol. receptors in atria and pulm venous system in chest.
Which receptors does ADH act on in kidney and blood vessels and what do these receptors do when ADH is bound?
Kidney= V2 receptors
Blood vessels= V1
- These receptors when activated cause more aquaporins to migrate to renal tubule membranes
Is the secretion of anterior pituitary hormones a balance between positive and negative hypothalmic influences?
- YES!
Is there a hypothalmic stimulator and inhibitor for each anterior pituitary hormone?
- YES!
What is hyperplasia?
- Increase in the number of cells
What is hypertrophy?
-Increase in the size of cells
What is GH secreted by and what does it stimulate?
- Secreted by anterior pituitary and stimulates insulin like growth factors to be secreted from LIVER
What do problems in the thyroid hormones, sex steroids and glucocorticoids lead to?
- Decrease in growth rate and neuro development
What do excess glucocorticoids lead to?
- Premature fusion of the epiphyses of bone bodies (long bones)
What 4 functions does GH have?
- Stimulates LIVER to release insulin like growth factor (IGF-1)
2INCREASES Ca2+ retention - INCREASES muscle mass (hypertrophy of sarcomeres)
- INCREASE in protein synthesis
What is a feature of GH and when does its secretion peak?
- Pulsatile and circadian secretion
PEAKS during SLEEP
What 6 things is GH secretion stimulated by?
- SLEEP
- EXERCSIE
- STRESS/TRAUMA
- FASTING/PROTEIN DEFFICIENCY
- HYPOGLYCEMIA
- GHRELIN
Which 5 things is GH secretion inhibited by?
- SOMATOSTATIN
- POST PRANDIAL HYPERGLYC
- INCREASED FATTY ACIDS
- INCREASED IGF-1 (Neg feedback)
- AGING
Which two chemical molecules are needed for bone growth?
- Ca2+ and PO43-
What does a Ca2+ and PO43- defficiency result in (bones)?
- Rickets
- Bowing of bones
What does GH stimulate in terms of bone growth?
- Stimulates LONG BONE GROWTH at epyphyseal cartilages
- Stimulates DEPOSITION of new cartilages and INCREASES osteoblast activity
What is the intake of calcium PER DAY and how much of this is abosrbed in the intestine and where does it go after absorption?
- 1g
- 35% reabsorption in intestine
- Goes to ECF–> Kidneys–> Excreted in urine (10%)
Which 4 things regulate the amount of Ca2+ that is ingested?
- VIt D
- PTH (parathyroid hormone)
- Cortisol
- T3/T4
What is the ECF calcium dependent on?
- How much is absorbed and excreted by the kidney and gut
How much Ca2+ is stored by the bones?
- 1kg (1,000,000mg)
Which 4 factors increase bone resoprtion (Ca2+ OUT of bone)?
- Vit D3
- PTH
- Cortisol
- T3/T4
Which 3 factors increase bone mineralisation?
`1. E2 (Estrogen)
- Testosterone
- GH (growth hormone)
Which 3 factors is balancing Ca2+ levels dependent on?
- Storage of calcium in bone (increasing or decreasing plasma calcium)
- Absorption from gut
- Actions of kidneys
Which two hormones regulate Ca2+?
- PTH (parathyroid hormone)
2. 1,25dihydroxy vitamin D (Calcitrol)
Where is PTH made and secreted?
- Made and stored in vesicles in parathyroid (contains Ca2+ binding receptor on cell membrane)
What stimulates PTH?
LOW Ca2+ level
What inhibits PTH?
HIGH Mg2+ level
What do catecholamines stimulate?
- PTH secretion
As Ca2+ levels decrease……….what increases?
- PTH levels increase
What is the half life of PTH, what type of hormone is it, and what stimulates its secretion?
- Large polypeptide chain (protein hormone)
- 2-4 min half life
- LOW Ca2+ levels stimulate secretion
What substance is bone made up of?
- Hydroxyapatite
[Ca10(PO4)6(OH)2]
Is bone CONSTANTLY being remodelled?
- YES!
If bone is being layed down what happens to Ca2_ and PO42-?
- Taken FROM plasma TO bone
If bone is being resorbed what happens to Ca2+ and PO42-?
- RELEASED from BONE TO PLASMA
Which structure does PTH act on?
- Kidney
What do osteoclasts do?
- Break DOWN bone
What does PTH stimulate osteoblasts to make and what does this thing do?
- RANK ligand (RANKL)
- RANK Ligand binds to RANK receptor on OSTEOCLASTS –> stimulates osteoclast activity
What do sex steroids stimulate the production of and what does this thing do?
- OPG protein
- Sits on RANKL and stops RANKL from binding to osteoclasts so inhibits GONE RESORPTION *
What are the 3 targets for PTH?
- Bone –> causes resoprtion (increased Ca2+ levels in plasma) and decreased PO43-
- KIDNEY—> Increases Ca2+ and decreases PO43- reabsorption (excretion occurs)
- Gut (indirectly to increase Ca2+ absorption)
- Increases 1,25OH VIt D3 (converts inactive form of Vit D to Active Vit D)–> ACTS ON GUT TO INCREASE CA2+ ABSORPTION
What type of hormone is VItamin D?
Steorid hormone
What is the rate limiting step in vitamin D formation (liver)?
- Adding the second OH group to C1 convertes inactive Vit D (25alphahydroxy vit D3) —-> 1,25dihydroxy-VitD3
- VIA 1ALPHAHYDROXYLASE
What is the enzyme 1alphahydroxylase stimulated by?
PTH in kidney and LOW PO43-
What does Vitamin D supress?
- PTH secretion
What does Vitamin D act on the gut to do?
- INCREASE Ca2+ reabsorption and INCREASE PO43- reabsorption
What does VItamin D stimulate the differentiation of ?
- Osteoblasts and RANKL production
Laying down bone will happen automatically IF there is enough….
Calcium and phosphate
What does Calcitronin (hormone) do?
- Decreases plasma Ca2+ concnetration and plasma PO43-
- Does’t have a massive effect on the plasma Ca2+ levels
- Acts on bone to inhibit osteoclasts resorption (OPPOSITE ACTION TO PTH)
What is Calcitronin used clinically for?
- To treat Pagets disease (disrupts replacement of old bone tissue with new bone tissue)
- to treat hyperglycemia (hyperparathyroidsim–> increases bone resorption, increases Ca2+ resorption in gut, decreases Ca2+ excretion (renal) –> hyperpolarises cells
- To treat osteoperosis
What is hypocalcemia and what is it caused by?
Cells depolarise much more easily (tetany, seizures)
- Caused by FAILURE of PTH, Vitamin D defficiency or resistance
Do you die if you have no adreal gland?
yes!
What is the adrenal gland under control by?
- ACTH (adrenocroticotropin releasing hormone)
Where in the adrenal medulla are the steroid hormones released from?
- The cortex
Which tissue is the adrenal medulla derived from?
-Neural Tissue –> catecholamines–> Adrenaline
What are the steps of the sympathoadrenal system (neural arm)?
STRESS (detected by higher brain centres)
BRAIN stimulated –> brainstem –> sympathetic nerves ACTIVATED (spinal cord pathways) –move down s.c.–> pre ganglionic fibres nerve endings SECRETE ADH onto CHROMAFIN cells in Adrenal MEDULLA –> Chromaffin cells release adrenaline (80% ) + NA (20%)
- Adrenaline–> SYSTEMIC CIRCULATION–> heart increase HR and contractility
- NA released at synapses of sympathetic nerves –> stimulate SA node and cardiomyocytes to INCREASE FORCE OF CONTRACTION
Which two aspects are organs getting a sympathetic response from?
- Release of NA
2. Adrenaline circulating
What is the sympathoadrenal system (endocrine arm)?
CRH (corticotropin releasing hormone) and ADH released from HYPOTHALAMUS –> Stimulates release of ACTH from pituitary –> acts on cortex (to release cortisol-steroid hormone)
What are the symptoms of addnsons disease?
- Fatigue
- Hypotension
- Skin pigmentation (degeneration of adrenal gland)
What occurs in Cushings syndrome?
- Too much cortisol is released
What hormone does the zona glomeulose (cortex of adrenal gland) cells reelase?
- Aldosterone (mineralcorticoid)
Which hormone does the zona fasciculate (cortex of adrenal gland) release?
- CORTISOL (glucocorticoid)
What does the zona reticularis cells (cortex of adrenal gland) release?
- Sex steroids (androgens–> pubertal growth)
also technically cortisol is released from here aswell
What are ALL steroids made from?
- Pregnenolone (cholesterol is substrate)
In the different layers of the adrenal cortex, what determines which hormone will be made by particular cells?
- Different enzymes produced by the different layers
Which two main things is alsdosterone important in?
- Conservation of Na+
2. Maintaining normal blood volume (water follows sodium)
When there is low Na+ or high K+ what does this cause (aldosterone)?
- Casues more aldosterone to be released from ADRENAL CORTEX
- acts on kidney tubules –> Na+ reabsorption INCREASES and K+ secretion increases
Does Na+ or K+ have a DIRECT effect on the adrenal glands?
- K+ has DIRECT EFFECT and Na+ has indirect effect
Which steroids does the adrenal cortex secrete?
- Sex steroids–> androgens (DHEA and androstenedione)
What is the precursor for pregnenolone/progesterone and thus DHEA and androstenedione?
- Cholesterol
- Need 17,20 lyase
What is the androgen level like compared to the gonads?
- It is LOW
What is Conn syndrome?
- Adrenal hyperfunction for aldosterone (excessive secretion of aldosterone)
What are the effects of Conn syndrome?
- retention of Na+ and H20
- Retention of Na+ and H20
- Systemic hypertension and urinary loss of K+- cardiac arrhythmia (normal K+ is low in plasma)
What does hypersecretion of estrogens lead to?
- Feminisation (breast development)
What does hypersecretion of androgens lead to?
- virilisation (Increase in facial hair and acne)
What is the major glucocorticoid in humans?
- Cortisol
What does the glucocoregulatory counter regulatory hormone do?
- Opposes action of insulin
- Just like glucagon adrenaline and GH
Do all cells have cortisol receptors?
- YES (pretty much)
Where (in tissue) is the main regulatory role of cortisol?-
- Skeletal muscle, liver and adipose tissue
Does cortisol act alone?
- NO! Acts in conjunction with glucagon, adrenaline, and GH
What is the main hormone secreted when responding to stress?
- Cortisol
Is cortisol secreted in non stress situations?
- YES! There is a basal level that is produced to maintain NORMAL blood pressure (A and NA)
What effect does cortisol have on the immune response?
- Inhibits immune system and inflammatory response
Which class of drug is prescribed to reduce inflammation?
- corticosterioid (glucocorticoids–> cortisol)
What is the secretion pattern of cortisol like?
- Pulsatile and circadium rhythm
When does cortisol level secretion peak?
- During sleep
- Cortisol pulses follow ACTH
Which 3 main factors stimulate the parvicelllar neurones in the PVN to secrete CRH and ADH?
- Circadium rhythm
- Stress
- Negative feedback
Where are CRH and ADH released into?
- Hypophyseal portal blood (local)
Are androgens also secreted with cortisol?
- YES! (negatively feedback to anterior pituitary)
CRH stimlates the secretion of ____ from the _____
CRH stimulates the secretion of cortisol from the adrenal gland
What does a decrease in CRH release and ADH have on the pituitary?
- Makes it less responsive to CRH and ADH
- Thus DECREASE in ACTH
What does a chronic high ACTH level lead to?
- (Hyppoplasia) –> Not enough ACTH
- Hypertrophy of adrenal cortex
What effect does cortisol have on metabolism in muscle?
- Increases plasma glucose
- Decreases protein synthesis
- Increases protein degradation (aa release)
- Decreases glucose uptake (so muscles are more dependent on on glycogen supply for energy)
What effect does cortisol have on metabolism in adipose tissue?
- Stimulates lipolysis–> glycerol + FAs
- Glycerol–> Glucose
- FAs –> Ketone bodies
What are some physiologyical effects of the stress response when A and NA released from adrenal medulla?
- Increased HR and BP
- Glycogen–> glucose
- Dilation of bronchioles
- Decreased blood to GIT
- Increased metabolic rate
What is the really general pathway for the stress response in terms of A and NA ?
- Stress–> nerve impulses–> Pre ganglionic symathetic fibres–> adrenal medulla
What is the pathway for the stress response in terms of Aldosterone and Cortisol?
- Stress (in hypothalamus)
- CRH released into local circulation (hypophyseal portal)
- CRH acts on Corticotroph cells of anterior pituitary to release ACTH —goes into systemic circulation—–> adrenal cortex
- Releases mineralcorticoids (aldosterone–> prolonged high ACTH) and glucocorticoids (cortisole)
What happens in the long term stress response?
- Retention of the Na+ and H20 by kidneys
2. Increase in blood volume and blood pressure
What is cushings syndrome?
- Too much cortisol
What is a primary cause of cushings syndrome?
- Tumor –> leading to hypertrophy
What is a secondary cause of cushings syndrome?
- versecretion by hypothalamus or pituitary - HIGH cortisol and HIGH ACTH levels
What are the effects of increased cortisol?
- Weight gain
- Fat deposits on face (moon face)
- Insulin resistance
- Protein wasting
- Calcium effects
- Increased MSH (skin pigmentation–> melanocyte skin hormone)
Why do people with cushings syndrome put on weight?
- High level of glucose in blood
What is addinsons disease?
- Decreased levels of cortisol
What is the primary cause of addinsons?
- Autoimmune destruction of adrenal cortex (low cortisol and increased ACTH –> but ACTH is independent)
What is a secondary cause of addinsons?
- Under secretion by the hypothalamus or pituitary
- DECREASED cortisol
- DECREASED ACTH or CRH (ACTH dependent)
What are the effects of decreased cortisol?
- Weakness
- Fatigue
- Anorexia
- Weight loss
What is the treatment for addinsons?
- Glucocorticoids (Cortisol)
What does glucocorticoid treatment for primary casue of addinsons turn off?
- Patients own ACTH (production of own cortisol)
