Endocrine 4 Flashcards
Where are the adrenal glands located?
Embedded above each kidney in a capsule of fat
What are the divisions of the adrenals?
Cortex and medulla
What does the adrenal cortex (outer) have a similar origin to?
Gonads
What does the adrenal cortex produce? (adrenal steroids)
Mineralocorticoids (outer gland) – aldosterone • Glucocorticoids (middle gland) – cortisol (corticosterone) • Androgen sex steroids (inner gland) – DHEA (dehydroepiandrosterone)
What is the adrenal medulla (inner) composed of?
Chromaffin cells
Where does the adrenal medulla originate from?
Sympathetic nervous system
What does the adrenal medulla produce?
Catecholamines
– epinephrine (adrenaline)
– norepinephrine (noradrenaline)
What are the 3 layers / zones that the adrenal cortex consists of?
- Zona glomerulosa – outermost layer
- Zona fasciculata – middle and largest portion
- Zona reticularis – innermost zone
What are the categories of adrenal steroids?
- Mineralocorticoids
- Glucocorticoids
- Sex hormones
Mineralocorticoids, role and main one
– Mainly aldosterone
– Influence mineral balance, specifically Na+ and K+ balance
Glucocorticoids, main one and role
– Primarily cortisol
– Major role in glucose metabolism as well as in protein and lipid metabolism
What are the sex hormones of the adrenal cortex similar to?
To those produced by gonads
What is the most abundant and physiologically important sex hormone produced by adrenal cortex?
Dehydroepiandosterone (male “sex” hormone)
What is aldosterone?
A major mineralocorticoid
What does aldosterone maintain?
electrolyte balance
Aldosterone feedback
- low plasma Na++ or high K+
- activates renin-angiotensin system
- Angiotensin II increases aldosterone release from adrenal glands
- acts on distal renal tubules
• increase Na++ & water retention
• increase excretion of K+ & H+ ions
What is cortisol (hydrocortisone)?
A major glucocorticoid in humans
Cortisol secretion rhythm regulation
Diurnal rhythm
Cortisol function
– plays role in stress – increase blood glucose – increase blood fatty acids – control water and electrolyte balance – anti-inflammatory/immunosuppressive
Cortisol feedback
negative feedback on hypothalamus (CRH) & anterior pituitary (ACTH)
Release of ACTH
Hypothalamus neurons CRF (41aa peptide) → anterior pituitary
ACTH → adrenal cortex corticosteriods
What does the adrenal cortex (sex h)
Both male and female sex hormones in both sexes
Dehydroepiandrosterone (DHEA)
The only adrenal sex hormone that has any biological importance
What is dehydroepiandrosterone (DHEA) overpowered by?
By testicular testosterone in males
What does DHEA govern in femailes
– Growth of pubic and axillary hair
– Enhancement of pubertal growth spurt
– Development and maintenance of female sex drive
Epinepherine and Norepinerphrine primary stimulius
Activation of sympathetic nervous system by stress
Where is Epinephrine / Adrenaline secreted?
Into blood
Where is Epinephrine / Adrenaline secreted?
Into blood
Where is Epinephrine / Adrenaline secreted?
Into blood
Funciton of Epinephrine / Adrenaline x 4
– “fight-or-flight” responses
– Maintenance of arterial blood pressure
– Increases blood glucose
– Increases fat metabolism (increase blood fatty acids)
Glucocorticoids x 4
hydrocortisone, prednisolone, dexamethasone, betamethasone
Glucocorticoids clinical
Replacement therapy: in adrenal failure (Addison’s disease)
Anti-inflammatory/immunosuppressive disorders ‘chemical’ treatment
Reduce T cell proliferation, release of IL-2, TNF-a, IL-1
Anti-inflammatory/immunosuppressive disorders x 6
– asthma (inhaler)
– eczema (topical cream)
– arthritis (systemic injections)
– ulcerative colitis (rectal suppositories)
– prevent graft rejection of the transplant
– cancer patients (anti-emetic; reduce oedema in brain tumours)
Benefit vs glucocorticoid use
Benefit > Risk of glucocorticoid use
Risk of glucocorticoid use x 4
– Immune system limited (delay tissue repair, gastric/peptic ulcers)
– Cushing’s symptoms
– Osteoporosis (alter function of bone cells osteoblasts/osteoclasts)
– Adrenal insufficiency due to sudden withdraw
What activity does fludrocortisone have?
Glucocorticoid and mineralocorticoid activity
How is fludrocortisone used as a treatment?
Used in mineralocorticoid replacement therapy (eg) in Addison’s disease.
What are the 3 major targets of mineralocorticoids?
Kidneys, bladder and colon
Addison’s disease hormone levels
Low glucocorticoid (cortisol) & mineralocorticoid (aldosterone)
Cause of primary Addison’s disease
Damage adrenal gland (TB or autoimmunity)
Cause of secondary Addison’s disease
Low ACTH release
Symptoms of Addison’s disease
- hypoglycaemia
- decreased liver glycogen
- fatigue, anorexia, nausea, weight loss, dizziness, hypotension, psychiatric
- death if untreated
Treatment for Addison’s disease
Steroid replacement therapy
Cushing’s disease hormone levels
Excess glucocorticoids (cortisol)
Cause of Cushing’s disease
ACTH secreting tumor in pituitary
Symptoms of Cushing’s disease
- hyperglycemia
- elevated blood pressure
- obesity (abdominal fat, thin arms & legs)
- muscle wasting, osteoporosis, cataracts
- poor wound healing
- buffalo hump, moon face, red cheeks
- psychiatric symptoms (depression, euphoria, hallucinations)
Treatment for Cushing’s disease
- remove tumor
- antiglucocorticoids
- surgical adrenalectomy
Hyperplastic of adrenal cortex image
Conn’s syndrome hormone levels
Excessive mineralocortocoids (aldosterone)
Primary Conn’s syndrome cause
tumour
Secondary Conn’s syndrome cause
Excessive renin-angiotensin action in kidney disease, cirrhosis of liver, congestive heart failure
Symptoms of Conn’s syndrome
- sodium and water retention
* increase in extracellular fluid and hypertension
Treatment for Conn’s syndrome
- antagonist of aldosterone (spirono-lactone)
* unilateral adrenalectomy
generalised stress response LEARN
- ↑ epinephrine secretion from adrenal medulla (chromaffin cells)
- ↑ CRH-ACTH-cortisol (HPA axis) that mobilises metabolic resources
- ↓ insulin & ↑ glucagon secretion to raise blood glucose & fatty acids
- ↑ renin-angiotensin-aldosterone system & vasopressin secretion to maintain blood volume and blood pressure
What does chronic stress cause?
Causes heart disease, hypertension, atherosclerosis, immune-suppression
What does prolonged release of CRH cause?
Anxiety & depression
What may CRF1 receptor antagonists treat?
Anxiety, depression, drug dependence and irritable bowel syndrome
Stress response from hypothalamus diagram
Cortisol feedback
Main glucocorticoids
Cortisol
Upstream hormones of cortisol
Adreno-corticotropic Hormone (ACTH)
Hypersecretion of cortisol causes
Cushing’s disease (high glucocorticoids)
Hyposecretion of cortisol causes
Addison’s disease
low corticoids
Main mineralocorticoids
Aldosterone
Upstream hormones of Aldosterone
Angiotensin II
Hypersecretion of aldosterone causes…
Conn’s Syndrome (high mineralocortocoids)
Hyposecretion of aldosterone causes…
Addison’s disease (low corticoids)
Hyposecretion of aldosterone causes…
Addison’s disease (low corticoids)
Fed state
Store amino acids, glucose and triglycerides
Hungary state
Mobilise stored reserves
Tissue to breakdown in blood diagram
Glycogenesis reaction
Glucose → glycogen
Glycogenolysis reaction
Glycogen → glucose
Gluconeogenesis reaction
Amino acids → glucose
Protein synthesis reaction
Amino acids → protein
Protein degradation
Protein → amino acids
Fat synthesis (Lipogenesis or Triglyceride synthesis)
Fatty acids and glycerol → triglycerides
Fat breakdown (Lipolysis or Triglyceride degradation)
Triglycerides → fatty acids and glycerol
Blood consequence of glycogenesis
↓ blood glucose
Blood consequence of protein synthesis
↓ Blood amino acids
Blood consequence of fat synthesis
↓ Blood fatty acids
Blood consequence of glycogenolysis
↑ Blood glucose
Blood consequence gluconeogenesis
↑ Blood glucose
Blood consequence of protein degradation
↑ Blood amino acids
Blood consequence of fat breakdown
↑ Blood fatty acids
Anabolism defn
Build up or synthesis of larger organic macromolecules from small organic subunits
Anabolism require..
ATP
Anabolism results in…
- Manufacture of materials needed by the cell
- Storage of excess ingested nutrients not immediately needed for energy production or needed as cellular building blocks
Catabolism defn
Breakdown or degradation of large energy rich organic molecules within cells
The two levels of catalytic breakdown are ….
- Hydrolysis of large cellular molecules into smaller subunits
- Oxidation of smaller subunits to yield energy for ATP production
Summary of the major pathways involving organic nutrient molecules diagram
Where does most interconversion of organic molecules occur?
In the liver
What happens to excess circulating glucose?
- Stored in liver and muscle as glycogen
- Once liver and muscle stores are “filled up”, additional glucose is transformed into fatty acids and glycerol and stored in adipose tissue
What happens to excess circulating fatty acids?
Becomes incorporated into triglycerides
What happens to excess circulating amino acids?
Converted to glucose and fatty acids
What is the circulating form of carbohydrate?
Glucose
What is the circulating form of fat?
Free fatty acids
What is the circulating form of protein?
Amino acids
What is the storage from of carbohydrate?
Glycogen
What is the storage from of fat?
Truglycerides
What is the storage from of protein?
Body proteins
What is the major storage site of carbohydrate?
Liver, muscle
What is the major storage site of fat?
Adipose tissue
What is the major storage site of protein?
Muscle
Carbohydrate percentage of total body energy content
1%
Fat percentage of total body energy content
77%
Protein percentage of total body energy content
22%
Reservoir capacity of carbohydrate
Less than a day’s worth of energy
Reservoir capacity of fat
About two months’ worth of energy
Reservoir capacity of protein
Death results long before capacity is fully used because of structural and functional impairment
Role of carbohydrate
First energy source, essential for brain
Role of fat
Primary energy reservoir, energy source during a fast
Role of protein
Source of glucose for the brain during a fast; last resort to meet other energy needs
Role of liver in metabolic states
- Primary role in maintaining normal blood glucose levels
- Principal site for metabolic interconversions such as gluconeogenesis
Role of adipose tissue in metabolic states
- Primary energy storage site
- Important in regulating fatty acid levels in the blood
Role of muscle in metabolic states
Muscle
- Primary site of amino acid storage
- Major energy user
Role of brain in metabolic states
- Normal can only use glucose as an energy source
- Does not store glycogen
Mandatory blood glucose levels be maintained
Factors that increase blood glucose
- Glucose absorption from digestive tract
- Hepatic glucose production; Through glycogenolysis and
gluconeogenesis
Factors that decrease blood glucose
- Transport of glucose into cells: for utilisation for energy production and for storage as glycogen through glycogenesis and as triglycerides.
- Urinary excretion of glucose
Hormones regulating metabolism
- Anterior Pituitary gland
- Growth hormone, ACTH, TSH
- Liver
- Somatomedins (IGF’s)
- Thyroid gland (T3 T4 )
- Thyroxine
- Gonads
- Sex steroids
- Adrenal cortex
- Glucocorticoids (cortisol)
- Adrenal medulla
- adrenaline (noradrenaline)
- Pancreatic (Islets of Langerhans)
- Insulin & glucagon
What do exocrine cells of islets of langerhans secrete?
Proteases into small intestine
How much of pancrease does the endocrine Islet of Langerhans comprise?
1%
What is the endocrine Islet of Langerhans surrounded by?
Capsule
Where are endocrine Islet of Langerhans located?
Scattered throughout pancreas
Endocrine Islet of Langerhans blood supply function
Rich blood supply for hormone drainage
Endocrine Islet of Langerhans composition
Clusters composed ~3000 endocrine secretory cells
What does pancreas removal cause
Symptoms of diabetes
↑[glucose]plasma 20-30mM
Location and structure of the pancreas diagram
Cell types in the islets of Langerhans diagram
3 secretory cells of islets of Langerhans
─ β cells
─ α cells
─ δ cells
What do the secretory cells of islets of Langerhans produce?
peptide hormones
Beta cells function
Insulin production - promotes glucose uptake
Alpha cells function
Glucagon production - opposite effect to insulin
Delta cells function
Somatostatin production -
potentiates glycogen breakdown activity of glucagon
Where is insulin stored and secreted from?
Cytoplasmic granules
Insulin fed state
Anabolic hormone
Insulin in fed state effects
- Glucose to glycogen
- Fatty acids to triglycerides
- Amino acid to protein
‘Organ’ effects of insulin
- ↓ glucose, amino acid and fatty acid in blood
- ↑ glucose, amino acid and fatty acid uptake in muscle
- ↓ breakdown of glycogen, fat (triglycerides) and protein
Glucagon in hungry state
Catabolic hormone
Effects of glucagon
- Glycogen to glucose
- Triglycerides to fatty acids
- Protein to amino acid
Effects of glucagon in blood
- ↑ glucose, amino acid and fatty acid in blood
- ↓ glucose, amino acid and fatty acid uptake in muscle
- ↑ breakdown of glycogen, fat (triglycerides) and protein
glycogenolysis/lytic
glycogen breakdown
gluconeogenesis
glucose synthesis
gluconeogenesis
glucose synthesis
lipolysis
lipid/fat breakdown
lipogenesis
Lipid/fat synthesis
What is insulin synthesised as?
Prohormone
What is insulin cleaved to?
Mature peptide
Half life of insulin and glucagon
I - t1/2 = 30 minutes
G - t1/2 = 10 minutes
Stimulation of insulin secretion by glucose via excitation secretion couplinf
- Glucose enters Beta cells by diffusion via GLUT- 2. Glucose is phosphorylated to glucose-6-phosphate.
- Oxidation of glucose-6-phosphate produces ATP.
- ATP acts on ATP-sensitive K+ channels, closing it.
- Reduced exit of K+ depolarises membrane.
- Depolarisation opens voltage-gated Ca2+ channels.
- Ca2+ enters Beta cell.
- Ca2+ triggers exocytosis of insulin vesicles.
- Insulin is secreted
Factors controlling insulin secretion
What is the most common of all endocrine disorders?
Diabetes Mellitus
Most prominent feature of Diabetes Mellitus?
Hyperglycemia
What is hyperglycemia
Elevated blood sugar
What is the only hormones capable of lowering blood sugar
Insulin
2 varients of Diabetes Mellitus
Type 1 Diabetes and Type 2 Diabetes
Diabetes word meaning
“siphon” or “running through” – reference to the large urine volume accompanying this condition
Mellitus work meaning
“sweet” – acquires its sweetness from secretion of excess glucose in this condition
x 6 points about Type 1 diabetes
- Symptoms develop rapidly
- Childhood onset
- Affects 10-20% diabetics
- Loss of b cell function
- Insulin secretion none/low
- Insulin injections for treatment
x 6 points about Type 2 diabetes
- Symptoms develop slowly
- Adulthood onset
- Affects 80-90% diabetics
- Insulin insensitivity
- Insulin secretion normal/high
- Treatment - diet/exercise and oral drugs
4 effects of severe diabetes
- Excessive eating
- Dehydration and thirst
- Coma
- Brain cells are glucose obligate cells
Excessive eating in severe diabetes
- Cells starved of carbohydrate
- Hypothalamic center leads to excessive eating
Dehydration and thirst in severe diabetes
- Low glucose uptake, blood glucose rises
- Glucose appears in urine, increases urinary vol
- Dehydration and thirst
Coma in severe diabetes
- Cells unable to use glucose increases
- Lipolysis generates fatty acids and ketoacids
- Ketoacids lower blood pH
- Decreased brain O2 and coma
Brain cells are glucose obligate cells in severe diabetes
- Low glucose, brain stops working
- Coma and respiratory paralysis
Glucose tolerance test chart
Counteracting actions of glucagon and
Insulin on blood glucose during absorption
of a high protein meal. diagram
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