Physiology 5 and 6 Flashcards
Describe the osmolarity of the tubular fluid leaving the loop of Henle
Hypo-osmotic to plasma
100mosmol/L
What is the osmolarity of the surrounding interstitial fluid of the renal cortex
300mosmol/L
What causes the osmotic gradient between the interstitial fluid and the tubular fluid
The tubular fluid leaving the loop of Henle is 100 and the cells that make up the wall of the nephron have an osmolarity of 300
Describe the concentration of surrounding fluid as the collecting duct descends through the medulla
It is progressively increasing (300-1200)
Where do all of the tubules empty into
Cortical collecting ducts
What is very important for salt balance in the distal tubule
The residual load
What mainly controls the regulation of fluid and NaCl
Hormones
Name the 4 main hormones involved in the the regulation of water and ion balance
ADH (vasopressin)
Aldosterone
Atrial natriuretic hormone
Parathyroid hormone
How does ADH work
It makes the cells more or less permeable to water to increase water resorption and decrease urine production
What does aldosterone do
It promotes Na reabsroption and promotes K ion secretion
What type of hormone is Atrial natriuretic hormone
Peptide
What is the function of Atrial natriuretic hormone
decreases Na resorption
What is the function of PTH
Increases Ca reabsorption by tubular cells and decreases phosphate ion reabsorption.
When is PTH released
When we become hypocalcaemic
This causes more calcium to be reabsorbed and bring calcium back to normal
Describe the permeability of the distal tubule
It has a low permeability to water and urea
Urea is concentrated and diluted in the tubular fluid
Concentrated
What does the concentrated urea help to establish
The osmotic gradient within the medulla
What are the two segments of the distal tubule
Early and Late
What do the cells of the early distal tubule express
A triple co-transporter (Na-K-2Cl)
Where else is the triple co-transporter found
In the apical membrane of the thick ascending limb of Henle
What do the cells of the late distal tubule do
They will increase potassium secretion and Na reabsorption
PTH stimulates them to also increase Ca reabsorption
Describe the properties of the early collecting duct
Similar to the late distal tubule: increased Ca reabsorption increased K secretion Increased Na reabsorption Increased H+ secretion
Describe the features of the late collecting duct
A low ion permeability
Permeability to water (and urea) influenced by ADH
The cells are more sensitive to ADH here
How is ADH synthesised and secreted
By neurones in the supraoptic and paraventricular nuclei in the hypothalamus (
Synthesised by nerve cells in the cell body and released by here terminal of the nerve cells
Where is ADH stored
In granules in the posterior pituitary
What is the plasma half life of ADH
10-15 mins
How is ADH released into the circulation
Action potentials cause calcium dependent exocytosis of the hormone to be released
What does ADH bind to
type 2 vasopressin receptors found on the basolateral membrane of the tubular cells
What does the binding of ADH to the type 2 vasopressin receptors do?
this initiates cell response where there is an increase in the cyclic AMP
What type of receptors are the type 2 vasopressin receptors
G protein coupled receptors
What does an increase in cyclic AMP result in
an increased expression of the water channels (aquaporins) at the apical membrane
Describe what happens when we are dehydrated
There is an increase in ADH released which binds to the type 2 vasopressin G protein coupled receptor. This causes an increase of intracellular cyclic AMP = increased number of aquaporins = more water reabsorbed
Describe what happens when we are overhydrated
There is an decrease in ADH released which binds to the type 2 vasopressin G protein coupled receptor. This causes a decrease of intracellular cyclic AMP = decreased number of aquaporins = less water reaborped
What happens o the collecting duct in the presence of minimal ADH
It is impermeable to water and so no water is reabsorbed
What are the 2 main factors that allow us to produce varying amounts of concentration of urine
ADH levels
corticomedullary concentration gradient
How does ADH affect the solute excretion
It has no affect at all - it only influences the water reabsorption.
It has an effect on the volume and water concentration of urine
What happens to the urine osmolarity as the plasma ADH increases (dehydration)
It increases
What receptors senses our hydration status and what do they do
hypothalmic osmoreceptors - they signal to the hypothalamic neurones and stimulate the release of ADH / decreased release of ADH
What receptors are activated if there is a substantial decrease in the circulating plasma volume (e.g. Haemorrhage)
The left atrial volume receptors
How does ADH work if there is a severe loss of circulating plasma volume
It promotes vasoconstriction which will increase total peripheral resistance which acts in a negative feedback fashion to increase arterial blood pressure
What are the 2 classifications of diabetes insidious
Central or nephrogenic
What are the main symptoms of diabetes insipidus
Large volumes of dilute urine (up to 20 litres per day)
constant thirst - makes the patient want to drink more and has a knock on effect
What is the treatment for central diabetes insipidus
ADH replacement
What is the treatment for nephrogenic diabetes insipidus
Drug treatment to reduce the urine output
Diabetes insipidus is a common side effect of what drug
lithium
What happens in central diabetes insipidus
Unable to produce or secreteADH from the posterior pituitary
What happens in nephrogenic diabetes insipidus
ADH is produced as normal but it does not exert its effect on the target cells
What is the most important stimulus for ADH release
Hypothalamic osmoreceptors
What substances inhibit ADH release
alcohol and ecstasy
What substance stimulates ADH release
Nicotine
What is aldosterone
Steroid hormone secreted by the adrenal cortex
When is aldosterone secreted
In response to risking K+ concentration or falling Na+ concentration in the plasma
Activation of the renin-angiotensin system
What does aldosterone do
Stimulates Na reabsorption and K+ secretion
An increase in K+ results in what
Direct stimulation of the cells in the adrenal cortex to release aldosterone
An decrease in Na results in what
the indirect release of aldosterone thought the activation of the juxtaglomerular apparatus (renin-angiotensin system, a
What would happen if we did not have aldosterone in our body
We would continue to secrete salt i the urine - this would have a knock on effect on plasma volume and therefore arterial BP
What enzyme concerts angiotensin 1 to angiotensin 2
Angiotensin converting enzyme (expressed on endothelial cells of capillaries primarily in the pulmonary circulation
Give an overview of how the renin-angiotensin system works
A decrease in circulating NaCl causes decreased ECF volume and Arterial BP
These act to increase the secretion of renting from the granular cells
Renin acts as an enzyme to cleave angiotensinogen (protein secreted by cells i the liver) that is then converted to angiotensin 1. Angiotensin converting enzyme then causes angiotensin 1 to angiotensin 2
Angiotensin 2 stimulates cells of the adrenal cortex to release aldosterone which will act on distal cells of the collecting duct to increase Na ion reabsorption to allow passive reabsorption of chloride ions, conserve salt, which also exerts an osmotic effect.
Angiotensin 2 also stimulates the release of ADH and contributes to arterial vasoconstriction
What are the 3 ways in which renin release from granular cells in JGA is controlled
- Reduced pressure in afferent arteriole (more renting, (more Na reabsorbed increased BP, BP restored)
- Macula densa cells sense the amount of NACl in the distal tubule (salt sensitive cells)
- Increased sympathetic activity as a result of reduced arterial blood pressure stimulates more renin secretion
What does aldosterone increase in the distal and collecting tubule
The sodium reabsorption
Most patents with hypertension have some issues with what
The renin-angiotensin system
what is the treatment for hypertension
Low salt diet, diuretics
ACE inhibitors: stop fluid and salt retention and arteriolar constriction
What type of diuretics are best in the treatment of hypertension
Loops - specifically target and inhibit the triple cotransporter in the ascending limb of the loop f Henle
Where is Atrial natruretic peptide (ANP) produced
The heart (stored in atrial muscle cells
When is ANP released
When the atrial muscle cells in the heart are stretched due to an increase in the circulating plasma volume
What does ANP promote and what does this achieve
excretion of Na and diuresis, thus decreasing plasma volume (opposite effect of aldosterone )
causes a decrease in the cardiac output which also decreases arterial blood pressure
What are the two mechanisms in which micturition or urination is governed by
Micturation reflex
Voluntary control
What is the difference between water diuresis and osmotic diuresis
Water –> there is an increased urine flow but not an increased solute excretion
Osmotic diuresis –> increased urine flow as a result of a primary increase in salt excretion
What are the two contirbuting components of the medullary osmolality
NaCl and urea (50% each)
What is the purpose of the countercurrent multiplication
To concentrate the medullar interstitial fluid
Why do we need the countercurrent multiplication
TO enable the kidney to produce urine of different volume and concentration according to the amount of circulating antidiuretic hormone (ADH)
What is the range of Volume of urine that can be produced
1-25ml/min
How does capillary blood equilibrate with interstitial fluid
Across the leaky endothelium
What happens to the blood osmolality as it dups into the medulla
It increases
water loss and solute gain
What happens to the blood osmolality as it rises back up into the cortex
It falls
Water gained and solute loss
What structure acts as the countercurrent exchanger
Vasa Recta
What structures act as a countercurrent system
Loop of Henle and Vasa recta
In what 3 ways is the blood flowing through the medulla that would wash away NaCl and urea prevented
Vasa recta capillaries follow hairpin loops
vasa recta capillaries freely permeable to NaCl and water
Blood flow to vasa recta is low (few juxtamedullary nephrons
What ensure that solute is not washed away
Passive exchange across the endothelium preserves medullary gradient
Where does most of the reabsorption occur
In the proximal tubule of the kidney
What makes up the medullary osmotic gradient
The countercurrent multiplier and the urea cycle
What preserves the medullary osmotic gradient
The countercurrent exchanger
What does a high medullary osmolarity allow
The production of hypertonic urine in the presence of ADH
