Urinary Session 5 Flashcards
How are sodium concentration changes seen?
Change in ECF volume
What volume do most people urinate on average?
1-1.5l per day
What is the normal range of urine osmolarity?
500-700 mOsm per litre
Does the number of osmoles or the volume they are excreted in vary in urine production?
Volume excreted in
Where are osmoreceptors found?
OVLT of hypothalamus, anterior and central to third ventricle
How do osmoreceptors detect plasma osmolarity?
Have fenestrated leaky endothelium therefore are in direct contact with the systemic circulation
What is the result of osmoreceptors detecting a change in plasma osmolarity?
Use two pathways to cause secondary responses to achieve two complimentary outcomes
Which two signalling pathways do the osmoreceptors use to cause secondary responses in changes of plasma osmolarity?
ADH and thirst
Where is ADH released from?
Posterior pituitary
What is the action of ADH on the collecting duct?
Acts on V2 ADH GPCRs –> cAMP –> PKA –> insertion of AQP2 in apical membrane and increased permeability to urea
What is ADH release coordinated with?
Degree of stimulation
Which areas of the nephron relatively unaffected by ADH release?
Glomerulus, PCT and loop of Henle
Describe the control of ADH release.
-ve feedback loop constantly responding to small stimuli
What stimulates the thirst pathway?
> /= 10% increase in plasma osmolarity
What causes feelings of thirst to stop?
Sufficient fluid ingestion despite no change yet in plasma osmolarity
What is meant by our hedonistic appetite for salt?
When plasma osmolarity is low we crave salt to counteract the deficiency
Describe the distribution of AQP2 in the absence of ADH.
None
How does the permeability of the apical and basolateral membranes of collecting duct cells to water compare?
Apical: variable with AQP2 due to ADH release
Basolateral: always permeable due to permanent AQP3&4 presence
Why are AQP3&4 channels always present in the basolateral membrane of collecting duct cells?
So any water that enters can move into the peritubular blood
What happens to AQP2 in the absence of ADH?
Endocytosed
Is volume or osmolarity more important for ECF?
Volume
What happens to the set-point of osmolarity if volume crashes?
Shifts down so kidney can conserve water and slope of plasma ADH level vs plasma osmolarity gets steeper
Is there always a basal level of ADH release?
Yes
What causes diabetes incipidus?
Lack of ADH from posterior pituitary
Acquired insensitivity of kidney to ADH
What does diabetes incipidus cause?
Inadequate water reabsorption in collecting leading to polyuria
How is diabetes incipidus treated?
ADH nasal spray/injections
What is syndrome of inappropriate ADH secretion (SIADH)?
Excessive ADH release from posterior pituitary or ectopically from tumour –> dilutional hyponatraemia –> low plasma sodium and high total body fluids
What is an ineffective osmole?
Solute that can move freely across a partially permeable membrane therefore cannot exert a osmotic effect as a gradient cannot be established
What is reflection coefficient?
How effectively an osmotic gradient can be maintained
Why is urea an ineffective osmole in most areas of the body?
Passes through lipid bilayers via transporters
What do osmolarity changes in ECF indicate?
Disorders of water balance
What is an effective osmole?
A solute that can be concentrated on one side of a partially permeable membrane so it can exert an osmotic effect due to its gradient
What does the reflection coefficient of an effective osmole tend towards?
1
Where does urea become an effective osmole?
Kidney
What is an essential mechanism caused by the active transport of NaCl in the TAL, recycling of urea and unusual arrangement of blood vessels in the medulla?
Corticopapillary osmotic gradient
Describe the osmotic state of the nephron surroundings at the cortico-medullary border in comparison to the medullary intersticium.
Cortico-medullary border: isotonic
Medullary intersticium: hyper osmotic up to 1000 mOsm per litre at papilla
What happens in countercurrent multiplication in the Loop of Henle?
Sodium pumped out to achieve maximum gradient –> water moves out of descending limb raising osmotic pressure in tubule –> fresh fluid enters glomerulus pushing concentrated fluid into ascending limb –> maximum sodium gradient created increasing external osmolarity further
What limits the final gradient in establishing countercurrent multiplication?
Diffusional processes
How can loop diuretics be used to prevent countercurrent multiplication and cause lots of dilute urine to be formed?
Block NaKCC transporters so medullary intersticium becomes isosmotic
What happens to urea in the PCT?
~45% of filtered urea is reabsorbed into peritubular capillaries
Describe the permeability of cortical CD cells to urea.
Impermeable
What happens to urea when it comes into contact with medullary CD cells?
Cells are permeable so allow movement into the intersticium and subsequent diffusion back into the loop of Henle
How is recycling of urea affected by ADH?
Increases to promote water reabsorption and decreases fractional excretion of urea
Why is urea recycling described as an ‘active process’?
Due to need for ADH secretion, not because of energy requirements
Why are osmoles not washed Out of the intersticium by movement of water out of the descending limb of the loop of Henle?
Opposing blood flow in vasa recta act as a counter-current exchanger
Describe the contents of blood in the vast recta as they move through the descending limb.
Isosmotic blood enters medulla –> sodium and chloride diffuse into lumen –> blood osmolarity increases as it reaches hairpin loop
Describe the contents of blood in the ascending limb of the vasa recta.
Blood starts off with higher solute content than surrounding intersticium –> water moves in from descending limb of the loop of Henle
Can the vasa recta carry out active transport?
No
What do the vasa recta use to carry out movement of substances?
NaCl gradient
Gradient of urea from cortex –> papilla
ADH presence
What can be said about the bloodflow in the vasa recta?
It is low (5-10% of total renal parenchymal flow)
Why is bloodflow in the vasa recta low?
Compromise delivery of nutrients and maintenance of medullary hypertonicity
What forms does plasma calcium take?
48% ionised
46% protein bound
7% complexed
What is 80% of protein-bound calcium bound to?
Albumin
What is plasma calcium complexed with?
Citrates, phosphates etc
Why does an adjusted calcium value need to be used to measure plasma calcium?
To negate effects of abnormal albumin values
What would you do if measured calcium level was within range when adjusted?
Investigate albumin levels
What percentage of dietary calcium is absorbed in the intestine?
20-40%
How does absorption of calcium change?
Increases in growth, pregnancy and lactation
Decreases in advancing age
What is calcium absorption in the gut under control by?
Calcitriol (1,25-(OH)2D)
What can decrease intestinal absorption of calcium?
Completing with phytates, oxalates etc
What action does the kidney have on calcium?
Filters 10 g of mainly ionised calcium per day, of which 98% is reabsorbed
What causes cellular and paracellular absorption of calcium in the ascending loop of Henle?
Calcitonin
PTH
Does paracellular reabsorption of calcium occur in the DCT?
No
What controls calcium reabsorption in the DCT?
PTH
How much calcium is excreted by the kidney?
~200 mg per day
Which three molecules regulate calcium homeostasis?
Vitamin D
PTH
Calcitonin
What is the mammalian form of vitamin D?
D3
Why is ergocalciferol, the fungal form of vitamin D, used for injections in the UK?
It is easier to synthesise than the mammalian form
What is the action of vitamin in calcium homeostasis?
Increases plasma concentration
Which type of vitamin D is usually given in deficiency?
Calciferol
What are the stages in vitamin D metabolism?
Calciferol –> calcidiol –> calcitriol or 24,25-(OH)2D
What determines the end product of vitamin D metabolism?
Circulating levels
What enzyme found in the liver needed for vitamin D activation?
25-hydroxylase
What enzyme is found in the kidney which is needed for vitamin D activation?
1-alpha-hydroxylase
Which form of vitamin D is given in renal failure or hypoparathyroidism?
Active form - calcitriol
What form of vitamin D is measured in laboratory tests?
Calcidiol
How is most of vitamin D need met?
Sunlight
What is the problem with vitamin D availability in Oct-Feb in the UK?
Isn’t enough UVB so have to rely on tissue stores, supplements and diet
What tissues does calcitriol affect?
Bone and intestines
What action does PTH have in calcium homeostasis?
Increase plasma levels
What effect does PTH have on bone?
Stimulates osteoclasts and slowly stimulates osteoblasts
Why does treatment with PTH analogue have. Period of bone formation?
Due to slow stimulation of osteoblasts
What effect does PTH have on the kidney?
Increases calcium and magnesium reabsorption
Decreases Pi and HCO3- reabsorption
Stimulates 1-alpha-hydroxylase
What cation does calcitonin have on calcium homeostasis?
Minor decrease in plasma levels
Does chronic excess of calcitonin lead to hypcalcaemia?
No
Does removal of parafollicular cells lead to hypercalcaemia?
No
What action does calcitonin take to decrease plasma calcium concentration?
Decreases bone resorption
Inhibits renal tubular calcium reabsorption
What is calcitonin used to treat?
Hypercalcaemia in malignancy
What are the actions of calcitriol?
Promotes receptors to increases availability of Ca2+ and Pi via intestinal uptake
Promotes osteoblasts activity and maturation of osteoclast precursors
Uses intestinal absorbed Pi to inhibit renal 1-alpha-hydroxylase
Promotes 24,25-(OH2)D synthesis
Exerts a small effect on renal Ca2+ and Pi reabsorption
Regulates cells differentiation and proliferation
Inhibits cellular growth
Stimulates insulin secretion
Modulation of immune and haemopoietic systems
Inhibit renin production
What are relatively common causes of hypercalcaemia?
Haematological and non-haematological malignancies
Primary hyperparathyroidism
What are the S/S of hypercalcaemia?
Stones, moans and groans:
Anorexia, diarrhoea, hypertension, polyuria, polysdipsia, gradual onset cognitive difficulties, apathy, depression
How do hypercalcaemic pts usually present?
AKI
What is the Tx for acute hypercalcaemia?
Normal saline to increase calcium loss in urine
Loop diuretics but not thiazide
Bisphosphonates to inhibit bone resorption
Calcitonin
Steroids if granulomas present to inhibit 1-alpha-hydroxylase action
Why can’t thiazides be used to treat acute hypercalcaemia?
These retain calcium
How does hypercalcaemia of malignancy compare to primary hyperparathyroidism?
Higher serum calcium levels
Quicker onset
Renal calculi are rare
Plasma intact PTH is suppressed
What can cause hypercalcaemia in malignancy?
Extensive bone metastases
Local osteolysis
A.a. Homology of PTHiP with N-terminal of PTH
Ectopic PTH
Cytokines causing increased osteoclast activity
How can primary, secondary and tertiary hyperparathyroidism be distinguished from each other?
Primary: reduced calcium and raised PTH
Secondary: reduced/normal calcium with raised PTH
Tertiary: with autonomous PTH secretion
What usually causes tertiary hyperparathyroidism?
Complication of secondary hyperparathyroidism
By 70 y.o. what percentage of males and females will have developed a symptomatic kidney stone?
Males: 11.0%
Females: 5.6%
What population are renal stones most likely to form in?
Caucasian males
Which population are renal stones least likely to develop in?
Asian females
What are the S/S of renal stones?
Asymptomatic
Haematuria
Renal colic
Associated complications of obstructed renal tract
Where may renal colic pain be felt?
Loin
Testicle
Labia
What is the general treatment for renal stones?
Maintain hydration
Restrict oxalate and sodium in diet
What types of renal stones can form?
Calcium oxalate Calcium Struvite Urate Cysteine
What are rare forms of renal stones often due to?
Inborn error conditions
What is the general pathogensis of renal stone formation?
Supersaturation of the urine with solutes –> free ion activities of components –> stone formation
How does hyperoxaluria cause renal stone formation?
Decreased calcium intake leads to oxalate being bound to and absorbed with FA
How can hyperoxaluria be managed to prevent renal stone formation?
Encourage high calcium intake so oxalate can complex and be lost in faeces
What can cause hyperuricosuria which can lead to renal stone formation?
Commonly outline rich diet
High cell turnover in leukaemia, lesch-nyhon syndrome
How does acidaemia causing hypocitraturia lead to renal stone formation?
Citrate cannot bind with calcium to keep it soluble
What can cause acidaemia leading to hypocitraturia and eventual renal stone formation?
Hypokalaemia
How does urine pH favour renal stone formation?
Acidic urine favours uric acid and cystine crystal formation
Alkaline urine favours calcium phosphate and struvite stones
Why can hypomagnesemia lead to renal stone formation?
Reduction in magnesium available to bind to oxalate and prevent stone formation
What factors effect solubility of solutes in the urine?
Urine pH
Volume
Total excretion
How are renal stones managed?
Less than 5mm pass spontaneously
6-7 mm ESWL (shock waves) or more invasive is necessary
