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
Describe the other available diuretics
Carbonic anhydrase inhibitors: Carbonic anhydrase causes Na+ reabsorption and urinary acidity (as causes HCO3- reabsorption). Blocking it stops Na+ reabsorption in PCT so more Na+ in distal nephron so less water moves out. Reduces urine acidity as more bicarbonate and less protons will go into the urine.
Loop Diuretic- furosemide: Blocks the triple transporter in the thick ascending limb of loop of henle. Reduces Na+ intake so more Na+ in the distal portion of the kidney so water cant be reabsorbed
Thiazides: blocks Na+Cl- reuptake transporter in distal collecting tubule, less sodium uptake, increases sodium in distal tubule so less water reabsorption.
Also increases calcium reabsorption. Havent blocked the Na+/K+ATPase on basolateral side which pumps 3 sodium out and 2 potassium in. Theres no sodium in the cells so then theres more potential for the 3Na+/Ca2+ antiporter to have to work to balance the sodium imbalance
Potassium sparing diuretics- spironolactone- aldosterone inhibitor: binds to MC receptor on the DCT and CD to inhibit function. Aldosterone increases Na+ uptake and decreases K+ so by blocking less Na+ uptake and more K+ kept
Enzyme released from the kidney into the plasma to stimulate Na+ reuptake is what
Renin from the juxtaglomerular cells
Describe the overall effect of all the diuretics with their location
Block renin: acts on juxtaglomerular cells to block renin production
ACEi: works on enzyme in lung affects entire nephron, decreases Na+ and water
Carbonic Anhydrase Inhibitors: PCT, less Na+ reabsorbed and less acidic urine
Loop Diuretics: Thick ascending limb, less Na+, Cl- and K+, less water
Thiazides : DCT, less Na+ and water, Higher Ca2+ reabsorption
Potassium Sparing Diuretics/Spironolactone: DCT and CD. More K+, less Na+
Heart arrhythmia are caused by low concentrations of what
K+, since it depolarises membranes causing action potentials: makes it exciteable
Is potassium low of high in ECF
ECF is high in sodium but LOW in potassium
How does the body respond to dietary potassium
Potassium is in all cells. Once eaten then insulin stimulates K+ uptake by stimulating the Na+/H+ exchanger which pushes sodium into cells and H+ out. Sodium is then higher in the cell so K+/Na+ ATPase used to swap and increase intracellular K+
Where in the kidney is potassium taken up
most in PCT (66%)
20% in thick ascending limb thru the Na+/2Cl-/K+ triple transporter
then negligible amounts in DT and CD
Where in the kidney is potassium stimulated to be secreted and what stimulates it
DCT and CD : principle cells, at basolateral side pushes K+ in from the blood and Na+ out through an ATPase. then K+ is pushed out through the cells excitability and concentration gradient into the tubular fluid.
Stimulated by : High plasma K+, high aldosterone, high tubular flow rate and high plasma pH
How does tubular flow stimulate K+ excretion
Distal cells have primary cilium that reach into the tubular fluid. If tubular low rate increases then the primary cilium is moved and stimulated PDK1 which increases Ca+ concentrations in the cell and stimulates K+ channels to open on the apical side so K+ flows into the tubular fluid
What are the causes and symptoms of hypokalaemia and hyperkalaemia
Hypokalaemia : Low dietary intake (processed food), diuretics: increase tubular flow rate so more K+ secreted, vomiting, diarrhoea, genetics
Hyperkalaemia: K+ sparing diuretics, ACE inhibitors, Elderly patients, severe diabetes and kidney disease
What syndrome causes a mutation in the Na+/Cl- channel in the distal nephron and what does it cause
Gitelmans syndrome, leads to hypokalaemia because need Na+/Cl- channel to increase Na+ concentration in the cell and then Na+ moves out and K+ in
Why do most diuretics increase potassium secretion
Increase flow rate which increases potassium excretion
if a patient is dehydrated what part of the nephron have the highest osmolarity
if a patient is dehydrated the tip of the loop of henle will have the highest osmolarity
Increase of what plasma solute will have no effect on ADH production
Urea
How will glucose, alcohol/ethanol and potassium plasma concentrations affect ADH secretion
Ethanol- inhibits ADH production and release and increases flow rate
Glucose: inc ADH to take up more water?
Potassium: inc ADH to take up more water?
One patient is given a thiazide diuretic, and one a loop diuretic, which one will have a higher urine osmolality
One with the loop diuretic will have a lower urine osmolality because loop diuretics take up Cl, K and Na, but thiazide diuretics only take up Na and Ca
urine osmolarity : one with a loop diuretic will have Na, K and Cl still in urine as blocked uptake, thiazide will mean Na and Calcium is in the urine
Why does potassium not have much of an effect on water reuptake
Amount of potassium in the plasma and extracellular is much lower so less likely to have and effect on water balance
What are the four main functions of the kidney
Homeostatic function : electrolyte, acid-base and volume
Excretory function: nitrogenous waste, hormones, peptides, salt and water
Endocrine function: Erythropoeitin is made in kidney stimulates RBC to be made. Has 1-alpha-hydroxylase vitamin D which activates vitamin D
Glucose metabolism: gluconeogenesis and insulin clearance
How does kidney failure affect function
Homeostatic: higher potassium as cant be excreted, lower bicarbonate (not taken up), more acidic blood, higher phosphate in blood, salt and water imbalance
Excretory: wont excrete urea, creatinine so higher in blood, will have a decreased insulin requirement as wont excrete it effectively
Endocrine function: No EPO so lowers calcium and causes anaemia, PTH will increase as trying to stimulate vitamin D to become active but the kidney cant produce the enzyme required
Glucose metabolism: insulin not cleared, and glucose not made
Increased cardiovascular risk
Why do kidney failure patients become tachypneic even with normal oxygen stats ad no lung problems
Kussmaul respiration: have an acidosis as not clearing H+, so clear it by breathing fastedr
How will kidney failure affect : urea, creatinine, sodium, potassium and haemoglobin
Urea, creatinine and potassium will rise
Haemoglobin and sodium will fall
How will kidney failure affect : pH, pCO2, pO2, Bicarbonate and base excess
High pH
low pCO2
high pO2
low bicarbonate
low base excess
What are the symptoms of a tubulointerstitial disorder
Lethargy, weakness, anorexia, volume depleted resulting in hypotension: loss of CRT and skin turgor as dehydrated.
High plasma urea and creatine
High K+, low Na+, acidosis and anaemia
On ultrasound will see two shrunken kidneys
How will the appearance of the kidneys on ultrasound differ between acute kidney failure, chronic kidney failure, Kidney failure due to diabetes or polycystic kidneys
Acute: kidney size wont be affected
Chronic: small kidneys
Due to diabetes/myeloma/amyloid: kidney size preserved
Polycystic kidneys: Large with cyct
How will the appearance of the kidneys on ultrasound differ between acute kidney failure, chronic kidney failure, Kidney failure due to diabetes or polycystic kidneys
Acute: kidney size wont be affected
Chronic: small kidneys
Due to diabetes/myeloma/amyloid: kidney size preserved
Polycystic kidneys: Large with cyct
What are the symptoms of acute or chronic kidney failure
high blood pressure, high urea, VERY HIGH creatinine, sodium, potassium and Hb will be normal
Kidney failure usually reduces salt and water secretion leading to hypertension, oedema and pulmonary oedema
Why is serum sodium not a good indicator of total sodium
May have a sodium concentration of 129 but severe oedema so they have extra ECF which would mean that if measured the actual sodium it would be much higher.
Serum sodium is an indicator of ECF
Why does kidney failure cause acidosis and what does this lead to
reduces excretion of H+ leading to anorexia and muscel catabolism
Potassium compensates for the high H+ concentration by moving H+ into the cell and K+ out. Leads to hyperkalaemia
What are the causes of hyperkalaemia and the symptoms
Lower distal tubule potassium secretion and acidosis
Symptoms: cardiac arrhythmias, neural and muscular activity, vomiting
how does hyperkalaemia change ECGs
peaked T waves, broad p wave, QRS widening, eventually asystole
How does kidney failure affect metabolism in detail
Low EPO so anaemia
GFR drops so leads to phosphate retension.
Low 1 alpha hydroxylase so leads to low levels of 1-25 vitamin D.
Phosphate binds to calcium in the blood so hypocalcaemia.
Lack of Vitamin D also leads to less calcium reabsorption from the gut, bone and urine
Low calcium leads to seconday hyperparathyroisidm because they detect low calcium and increase PTH to try to increase. 1-25 Vit D also acts as a PTH suppressor so both stimulate PTH. Overtime glands get larger and larger
What cardiovascular risks does kidney failure put the patient at risk of
Hypertension, Diabetes, Lipid abnormalities
Inflma, Oxidative stree and brittle bone/other bone problems
How is kidney failure managed
CORRECT VOLUME FIRST
If hypovolaemic: fluids
If hypervolaemic: diuretics/dialysis
TREAT HYPERKALAEMIA
sodium bicarbonate or insulin dextrose : both drive K+ into cells, which also corrects acidosis
diuretics/dialysis: drives K+ out of the body
potassium binders: gut absorption
What is the long term management of kidney failure
Acute then treat that, it may be reversible
If CKD: end stage risk assessment.
eythropoeitin injections, diuretics to correct salt-water, phosphate binders, 1,24 Vit D supplement,
haemodialysis, periotoneal dialysis
transplant is best
How is kidney failure risk calculated
Kidney failure risk equation, only use if STABLE CKD not if eGFR is rapidly declining
What are the negatives of urea, creatinine and creatinine clearance being used to assess GFR
Urea: diet, catabolic state, GI bleeding, drugs all affect
Creatinine: muscel mass, age, race, sex affects, only the trend is useful
Creatinine Clearance: elderly patients struggle to collect sample, at low GFR it overestimates as some creatinine is always secreted
What are the two dialysis methods
Haemodialysis: run the patients blood next to a semipermeable membrane which is next to a dialyzer. Fresh dialysate will run the opposite way to which the patients blood comes in, required dialysis centre visits, 3-4.5 hours 3 times per week, strict dietary constraints, needs access
Periotoneal dialysis: run dialysis in the peritoneal cavity which is next to abdominal cavity. At home, 7 days a week, lesser meal constraints, can travel with the machine, can do any time but chance of infection
What factors influence whether someone can be a kidney donor
Age, mental health, comorbidities, future pregnancy
Has to have two healthy kidneys: normal sized, normal GFR, no blood or protein in the urine.
Kidney match: have to have blood type compatibility, HLA typing and a serum crossmatch
In kidney transplantation what happens to the native kidney
Transplanted kidney is in a different anatomical location to native kidneys as the native kidney remains inside
After kidney transplant surgery what precautions should the patient take
take flu jabs and immunosuppressive medications (not tacrolimus tho) , avoid live vaccines, alcohol, NSAIDs, drugs, alcohol, smoking
low salt and sugar diet, avoid raw eggs/meat and unpasturised cheese, seville oranges, earl grey tea, grapefruit,
Psychiatric disorders, Cancer CVD and diabetes are all risk factors so : seek help, check skin and breasts, use suncream, measure BP, active lifestyle
How does kidney cancer present
Painless haematuria (if pain could be a kidney stone or UTI)
May feel loin pain, a palpable mass, get boney mets, haemoptysis
What investigations should be done if (1) patient presents with painless haematuria (2) persistant non-visible haematuria (3) kidney cancer is suspected
If painless and visible haematuria: Flexible cytoscopy, CT urogram then assess renal function
persistant non visible haematuria: flexible cytoscopy, US of kidney ureter and bladder
Kidney cancer: CT renal, staging chest CT, bone scan if symptomatic for bony mets
same investigations for bladder and kidney cancer
How is kidney cancer staged and graded
t1 smaller or euqal to 7cm, t2 over 7cm, t3 out kindey but not the fascia or adrenal, t4 beyond
n1- met in one lymph node
m1 distant
Fuhrman grade: 1well differentiated ,2, 3+4 poorly
How is kidney cancer managed
Partial nephrectomy - T1 tumours, one kidney
Radial Nephrectomy
Cryosurgery: if small tumours and unfit for surgery
Receptor Tyrosine Kinase Inhibitors: mets
What can cause kidney cancer
smoking, obesity, dialysis, high BP, genetics
How would bladder cancer present
Painless haematuria, may get:
suprapubic pain, UTI symptoms, mets- bone, swelling
How is bladder cancer treated
cytoscopy and transurethral resection of the bladder lesion, cut out the tumour and test: can be curative
How is bladder cancer managed
Non muscle invasive: if low grade cancer cells looking liek theyll grow then cystoscopic survaellence of intravesicula chemo.
If invades the muscles: cystectomy, radiotherapy, chemo, palliative
What are the risk factors for prostate cancer
Age, western-esp scandinavian, african americans
How is prostate cancer investigated
asymptomatic so by chance as a met or in a screening exam
Blood tests: PSA may be raised, but UTI, prostatitis can also cause
MRI: image look at volume and PSA density
Trans perineal prostate biopsy
How is prostate cancer managed
Dependent on grade and comorbidities
if young/fit: low grade would surveillance, high grade do radiotherapy/ radical prostatectomy
Monitor PSA after every 6 months for both, should be undetectable, if over 0.2 then relapse
if old/unfit and high grade then hormone therapy, if low grade just wait
What risks does prostatectomy have?
removes proximal urethral sphincter and changes urethral length so urinary incontinence and bladder function affected
may damage cavernous nerves which cause erectile dysfunction
If painless visible haematuria what investigation
Cytoscopy and imaging
What are the serum tumour markers for testicular cancer
1- Alpha-fetoprotein AFP: half life 4.5 days, high in pations with yolk sac component within a teratomatous germ cell tumour
2- Beta subunit of human chorionic gonadotrophin HCG: placental syncitiotrophoblastic cells secrete, half life of 1-1.5 days, elevated in germ cell tumours with syncitiotrophoblast cells
3- lactate dehydrogenase: general tumour marker
How to manage suspected testicular cancer
Testicular ultrasound
biopsy
serum tumour markers
How is testicular cancer diagnosed
serum tumour markers
CT
Testes ultrasound
one possible treatment for testicular cancer
Radical orchidectomy
What are the symptoms of penile cancer
Difficulty/pain on retracing foreskin
spraying of stream
If a patient had a prostatectomy and is experiencing bladder incontinence what is the treatment
building the pelvic floor muscles or artificial urinary sphincter device
If a patient had a prostatectomy and is experiencing erectile dysfunction
PDE5 inhibitors, prostaglanding E1 injections and penile prosthesis devices
What are the markers of a UTI on a blood test
nitrate and leukocyte positive
Where do the left and right ureters drain in a female
left into para aortic nodes, right into right paracaval and interaortocaval lymph nodes
What is the blood supply of the bladder
superior and inferior branches of internal iliac artery
What is the difference between female and male venous drainage of the bladder
Female: vesical plexus into internal iliac vein
Male: prstatic venous plexus into internal iliac
Describe the process of micturition
start: when bladder is empties the stretch fibres are inactivated, T11-L2 sympathetic nervous system is stimulated and activates Beta3 receptors through release of NA to relax detrusor muscle
filling phase: bladder fills and distends, no intravesical pressure. urethral sphincter contracts to close urethra.
voiding: Bladder filling activates M3 receptors of parasympathetic S2-S3, will release ACh to bind and activate M3 receptors to inhibit internal urethral sphincter to relax it and open. Also causes detrusor to contract : bladder contracts and expels urine, internal urethral sphincter relaxes
What types of urinary incontinence are there
Stress urinary incontinence: leakage in effort or exertion (sneeze or cough). Due to impaired bladder and urethral support, impaired urethral closure
Overactive bladder- Urge urinary incontinence: urinary urgency, frequency and nocturia, with or without incontinence. Due to involuntary detrusor muscel contractions,
Overflow incontinence: so full leaks, chronic retention due to obstruction or atonic bladder like underactive detrusor, bladder denervation, bladder neck stricture, faecal obstruction
Continuous incontinence: leak all the time, vesicovaginal fistula, ectopic ureter
Funtional incontinence: cognitive impairment or mobility limitation preventing use of toilet, bladder is normal just cant get to bathroom
What are risk factors of stress urinary incontinence
ageing, obesity, smoking, pregnancy, delivery route
How is stress urinary incontinence investigated
History and stress test
urodynamics- urinary leakage during inc in intrabdominal pressure
How is stress urinary incontinence managed
Physio
or surgical mid urethral sling, periurethral bulking if due to sphincter
What are risk factors of urge urinary incontinence
Age, prolapse, high BMI, IBS, bladder irritants like caffiene or nicotine
What are the symptoms of urge urinary incontinence
urgency, frequency, nocturia, imapcts quality of sleep so anxiety and depression possible
men would have large prostate (bladder outflow obstruction)
women would have prolapse
What are the investigations fo an overactive bladder
Dipstick (as may be infection)
Voiding diary
Asses post void residual via US scan
urodynamics
cystoscopy
How is an overactive bladder managed
Lifestyle: less coffee or nicotine
retrain bladder with physio
Antimuscarinic drugs (M3 blocked so detrusor doesnt contract)
Beta 3 agonist (keeps detrusor relaxed
BOTOX in detrusor stops ACh release to make detrusor contract
cystoplasty (make bladder bigger with bowel), urinary diversion
What is benign prostatic hyperplasia
non malignant growth of prostate, UTI symptoms as will compress ureter and stop bladder outflow, usually older people
Testosterone affecting prostate tissue is a risk factor
What are the symptoms of benign prostatic hyperplasia
hesistancy of urination
poor stream
dribbling after micturition
nocturia, high frequency
acute retention
What causes should be excluded if present with urination hesitancy, poor stream, nocturia etc
Bladder or prostate cancer
Cauda equine
High pressure chronic retention
then : infections, prostatitis, neurogenic bladder, urinary stones
How is benign prostatic hyperplasia investigated
urine dip, voidal diary, post void residual
PSA antigen from bloods to predict prostate volume
US of renal tracts
urodynamics
cytoscopy if think cancer
How is benign prostatic hyperplasia managed and thr complications
weight loss, less caffiene and nicotine in evening
alpha blocker alpha 1-AR is on prostate smooth muscle and bladder neck. Block to relax so can pee
5- alpha reductase inhibitor stops testosterone being converted to DHT which enlarges prostate, shrinks prostate to improve urinary flow
transurethral resection of prostate (take some out)
complications: progressive bladder distention, chronic painless retention and overflow incontinence. can lead to bilateral upper tract obstruction and renal impairment - renal disease
