Lecture 15 Flashcards by Teruka Taketa

What are three hormones needed for body fluid homeostasis?

Vasopressin (Anti-diuretic hormone ADH)
Aldosterone
Renin angiotensin

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Which gland releases vasopressin?

neurosecretory gland

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What fires action potentials after being stimulated?

Pituitary stalk

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Which part of the kidney does vasopressin have an effect on?

Level of collecting duct

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What does vasopressin do?

Regulates body fluid osmolality
- How concentrated a solution is
Conserves H2O
- Stimulates the kidney to retain more water
- In cardiovascular system: changes how concentrated the plasma is
- When body fluid osmolality increases, vasopressin increases (needs to be diluted by more water retention)
- When body fluid osmolality decreases, vasopressin decreases (more water secreted in urine)

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What do Hypothalamic osmoreceptors look for?

Osmolality of plasma

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The frequency of action potential is affected by…

Level of osmolality

- Detect changes of +/- 3 mosmol/kg H2O (sensitive)

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What do hypothalamic osmoreceptors stimulate?

Supra-optic and paraventricular nuclei

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What does stimulation of Supra-optic and paraventricular nuclei lead to?

Release vasopressin from posterior pituitary

2. Feeling of thirst

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What is being detected if vasopressin levels are high?

Solute ingestion or H2O deficiency (not drinking enough)

Stress and drugs

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What is an example of a substance that increases vasopressin levels?

Nicotine
 - Vasopressin levels for smokers will be higher than normal people
Ecstasy (3,4-Methylenedioxymethanphetamine)
 - If you drink large volumes of fluid..
 - can't excrete excess fluid
 - build up
 - end up with oedema in brain
 - death

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What is being detected if vasopressin levels are low?

Excessive fluid ingestion

Drugs

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What drugs can decrease vasopressin levels?

Alcohol

people have background release of vasopressin
vasopressin levels drop further
fluid that kidney would have retained would be lost
hangovers due to dehydration

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How is vasopressin incorporated in the Principal cell model?

Vasopressin B2 on basolateral membrane stimulates Protein kinase A (PKA)

adds phosphate groups to proteins in vesicles which fuse to the apical membrane
moving aquaporin 2 channels to apical membrane
more water reabsorbed
So much aquaporin 3 and 4 on basolateral membrane but they are not affected by vasopressin but aquaporin 2 is regulated (Shuttle-link hypothesis)

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What does vasopressin do in the Principal cell?

Increases water reabsorption

leads to fall in body fluid back to normal
fall in body fluid osmolality

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How much urine would humans excrete if there was no vasopressin?

23l

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What is Diabetes insipidus?

A condition in which too much urine is produced

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What are the two types of Diabetes insipidus?

Acquired (due to damage to posterior pituitary etc)

Inherited

What is central diabetes insipidus?

No release of vasopressin
Easy to treat
e.g. Nasal spray DDAVP (synthetic vasopressin)
Few impacts on day-to-day life

What is nephrogenic diabetes insipidus?

Kidney doesn't respond to vasopressin
Defective V2 receptor
Water channel defect
Doesn't activate PKA
No effective treatment

What are the three main components of the adrenal gland from inward to outward?

Adrenal medulla
Adrenal cortex
Capsule

What are the three zones of the adrenal cortex?

Zona reticularis
Zona fasciculata
Zona glomerulosa

WHich zone of the adrenal cortex releases aldosterone?

Zona glomerulosa (released in circulation)

What is a mineralcorticoid?

Hormone that regulates mineral content of body
Minerals: Na,K in plasma
Regulates Body fluid volume
Very sensitive
Controls total Na content but not concentration

What are mineralcorticoids released in response to?

Increase in plasma K - 0.1mM Decrease in plasma Na - minor concentration maintained by osmoregulation Decrease in extracellular fluid volume - via renin angiotensin

What do mineralcorticoids act on?

Late distal tubule, collecting duct

What causes the release of aldosterone?

Increase in reabsorption of Na Increase in reabsorption of water Increase in secretion of K and H

What is found inside the Principal cell?

``` Aldosterone Cytosolic receptor Nucleus RNA transcription Protein synthesis Na reabsorption K secretion H secretion ```

What are main features of aldosterone?

Lipid-soluble: moves across membrane Bids to mineralocorticoid receptor in the cell Goes to nucleus Makes more of transport proteins such as ENaC, ROMK and ATPase

How fast is the genomic effect of aldosterone?

Slow (hours to days for response)

What does aldosterone do in alpha intercalated cells?

Aldosterone inside cells - production of H pump - genomic action Cell give plasma parameters back to normal

What is the net effect in alpha-IC cells by aldosterone?

Increase in plasma Na Decrease in plasma H Decrease in plasma K Increase in extracellular fluid volume

Which system does aldosterone coordinate its response with?

Renin angiotensin system

What are diseases related to aldosterone?

Liddle's syndrome - Disconnect between aldosterone and ENaC -Leads to high Na reabsorption - leads to low aldosterone - leads to lots of reabsorption of water - leads to hypertension - increases number of Na channels in principal cell Pseudohypoaldosteronism - salt loss but high aldosterone - loss of response to aldosterone - mutations in mineralocorticoid receptor - no action - low blood pressure

What does renin angiotensin regulate?

Body fluid volume | Concentration of plasma Na and K

Where is renin released from?

Juxtaglomerular apparatus (JGA) from kidney

What are features of juxtaglomerular apparatus?

Vesicles contain renin (looks like granules) | Cell's (macula densa) flow rate in tubular fluid that acts on tubule

The juxtaglomerular apparatus catalyzes conversion from angiotensiogen to angiotensin I. Where does this take place?

In cell capillaries

Where are most of angiotensin II made and why?

Lungs; has the most capillaries

What does Angiotensin II do?

Minimal role in diuretic effect Active levels on arterioles to promote constriction - increases blood pressure If blood pressure drops... - causes vasoconstriction (one-way) - body can handle water handling side Vasoconstriction helps maintain blood pressure

What net effect does the renin angiotensin cascade have?

Increased plasma Na + extracellular fluid volume | Decreased blood pressure

What do ACE (angiotensin converting enzyme) inhibitors do?

Prevent production of angiotensin II Blood pressure is going to drop to a more normal level Another way to treat hypotension

When integrating volume and osmolality regulation, which takes priority?

Volume; vasopressin system is much faster than aldosterone | Must stop vasopressin system from working