Urology and Renal Flashcards
How is osmolarity calculated
concentration X number of dissociated particles (e.g glucose would be x1 but NaCl would be x2)
UNITS: osm/L if the solute is in mol/L, mOsm/L if solute i mmol/L
What is the relationship between osmotic pressure and number of solute particles
directly proportional
Describe body fluid distribution
2/3 Intracellular fluid
1/3 Extracellular fluid - 25% plasma, 75% (Interstitual fluid mostly and small amount of transcellular)
What fluid loss is unregulated
sweat ,faecrs, vomit, water evaporation from respiratory lining and skin
Describe the renal regulation of water loss
High water intake = increase in extracellular fluid, decreases Na+ conc and therefore osmolarity decreases (more water less particle). Produce hypoosmotic urine : pee more water than solute to normalise the osmolarity
Low water intake= decrease in extracellular fluid, so higher Na+ concentration, and increased osmolarity. Produce hyperosmotic urine (pee more solute than urine) to normalise osmolarity
Where in the kidney is water reabsorbed, how is it reabsorbed
Passive- osmosis
most in proximal convuluted tubule
Some in thin descending limb
Thick ascending limb is impermeable to water
some in collecting duct
For water to be absorbed the medullary interstitium needs to be what
Hyperosmotic in Loop of Henle and Collecting Duct
How are concentration gradients formed in the loop of henle for water reabsorption
1- isoosmotic filtrate arrives
2- active salt reabsorption: thick ascending limb, salt actively transported into medullary interstitium so its osmolality rises . This causes
3- passive water reabsorption: water passively moves into the medullary interstitium to reduce osmolality
4- Fluid flow. As urine is continually being produced, new isoosmotic tubular fluid enters the descending limb, which pushes the fluid at higher osmolarity down the tube and an osmotic gradient begins to develop.
How is urea recycled in the kidneys
Urea reaches the collecting duct and throught the UT-A1 on apical side and UT-A3 on basolateral is reabsorbed into the medullary interstitium. The urea here will then either enter the vasa recta through UT-B1 or into the thin descending limbs tubule through UT-A2. At the proximal convuluted tubule most urea and water is reabsorbed so by urea moving back into the TDL tubule the conc and osmolality increases. TAL is impermeable to water and urea so only reabsorbed when reach DCT and CD which it will move through aquaporins and UT-A1 back into the medullary interstitium because at that point osmolality of medullary interstitium is high from Na+ and Cl- but has low urea content so will move down conc gradient out the tubule. It means that less water is used to get rid of urea and urine can become concentrated still
What effect does ADH/Vasopressin have on urea recycling
increases UT-A1 and UT-A3 numbers so in the DCT and CD urea can be passively absorbed just like water
How is ADH stimulated and inhibited what factors
Change in plasma osmolality is detected by osmoreceptors in the hypothalamus (supraoptic and paraventricular nuclei then stimulate posterior pituitary to release). Change in blood pressure is detected by baroreceptors in carotid sinuses and the aortic arch and transmitted to hypothalamus
Inc plasma osmolality or hypovolaemia means we would want to conserve water so it stimulates ADH to open aquaporin-2 channels. Nausea, Angiotensin II and nicotine also stimulate ADH increase (retaining water)
If there’s decreases plasma osmolality or hypervolaemia aquaporins must be shut to get rid of water by inhibiting ADH. Ethanol and Atrial natriuretic peptide both cause ADH inhibiton too
How does ADH affect the kidneys
Principal cells lining the CD and DCT, ADH will bind to the V2 receptor which starts G protein cascade (AC converts ATP to cAMP which then activates protein kinase A), so aquaporin 2 channels are secreted and inserted into the apical membrane, ad AQP3 channels on the basolateral membrane to reach the blood. can also enter blood through AQP4 but DH affects AQp3
Describe how water moves through the kidney tubule
Isoosmotic when reaches TDT, water passively moves out, then at TAT Na+Cl- actively moved out, fluid becomes hypoosmotic
How is Cl- and Na+ reabsorbed in the thick ascending limb
on apical/tubule lining : Na+/K+/2CL- symporter moving these into the cell, K+ is pushed back into the lumen by another channel.
on basolateral side: Na+/K+ ATPase pump moves 3Na+ out and 2K+ in. There is also a K+ and Cl- symporter
How is diuresis achieved
Low ADH so AQP2 is absent so the hypoosmotic fluid (high water, low Na+/Cl-) when reaches DCT and CD no water can be reabsorbed so result is hypoosmotic fluid still flowing through.
At the principal cells of the collecting duct, further Na absorption occurs as it moves into the cell on the apical side. It is then transported through the basolateral side by a Na+/K+ Atpase pump (3 Na+ in blood and 2K out)
Hypoosmotic fluid is thus excreted
How is antidiuresis achieved
High ADH level.
ADH inserts AQP2 in DCT for water reabsorption from the hypoosmotic fluid to make it hyperosmotic and low volume.
ADH also increases Na+ reabsorption in TAL (Na+/K+/2Cl- symporter), DCT (Na+/Cl- symporter), CD (Na channel)
What are the three ADH related disorders, describe them
Central Diabetes Insipidus: decreased/ no release of ADh. get polyuria and polydypsia. Treat with external ADH
SIADH - Syndrome of inappropriate ADH secretion : increased production and release of ADH, lots of water reabsorbed so hyperosmolar urine, hypervolaemia, hyponatraemia. Treat with non-peptide inhibitor of ADH and its receptr (conivapatan and tolvaptan)
Nephrogenic Diabetes Insipidus: less/mutant AQP2 so ADH cannot wok, causes polyuria and polydipsia (lose a lot of water). Treat: Thiazide diuretics and NSAIDs to slow down filtration at Bowmans
How does diet and metabolism affect acid-base balance
Lose base in faeces so becomes more acidic
What is the role of kidneys in acid-base regulation
Secrete and excrete H+
Reabsorb HCO3-
Produce ner HCO3-
Where does reabsorption of HCO3- occur in the kidney
80 in PCT: CO2 moves into the cells lining the PCT by diffusion from blood, carbonic anhydrase within the kidney converts this to H+ and HCO3-. Proton is transported into tubular fludi through NA+/H+ antiporter (NHE3) and H+ATPase pump (V-ATPase). Once in tubular fluid it binds with bicarb there to become water and Co2 again. Bicarbonate in the cells lining the PCT are pumped into the blood through NBC1 Na+/HCO3- symporter
10 in TAL,
minimal in DCT and CD: alpha-intercalated cells pump H+ into tubular fluid through H+ATPase pump (V-ATPase) and the H+/K+ ATPase = HCO3- REABSORP and H+ SECRETION. beta intercalated cells use Cl-/HCO3- antiporters to move HCO3 into the tubular fluid, and then V-ATPase H+/ATPase moves H+ into the blood. HCO3- SECRETION and H+ REABSORPTION
What is the Henderson - Hasselbalch equation and how does it explain the cause of acid-base disorders
pH= pK (dissociation constant) + log (base conc/acid conc)
Aka : acid conc= (24 x PCO2)/(base conc)
shows that acid con/[H+] is directly proportional to the partial pressure of CO2.
IF CO2 is high then is a resp disorder
If base is disturbed then metabolic
How do alkalosis and acidosis affect alpha and beta intercalated cells
Alkalosis = high bicarbonate, so beta intercalated cells work to increase HCO3- secretion into tubular fluid whilst reabsorbing H+
ACidosis= high H+, so alpha interCalated cells work to reabsorb HCO3- and secrete H+
How do the kidneys produce bicarbonate ions
In PCT, glutamine molecules within the tubule linings cells give rise to two ammonium ions and one divalent ion (A2-). This divalent ion gives rise to two bicarbonate ions which are then reabsorbed. If the ammonium ions enter blood circulation they will go to the liver which will turn it into one urea and one proton per each ammonium. Since its two ammonias there will be two protons made, these protons will have to be neutralised by the two bicarbonates so it would be net zero.. THEREFORE the ammonia must be excreted to prevent this. This can be done through the sodium/proton antiporter (NEH3) on the apical membrane where oNa+ will be reabsobed and ammonia secreted into the tubular fluid OR by changing the ammonium ions into ammonia gas which is released into the tubular fluid and gotten rid of. Must get rid of ammonia ions to conserve bicarbonate ions.
We also produce bicarbonate ions int the DCT and CD area, along with the bicarbonate buffer system there are other systems too. The renal system has a phosphate buffer system, the phosphate neutralises the proton when it reached the tubular fluid so we gain a bicarbonate ion.
General rule of metabolic and respiratory causes of alkalosis and acidosis
if metabolic then both pH and HCO3 will rise together or decrease together
If acidic then PCO2 and pH will be opposite
Describe the compensatory response to metabolic acidosis, metabolic alkalosis
Metabolic acidosis : low HCO3- and low pH, will decrease ventilation slightly but mostly inc HCO3 reabsorption and production
Metabolic alkalosis: high HCO3-, high pH= hyperventilation (reduces H+) and HCO3- excretion
Describe the compensatory response to respiratory acidosis and respiratory alkalosis
Respiratory acidosis: high PCO2, low pH= if acute then intracellular buffering where CO2 will enter cells CA will hydrate and make bicarbonate and proton. Proton neutralised by proteins leaving a bicarbonate. If chronic then increase HCO3- reabsorption and production by working on alpha intercalated cells
Respiratory alkalosis: low PCO2, high pH= intracellular buffering left shift as bicarbonate produces carbonic acid, reducing HCO3-. If chronic then decreased HCO3- reabsorption and production by working on beta intercalated cells
Define osmolarity
measure of the solute (particle) concentration in a solution
1 osmole = 1mole of dissolved particles in 1 litre
1 osmole of NaCL= 2 dissolved particles SO 1 osmole of NaCl= 0.5molNaCl as 1 mole of NaCl is 2 osmoles
What is the usual plasma osmolality
285-295mosmol/L
What is the most prevalent solute in ECF
sodium
How does sodium affect blood pressure
High dietary sodium= more water retention and intake = higher ECF volume so higher BP and BP.
reverse is also true
How is sodium intake regulated
If sodium is low lateral parabrachial nucleus increases appetite for Na+, the salty receptors are on the tip of tongue at sides
if euvolemic sodium or low sodium then inhibit Na+ intake/ aversive.
How does blood pressure affect sodium excretion
Renal Plasma Flow and GFR are proportional to blood pressure/mean arteriole pressure. This causes excretion of sodium as the amount of sodium going through increases and the time decreases so More sodium in DCT than normal as wasnt time to take out . Eventually after 100mmHg RPF and GFR plateau to conserve Na+
When there is high sodium in the tubule what happens
Macula densa senses if there is high Na+ in the distal convuluted tubular fluid as it is in close proximity to the end part of the thick ascending limb, it therefore, senses increased sodium/cl/k triple transporter function. Increased tubular sodium is usually because blood pressure is high and it cannot absorb fast enough
Macula densa then releases adenosine which the extraglomerular mesangial cells (between glomerulus and DCT) sense. Extraglomerular mesangial cells then interact with the smooth muscle cells to make the afferent arteriole contract which reduced GFR.
Release of adenosine also leads to a reduction in renin, stopping further water reabsorption and higher blood pressure
How is sodium retained/ sodium absorption increased
Increased sympathetic activity stimulates the juxtglomerular cells of the juxtaglomerular apparatus to release renin. Renin cleaves angiotensinogen made by the liver to angiotensin I. ACE from the lung cleaves Angiotensin I to Angiotensin II. Angiotensin II binds to the zona glomerulosa and stimulates the synthesis of aldosterone. Aldosterone works on the distal convuluted tubule and collecting duct to absorb more Na+. Angiotensin II also directly works on PCT to take up sodium
Increased sympathetic stimulation contracts afferent arterioles smooth muscle cells which increases vascular resestance to reduce RBF/GFR. This means slower filtration of blood and less sodium lost
Increased sympathetic activity directly acts on the proximal collecting duct to take up more sodium.
How is sodium excretion regulated
Atrial naturietic peptide acts as a vasodilator of the afferent arteriole, increasing GFR so lowering sodium reuptake. Has effects on PCT, DCT and CT (entire system). It also suppressed production of renin by stopping juxtaglomerular cells from making
Describe how the body will respond to a reduction in blood pressure and fluid volume
Will increase B1 sympathetic activation : contract afferent arteriole, stim juxtaglomerular cells to make renin which will result in aldosterone increasing Na+ uptake. water will follow.
Describe how the body will respond to an increase in blood pressure and fluid volume
Decrease B1 sympathetic activation. B1 symapthetic system inhibits atrial naturietic peptide. By decreasing B1 sympathetic, ANP is made. ANP stops renin production and vasodilates (stops vasoconstriction of the afferent arteriole)
What type of hormone is aldosterone
Steroid hormone
When is aldosterone released
Angiotenin II levels
Low blood pressure
What does aldosterone do
Increases sodium reabsorption in principal cells
Increases potassium secretion in principal cell H+ secretion in alpha intercalated cells
How does aldosterone work
A steroid hormone so lipid soluble, moves through cell membrane and is bound to HSP90, it then binds to mineralcorticoid receptor and the HSP90 is removed. It will become a dimer and translocate into the nucleus . In the nucleus it binds to DNA and stimulates the production of mRNA for certain genes that code for sodium channels and the Na+/K+ ATPase. It also stimulates production of regulatory proteins to stimulate activity of the transporters it is making. For example, ENaC which stimulates activation of Na+ absorption from collecting duct
How does hypoalsosteronism and hyperaldosteronism affect ECF, renin, ANP and BNP
Hypoaldosteronism: less reabsorption of sodium, ECF volume low, juxtaglomerular cells make renin, AGTII and ADH. Dizziness, Low BP, salt craving, palpitations
Hyperaldosteronism : reabsorb sodium in DCT, water follows: ECF inc= hypertension. Hypertension= less renin from juxtaglomerular cells so less AGTII and ADH. Inc ANP and BNP to vasodilate afferent arteriole.
high BP, muscle weakness, polyuria, thirst
What syndrome has normal/low aldosterone levels but clinically appears to be hyperaldosteronism
Liddle’s Syndrome: High BP due to a mutation in the ENaC sodium channel on the apical principal cells that aldosterone activates. Switches it to be constantly on causing sodium retention and thus hypertension
How does spirinolactone work
Spironolactone is a potassium sparing diuretic like eplerenone that competitively inhibits mineralocorticoid receptors in the distal convoluted tubule to promote sodium and water excretion and potassium retention
How will spirinolactone effect (1)hypertension (2) normal BP (3) Liddles Syndrome
(1) Blocks aldosterone and the MC receptors it binds to, reducing sodium uptake and water reabsorption to reduce blood pressure
(2) Will cause a reduction in blood pressure (hypovolaemia) as more sodium and water is excreting.
(3) No effect as mutation in the sodium channels, so aldosterone increase or blocking aldosterone with spirinolactone wont have an effect. Aldosterone increases channel expression and regulatory proteins to stimulate the channels so if channel faulty there will be no change
Describe how the body detects low and high blood pressure
Heart lower pressure system includes right atrium, right ventricle and the pulmonary vasculature. This system detects both high and low pressure. If there is low pressure then theres reduced baroreceptor firing which sends afferent signals to the brainstem to increase sympathetic activity and ADH release. If there is high pressure then atrial stretch causes ANP and BNP to be released causing water loss
Vascular system is a high pressure system composed of the carotid sinus, aortic arch and juxtaglomerular apparatus (pulmonary vasculature too). If there is low pressure then basoreceptors fire less, acts on juxtaglomerular cells to increase renin release, also sends afferent signals to brainstem to increase sympathetic activity and ADH release
What is ANP
Arial Natriuretic peptide : peptide made in the atria (BNP made here too) in response to atrial stretch.
ANP binds to guanlyl cyclase domain of GTP and converts to cyclic GMP which activates protein kinase G causing:
- vasodilation of blood vessels
- inhibition of sodium reabsorption in proximal tubule and in collecting ducts
- inhibits renin and aldosterone release
-reduces blood pressure
How does the body respond to volume expansion and volume contraction
Volume expansion/increase: less sympathetic activity so less vasoconstriction, less sodium reuptake, less renin production (less ANGTII and aldosterone) increased sodium and water excretion. Heart also detects higher BP, increasing ANP and BNP. ANP and BNP work on brain to decrease AVP
Volume depletion/contraction: more sympathetic activity, stimulates sodium uptake by increasing renin which increases aldosterone. Also works on the heart to decrease ANP and BNP so aldosterone and renin can be released, sodium can be uptaken, bp can increase and vasoconstriction may occur. Also works on the brain to stimulate AVP. net reduction in sodium and water excretion
How does increase sodium levels reaching the collecting duct affect water secretion/ reabsorption
If there are increased sodium levels in the distal convuluted tubule then the osmotic gradient across the membrane is dampened. water moves from hypoosmolar regions into the medullary interstitial which is hyperosmolar SO by making both regions hyperosmolar then water cant move through so more excretion
How does sodium affect ECF volume
More sodium excretion = less ECF/ less BP/ less Na+
Less sodium excretion = more ECF/more BP/more Na+
What diuretic affects the renin angiotenin system
ACEi : leads to less angiotensin II which means vasodilation, higher vascular volume which lowers BP. It acts on the kidneys to decrease Na+ reuptake in the PCT which increases Na+ in the distal nephron so the DCT is hyperosmolar and water cant move across the gradient as both regions hyperosmolar.
Also works on the adrenal glands to decrease aldosterone as less AGTII. This means less Na+ uptake in the DCT so more Na+ in the distal nephron: again water cannot move from hyperosmolar to hyperosmola
