Endocrine System Flashcards
How is hormone secretion regulated?
1) Humoral e.g high blood glucose = insulin secretion
2) Neural e.g. SNS = epinephrine
3) Hormonal e.g. pituitary gland hormones = testosterone
Name the endocrine glands (11)
1) Pituitary gland
2) Hypothalamus
(3) Pineal gland)
4) Thyroid gland
5) Parathyroid gland
(6) Thymus)
7) Pancreas (Islets of Langerhans)
8) Endocrine cells in GI Tracts
9) Adrenal (supra-renal) Glands
10) Gonads: ovaries and testes
11) Placenta gland
What are the classification of endocrine hormones?
1) Steroid
2) Non- steroid
Name the steroid endocrine hormones (5)
1) Cortisol
2) Aldosterone
3) Testosterone
4) Oestrogen
5) Progesterone
(Based on cholesterol ring structure)
What are the classes of non-steroid endocrine hormone?
1) Amino acid derivatives
2) Peptides
3) Glycoproteins
What are the non-steroid endocrine amino acid derivatives?
1) Amines
Adrenaline/ epinephrine
Noradrenaline /norepinephrine
Melatonin
2) Iodinated amino acids
tri-iodo-thyronine (Thyroxine)
tetra-iodo-thyronine
What are the non-steroid endocrine peptides?
1) Long chain ('proteins')
antidiuretic hormone
oxytocin
melanocyte stimulating hormone
somatostatin
thyrotropin releasing hormone
gonadotropin releasing hormone
atrial natriuretic hormone
2) Short chain ('proteins')
growth hormone
prolactin
parathyoid hormone
calcitonin
adrenocorticotropic hormone
insulin
glucagon
GI tract hormones (secretin, CCK, gastrin)What are pro-hormones?
inactive precursor to peptide hormones
Describe the processing of pro-hormones
In endoplasmic reticulum, the pre pro-hormone –> pro-hormone. Pro-hormone packaged in golgi apparatus and becomes active. Active hormone secreted
What are glycoproteins
carbohydrate groups attached to the amino acids
What are the non-steroid endocrine glycoproteins? (4)
- Follicle stimulating hormone
- Luteinizing hormone
- Thyroid stimulating hormone
- Chorionic gonadotropin
Name three “local tissue” hormones (paracrine)
Prostaglandins
Leukotrienes
Thromboxanes
What are the functions of local tissue hormones
regulation of blood flow
haemostasis
mucosal protection (stomach)
inflammation
How do non-steroid hormones act on target cells
via second messenger in target cells
Name two common second messengers
Cyclic AMP
Calcium ions
Do steroid hormones need the use of second messengers?
No, because they pass through the outer cell membrane to reach intra cellular receptors
Give a brief overview of hormone action
1) synthesis/ storage
2) released in response to a stimulus
3) transport in blood
4) action on target cell (2nd messenger)
5) metabolism (liver) /excretion (kidney)
Target cell mechanism of steroid hormones
1) Plasma protein carrier molecules in blood vessel carries the steroid hormone
2) Enters the cell via cell wall
3) Steroid hormone attaches to hormone-receptor complex
4) transcription ->mRNA
5) ribosomes -> protein
- making proteins takes time
Target cell mechanism for non-steroid hormones
1) non steroid hormone (first messenger) attaches to protein receptor in cell wall
2) enters cell
3) causing GTP to couple with G protein
4) activating adenyl cyclase -> ATP
5) cAMP (second messenger)
6) Activates protein kinase
7) Activates specific enzyme
8) Substrate becomes product
How are most hormone systems regulated
negative feedback
How does negative feedback work in parathyroid glands with plasma ca2+ concentration
Low plasma calcium concentration
Parathyroid gland secrete parathyroid hormone
actions on target cells
increase in plasma calcium concentration
feedback to parathyroid gland
what is excess secretion called?
Hypersecretion
What is decreased secretion called?
hyposecretion
What is upregulation?
More receptors, in target cell, increases sensitivity
What is downregulation?
Less receptors, in target cell, decreases sensitivity
What is hyper function?
Excess production and secretion
Up regulation of receptors
What is hypo function?
Decreased production and secretion
Down regulation of receptors
receptors non-functioning
the connection between the hypothalamus and the pituitary gland is called
Infundibulum
What is the function of the hypothalamus? (4)
Thermoregulation Circadian Rhythm Motivation Emotions Hormone secretion 1) Primary hormones 2) Trophic hormones
Describe how thermoregulation works
Core temperature is down ->
thermoregulator in hypothalamus ->
compare to set point ->
Effectors -> heat production -> raise temperature -> (or heat loss)
When is your body temperature lowest
When you are sleeping
When does your set temperature raise?
After meals
How do hormones pass from the hypothalamus to the anterior pituitary?
Via blood vessels: Hypothalamic - pituitary portal vessels
What hormone does the hypothalamus secrete
releasing hormone (from neurosecretory cell)
What does the releasing hormone from the hypothalamus cause?
They trigger secretion of hormones from anterior pituitary
How to hormones produced in the hypothalamus pass to the posterior pituitary
Via nerve axons ->
then released in to circulation
Where is the Adenohypophysis?
Anterior pituatory
Where is the Neurohypophysis?
Posterior pituatory
Name hypothalamic hormones (trophic)
Corticotrophin releasing hormone (CRH) Gonadotrophin releasing hormone (GRH) Thyrotropin releasing hormone (TRH) Growth hormone releasing hormone (GHRH) Somatostatin (SS) (GH inhibiting hormone) Prolactin releasing hormone (PLRH) Dopamine (DA) ( also PLIH)
Name some anterior pituitary hormones
Adrenocorticotropic hormone (ACTH) Follicle stimulating hormone (FSH) Luteinising hormone (LH) Thryroid stimulating hormone (TSH) Growth hormone (GH) Prolactin (PL)
Describe the negative feedback involving corticotrophins
Stressor -> Hypothalamus -> Hormone 1: corticotrophin releasing hormone Anterior pituitary gland -> Hormone 2: Adrenocorticotropin releasing hormone (ACTH) -> Adrenal cortex -> Hormone 3: cortisol -> Action
Describe the negative feedback involving Gondotropins
Stimulus ->
Hypothalamus ->
hormone 1: gondatropin release hormone
anterior pituitary gland ->
Hormone 2: Follicle stimulating hormone (FSH)
ovaries or testes
ovum maturation & oestrogen production/ sperm production
or Hormone 2: Luteinising hormone (LH)
ovaries or testes
ovulation (oestrogen/ progesterone) / testosterone production
Describe the negative feedback involving Thyrotrophins
Stimulus -> Hypothalamus -> hormone 1: Thyrotrophins releasing hormone anterior pituitary gland -> Hormone 2: Thyroid stimulating hormone thyroid gland Hormone 3: thyroid hormones action
Describe the negative feedback involving Somatotrophins
Hormone 1: Growth hormone releasing hormone or Growth hormone inhibiting hormone
Hormone 2: growth hormone
action
Describe the negative feedback involving Prolactin
Hormone 1: Prolactin RH or Prolactin IH
Hormone 2: Proaction
action: breast development and milk production
Name some posterior pituitary hormones
Antidiuretic hormone (ADH) Oxytocin
What neurons produce oxytocin and antidiuretic hormone?
supraoptic nucleus (Oxy) paraventricular nucleus (ADH)
Describe the pathway involving antidiuretic hormone
Stimulus -> Hypothalamus -> hormone 1: ADH (axonal transport) posterior pituitary gland -> Hormone 2: ADH in plasma Kidney action: water reabsorption in collecting duct
Describe the pathway involving antidiuretic hormone
Stimulus: uterus stretching or infant suckling
Hypothalamus
Hormone 1: oxytocin (axons)
posterior pituitary gland
Hormone 2: oxytocin in plasma
action: contraction of uterus (parturition) or milk ejection
What hormones do the thyroid gland produce?
T3, T4
Thyroid hormone
calcitonin (regulates calcium lvl)
Where are thyroid hormones produced?
From cells around the follicles
Where is Calcitonin produced?
from para-follicular C cells
What is T4 a precursor for?
T3, which is more potent
What are the actions of thyroid hormones?
Increase metabolic rate of all cells
Determines basal metabolic rate
Essential for normal fetal and childhood growth
Permissive effect on action of adrenaline by up regulating adrenoreceptors.
Name the disorders of thyroid hormones when there is under secretion
Hypothyroidism (congenital)
Cretinism, Myxoedema (Adult)
Name the disorders of thyroid hormones when there is over secretion
Hyperthyroidism
Grave’s disease
Exophthalmos - eye bulging
What is simple goitre
Thyroid swelling associated with iodine deficiency
How does simple goitre occur?
Hormone is produced but in low levels
low levels of thyroxine result in increased secretion of Thryoid Stimulating Hormone (TSH) -> thyroid swelling
What is used to cure simple goitre?
Iodine
What hormones do parathyroid glands produce?
Parathyroid hormone
What does parathyroid hormone do?
regulate blood calcium levels
Where do the pancreatic islets contain?
Alpha cells - secrete glucagon
Beta cells - secrete insulin
Delta cells - secrete somatostatin
How much of the pancreatic tissue does the islets of Langerhans occupy?
1 -2 %
What do the islets of Langerhans produce?
Insulin
Glucagon
Somatostatin
Describe how the secretion of insulin is promoted
Insulin is released in response to: increased blood glucose increase blood amino acid glucose- dependent insulinotropic peptide vagus nerve activity
What does insulin do?
- lowers blood glucose
- facilitates glucose entry into:
Muscle cells
adipocytes
(but not liver - as glucose uptake by liver is not insulin-dependent)
Promotes formation of:
Glycogen
triglycerides
facilitates protein synthesis
What inhibits secretion of insulin
increased adrenaline
sympathetic nerves
somatostatin - causes body tissue to be less sensitive to insulin so more glucose available
When is glucagon released?
When there is low blood glucose?
What does glucagon do?
Acts to raise blood glucose
by:
glycogenolysis in liver
gluconeogenesis in liver
lipolysis and ketone synthesis
What promotes secretion of glucagon?
decreased blood glucose
increased blood amino acid
Cholecystokinin
autonomic nerve activity
What inhibits glucagon secretion
Insulin
somatostatin
What is diabetes mellitus
elevated blood glucose concentration
reduced glucose uptake by cells
metabolic changes:
gluconeogenesis; lipolysis
What are the clinical features of diabetes mellitus
polyuria (increased urine production)
polydipsia ( increased fluid intake; thirst)
Glycosuria (glucose in urine)
Diabetic neuropathy
skin and oral diseases including periodontitis, xerostomia
What are the feature of diabetes mellitus type 1
insulin dependent decreased insulin secretion because of destruction of beta-cells Autoimmune? 10% of cases "Early" onset insulin injections and diet
What are the features of diabetes mellitus type 2
insulin independent insulin level "normal" decrease target cell responsiveness to insulin related to overweight "Late" onset Diet, oral hypoglycaemic agents
Where are the Adrenal Glands
On top of the kidneys (supra-renal)
Name the sections of the adrenal gland
Cortex
Medulla
Capsule
Name the sections in the adrenal gland cortex
zona glomerulosa
zona fasciculata
zona reticularis
What hormones are produced in the adrenal gland cortex
Corticosteroids:
Aldosterone
Cortisol
Androgens
What hormones are produced in the adrenal gland medulla
The Medulla is a modified sympathetic ganglion which secretes adrenaline/epinephrine
Where cortisol produced?
The cells of zona fasciculata of adrenal cortex
What controls cortisol?
Adrenocorticotropic hormone (ACTH) from the anterior pituitary
What are the actions of cortisol?
Metabolic effects
permissive effects
anti-inflammatory, immunosuppressant
What type of hormone is cortisol?
Glucocorticoid hormone
What type of hormone is aldosterone?
Mineralocorticoid
Where is aldosterone produced?
cells of zona glomerulosa
What controls the release of aldosterone?
renin-angiotensin system
What are the actions of aldosterone?
Promotes reabsorption of Na+ and H2O in kidney (DCT)
Increases excretion of H+ and K+
Describe the renin - angiotensin aldosterone system
1) Stimulus occurs in the juxta-glomerular apparatus
2) Renin acts on angiotensionogen to form angiotensin 1
3) Angiotensin converting enzyme (ACE) acts on angiotensin 1 to form angiotensin II
4) causing the adrenal cortex to increase aldosterone release
5) increased Na+ is reabsorbed in cortical collecting ducts
What type of hormone is androgens?
Gonadocorticoid hormone
Where is androgen produced?
zona fasciculata and
zona reticularis
What are the actions of androgens?
Contribute to growth and 2 sexual characteristics in boys and girls
pubertal growth spurt
What occurs with excess glucocorticoid
Cushing’s syndrome
What are some characteristics of Cushing’s syndrome?
Moon face Red cheeks Fat pads Bruisability with ecchymoses Thin skin Pendulous abdomen striae (stretch marks) poor muscle development poor wound healing
What occurs with excess androgens?
Andro-genital syndrome
What are the characteristics of andro-genital syndrome
Baldness/ receding hairline Hirsutism (excess body hair) Androgenic flush small breasts male escutcheon (pubic hair distribution) Heavy arms and legs enlarged clitoris
What is the adrenal medulla controlled by?
pre- ganglionic sympathetic nerve (because it is a modified sympathetic ganglion)
What does the adrenal medulla produce?
adrenaline - this augments the action of the sympathetic nervous system
What does adrenal insufficiency cause?
Addison’s disease
What is Addison’s disease?
Decreased adrenal function and reduced levels of adrenal hormones:
glucocorticoids
mineralocorticoids
Very serious condition
How is water gained in the body?
ingestion
formed during metabolism
Food 700 ml/day
Drink 1400
Metabolic 300
total: 2400
How is water lost from the body?
Excretion: urine and faeces
Evaporation: sweat, in expired air
Urine 1500
Faeces 100
Evaporative sweat, breathing 800
total: 2400
In water balance which function is the only one under homeostatic control
urinary excretion
What are the structures in a nephron?
Glomerulus Proximal convoluted tubule Loop of Henle Distal convoluted tubule collecting ducts
What is the purpose of glomerulus?
Filtration of blood plasma (from blood cells)
What is the glomerular filtration rate?
It is the rate at which the kidneys filter blood
It is 120ml/min
What is the renal blood flow?
1200ml/min
How do the filtration pressures change in the glomerulus?
Pressures vary along length of glomerular capillary from afferent arteriole to efferent arteriole
capillary hydrostatic (blood pressure) 45-50mmHg
Plasma protein oncotic pressure 25-35mmHg
Capsular pressure 10mmHg
Net filtration pressure 10-15mmHg
What occurs in the proximal convoluted tubule?
Obligatory reabsorption of 60 - 70% of the glomerular filtrate (no control over what is reabsorbed)
reabsorbs : ions, small organic molecules
secretes: H+ (acid - base balance)
Active transport, facilitated diffusion
What is the renal blood flow?
1200ml/min
How do the filtration pressures change in the glomerulus?
Pressures vary along length of glomerular capillary from afferent arteriole to effectent arteriole
What is the net reabsorption of fluid in the Loop of Henle?
10% of glomerulus filtration rate
What occurs in the Loop of Henle
important for urine concentration (countercurrent exchange)
concentration of urine depends on active transport pumps in thick, ascending limb of the loop of henle
In the distal convoluted tube - what hormones control its activity?
Aldosterone
Atrial natriuretic hormone
Anti diuretic hormone
Parathyroid hormone
What is the net reabsorption of fluid in the Loop of Henle?
10% of glomerulus filtration rate
What occurs in the distal convoluted tubule?
Reabsorption: Water, Na+, Cl-, Ca2+
Secretion of H+, K+
In the distal convoluted tube - what hormones control its activity?
Aldosterone
Atrial natriuretic hormone
Anti diuretic hormone
Parathyroid hormone
What happens in the collecting duct?
Water reabsorption -> moves along osmotic gradient (count current exchange mechanism)
- > used ADH
- > creates membrane channels for water reabsorption
What hormones regulate water and electrolytes
ADH
Renin-angiotensin-aldosterone
Atrial Natriuretic Hormone (ANH, ANF, ANP)
What is the main control for water?
ADH
What is ADH also know as?
Vasopressin
What does ADH do?
Acts on distal convoluted tube (distal end) +
collecting ducts
-> increase water permeability
-> inserts aquaporin channels
-> passive water movement along osmotic gradient between tubule lumen and interstitial fluid
Describe the ADH secretion pathway
1) decreasing plasma volume (/blood pressure) (a bleed)
decreasing baroreceptor distension (low pressure receptors in atria and great veins)
increased ADH (from p. pituitary)
increased water permeability of collecting ducts
2) increased plasma osmolarity (dehydration)
increased osmoreceptor activation (In hypothalamus)
increased ADH (from p. pituitary)
increase water permeability of collecting ducts
What increases ADH secretion?
Decreased ECF volume
Increased ECF osmolarity
What effect does ADH have on blood vessels?
Constriction
What does drinking 1 litre of fluid do to urine output?
- isotonic NaCal output around 50ml/30mins
- Water output varies
What determines control of electrolytes?
The kidneys - how much is excreted
homeostatic control
Where are electrolytes found?
ICF + ECF
name the electrolytes?
Na+
Ca2+
K-
H+
What controls Na+
1) Renin-angiotensin-aldosterone system
- > reabsorbs Na+ (and water)
- > exchange for K+ and H+
- > angiotensin = potential vasoconstrictor
2) Atrial Natriuretic Hormone
- > increases excretion of Na+ (and water)
- > opposite effects to aldosterone
Describe the ANH section pathway
Increased plasma volume increased atrial distention increased ANH release decreased Na+ absorption + increased GFR increased Na+ excretion
What regulates K+?
Aldosterone
Na+ is swapped for K+ and H+
What does ECF [K+] effect
Membrane potential
Nerve/muscle function
What occurs when there is hypo secretion of ADH?
Diabetes insipidus
-> increased urination
What occurs when there is hyper secretion of ADH?
Syndrome of inappropriate ADH (SIADH)
excess ADH = water retention
What effect does K+ have on muscle function?
Increased ECF [K+] -> depolarisation
- > axons to fire AP
- > MP ≠ resting levels
- > axons = extended refractory period
What is used in sensitive toothpaste?
K salt
What do the manufacturer’s of sensitive toothpaste claim?
K+ ions diffuse from the paste along tubules Raise [K+] at inner end of tubule nerves depolarised Na+ channels inactivated prolonged refractory period
What is the problem with sensitive toothpaste?
K+ build up does not persist
Describe the pathway for renin secretion
1) Decreased plasma volume (dehydration?)
leads to increases sympathetic nerve activity in J-A apparatus
decreased renal blood flow
decreased stretch of JG baroreceptors
J-G A
increased secretion of renin
2) from decreased renal bF decreased GFR decreased Na+ in tubular fluid macula densa J-G A increased secretion of renin
What does decreased blood volume result in?
Fall in blood pressure
impaired delivery of nutrients to cells
ie. shock
What are the physiological responses to blood loses
Immediate: stop the bleeding (haemostasis)
Short term: restore blood pressure
Medium term: restore fluid volume
Long term: replace blood constituents
What components occurs in the immediate physiological responses to blood lose?
1) Vascular response
2) Platelet response
3) Plasma response (coagulation)
What occurs in the vascular response?
1) Smooth muscle (of blood vessel)
- spasm due to trauma
- > decrease in blood flow + increase blood pressure
* myogenic response (constriction of blood vessels)
* humoral factors (vasoconstriction)
2) Endothelium
- When injured secrete: platelet adhesion and aggregation (initial formation of clot?)
- Normally release: anticlotting and fibrinolysis
What occurs in the platelet response?
1) Damage to blood vessel
- > turbulent blood flow
- > platelets come into contact with vessel wall (collagen)
2) Aggregate: platelets adhere; clump together
3) Release chemicals that cause further aggregation (positive feedback)
4) formation of platelet plug
What mechanism does platelet plug formation use?
Positive feedback
What chemical use involved in platelet formation?
ADP induced Thromboxane A2
- > vasoconstrictor
- > platelets; aggregate + release of chemicals
Where are most clotting factors made?
The liver
What does the synthesis of several clotting factors require?
vitamin K
How are clotting factors activated?
Enzyme cascade
What occurs in coagulation?
Plasma proteins and tissue components combine:
Fibrinogen -> fibrin to form blood clot
- Numerous clotting factors are involved
- > made in liver
- > need vit K.
- > enzyme cascade
Describe the coagulation: common pathway
Prothombin -> (Factor Xa (ca2+, phosopholipid, Factor V) -> Thrombin
Thrombin -> (Factor XIII) -> Factor XIIa
Fibrinogen -> (Thrombin) -> soluable fibrin
Soluable -> (Factor XIIIa) -> insoluable fibrin
Name the blood clotting factors
1 Fibrinogen 2 Prothrombin 3 Tissue factor (Thromboplastin) 4 Calcium ions 5 Proaccelerin 6 7 Proconvertin 8 Antihaemophilic globulin 9 Christmas factor 10 Stuart - Prower factor 11 Plasma Thromboplastin antecedent 12 Hageman factor 13 Laki -Lorkand factor
Some factors may be missing due to genetics e.g. haemophilia.
What are the two coagulation pathways?
Intrinsic + extrinsic
Describe the coagulation intrinsic and extrinsic pathways
Factor X -> (phospholipid, calcium ions (important)) Factor Xa ->
Describe the coagulation intrinsic pathway
Intrinsic pathway:
Vascular damage,
contact activation involving factors XII, XI, IX, VIII
Describe the coagulation extrinsic pathway
extrinsic pathway:
Tissue damage,
Tissue factors (‘tissue thromboplastin’) factor VII
When is the extrinsic pathway more important?
in initiating clotting after an injury
When does the intrinsic pathway occur?
It serves to maintain the process once it has started
Maybe have a role in thrombosis -> blood clot forms inside an intact blood vessels.
What is Fibrinolysis?
When the blood clot is broken down
What is the enzyme in fibrinolysis
Plasmin
Describe the fibrinolysis pathway
Plasminogen -> (Plasminogen activator) -> Plasmin
Fibrin -> (Plasmin) -> Soluble fibrin fragments
What components occurs in the short term in physiological responses to blood lose?
Overall restore blood pressure
Haemorrhage: changes in blood pressure
- Loss of blood volume
- Fall in blood pressure
- compensatory mechanisms triggered by the arterial baroreceptors
What are baroreceptors reflexes mediated by?
Sympathetic nerves + hormones: Adrenaline Angiotensin II Vasopressin (ADH) -> mechanism for restoring BP
Describe the baroreceptor flexes
deceased blood volume
decreased blood pressure
decreased baroreceptor firing
CVS centres (brainstem)
increase in sympathetic NS activity
1) increased heart rate -> increased cardiac output
2) ventilation control-> increased stroke volume -> increased cardiac output -> increased mean arterial BP
3) venous constriction -> increased stroke volume etc
4) arteriole constriction -> increased peripheral resistance -> mean arterial BP
Describe what occurs what happens in a haemorrhage to stroke volume, heart rate , cardiac output (SV x HR), total peripheral resistance, mean arterial pressure (CO x TPR)
SV: decrease HR: increase CO: decrease TPR: increase MAP: decrease
What components occurs in the medium term in physiological responses to blood lose?
restore blood volume:
- Shifting interstitial fluid back into blood vessels
- Decrease fluid loss in kidney
- Increasing fluid intake
What factors are important in Starling’s Forces?
Hydrostatic pressure (blood pressure) Oncotic pressure (plasma proteins)
Normally in Starling forces describe the pressures
Arterioles: 35mmHg hydrostatic pressure
Venules: 15mmHg hydrostatic pressure
Oncotic pressure remains constant at 25mmHg
more filtration on arteriole end
more reabsorption on venules end
filtration ≈ reabsorption
Through baroreceptor reflexes reduced arterial blood pressure causes:
1) vasoconstriction of arterioles
Increased TPR
Decreased capillary BP
-> causes decrease of hydrostatic pressure pushing fluid out of the capillary
-> more fluid is drawn back into the capillaries by the oncotic pressure
What occurs to the Starling forces in a capillary during a haemorrage?
-> constricted arteriole oncotic pressure (plasma protein) does not change: 25mmHg hydrostatic pressure: 25mmHg -> 10mmHg
reabsorption > filtration
During the medium term of haemorrhage - describe the decrease of fluid loss in the kidney
decreased Glomerular filtration increased reabsorption of Na+ and water by stimulating release of: renin- angiotensin-aldersterone antidiuretic hormone -> both are vasoconstrictors
What area is important in thirst?
Hypothalamus
What promotes thirst?
increased plasma osmolarity decreased ECF volume Angiotensin II -> promotes thirst Dry mouth stretch receptors in stomach suppress drinking: feed forward regulation
Long term response in haemorrhage
restore plasma protein (replaced from liver 3-4 days) replace blood cells esp RBC erythropoiesis -> regulated by erythropoeitin (EPO) -> EPO released from kidney -> Stimulated RBC production in bone marrow -> return to normal in 2-3 months
Describe the Erythropoietin pathway
decreased RBC numbers -> decreased oxygen delivery -> kidney -> erthropoietin -> red bone marrow -> increased RBC production
What is shock?
inadequate blood flow to tissues
What is inadequate blood flow associated with
decreased cardiac output
decreased blood or ECF volume
what are the 2 main types of shock
reversible and irreversible
what types of shock are there
1) hypovolaemic shock
reduced ECF, due to haemorrhage, sweating, diarrhoea, burns etc
2) low resistance (distribution shock)
reduced peripheral resistance, due to widespread vasodilation e.g. anaphylactic shock
3) cardiogenic shock
heart fails as pump
What are some types of stressor:
1) Physical Injury, surgery Infection, shock Pain Exposure to cold Sustained exercise
2) Threats
Imprisonment
torture
exams
What body systems are involved in stress?
Nervous
Endocrine
Immune
What do the effects of stress depend on?
- duration and severity of stressor
- effectiveness of any responses
What are the stages in stress
1) Alarm reaction Fight, flight, fright response Physiological effects 2) Resistance phase adaptation to stressor 3)Exhaustion phase e.g sleep deprivation severe, persistant stress responses futile; system fail pathological effects
What is General Adaptation Syndrome (Seyle)
The stages in stress
- alarm reaction
- resistance phase
- exhaustion phase
What are the components of the alarm reaction
Physiological response to threat Neural: Sympathetic NS Hormonal: Adrenal glands: 1) Adrenaline (Adrenal medulla in thoraco-lumbar) 2) Corticosteroid (Adrenal cortex)
In the alarm reaction, what occurs in the neural component?
1) Increased cardiac output
Increased heart rate
increased ventricular contractility
2) redistribution of cardiac output
Increased flow to muscles
Decreased flow to gut, kidney
3)Metabolic
Glycogen breakdown -> glucose release
Mobilisation of fat stores (release of free fatty acids)
4) Stimulation of adrenaline release
In the alarm reaction, what occurs in the hormonal component?
- Adrenaline released from adrenal medulla (functionally part of SNS.
-> augments and prolongs actions on SNS
increases cardiac output
redistribution of cardiac output
metabolic effects - Glucocorticoids secreted from adrenal cortex
E.g steroid like cortisol
Cortisol compliments actions of SNS and adrenaline
harmful if persistent, high secretion
What is the main stress hormone
Cortisol
What are the actions of Cortisol
1) metabolic Increased energy production from glucose, amino acids and fats increased protein breakdown 2) enhances the actions of adrenaline "permissive effect" 3) Anti-inflammatory action 4) Immunosuppression
Glucocorticoids have an anti-inflammatory and immunosuppressant action. What can happen in the immune system?
- Inhibit release of prostaglandins + leukotrienes
- Inhibit macrophages and helper T lymphocytes
Many people receive corticosteroid drug therapy. What can it cause
Increased incidence of illness at times of stress
What is one reason someone might be taking corticosteroids?
As an anti-inflammatory for arthritis
What can long term use of corticosteroids potentially do?
Disrupt normal control mechanism:
- suppress Corticotrophin Releasing Hormone (CRH) an Adrenocorticotrophic Hormone (ACTH) release -> and therefore the naturally stress response
- makes patients are risk during e.g dental extractions
What is stress analgesia?
When pain is diminished during physical stress
What causes stress analgesia?
Release of
1) endogenous opioid peptides
2) endrophins
3) enkephalins in CNS
- > suppress nociception and pain
How is stressed assessed?
changes in:
HR
BP
What increases dental stress in patients
Anticipation of treatment = stressful
Oral surgery > scaling
effects greater in : anxious patients < dental phobics
pain increases amount of stress
LA, noise, masks + gowns, if child = stressful
women = high HR.
women and men = no diff in BP
Talk about the size of stress-induced effects
Range of changes:
Sys BP + 5-20mmHg
Dia BP + 4-8mmHg
HR +20
example of BP during treatment without LA
210/115 mmHg
What increases dental stress in dentists
When standing
Complex procedure
anxious patient
What happens to the individual if the stressors continue to present?
1) Adaptation phase (resistance)
- persistant exposure to stressor = diminished response to stress
- effective is perceived threat is removed
2)Exhaustion phase Adrenal failure immunosuppression peptic ulcers CVS disease death
What are the functions of calcium
bone and tooth structure mineral store AP (cardiac muscle) Membrane excitability 2nd messenger - non steroid hormone action - gland secretion - Muscle: excitation - contraction coupling co factor in metabolic pathway blood clotting
Calcium concentrations
Diffusible calcium
- ionised calcium 1.2mmol/l
- calcium bound to citrate 0.2mmol/l
Non-diffusible calcium
- calcium bound to protein 1.2mmol/l
total 2.6mmol/l (Homeostatic conc.)
Describe the calcium turnover pathway
Calcium from diet -> GI tract -> faeces
calcium in GI tract plasma and interstitial fluid exchangeable bone ‘stable bond’
Plasma and interstitial fluid kidney -> urine
What hormones are used in calcium homeostasis
1) Parathyroid hormone
2) Calcitonin
3) Vitamin D
How is parathyroid hormone involved in calcium homeostasis
Low plasma Ca2+ concentration -> PTH secretion
-> increase plasma Ca2+ by
1) increased reabsorption of bone (osteoclasts)
2) Increase Ca2+ reabsorption in kidney (with decreased PO4 resorption)
3) Increase uptake of Ca2+ from intestines (assisted by Vit D)
Describe the parathyroid hormone pathway for calcium homeostasis
decreased plasma Ca ->
PT gland -> PTH ->
1) Kidney: formation of 1,25 OH vit D ->
Intestines: increased absorption of Ca
2)Kidney: Increased Ca resorption
Increase PO4 excretion
3) Bone: resorption + release of Ca +PO4
All lead to Increased Plasma Ca
How is Calcitonin involved in calcium homeostasis
responds to high plasma Ca
-> Calcitonin secreted from thyroid glands
Lowers plasma Ca by:
- increased formation of bone (osteoblasts)
- decreased ca resorption in kidney
- no major role in calcium homeostasis
describe the calcitonin pathway in calcium homeostatsis
increased plasma ca thyroid gland (c-cells) release calcitonin 1) Kidney: increase ca excretion 2) Bone: deposition lowers plasma ca
Describe the vit D pathway in calcium homeostatsis
Overall: increased levels of plasma Ca and Po
Dietart Vit D + 7-dehydrocholesterol synthesised in skin -> Vit D3 (cholecalciferol) -> (Liver + 25hydroxylase) -> 25(OH)cholecalciferol -> kidney 1alpha hydroxylase (regulated by PTH)-> 1,25 (OH2) Cholecalciferol or calcitrol 1) Intestine: Ca resorption 2) Kidney: Ca retention; PO retention 3) Bone: Ca release; PO4 released
-> all Plasma: increased Ca and PO4
What hormones cause increased bone formation and increased bone mass
Calcitonin Growth Hormone IGF Insulin Oestrogen Testosterone
What hormones cause increase bone resorption and decreased bone mass
Parathyroid hormone
Cortisol
Thyroid Hormones
What do osteoblasts do?
Synthesis and secrete collagen fibres
- > forming matrix
- > later mineralised by calcium salts
What are osteocytes?
trapped osteoblasts in the bone matrix
lie within bony lacunae
contact other cells via long cytoplasmic processes
What are osteoclasts?
Reabsorb bone large multinucleated cells derived from macrophages lie in depressions: Howship's lacunae
Describe bone remodelling
1) Resting bone surface: PTH + collagenase = osteoclast precursor
2) Reabsorption: osteoclasts
3) Reversal: mononuclear cells
4) Formation: secretion of osteoblasts
5) Reminerization: osteoids
6) Resting: inactive osteoblasts
What is hypercalcaemia?
Raised [Ca2+]
What is hypocalcaemia?
Reduced [Ca2+]
What causes Hypocalcaemia Tetany?
Decrease Ca2+ intake
Excess loss of Ca2+
Alkalosis -> low [Ca2+] in blood
What occurs in Alkalosis?
Low [Ca2+] in blood = increased nerve excitability
pins and needles; muscle spasms
Trousseau’s sign
Chvostek’s sign
What can cause alkalosis?
Hyperventilation
by blowing off CO2
How can you cure alkalosis?
rebreathing expired air into a bag
trapped CO2 in patient’s lungs
Name some disorders of hormones regulating calcium
Over secretion + under secretion of:
1)PTH
hyperPT: Osteitis Fibrosa Cystica
hypoPT: defective mineralisation
2)Vit D
Rickets (children)
Osteomalacia (adults)
3) Calcitonin
No effect -> no essential for regulation of plasma [Ca2+]
What is Osteitis Fibrosa Cystica?
Areas of demineralisation in skull and leg bones
Primary hyperparathyroidism
What is vit D deficiency?
Dietary deficiency failure to synthesis in body: reduced Ca up from GI track undermineralised bone bone lack rigidity
Name some bone diseases
Osteoporosis - decreased bone mass and density
Osteopetrosis - increased bone mass and density
What is osteoporosis?
Reduced bone density Loss of matrix with 2ndry loss of mineral fractures common common in elderly in both genders menopause other causes: Corticosteriods nutrition deficiency
What is osteropetrosis?
Increased bone density reduced blood supply prone to fracture and chronic infection difficult extraction tooth roots indistinct on radiographs mandible > maxilla
What is hyperplasia?
Increase in cell numbers
What is hypertropia
Increase in cell size
Which cells can regenerate?
Skin
Liver
Blood
Which cells can’t regenerate?
Nerve
What affects growth?
Genetics
Environment:
Nutrients
Disease
Growth factors e.g hormones
Which hormones influence growth?
Thyroid
Growth H
Sex H
others: Insulin Cortisol Vit D PTH
In growth, what does the thyroid hormone do?
Indirect effect
Needed for:
Normal development + growth
protein synthesis in brains of fetus and infant
normal development of neurons
Faciliates:
actions of growth hormone
SNS
Symptoms of hypothyroidism
Deficiency of thyroid hormone
Fetal/neonate ->
sparse hair
large tongue
permanent mental impairment
in childhood ->
impedes brain development and skeletal growth
delayed tooth eruption
Treatment: Thyroxine
recovery: depends on onset and duration.
Growth hormone
mainly indirect
Metabolic and growth-promoting actions
Growth action: in postnatal period, infancy and adolescence
Metabolic action (indirect):
- increases blood glucose levels (anti insulin)
- decreases glucose uptake in calls
- increases lipolysis - making fatty acids available for
- energy production
- facilities uptake of AA for protein synthesis (esp. liver and muscle)
IGF-1 (from liver) exerts effects:
- cartilage, bone, soft tissue, viscera
- IGF-1 -> cartilage proliferation in long bones, until epiphyses (growth centres) close
Types of dwarfism
hypothyroid
hypopituitary
Sex hormones
Testostetone, oestrogen
-> growth spurts
Mediated by:
increases secretion of GH and IGF-1:
-stimulate bone growth but accelerate closure of epiphyseal growth plates
testosterone:
anabolic effects on protein synthesis, increase muscle bulk
In growth, what does insulin do?
no direct effect on growth promoting actions but:
Promotes foetal growth
promoting post-natal growth by stimulating secretion of IGF-1
Faciliating protein synthesis (by making glucose available for energy production)
In growth, what does cortisol do?
higher then normal level -> inhibits growth
stimulates protein catabolism
suppresses bone growth
promotes bon resorption -> osteoporosis
childhood: stress/illness = cortisol = growth inhibition
In growth, what does, Vit D + PTH do?
contribute to growth by
- ensuring Ca2+ + PO4 available for bone formation
- Vit D = Ca2+ absorption in gut
- PTH raises plasma Ca2+
What occurs if there is excess growth hormone?
Childhood:
Gigantism
Adulthood:
Acromegaly (Hands, feet, jaw = bulky)
Class 3 - greater growth of mandible/gap between teeth
What do you see in tumour of pituitary gland
Enlarged sella turcica
Achondroplasia
Defective cartilage growth
- effects:
long bones
cartilage growth centres e.g spheno-occipitial synchondrosis (in cranial base)
What happens to cells in ageing?
Decline in ability of cells to divide as they divide, accumulate: Errors in DNA sequence Abnormal proteins Damage to organelles e.g. mitochondria free radicals; shortening of telomeres
What is apoptosis
programmed cell death
occurs in:
development - tooth germs, nervous system
to replace worn out cells
to destroy tumour cells
