Urinary Flashcards
What are the 3 important characteristics of substances that can be used to measure GFR?
Must be freely filtered across the glomerulus
Must not be secreted, reabsorbed, or metabolised by the cells of the nephron
Must pass directly into the urine
What percentage of th embodies total blood flow goes to the kidney?
20-25%
~1200ml/min
At what spinal level are the kidneys?
T11/T12
What is the trigone?
The shape adapted by the empty bladder due to the 2 uretas and 1 urethra
What are the 4 major functions of the kidney (in order of importance)
- To maintain a stable internal environment to enable function in all parts of the body (controls conc of ions and small organic molecules)
- Excretion of waste products
- Endocrine (synthesis of renin, erythropoietin, prostaglandins)
- Metabolism (active form of Vit D, catabolism of insulin, PTH calcitonin)
Define osmolarity
Number of osmosis of solute per litre mmol/l
Define osmolality
Solute per kilogram of solvent milli-osmole
Do machines measure osmolarity or osmolality?
Osmolality (milli-osmole)
Relative to to ICF, what is the concentrations of Na+ and K+ in the ECF?
High Na+, low K+
What must kidneys do? (4 things)
Control volume
Control osmolarity
Help control pH
Excrete waste products
What is the functional unit of the kidney?
The nephron (1.5 million of them in each kidney!)
What percentages of components have been reabsorbed from the tubule by the end of the PCT?
~60-70% of Na+ and H2O
~80-90% of K+
~90% of bicarbonate
~100% of glucose and amino acids
How do reabsorbed materials leave the PCT?
Via the peritubular capillaries
What is the major function of the loop of henle?
Creating a gradient of increasing osmolarity in the medulla by counter current multiplication, allowing formation of concentrated urine (more conc. than plasma)
What is the distal convoluted tubule the major site for?
Site of variable reabsorption of electrolytes and H2O.
The fluid leaving the loop of henle is hypotonic, the DCT removes yet more Na+ and Cl-, and actively secretes H+. H2O may or may not follow electrolytes (if not large volume of urine)
How does the distal convoluted tubule function as the major site of variable reabsorption?
The fluid leaving the loop of henle is hypotonic, the DCT removes yet more Na+ and Cl-, and actively secretes H+. H2O may or may not follow electrolytes (if not large volume of urine)
What controls the Na+ recovery system/DCT/ECF volume
Renin angiotensin hormone system
What controls the recovery of water in the kidney/distal nephron?
ADH hormone system. Controls the permeability of DCT and collecting duct to H2O, controlling ECF osmolarity
What is in the cortex of the kidney?
Renal corpuscles
What is in the medulla of the kidney?
Tubules
What is in the terminal end of the renal artery/vein of the kidney?
Glomeruli, vasa recta
What is the renal corpuscle?
Glomerulus + bowmans capsule
What does the renal corpuscle do?
Produces the ultrafiltrate
Where are podocytes found, and what do they do?
Line the glomerulus, surrounding capillaries like a mesh, allowing filtration sites (spaces between podocyte processes)
What type of cells are in the proximal convoluted tubule?
Simple cuboidal epithelium with pronounced brush border
What are the 4 parts of the loop of henle?
- Pars recta
- Thin descending limb
- Thin ascending limb
- Thick ascending limb
What type of cells are in the thin descending limb of the loop of henle?
Simple squamous
No active transport occurring (looks like a capillary with no RBC)
What type of cells are in the thin ascending limb of the loop of henle?
Simple squamous
No active transport occurring (looks like a capillary with no RBC)
What type of cells are in the thick ascending limb of the loop of henle?
Simple cuboidal
Active transport occurs
What type of cells are in the distal convoluted tubule?
Simple cuboidal
Like PCT, but larger lumen and no brush border
What is the juxtaglomerular apparatus comprised of?
Macula densa of DCT
Juxtaglomerular cells (of afferent arteriole of glomerulus)
Extraglomerular mesangial cells (AKA lacis cells)
How does the collecting duct look hisiologically?
Continuation of DCT (simple cuboidal epithelium), similar to thick loop of henle, but lumen is larger and more irregular (rather than circular)
What is the renal pyramid?
A series of progressively larger ducts formed by merging collecting ducts. Empties at renal papilla.
What does the ureta look like histiologically?
Muscular tube with 2 layers of smooth muscle (and a 3rd layer in the lower third).
Lined by transitional epithelium
What other names might transitional epithelium go by?
Urinary epithelium
Urothelium
What does the bladder look like histiologically?
3 layers of muscle, outer adventitia, transitional epithelium.
What are the 4 types of epithelium in the male urethra?
Pre-prostatic
Prostatic
Membranous
Spongy
What is the passage of a RBC through the kidney?
Renal artery, One of the 5 segmental arteries, Interlobal arteries, Arcuate arteries, Cortical radiate artery , Afferent arteriole, Glomerulus, Efferent arteriole, Peritubular capillaries, Cortical radiate vein, Arcuate vein, Interlobal vein, Renal vein
Is the diameter of the afferent or efferent arteriole wider?
Afferent (creates hydronic pressure)
What are the 2 types of kidney nephrons?
Cortical
Juxtamedullary
Describe a cortical nephron
Superficial glomeruli, short loop of henle, next to outer cortex, high concentration of renin. Constitutes 80% of nephrons
Describe a juxtamedullary kidney nephron
Glomeruli very close to medullary border. Long loop of henle. Produces concentrated urine. Minimal renin conc. constitutes 20% of nephrons
What rate is the average glomerular filtration rate?
90-120mL/min/1.71m2
How much plasma delivered to the glomerulus is filtered out?
~20%
~1% leaves the body
What are the 3 main components to the filtration barrier?
Capillary endothelium (permeable) Basement membrane (acellular gelatinous layer of collagen/glycoproteins. Permeable to small proteins. Glycoproteins are negatively charged and repel Protein movement) Podocyte layer (pseudopodia interdigitate, forms filtration slits)
Which molecules filter better through the glomerulus, positive or negatively charged ones?
Positive
What is the largest molecule that can diffuse through the glomerulus?
Insulin (5200molecular weight)
What are the 3 forces involved in the filtering if plasma?
- Hydrostatic pressure in capillary
- Hydrostatic pressure in bowmans capsule
- Oncotic pressure difference between capillary and tubular lumen
What is the main mechanism of autoregulation of the kidney?
Via changing diameter of afferent/efferent arterioles to control pressures and filtration rate in the glomerulus
What happens to the afferent arteriole when blood pressure increases?
Constriction (GFR is kept constant)
What happens to the afferent arteriole when when blood pressure decreases?
Dilation (GFR is kept constant)
What are the limits of BP where the kidney can compensate for to keep GFR constant?
80-180 mmHg
What is tubular glomerular feedback?
Changes in tubular flow rate as a result of changes in GFR changes the amount of NaCl that reaches the distal tubule.
What would the tubular glomerular feedback response to increased blood pressure be?
Increased Na+ and Cl- retention
What do MD cells in DCT respond to? What does this contribute to?
Changes in NaCl arriving in the DCT.
Contributes to regulation of arterial tone and therefore filtration rate
What can the juxtaglomerular apparatus release to reduce GFR?
Adenosine (vasodilator of efferent arteriole)
What can the juxtaglomerular apparatus release to increase GFR?
Prostaglandins (vasodilator of afferent arteriole)
What happens if NaCl increases?
GFR needs to decrease
Adenosine released (vasodilator of efferent arteriole)
This reduces pressure gradient across glomerulus and therefore slows GFR
What happens if NaCl decreases?
GFR needs to increase Prostaglandins released (vasodilator of afferent arteriole)
What is the relationship between GFR and distal salt concentration limited to?
Acute changes
Long standing primary disturbances in body fluid volume not regulated like this
Where does the majority of reabsorption take place?
PCT
On which membrane is the 3Na2KATPase located?
Basolateral
How does Na+ move across the apical membrane in the PCT?
Down a concentration gradient
How does water move into the PCT?
Down the osmotic gradient
What Na+ transporters are present in the PCT?
NaH antiporter
Na-glucose symporter
What Na+ transporters are present in the Loop of Henle?
Na-K-2Cl symporter
What Na+ transporters are present in the early DT?
NaCl symporter
What Na+ transporters are present in the late DT/CD
ENaC (epithelial Na+ channels)
What does SGlut transport?
2Na+ and 1 glucose
Against the glucose gradient,
On which membrane is SGlut found?
Basolateral membrane
What has normally been reabsorbed by the end of the PCT?
100% filtered nutrients 80-90% filtered HCO3- 67% filtered Na+ 65% filtered H2O 65% filtered Cl- 65% filtered K+
Where does the majority of drug metabolism take place?
Liver
Where does the majority of drug excretion occur?
Kidney
What does xenobiotic mean?
Foreign
What is clearance of a drug?
It’s rate of elimination by liver and kidney
What does half life describe?
The rate a drug is removed from the body
What is clearance rate proportional to?
The drugs free concentration in plasma
How does lipophilicity effect drug clearance?
The more lipophilic a drug is, the more easily it can diffuse back out of the lumen into the plasma
How does hydrophilicity effect drug clearance?
(Residual electrical charge)
The more charged a drug molecule is, the less easily it moves back out of the lumen.
How does the degree of binding to plasma protein effect drug clearance?
If lots, reduces the amount available for glomerular extraction
How does the degree of binding to tissue protein effect the clearance of a drug?
Effectively removes drug from the plasma, thus decreasing amount available for renal clearance
What is Vd?
The apparent volume of distribution
How is Vd calculated?
By measuring real plasma concentration of a drug (it’s impractical to measure drug concentration in all compartments of the body, so it’s generalised into a single number)
What’s it mean about a drug if Vd is high?
Lipohilic, leaves plasma
Reduces amount of drug available in plasma for excretion by kidney
What’s it mean about a drug if Vd is low?
Highly charged, confined to plasma
Increases amount of drug available in plasma for excretion by kidney.
What are xenbiotics?
Things the body sees as ‘foreign’ e.g. Drugs
What do the phase 1 and phase 2 enzyme systems work to achieve on xenobiotics?
Increase their ionic charge, therefore reducing lipophilicity, thus making it more difficult for the metabolised drug molecule to diffuse back out of tubular lumen and back into plasma
Why is reducing lipophilicity of xerobiotics beneficial?
Makes it more difficult for the metabolised drug molecule to diffuse back out of tubular lumen and back into plasma, thus increasing its secretion
What effect does acidic urine have on weak acidic anions?
Weak acidic anions more likely to be protonated - making them electrically neutral and therefore more lipophilic
What effect does alkaline urine have on weak acidic anions?
Weak acidic anions not protonated - more excreted.
What effect does alkaline urine have on weak bases?
Weak bases more likely to lose a proton, making them electrically neutral and more lipophilic (thus easier to cross nephron)
What effect does acidic urine have on weak bases?
Weak bases not deprotonated - more excreted
What effect will heart disease (or reduced renal vascular supply) have on the GFR?
Reduce GFR, and thus will reduce clearance
What effect does hepatic disease have on renal clearance?
Reduced drug metabolism, so reduced renal clearance
Reduced production of plasma proteins, so increases clearance of drugs bound to this (providing renal function is normal)
Define renal clearance
Volume of plasma required to ‘totally’ remove a given solute per unit time
What do you need to know before you are able to calculate renal clearance?
Conc. of physiological marker in plasma and urine
Give examples of good physiological markers
Inulin
Creatinine
What must physiological markers be in order to be of use?
Must not be synthesised, degraded or stored in the kidney
What are the 2 compartments in the body in which water is found? What separates them?
Intracellular fluid ICF
Extracellular fluid ECF
Separated by a cell membrane
Approximately how much water is in a 70kg male?
42 litres
Approximately how much water is ICF and ECF in a 70kg male?
28l ICF
14l ECF
What is the major osmotically active effective solute in the ECF?
Na+
What does concentration of Na+ in blood effect?
Effective circulatory volume
And therefore blood pressure
Other than via the kidneys, how else is Na+ lost from the body?
Sweat, Faeces
Although generally only small amounts
What do changes in osmotic pressure and hydrostatic pressure in peritubular capillaries alter?
Proximal tubule Na+ reabsorption (and hence water reabsorption)
What stimulates proximal tubule Na+ reabsorption?
RAAS
What are the targets within the kidney nephron for the hormone aldosterone?
Principle cells of DCT and CD
How does the kidney nephron counteract an increase in renal artery BP?
Reduced number of Na-H antiporter
Reduced Na-K ATPase activity in proximal tubule
Reduced Na+ reabsorption in proximal tubule
Reduced water reabsorption in proximal tubule
This causes increased Na+ excretion and therefore increased H2O excretion - pressure diuresis
Decreases ECF volume
What effect does increased blood pressure have on the kidney nephron?
Increases peritubular capillary pressure
Increased renal interstitial pressure
Decreased fluid absorption
Independent of vasomotor activity
What effect does high ECF volume have on the renal nephron?
Increased renal artery pressure, large pressure natriuresis and diuresis
What effect does low ECF volume have on the kidney nephron?
Decrease in renal artery pressure, small pressure naturesis and diuresis
What drives Na+ reabsorption in the kidney nephron?
3Na+ - 2K+ - ATPase on basolateral membrane
What is reabsorbed along with Na+?
Cl-
Is Cl- absorption active or passive?
Both
What is Cl- reabsorption dependent on?
Na+ reabsorption - maintains electro-neutrality
What apical Na+ transporter is in the PCT of the kidney nephron?
Na-H antiporter
Na-Glucose symporter
Na-AA cotransporter
Na-Pi
What apical Na+ transporter is in the loop of Henle of the kidney nephron?
NaKCC symporter
What apical Na+ transporter is in the early DT of the kidney nephron?
NaCl symporter
What apical Na+ transporter is in the late DT and CD of the kidney nephron?
ENaC
Epithelial Na+ channel
What are the different possible types of apical Na+ transporter?
Na H exchange Co-transport with glucose Co-transport with AA or carboxylic acids CO-transport with phosphate Aquaporin
What is the driving forever for reabsorption in the PCT?
Hydrostatic forces in interstitium
Oncotic forces in peritubular capillary (increased due to loss of 20% filtrate at glomerulus, but cells and Protein left in blood)
What are the mechanisms for glomerulotubular autoregulation?
Myogenic action - vasculature reacts to changes in BP
Tubulo-glomerular feedback - 2nd line of defence, alters Na+ excretion
What is the equation used to calculate filtered load?
Filtered load = GFR x Concentration
What occurs primarily in the descending limb of the loop of henle?
Water reabsorption
This concentrates Na+ and Cl- ready for active transport in the ascending limb
What primarily occurs in the thin ascending limb of the loop of henle?
Na+ reabsorption, passively
What primarily occurs in the thick ascending limb of the loop of henle?
Na+ reuptake, and therefore Cl- reuptake also
Na+ reuptake via NKCC2 transporter, powered by 3Na+/2K+ ATPase
K+ ions diffuse via ROMK back into lumen to maintain activity of NKCC3 and Cl- ions move into interstitium
Which part of the nephron is most sensitive to hypoxia?
Thick ascending limb as it is very energy dependent
What can the ascending limb also be known as?
They diluting segment
Absorbs NaCl but not H2O
Is tubule fluid leaving the loop of Henle hyper, hypo, or iso -osmotic?
Hypo
What Na+ transporter is present in the early DT and what type of diuretics is it sensitive to?
NCC transporter
Sensitive to thiazide diuretics
What form of diuretics are ENaC transporters sensitive to? Where in the nephron are they found?
Amiloride diuretics
Late DT and CD
Where is the major site for Ca2+ reabsorption in the kidney nephron?
DCT
What controls Ca2+ reabsorption in the kidney nephron?
Hormones - PTH, 1,25-dihydroxyvitamin D
What happens to cytosolic Ca2+ in DCT cells?
Immediately bound by calbindin to basolateral aspect of DCT cells
Then transported out by NCX (sodium calcium exchanger)
What is the collecting duct divided into?
Cortical and medullary regions
What are the 2 distinct cell types found in the cortical collecting duct?
Principle cells
Type B intercalated cells
What do principle cells in the CCD do?
Reabsorption of Na+ via ENaC
Comprise 20% of cells
What do type B intercalated cells in the CCD do?
Active reabsorption of Cl-. Secretion of H+ (AIC) or HCO3- (BIC) more in acids and bases
What are the 2 types of intercalated cells?
Acid secreting - AIC
Bicarbonate secreting - BIC
Where are intercalated cells found?
In cortical and outer medullary collecting duct
What does a principle cell do?
Absorption of Na+ via ENaC on apical membrane (powered by 3Na/2K ATPase
How is Cl- absorbed in the CD?
Principle cells reuptake of Na+ produces luminal (-Ve) charge, which is the driving force for Cl- reuptake via paracellular route
How is blood pressure regulated short term?
Adjustment of sympathetic and parasympathetic input to the heart to alter CO.
Adjustment of sympathetic input to peripheral resistance vessels to alter TPR.
What is the baroreceptor reflex?
Nerve endings in the carotid sinus and aortic arch are sensitive to stretch.
Increased BP causes stretch - activates afferent pathways - medulla - efferent pathways - activators to decrease BP activated
What is control of BP long term directed at?
Control of blood Na+ and thus extracellular fluid volume/plasma volume
What are the 3 parallel neurohumoral pathways used for long term regulation of BP?
Renin-angiotensin-aldosterone system (RAAS)
Sympathetic nervous system
Antidiuretic hormone (ADH)
Atrial natriuretic peptide (ANP)
Where is renin released from?
Granular cells of juxtaglomerular apparatus (JGA)
What stimulates renin release?
Reduced NaCl delivery to distal tubule
Reduced perfusion pressure in the kidney (detected by baroreceptors in afferent arteriole)
Sympathetic stimulation to JGA
How is angiotensin converted to angiotensin 2?
Angiotensin - angiotensin 1 (catalysed by renin)
Angiotensin 1 - angiotensin 2 (catalysed by angiotensin converting enzyme ACE)
What does Angiotensin 2 stimulate?
Vasoconstriction Na+ reabsorption at kidney Stimulates aldosterone (from adrenal cortex)
How many types of angiotensin 2 receptors are there? What are they called?
2
AT 1 and AT2
(Most actions are via AT1)
What type of receptor is AT1?
G-protein coupled receptor
What is angiotensin 2s action at arterioles?
Vasoconstriction
What is angiotensin 2s action at the kidney?
Stimulates Na+ reabsorption
What is angiotensin 2s action at the sympathetic NS?
Increased release of NA
What is angiotensin 2s action at the adrenal cortex?
Stimulates release of aldosterone
What is angiotensin 2s action at the hypothalamus?
Increases thirst sensation (stimulates ADH release)
What are the direct actions of angiotensin 2 on the kidney?
Vasoconstriction of afferent and efferent arteriole
Enhanced Na+ reabsorption at the PCT (stimulates Na-H exchanger NHE3 in apical membrane)
Describe the action of aldosterone on the kidney
Acts on principle cells of collecting duct
Stimulates Na+ (and therefore water) reabsorption
Activates apical Na+ channel (ENaC) and apical K+ channel
Also increases basolateral Na+ extrusion via Na/K/ATPase
How does ACE further augmentate the vasoconstrictor effects of angiotensin 2?
ACE is also one of the kinase enzymes that breaks down the vasodilator bradykinin
What effect does high levels of sympathetic stimulation have on the kidney?
Reduces renal blood flow (Vasoconstriction of arterioles, decreased GFR, decreased Na+ excretion)
Activates apical Na/H exchanger and basolateral Na/K ATPase in PCT.
Stimulates renin release from JGcells, leading to increased angiotensin 2 levels and increased aldosterone levels (increased Na+ reabsorption)
What direct effects does sympathetic stimulation of kidney have?
Acts on arterioles to reduce renal blood flow
Stimulates granule cells of afferent arteriole to release renin (via RAAS axis)
Stimulates Na+ reabsorption from PCT
What is ADHs main role?
Formation of concentrated urine by returning water to control plasma osmolarity.
Increases H2O reabsorption in distal nephron
What stimulates ADH release?
Plasma osmolarity
Severe hypovolaemia
What is ADH also known as?
Arginine Vasopressin.
What do atrial natriuretic peptides ANP do?
Promote Na+ excretion
Where are atrial natriuretic synthesised/stored?
In atrial myocytes.
Released from atrial cells in response to stretch (low pressure/volume sensors in atria)
What effect does reduced effective circulation volume have on the release of ANP?
Inhibits release of ANP to support BP (reduced filling of heart, less stretch, less ANP released)
What are the actions of atrial natriuretic peptide ANP?
Causes vasodilation of the afferent arteriole
Increased blood flow increases GFR
Also inhibits Na+ reabsorption along the nephron
Acts in opposite direction to other neurohumoral regulators (causes natriuresis, loss of Na+ in urine)
If circulating volume is low, ANP release is inhibited, supports BP
What do prostaglandins act as?
Vasodilators
What effect can locally acting prostaglandins (mainly PGE2) have upon the kidney glomerulus?
Enhance glomerular filtration and reduce Na+ reabsorption
When is the vasodilator effects of prostaglandins important in the kidney?
When levels of angiotensin 2 are high; acts as a buffer to excessive vasoconstriction produced by SNS and RAAS. Helps to maintain renal blood flow and GFR in the presence of vasoconstrictors
What do NSAIDs do?
Inhibit cyclo-oxygenase (COX) pathway involved in the formation of prostaglandins.
When must you be careful of prescribing NSAIDs?
Administration of NSAIDs when renal perfusion is compromised can further decrease GFR - acute kidney failure
Where is dopamine used in the kidney formed?
Locally in the kidney from circulating L-DOPA.
Where in the kidney are dopamine receptors found?
Present on renal blood vessels and cells of PCT and TAL
What does dopamine cause in the kidney?
Vasodilation and increases renal blood flow
Reduces reabsorption of NaCl; inhibits NH exchanger and Na/K ATPase in principle cells of PCT and TAL
What is essential, or primary hypertension?
The cause is unknown (95% of cases)
What is secondary hypertension?
The cause can be defined e.g. Renovascular disease, aldosteronism, cushings, chronic renal disease
It’s important to treat the primary cause!
How may renovascular disease cause secondary hypertension?
Occlusion of renal artery (renal artery stenosis) causing a fall in perfusion pressure of that kidney. Decreased perfusion pressure leads to increased renin production, activation of RAAS. Vasoconstriction and Na+ retention at other kidney.
How may renal parenchymal disease cause secondary hypertension?
Earlier stage may be a loss of vasodilator substances. In later stages Na+ and H2O retention due to inadequate glomerular filtration (volume-dependent hypertension)
How might Conns syndrome cause secondary hypertension?
Conns syndrome - aldosterone secreting adenoma (hypertension and hypokalaemia)
How might Cushing’s syndrome cause secondary hypertension?
Excess secretion of glucocorticoid cortisol. At high concentrations, acts on aldosterone receptors, Na+ and H2O retention
How might a tumour of the adrenal medulla cause secondary hypertension?
Phaeochromocytoma - secretes catecholamines (noradrenaline and adrenaline)
What hypertension drugs target the RAAS?
ACE inhibitors. Prevent the formation of active angiotensin 2
What hypertension drugs target vasodilators?
L-type Ca2+ blockers
How do L-type Ca2+ channel blockers work to reduce hypertension?
Reduce Ca2+ entry to vascular smooth muscle cells - relaxation.
What diuretics are generally used for hypertension?
Thiazide diuretics
Inhibit Na/Cl CO-transporter on apical membrane of cells in distal tubule
Are beta blockers used to treat hypertension?
No
Will reduce effects of sympathetic output (decreasing HR and contractility). Would only be used if other indications such as previous MI
What proportion of total body fluids is ECF and ICF ?
1/3 ECF
2/3 ICF
Where is the majority of the K+ in the body?
ICF (98% - mainly in skeletal muscle cells, liver, RBC, bone)
What maintains the difference between ICF and ECF K+ levels?
Na+/K+ ATP ase
Why is maintaining ECF K+ conc so low so important?
Due to K+S effect on the resting membrane potential
And therefore it’s effects on excitability of cardiac tissue - life threatening arrhythmias with hyperkalaemia/hypokalaemia
What effect does low K+ level have on excitability?
Further to reach threshold potential - decreased excitability
What effect does high K+ level have on excitability?
Decreased distance to threshold potential - increased excitability
How is K+ immediately regulated?
By internal balance - moving K+ between ECF and ICF
How is K+ regulated longer term?
External balance - adjusting renal K+ excretion
Describe the events that follow K+ consumption
Intestine and colon absorb dietary K+
Blood K+ increases, potentially to dangerous levels
BUT 4/5 K+ moves into cells within minutes
After slight delay, kidneys begin to excrete K
Excretion complete in 6-12hrs
What mediates movement of K+ from ECF to cells?
Na+/K+ ATPase
What mediates the movement of K+ from cells to ECF?
K+ channels
List 3 factors that increase K+ uptake by cells
Hormones (act via Na+/K+ATPase) e.g. Insulin, aldosterone, catecholamines
Increased K+ conc. in ECF
Alkalosis (low ECF H+ conc)
List 5 factors that promote K+ shift out of cells
Exercise Cell lysis Increased in ECF osmolality Low ECF K+ conc Acidosis (increased ECF H+ conc)
What does K+ in splanchnic blood stimulate?
Insulin secretion by pancreas
What effect does insulin have on K+ uptake by cells?
Increases, as increases activity of Na/K ATPase
How would you treat hyperkalaemia?
IV insulin and dextrose
What effect does K+ in blood have on aldosterone secretion?
Stimulates secretion
How does aldosterone stimulate K+ uptake?
Stimulates Na/K ATPase
How do catecholamines stimulate K+ uptake?
Act via beta2 adrenoreceptors, which stimulate Na/K ATPase and thus cellular uptake of K+
What is produced during high intensity exercise and trauma to offset high ECF K+ rise?
Increased catecholamines
Offset K+ rise by increasing K+ uptake by other cells
Describe how K+ is released during exercise
Net release of K+ during recovery phase of action potential, K+ leaves cell
Skeletal muscle damaged during exercise, releases K+
Increase in plasma K+ proportional to intensity of exercise
What prevents dangerously high ECF K+ levels during exercise?
K+ uptake by non-contracting tissues
Describe the effects of acidosis on potassium balance in a cell
Acidosis
H+ shift into cells
Reciprocal K+ shift out of cells
Describe the effects of alkalosis on the K+ balance of cells
Shift of H+ out of cells
Reciprocal K+ shift into cells
Does acidosis lead to hyper or hypo kalaemia?
Hyperkalaemia
Does alkalosis lead to hyper or hypo kalaemia?
Hypokalaemia
Describe the movement of K+ and H+ ions in hyperkalaemia
Hyperkalaemia, shift of K+ into cells
Reciprocal shift of H+ out of cells
Hyperkalaemia leads to acidosis
Describe the movement of K+ and H+ ions in hypokalaemia
Hypokalaemia, shift of K+ out of cells
Reciprocal shift of H+ into cells
Hypokalaemia leads to alkalosis
Where is K+ excretion monitored?
Late DT and cortical collecting ducts of kidney nephron
Describe what happens to K+ in the kidney
K+ freely filtered at glomerulus
K+ reabsorbed at proximal tubule (67%), thick ascending loop of henle (20%), distal tubule, cortical collecting duct (via intercalated cells), medullary collecting duct
K+ secreted at distal tubule & cortical collecting duct (principle cells)
Describe how K+ secretion occurs in principal cells in the distal tubule
Na/K ATPase activity in basolateral membrane increases intracellular K+, and decreases intracellular Na+
Na+ moves from lumen into cell down its conc. gradient (via apical ENaC), creating an electrical gradient
This together with high intracellular K+ creates a favourable electrochemical gradient for K+ secretion via apical K+ channels
What effect does aldosterone have on K+ secretion by principal cells of kidney?
Increases K+ secretion
Increases transcription of relevant proteins (increases Na/K ATPase, increases K+ channels, increases ENaC)
What effect does ECFs K+ concentration have on K+ secretion by principal cells of kidney?
Directly stimulates Na/K ATPase and increases permeability of apical K+ channels
Also stimulates aldosterone secretion
What effect does acidosis have on K+ secretion by principal cells of kidney?
Acidosis decreases K+ secretion (inhibits Na/K ATPase, decreases K+ channel permeability)
What effect does alkalosis have on K+ secretion by principal cells of kidney?
Increases K+ secretion
Stimulates Na/K ATPase, increases K+ channel permeability
What effect does increased distal tubular flow rate have upon K+ secretion?
Washes away luminal K+, increasing K+ loss
What effect does increased Na+ delivery to distal tubule have on K+ secretion?
More Na+ absorbed by principal cells, resulting in more K+ loss
How is K+ absorbed by intercalated cells?
Actively, via H+/K+ ATPase in apical membrane
Where are intercalated cells in the kidney?
Distal tubule
Cortical collecting duct
What can changes in ECF K+ concentration effect?
Alter cell membrane resting potential
Alter neuromuscular excitability
Resulting in arrhythmias, CA, muscle paralysis
What might cause hyperkalaemia?
Increased K+ intake (unlikely unless inappropriate use of IV K+) Decreased renal excretion (kidney injury, low aldosterone state, drugs blocking K+ excretion - ACE inhibitors, K+ sparing diuretics) Internal shifts (diabetic ketoacidosis, cell lysis, metabolic acidosis)
What are the clinical features of hyperkalaemia?
Heart - altered excitability, arrhythmias, heart block
GI - neuromuscular dysfunction - paralytic ileus
Acidosis
What is the emergency treatment for hyperkalaemia?
IV calcium gluconate (reduce K+ effect on heart)
IV Glucose and insulin (shift K+ back into ICF)
Nebuliser beta agonists (salbutamol)
Remove excess K+ (dialysis)
What is the long term treatment for hyperkalaemia?
Treat cause
Reduce K+ intake
Measures to remove excess K+ (dialysis in acute or chronic kidney injury).
Oral K+ binding resins to bind K+ in gut
What may cause hypokalaemia?
Problems of external balance - excessive loss GI, diarrhoea, vomiting). Renal loss of K+ (diuretic drugs, osmotic diuresis, high aldosterone levels)
Problems of internal balance (shifts of K+ into ICF e.g. Metabolic alkalosis)
What are the clinical features of hypokalaemia?
Heart - altered excitability, arrhythmias
GI - neuromuscular dysfunction, paralytic ileus
Skeletal muscle - neuromuscular dysfunction, muscle weakness
Renal - unresponsive to ADH
What effect does hypokalaemia have on heart muscle excitability?
Hypopolarised RMP - more fast Na+ channels available in active form, heart more excitable
What is the treatment for hypokalaemia?
Treat cause Potassium replacement (IV/oral). If due to increased mineralocorticoid activity (high aldosterone levels), K+ sparing diuretics, which block action of aldosterone on principal cells.
What are the ECG features of hyperkalaemia?
High T wave, depressed ST segment, prolonged PR interval, P wave absent (atrial standstill), intraventricular block, ventricular failure
What are the ECG features of hypokalaemia?
Low T wave, high U wave, low ST segments
What cells do K+ absorption at the collecting duct?
Alpha-intercalated cells
How is K+ absorbed in the kidney medulla?
Luminal and transcellular absorption
How is K+ absorbed in the PCT?
Paracellularly (solvent drag early, lumen - positive potential late)
How is K+ absorbed in the TAL?
Transcellular and paracellular (NKCC2, lumen positive potential K+ and Cl-)
Why does K+ absorption require such fast balancing?
Amount of K+ absorbed in the GI after a meal is approximately equal to the amount of K+ present in the ECF
What effect does adding HCO3- have on K+ absorption into the ICF?
Aids K+ to ICF absorption
What pH should the blood be at?
pH 7.35-7.45
What concentration of H+ ions should be in the blood?
44.5-35.5 nmol/l
What effect does alkalaemia have on Ca2+ ions? What are the consequences of this?
Lowers free Ca2+, causing Ca2+ ions to come out of solution. This increases neuronal excitability, can lead to paraethesia and tetany
What can Ca2+ ions coming out of solution lead to?
Increased neuronal excitability, can lead to paraethesia and tetany
How does acidaemia effect electrical excitability?
Increases plasma K+ conc
What effect may increased H+ conc have on proteins? What can this effect?
Denatures/disturbs them. Can effect muscle contractility, glycosis, hepatic function
At what pH is acidosis life threatening?
Below pH 7.0
How is plasma pH determined?
Ratio of the concentrations of HCO3-/pCO2 (via hendleson-hasselbalch equation)
Should be maintained at a 20:1 ratio CO2:O2
What ratio should CO2:O2 be in the blood?
20:1
What effect can hypoventilation have on plasma pH
Hypoventilation - hypercapnia - fall in plasma pH
Respiratory acidaemia
What effect can hyperventilation have on plasma pH?
Hyperventilation - hypocapnia - plasma pH rise
Respiratory alkalosis
What controls pCO2?
Central chemoreceptors (change respiratory rate for disturbances in pCO2). Slower response, but account for ~80% of effect. Peripheral chemoreceptors detect changes in pCO2 and pH of plasma. Respond rapidly but have overall smaller effect.
What can compensate for changes in pCO2?
Changes in HCO3-
Ratio = pH
What controls the concentration of HCO3- in the blood?
Kidneys (despite RBCs producing it)
What happens, with regard to HCO3-, to acid produced by tissues?
Reacts to form CO2, which is blown off at the lungs. This leads to a fall in HCO3-, therefore a decrease in pH
This can be compensated for by increasing ventilation.
What chemoreceptors detect a change in plasma pH?
Peripheral
When might plasma HCO3- levels rise?
E.g. After much vomiting
How might increases in plasma HCO3- be compensated for?
Decreasing ventilation
How can the kidney correct disturbances in pH?
Varying excretion of HCO3- (very easy to lose it)
Making more HCO3-
How do kidneys produce more HCO3-?
Have a very high metabolic rate, so produce lots of CO2, which then reacts with H2O, producing HCO3- (which enters plasma) and H+ (which is excreted in urine)
Kidney can also make HCO3- from amino acids (producing NH4+, which enters urine)
Where is 80% of HCO3- reabsorbed in the kidney nephron?
In the PCT
What drives HCO3- reabsorption in the PCT?
Na+ gradient (established by NaK ATPase)
Describe HCO3- recovery in the PCT
Na+ movement down gradient (established by NaK ATPase) drives H+ movement out of cells via NHE-3
H+ in lumen reacts with HCO3- to form CO2 (carbonic anhydrase is present on apical membrane and inside tubular cells)
CO2 moves into the cell and reacts with H2O to form more HCO3-, which moves across basolateral membrane to ECF (Na3HCO3- cotransporter)
Describe the creation of HCO3- in the proximal tubule. What happens to the products?
Glutamine is converted to alpha-ketoglutarate, producing HCO3- and ammonium NH4+
HCO3- enters ECF
NH4+ enters lumen
Describe the creation of HCO3- in the distal tubule
Metabolic activity produces CO2, so H+ ions need to be secreted and buffer to keep producing HCO3- (Na+ gradient not enough to drive secretion of H+), via H+ATPase.
H+ buffered by filtered HPO4+ and excreted NH4+
What is the lowest pH of urine?
pH 4.5
How is the lowest possible pH of urine (4.5) achieved?
No HCO3- is secreted (all has been recovered)
Some H+ buffered by phosphate, some has reacted with ammonia to form NH4+
Approximately how much H+ is secreted per day?
50-100mmol
Needed to keep the concentration of HCO3- normal
What controls H+ secretion?
Kidneys
What happens if ECF concentration of HCO3- is low?
More HCO3- moves out of cells to ECF, more H+ in cells
What is the kidney cellular response to acidosis?
Decreased pH enhances the activity of Na+/H+ exchanger
Decreased pH enhances ammonium production in proximal tube
Decreased pH enhances activity of H+ ATPase (proton pump) in distal tube
Increased capacity to export HCO3- from tubular cells to ECF
What is the anion gap?
Associated ion with metabolic acids (e.g. Lactic, keto…) left after H+ reacts with HCO3- to produce CO2 (exhaled).
Anion replaces HCO3-
How is the anion gap calculated?
The difference between the concentrations of
(Na+ + K+) - (Cl- + HCO3-)
Main cations - main anions
What is a normal value for the anion gap?
10-15mmol/l
What does an increased anion gap indicate?
HCO3- has been replaced by an anion other than Cl-
Do all metabolic acidosis create an anion gap?
Nope
What does a fall in pH stimulate in the kidney?
Acid secretion
HCO3- recovery
What does a rise in the pH of tubular cells lead to?
A fall in H+ excretion and reduction in HCO3- recovery
When is HCO3- excretion compromised?
If there is also volume depletion
Capacity to lose HCO3- is reduced because of high rate of Na+ recovery
Recovering Na+ favours H+ excretion and HCO3- recovery
What effect does hyperkalaemia have on HCO3-?
K+ moves out of cells H+ moves into cells Favours H+ excretion HCO3- recovery More K+ reabsorption in distal nephron
What effect does hypokalaemia have on HCO3-?
K+ moves into cells
H+ moves out of cells
Favours HCO3- excretion (H+ recovery)
Less K+ reabsorbed in nephron
What value are most body fluids osmotically, so that they are isotonic to cells?
280-310mOsm/kg
Through what range can urine osmolarity go through?
50-1200 mOsm/kg
What approximate value is urine osmolarity in a normal hydrated person?
500-700mOsm/kg
What do disorders of water balance manifest as?
Changes in body fluid osmolarity
What detects changes in plasma osmolarity?
Hypothalamic osmoreceptors
What are the 2 efferent pathways to effect plasma osmolarity?
ADH and thirst
Effects kidney and brain (behavioural), water excretion and water intake
Where are osmoreceptors in the brain located?
Organum vasculosum of the lamina terminalis (OVLT), which is anterior and ventral to the third ventricle
What feature of the organum vasculosum of the lamina terminalis (OVLT) aids its ability to detect plasma osmotic changes?
Fenestrated leaky endothelium, exposed directly to systemic circulation (on plasma side of blood brain barrier) - in direct contact with plasma
What does the organum vasculosum of the lamina terminalis (OVLT) do?
Senses changes in plasma osmolarity, signals secondary responses - concentration of urine or thirst
Under what conditions is ADH released?
Predominant water loss
Where is ADH secreted from?
Posterior pituitary gland
What controls ADH secretion?
Negative feedback loops
Should ADH conc. ever reach zero?
Nope
What is more important, blood osmolarity or volume?
Volume!
When faced with circulatory collapse, kidneys continue to conserve H2O even if this will reduce osmolarity of body fluids
What is the analogue of thirst?
Salt ingestion
Where is ADH produced?
Produced by neurosecretary cells in the hypothalamus
What sort of peptide is ADH?
Small, 9 AA long
What are some other names for ADH?
Vasopressin, argipressin, arginine vasopressin AVP
What effect does ADH have on the kidney?
Increases permeability of collecting duct to water and urea
What is diabetes insipidus?
When plasma ADH levels are too low
What might cause diabetes insipidus?
Damaged hypothalamus or pituitary glands e.g. Brain injury (base of skull fracture), tumour, aneurism ect
What is nephrogenic diabetes insipidus?
Kidney insensitivity to ADH (acquired)
What effect does diabetes insipidus have on the kidney?
Water is inadequately reabsorbed from the collecting ducts, so a large quantity of urine is produced
How can you manage diabetes insipidus?
ADH injections
ADH nasal spray
What is SIADH?
Syndrome of inappropriate ADH secretion
What characterises SIADH?
Excessive release of ADH from PP gland or another source. Dilutional hyponatriemia, in which the plasma sodium levels are lowered and total body fluid is increased.
What aquaporin channels are present in the proximal tubule?
AQP1
AQP7
What aquaporin channels are present in the thin descending limb?
AQP1
What aquaporin channels are present in the ascending limb?
None
What aquaporin channels are present in the collecting duct?
AQP2
AQP3
AQP4
Mostly in medullary portion
What happens in the kidney if there is little ADH present?
No aquaporin in basolateral membrane of latter DCT and collecting ducts
Therefore limited water reuptake in latter DCT/collecting ducts
Tubular fluid rich in water passes through the hyperosmotic renal pyramid with no change in water content
Loss of a large amount of hyposmotic urine - diuresis
What happens in the kidney if ADH is present?
ADH causes insertion of aquaporin channels to basolateral membrane, enabling water to move out of collecting duct into hyperosmotic environment
How is a counter current established in the kidney?
Juxtamedullary nephron - long loop of henle establishes gradient vertically, vasa recta helps maintain this osmotic gradient
What effect does the thick ascending limb have on establishing the medullary gradient?
Removes solute without water, therefore increasing osmolarity of the interstitium
Describe the action of loop diuretics
Block NaK2Cl transporters, medullary interstitium becomes isotonic and copious amounts of dilute urine is produced
Describe the action of the descending limb with regards to osmolarity
Highly permeable to water (due to AQP1 channels), which are always open. Not permeable to Na+, so Na+ remains in descending limb and its concentration increases
What is the maximum osmolarity at the tip of the loop of henle?
1200mOsm/kg
Describe the action of the ascending limb with regards to osmolarity
Actively transports NaCl out of tubular lumen into interstitial fluid. Impermeable to water. Osmolarity decreases. Fluid entering DCT has a low osmolarity of 100mOsm/kg; it is hyposmotic
What is counter current multiplication?
Active transport of Na+ out of ascending limb increases its concentration in the interstitial fluid surrounding the loop of henle. This is enabled by the vasa recta
What enables counter current multiplication?
The vasa recta
At what level is the osmolarity at the corticomedullary border?
Isotonic (~300mOsm/kg)
What level of osmolarity is the medullary interstitium?
Hyperosmotic (up to 1200mOsm/kg at papilla)
What aids osmotic gradient in the kidney?
Urea (not usually an effective osmole)
What determines whether a substance is an effective osmolarity?
If a membrane enables certain solute to cross freely, then it is totally ineffective at exerting an osmotic force across the membrane
Is urea hydrophilic or hydrophobic?
Hydrophilic
Where is urea reabsorbed?
Medullary collecting duct
Cortical collecting duct cells are impermeable to urea
What effect does ADH have on urea in the kidney?
Fractional excretion of urea decrease, and urea recycling increases
What maintains the concentration gradient produced by the loop of henle?
The vasa recta, acts as a counter current exchanger
What is bloodflow in renal medulla like?
Low (5-10% total RPF)
Needs to deliver nutrients and maintain medullary hyper-tonicity
Has the vasa recta got any capacity for active transport?
Nope
Describe osmotic stratification in medullary interstitium if ADH is present
Counter current multiplier give NaCl gradient
Also cortex to papilla gradient of urea
Describe what happens in the descending limb of the vasa recta
Isoosmotic blood enters hyperosmotic mileu of medulla (high concentration of Na+ ions, Cl- ions, and urea)
Ions and urea diffuse into lumen of vasa recta
Osmolarity of blood in vasa recta increases as it reaches tip of loop
Describe what happens in the ascending limb of the vasa recta
Blood ascending has higher concentration of solute than surrounding interstitium
Water moves in from the descending limb of the loop of henle
Define ‘diuretic’
A drug/substance that promotes diuresis
Usually by increasing renal excretion of water and sodium, therefore causing a reduction of ECF volume
When might diuretics be useful, in general?
Conditions where Na+ and H2O retention cause expansion of ECF volume e.g. HF, cirrhosis, nephrotic syndrome
What are the stages in the formation of urine?
1 - Filtration
2 - Selective reabsorption of most of the solutes and water
3 - Secretion of substances
How do diuretic generally work?
Blocking reabsorption of Na+ and H2O by the tubule fraction excretion (FE)
What channel is common to all segments of the tubule?
Na+/K+ ATPase
What channels are on the apical membrane of the proximal CT?
NaH Antiporter
Na-Glucose symporter
Na-AA symporter
What channels are on the apical membrane of the loop of henle?
Na-K-2Cl symporter
What channels are on the apical membrane of the early DT?
NaCl symporter
What channels are on the apical membrane of the late DT and CD
ENaC
Epithelial Na+ Channels
Describe tubular reabsorption of Na+ by principle cells of late DT and CD
Na-K-ATPase in basolateral membrane pumps out Na+
Na+ enters cells via ENaC on apical membrane
Na+ reabsorption favours K+ secretion by creating a luminal negative potential (secreted via K+ channels)
What effect does aldosterone have on the expression of Na+ channels?
Increases expression of NaK ATPase, ENaC and K+ channels.
What effects do diuretics blocking ENaC have on K+ secretion?
Diuretics blocking ENaC also reduces K+ secretion
What are common sites of action of diuretics?
Loop of henle - loop diuretics
Distal convoluted tubule - thiazide diuretics
Collecting duct - potassium sparing diuretics
Aldosterone antagonists
Give some examples of loop diuretics
Furosemide
Bumetanide
Give some examples of thiazide diuretics
Metalozone
Indapamide
Bendroflumethiazide
Give an examples of potassium sparing diuretics
Amiloride, trimterene
Aldosterone antagonists
Give an example of an aldosterone antagonist
Spirolactone
Describe the classification of diuretics
Loop diuretics - inhibitors of Na-K-2Cl symport
Thiazide diuretics - inhibitors of NaCl symport
K+ sparing diuretics - inhibitors of renal Na+ channels/aldosterone antagonists
Inhibitors of carbonic anhydrase
Osmotic diuretics
Give an example of a diuretic that works via inhibiting carbonic anhydrase
Acetazolamide
Give an example of an osmotic diuretic
Mannitol
What are the 4 mechanisms via which diuretics may work?
- By direct action on cells to block Na+ transporters in the luminal membrane (drug secreted into lumen in PCT, acts from within lumen on transporters)
- By antagonising the action of aldosterone
- By modification of filtrate content, osmotic diuretics (small molecules freely filtered at glomerulus, but not reabsorbed. Increase osmolarity of filtrate, reducing H2O and Na+ reabsorption throughout tubule)
- By inhibiting activity of enzyme carbonic anhydrase in the PCT (interferes with Na and HCO3- reabsorption in PCT)
Upon what transporters do diuretics acting on the loop of henle work on?
NaK2Cl transporter
What proportion of filtered Na+ is absorbed in the loop of henle?
25%
What helps drive absorption of Ca2+ and Mg2+?
K+ that has been carried across apical membrane drifts back via K+ channels, creating luminal positive gradient…
Describe the action of loop diuretics
Secreted into lumen in the PCT and travel downstream to act on the loop of henle
Very potent diuretics (20-30% of filtered Na+ reabsorbed in the loop) - segments beyond have limited capacity to reabsorbed the resulting flood of Na+ and H2O
How do loop diuretics get into the tubular lumen?
Secreted into lumen in the PCT via organic anion pathway
When might you use loop diuretics?
Heart failure (diuretic effect = vaso/venodilation, decreases pre/afterload on heart)
Acute pulmonary oedema (furoseminide IV for rapid access)
Fluid retention and oedema in nephrotic syndrome, renal failure, cirrhosis of liver
Hypercalcaemia (impairs Ca2+ reabsorption, increasing urinary excretion of Ca2+)
What sort of diuretics act on the early distal tubule?
Thiazides
What channel do thiazide diuretics block?
NaCl transporter
What effect can thiazide diuretics have on Ca2+ reabsorption?
Increased Ca2+ reabsorption
Describe how thiazide diuretics work
Secreted into lumen in PCT, travel downstream to act at DCT
Block NaCl transporter in DCT
Increase Na+ (and H2O) loss in urine
Reduces Ca2+ loss in urine (increases Ca2+ reabsorption)
How do thiazide diuretics get into the tubular lumen?
Secreted into lumen at PCT
What potency do thiazide diuretics have?
Less than loop diuretics!
Only 5% Na+ reabsorption inhibited
Therefore ineffective in renal failure
How much Na+ reabsorption is inhibited by thiazide diuretics?
~5%
What are thiazide diuretics primarily used to treat?
Hypertension
What diuretics act on the late DT and CD?
Inhibitors of epithelial Na+ channels
Aldosterone antagonists
What are some features of diuretics acting on the late DT and CD?
Mild diuretics affecting only 2% of Na+ reabsorption
Reduce Na+ channel activity (directly or indirectly)
Reduce loss of K+
Risk of hyperkalaemia
What is a risk of diuretics acting on the late DT and CD?
Can produce life-threatening hyperkalaemia, especially if used alongside ACE inhibitors, K+ supplements or in patients with renal impairment
When would you use spironolactone? (An aldosterone antagonist)
Treatment of hypertension due to primary hyperaldosteronism (com’s syndrome - adrenal hypertension)
Treatment of ascites and oedema in cirrhosis
In addition to loop diuretics to in heart failure
As additional therapy in hypertension not controlled by ACE inhibitors ect
What are ENaC blockers?
Mild diuretics with a K+ sparing effect
When are ENaC blockers used?
In combination with K+ losing diuretics to minimise K+ loss
Where is carbonic anhydrase found in the kidney?
Within the brush border of PCT cell
What is a risk of using carbonic anhydrase inhibitors?
Can cause metabolic acidosis due to loss of HCO3- in urine
When might you use osmotic diuretics?
Useful for cerebral oedema (IV)
What are some possible consequences of using osmotic diuretics?
Can cause loss of H2O, Na+ and K+ in the urine
How is K+ secreted in the DT and CD?
Passive process
Driven by electric-chemical gradient. Rate of K+ secretion depends on the concentration gradient across apical membrane, and the rate of Na+ absorption - inward movement of Na+ ions creates a favourable lumen negative gradient for K+ secretion
What does the rate of K+ secretion in the DT and CD depend on?
Rate of K+ secretion depends on the concentration gradient across apical membrane, and the rate of Na+ absorption - inward movement of Na+ ions creates a favourable lumen negative gradient for K+ secretion
List some things other than diuretic use which may contribute to hypokalaemia
Excess diuresis reduces ECF volume Activation of RAAS Increased aldosterone secretion Increased Na+ absorption and K+ secretion Hypokalaemia
What effect do loop diuretics have on K+ excretion?
Increase Na+ absorption by principal cells, favourable electrical gradient for K+ excretion
(Also loop and thiazide diuretics - both increase Na+ and H2O delivery to late DT and CD)
Describe effect of thiazide diuretics on K+ secretion
Faster flow rate of filtrate in tubule lumen, K+ secreted into lumen is washed away faster, lower K+ concentration in lumen. Favourable chemical gradient for K+ secretions
What is particularly at risk of happening when K+ sparing diuretics are used?
Hyperkalaemia
Na+ reabsorption reduced, less K+ lost in urine
What is it important to measure when using diuretic therapy?
Electrolyte Na/K levels
When are diuretics used?
Conditions with ECF expansion and oedema
How does congestive heart failure cause peripheral oedema?
Increases systemic venal pressure
How does reduced renal perfusion lead to expansion of the ECF?
Activation of RAAS, Na+ and H2O retention
What is nephrotic syndrome?
Glomerular disease - increase in GBM permeability to protein. Proteins are filtered and lost in urine, causes low plasma albumin, results in low plasma oncotic pressure - peripheral oedema.
Reduced circulatory volume - RAAS activated - expansion of ECF - more oedema
Where is splanchnic circulation?
GI
Is ascites transudate or exudate?
Transudate
What might cause bladder stones?
- Bladder outflow obstruction - urethral stricture, neuropathic bladder (doesn’t contract normally), prostate obstruction
- Presence of foreign body - catheter, non-absorbable sutures
- Some are passed down from upper urinary tract
What are the consequences of bladder stones?
Can cause urine outflow obstruction. Anuria/painful bladder distension
What are some other names for renal stones?
Kidney stone, renal calculus, nephrolith
When do renal stones generally present?
30+yrs
2:1 male:female
What can renal stones be made of?
Calcium stones: Calcium oxalate - usually with calcium phosphate (apatite) Calcium phosphate alone Uric acid Struvite 'infection stones', urease stones, triple phosphate stones (magnesium ammonium phosphate hexahydrate, from infection by bacteria that have urease) Other types (rarer) Cysteine stones Drug stones Ammonium acid rate stones
What causes struvite ‘infection stones’ (urease stones, triple phosphate stones)
Magnesium ammonium phosphate hexahydrate, from infection by bacteria that have urease
When are renal stones comprised of calcium phosphate alone seen?
Frequently in hyperparathyroidism and renal tubular disease
When might cysteine stones occur?
Rare genetic disorder cystinuria
Give some examples of kidney stones that occur as a result of drugs
Indinavir (treatment for HIV)
Triamterene (diuretic)
Sulphadiazine (sulphonamide antibiotic)
Why do urinary stones form?
If there is urine supersaturation with minerals - solvent contains more solute than it can hold in solution. Seed crystals form by nucleation - 1st step is formation of a new structure by self assembly. A physical, not chemical reaction.
In what circumstances might urinary stones form?
Decrease in water content - dehydration
Increase in mineral content - hypercalcaemia and hypercalciuria, hyperoxaluria, hyperuricaemia, hyperuricosuria, cysteinuria
Decrease in solubility of solute in urine - some solute more soluble at high pH and some at low pH
What stones does acid urine favour the formation of?
Calcium oxalate and uric acid stones
What stones does alkaline urine favour the formation of?
Calcium phosphate stones
What renal tubular acidosis result in?
Persistently alkaline urine and decreased urinary citrate excretion
What happens to calcium phosphate in alkali?
Precipitates
What happens to calcium phosphate in acid?
Dissolves
What happens if you put a bone in vinegar (ethanoic acid)?
Goes rubbery - calcium phosphate has dissolved away
What is a likely cause of uric acid and cysteine stones?
Supersaturation
How do calcium oxalate stones form?
75% grow like stalactites attached to exposed interstitial deposits of calcium phosphate ‘Randall’s plaque’ on the tips of renal papillae (composed of a core of calcium phosphate surrounded by calcium oxalate)
Otherwise, can form on plugs protruding from ducts of bellini or free in solution
List some causative factors for urinary stones
Urine status - low urine flow, obstruction, infection
Genetic/congenital factors - primary metabolic disturbances e.g. Cystinuria, kidney abnormalities e.g. Polycystic kidneys, medullary sponge kidneys
Drugs
Describe the presentation of calcium oxalate stones
5% associated with hypercalcaemia and hypercalciuria - treatable!
55% have hypercalciuria without hypercalcaemia - can be associated with hyperabsorption of calcium from the gut or impairment in renal tubular absorption of calcium
5% association with hyperoxaluria - hereditary or secondary to intestinal over absorption in patients with enteric disease
What might cause calcium oxalate stones due to hypercalciuria and hypercalcaemia?
Hyperparathyroidism, diffuse bone disease, sarcoidosis
Proportionally, how much Ca2+ is locked away in bone?
Over 99%
ECF conc 1000-10000 times lower than ICF
Cell membranes pump out Ca2+
What regulates Ca2+ conc in the ECF?
PTH
Calcitriol
1,25 dihydroxy vitamin D
Calcitonin
Have effect in gut, kidney and bone
Where are Ca2+ sensing receptors located in the body?
Parathyroid glands, kidney, brain and other organs
How does PTH increase serum calcium?
Increases osteoclastic resorption of bone (rapid)
Increases intestinal absorption of Ca2+ (slow)
Increases synthesis of 1,25-(OH)2D3
Increases renal tubular resorption of Ca2+
Increases excretion of phosphate
How does vitamin D effect Ca2+ levels?
Increases Ca2+ absorption in the gut
Increases calcification and resorption in bone
Where is calcitonin produced?
Thyroid C cells
How does calcitonin decrease serum Ca2+?
Inhibits osteoclastic bone resorption
Increases renal excretion of calcium and phosphate
What is the most common metabolic abnormality in Ca2+ stone formation?
Hypercalciuria
What might cause hypercalciuria?
Hypercalcaemia
Excessive dietary intake of Ca2+
Excessive resorption of Ca2+ from skeleton (prolonged immobilisation, weightlessness)
Idiopathic (increased absorption of Ca2+ from the GIT)
What can be given to astronauts to help prevent them getting hypercalciuria due to resorption of unused skeletal bones?
Potassium citrate
What are the possible causes of hypercalcaemia?
Hypersecretion of PTH, resulting in increased bone resorption Destruction of bone tissue Other mechanisms (excessive Vit D ingestion, thiazide diuretics, sarcoidosis, milk-alkali syndrome - excessive Ca2+ intake)
What is sarcoidosis?
Macrophages activate Vit D precursor
What might lead to hypersecretion of PTH?
Primary - parathyroid hyperplasia or functional tumour
Secondary - to renal failure (which causes retention of phosphate and hence hypocalcaemia)
Ectopic - secretion of PTH related protein by malignant tumour (legal squamous cell carcinoma of lung)
What might cause destruction of bone tissue (leading to hypercalcaemia)?
Primary tumour of bone marrow (e.g. Myeloma)
Paget’s disease of bone (accelerated bone turnover)
Immobilisation (reduces bone formation whilst reabsorption continues
Diffuse skeletal metastases
What are the most common causes of hypercalcaemia?
Hyperparathyroidism and malignancies
What are the main clinical signs of hypercalcaemia?
Bones, stones and moans.
Painful bones - fractures
Renal stones
Abdominal groans - constipation, peptic ulcers pancreatitis, gallstones
Psychic moans - depression, lethargy, seizures
Severe muscle weakness (opposite of tetany in hypocalcaemia!)
What is hyperoxaluria?
Rare autosomal recessive genetic disorder of oxalate synthesis (primary hyperoxaluria types 1 and 2)
Increased intestinal oxalate absorption secondary to GI disease (England chrons disease) usually with an intestinal resection (increased absorption of oxalate from colon)
Dietary habits - high oxalate intake (spinich, rhubarb, tea, nuts)
Low calcium intake (increases GI absorption of oxalate)
What type of stones are generally present with UTIs?
Struvite stones (mixed infection stones)
What are struvite stones comprised of?
Magnesium ammonium phosphate with variable amounts of calcium
What sort of infections usually produce struvite stones? Why?
Infection with organisms with the enzyme urease which hydrolyses urea to ammonium hydroxide (proteus species e.g. Proteus mirabilis)
Also production of mucoprotein from infection provides an organic matrix on which stones can form
What are particularly large urinary stones called?
Staghorn calculus
When are staghorn calculus predominantly seen?
In people predisposed to UTIs - spinal cord injury, neurogenic bladder, vesicoureteric reflux, obstruction uropathy
When are uric acid stones seen?
In hyperuricaemia, and in people with tendency to have urine with pH of less than 5.5
What is a key fact about uric acid stones?
They are radiolucent - can’t be seen on X-ray
What is hyperuricosuria?
High uric acid in urine
What is hyperuricaemia?
High uric acid in blood
What is the endpoint of purine metabolism?
Uric acid
When might hyperuricaemia be seen?
Seen in idiopathic gout
Secondary consequence of increased cell turnover (lympho or myeloproliferative disorders) after chemotherapy (tumour lysis syndrome)
How do renal stones present?
Asymptomatic, but can be seen on radiography
Renal colic, dull ache on loins
Recurrent UTIs
Urinary tract obstruction
Haematuria
Renal failure
If urinary tract obstruction and fluid intake is increased, result is an increase in pain
How long do renal bouts generally last?
20-60mins
What causes bouts of renal colic?
Caused by peristaltic contractions or spasms of the ureter as it attempts to expel stone
Where is the pain in renal colic felt?
Radiates from flank to iliac fossa and inner thigh (in distribution of 1st lumbar nerve)
What often accompanies the pain felt in renal colic?
Nausea/vomiting, pallor, sweat, restlessness. Haematuria common.
What generally happens to untreated renal colic?
Subsides in a few hours
What is urolithiasis?
The formation of stony concretions in the bladder or urinary tract
What does MSU stand for (with regards to urinary investigations)
Midstream specimen of urine
What might you be looking for in a MSU (midstream specimen of urine)
RBCs, urinary casts, urinary crystals, culture, (cause or consequence of stones?)
What might you be looking for in a serum test when investigating urinary stones?
Urea, creatinine, electrolytes, calcium levels
What investigations might you do in urolithiasis?
MSU (midstream sample of urine) Serum Plain abdominal x-ray CT kidney, ureter and bladder Pass urine through serve to catch calculi for chemical analysis
Why aren’t x-rays the best way to look for calculi?
60% of stones are radiopaque (mostly Ca2+ containing stones). Uric acid stones are radiolucent
Why is a CT of the kidney, ureter and bladder good for use in urolithiasis?
Better than USS - almost all stones can be seen. Ideally during pain.
Can see stones and dilated renal pelvis
Can see uric acid stones
Identifies any primary renal disease predisposing to stone formation
What size urological stones can usually be passed (90%)?
<5mm diameter
What size urological stones usually require intervention to be passed?
> 7mm diameter
What are some possible complications of uric stones?
Acute pyelonephritis +- gram negative septicaemia
Pressure necrosis of the renal parenchyma
Urinary obstruction and hydronephrosis
Ulceration through the wall of the collecting system
What are the possible treatments for renal colic?
Analgesia (IV diclofenac or pethidine), warmth to site of pain, bed rest
Ureteroscopy (usually for stones in lower ureter - like endoscopy…)
Percutaneous nephrolithotomy (surgery)
Extracorporal shock wave lithotripsy ESWL
What does ESWL stand for?
Extracorporal shock wave lithotripsy
When might you use ESWL (Extracorporal shock wave lithotripsy)?
Most commonly for renal stones near the pelvis
How does ESWL (Extracorporal shock wave lithotripsy) work?
Lithrotriptor delivers external, focused, high intensity probes of ultrasonic energy. Takes 30-60 mins. Fragments stones, so they can then be passed spontaneously.
How can you prevent getting urinary stones?
Keep hydrated!
Decrease excretion of Ca2+ or oxalate (thiazide diuretics)
Potassium citrate alkalinise urine - reduces risk of calcium oxalate, uric acid and cysteine stones. Also forms soluble complexes with Ca2+. Can induce phosphate stones
What effect doe thiazide diuretics have on Ca2+ conc. in the urine?
Decreases such
What percentage of women will have had at least 1 UTI by the age of 24?
~30%
What are UTIs a common source of?
Gram negative septicaemia
In whom do most UTIs occur?
Females (shorter urethra)
Obstruction - enlarged prostate, pregnancy, stones, tumours
Neurological problems - incomplete emptying, residual volume
Ureteric reflex - ascending infection from bladder especially in children
What might cause a urinary tract obstruction at the PUJ?
Calculi
What might cause a urinary tract obstruction at the ureta?
Calculi, Ca2+, retroperitoneal fibrosis
What might cause a urinary tract obstruction at the bladder?
Neuropathic bladder
What might cause a urinary tract obstruction at the VUJ?
Calculi
What might cause a urinary tract obstruction at the bladder neck?
Hypertrophy
What might cause a urinary tract obstruction at the prostate?
BPH/Ca2+
What might cause a urinary tract obstruction at the urethra
Stricture
What adaptations enables bacteria to colonise the urinary tract?
Fimbriae allow attachment to host epithelium. K antigen permits production of polysaccharide capsule. Haemolysins damage host membranes and cause renal damage. Urease breaks down urea creating a favourable environment for bacterial growth.
What is cystitis?
Frequency and dysuria (lower UTI)
What is acute pyelonephritis?
Upper UTI
What is chronic pyelonephritis?
Renal inflammation and fibrosis due to recurrent and persistent renal infection, vesicoureteral reflux, or other cause of urinary tract obstruction
When might asymptomatic bacteriuria become a problem?
If patient then becomes pregnant
What are some clinical signs and symptoms of lower UTI?
Dysuria, frequency, urgency, sometimes low grade fever
What are some clinical signs and symptoms of upper UTI (pyelonephritis)?
Fever, loin pain, may have dysuria/frequency
What is an uncomplicated UTI?
‘An infection by a usual organism in a patient with a normal urinary tract and normal urinary function’
What is a complicated UTI?
UTI when one or more factors present that predispose the person to persistent infection, recurrent infection, or treatment failure.
Give some examples of when an UTI could be classed as ‘complicated’
Abnormal urinary tract (e.g. Vesicoureteric reflux, indwelling catheter ect.) Virulent organism (e.g. Staph aureus) Impaired host defences (e.g. Poorly controlled diabetes, immunosuppression) Impaired renal function
IN PRACTISE, what is classed as an ‘uncomplicated’ infection?
Healthy, non-pregnant, woman of child bearing age.
All others are treated as ‘complicated’ (so culture urine)
What is the clinical consequence of a UTI being classed as uncomplicated?
No need to culture urine
How might you obtain a specimen collection for a UTI?
MSU - cleansing not required in women Clean catch in children - no antiseptic Collection bag (20% false positives) Catheter sample Supra-pubic aspiration Transportation (4 degrees C, +- boric acid)
What does dipstick testing analyse?
Leucocyte esterase
Nitrile
Haematuria
Proteinuria
How is the turbidity of urine relevant to infection?
If urine is clear, infection is unlikely
What is dipstick testing useful for?
Useful to exclude UTI in children >3yrs, men with mild/non-specific symptoms, elderly/institutionalised women
When is dipstick testing not useful?
Acute uncomplicated UTI in women
Men with typical/severe symptoms
Catheterised patients
Older patients without features of infection (asymptomatic bacteriuria common)
Why is culturing urine beneficial?
Investigation of children, males, and other 'complicated' infections Increased sensitivity Epidemiology of isolates Susceptibility data Control of specimen quality
What would you analyse in a urine culture report?
Clinical details again - symptoms, previous antibiotics (might decrease sample size) Quality of specimen Delays in culture Microscopy (if available) Organisms isolated
What is urethral syndrome?
Low-count bacteriuria Fastidious organisms Vaginal infection/inflammation Sexually transmitted pathogens -urethritis Mechanical, physical and chemical causes
When is imagine of the urinary tract particularly useful?
In septic patients to identify renal involvement.
Considered in all children with UTI
What might cause sterile pyuria?
Antibiotics, urethritis (chlamydia/gonococci), vaginal infection/inflammation, chemical inflammation, tuberculosis, appendicitis, fastidious organisms
With whom is there a high prevalence of asymptomatic bacteriuria?
High prevalence in older people, particularly elderly females
What is often associated with pyuria? What is a consequence of this?
Associated pyuria
Therefore positive dipstick/culture - so do not routinely dipstick/culture
Is asymptomatic bacteriuria associated with increased risk of morbidity/mortality?
Nope
When might asymptomatic bacteriuria require treatment?
In pregnancy and urological surgery
What is the treatment for UTI?
Increase fluid intake Address underlying disorder 3 day course for uncomplicated UTI 5-7 day course for complicated UTI CSU - only treat if systemically unwell
What is the length of course for an uncomplicated UTI?
3 day course for uncomplicated UTI
What is the length of course for an complicated UTI?
5-7 day course for complicated UTI
What is the treatment for simple cystitis?
Uncomplicated infections can be treated with trimethoprim or nitrofurantoin.
3 day course just as effective as 5 or 7 days, but decreases risk of resistance
What is the treatment for complicated lower UTI?
Trimethoprim, nitrofurantoin or cephalexin may be used - review susceptibility report. 5-7 day course. Post treatment follow up cultures in paediatric patients and pregnant women
Why is amoxicillin not appropriate treatment for complicated lower UTI?
50% of isolates are resistant
What is the treatment for pyelonephritis/septicaemia?
14 day course. Use agent with systemic activity (not nitrofurantoin). Possibly IV initially unless good PO absorption and patient well enough. Co-amoxiclav, ciprofloxacin, gentamicin.
How is gentamicin administered?
IV only
Is gentamicin nephrotoxic?
Yes
When is prophylaxis used for UTI?
If 3 or more episodes in one year with no underlying testable condition
What prophylaxis might be used for UTI?
Trimethoprim or nitrofurantoin
Single nightly dose, ensure all breakthrough infections are documented
What nerve roots innervates the detrusor muscles?
S2, 3, 4 (keeps the piss off the floor)
Pelvic nerves
What nerve roots control the urinary sphincter?
Pudendal nerve S2, 3, 4
What normally happens as the bladder fills?
Compliance (receptive relaxation). Sensation of bladder filling, nodetrusor contraction
What normally happens on voiding of the bladder?
Voluntary initiation, complete emptying
What lower neurological problems might occur with bladder emptying?
Low detrusor pressure. Large residual urine +- overflow incontinence. Reduced perional sensation, lax anal tone.
What upper neurological issues may occur with bladder emptying?
Constant contractions. High pressure, dilated ureters, thickened detrusor. Urine goes back up to kidneys, can damage them. Poor coordination with sphincter. Detrusor sphincter dyssunergia.
List some storage symptoms of lower UTIs
Frequency, urgency, nocturia, incontinence
List some voiding symptoms of lower UTIs
Slow stream, splitting/spraying, intermittency, hesitancy, straining, terminal dribble.
List some post-micturition symptoms of lower UTIs
Post micturition dribble. Feeling of incomplete emptying
What is stress urinary incontinence?
The complaint of involuntary leakage on effort or extortion or sneezing/coughing
What is urge urinary incontinence?
The complaint of involuntary leakage of urine accompanied by or immediately proceeded by urgency
What is mixed urinary incontinence?
The complaint of involuntary leakage of urine associated with urgency and also exertion, effort, sneezing or coughing
What are the types of urinary incontinence?
Stress urinary incontinence
Urge urinary incontinence
Mixed urinary incontinence
Overflow incontinence
What is overactive bladder syndrome?
Urgency, frequency, nocturia
Prevalence is much higher than that of urgency urinary incontinence
What are the risk factors for urinary incontinence?
O&G: pregnancy/childbirth, pelvic surgery, pelvic prolapse
Predisposing: race, family predisposition, anatomical abnormalities, neurological abnormalities
Promoting: co-morbidities, obesity, age, UTI, drugs, menopause, increased infra-abdominal pressure, cognitive impairment
How is the type of UTI categorised?
History
How would one examine a patient with a UTI?
BMI, abdominal examination to exclude palpable bladder. Digital rectal exam - prostate (male), limited neurological exam. Females - external genitalia (stress test - cough). Vaginal exam
What investigations would you do for a patient with urinary incontinence?
Mandatory: dipstick (UTI - haematuria, proteinuria, glucosuria)
Consider: basic non-invasive urodynamics, frequency - volume chart, bladder diary (>3days), post-micturition residual volume (in patients with voiding dysfunction)
Optional: invasive urodynamics (pressure - flow studies +-video). Pad tests. Cystoscopy
How would you determine how to manage a patient with urinary incontinence?
Depends on symptoms, degree of bother, effects of treatment on other symptoms, previous other treatments.
Should be individualised, systematic approach
Describe conservative management of urinary incontinence
Modify fluid intake, weight loss, stop smoking, avoid constipation, decrease caffeine intake, timed voiding (fixed schedule)
How might you manage contained incontinence (for patients unsuitable for surgery who have failed conservative or medical management)?
Indwelling catheter (urethral or suprapubic), sheath device (adhesive condom attached to catheter tubing bag), incontinence pads
What might pelvic floor muscle training be used for?
Stress urinary incontinence specific management.
8 contractions, thrice daily. At least 3 months duration
What pharmacological treatments might be used for stress urinary incontinence?
Duloxetine - combined noradrenaline and serotonin uptake inhibitor. Increases activity in the striated sphincter during filling phase. Not recommended by NICE as 1st or 2nd line, but can be offered as an alternative to surgery.
What surgical options are there for females with stress urinary incontinence?
Permanent intention - low tension vaginal tapes (commonest), open retropubic suspension procedures, classical sling procedures. Temporary intention (e.g. If further pregnancies are planned) - intramural bulking agents
What surgical options are there for males with stress urinary incontinence?
Artificial urinary sphincter. Male sling procedure
Describe urgency urinary incontinence specific management
Bladder training - schedule of voiding e.g. Every hr, must wait in between. Increase intervals by 15-30mins each week until 2-3hr interval has been reached. At least 6wks duration
What pharmacological treatments are available for urge urinary incontinence?
Anticholinergics - acts on muscarinic receptors M2 M3
Oxybutynin
Beta3 adrenoceptor agonist mirabegron. Increases bladder capacity to store urine.
What side effects occur with anticholinergics (act on muscarinic receptors)
Due to their effects on other M receptors at other sites
M1 - CNS, salivary glands
M2 - Heart smooth muscle
M3 - Smooth muscle (ocular and intestinal), salivary glands
M4 - CNS
M5 - CNS, eye
Describe how botulinum toxin might be used to treat urge urinary incontinence
Potent biological neurotoxin. Inhibits release of ACh at pre-synaptic neuromuscular junction causing targeted flaccid paralysis. Mainly type A used clinically
Duration of action only 3-6months (needs to be redone)
Describe how surgery may be used to treat urge urinary incontinence
Sacral nerve neuromodulation (probe inserted which disrupts the nerve signals from spinal cord)
Autoaugmentation, augmentation cytoplasy, urinary diversion (no bladder at all)
What are the ‘compartments’ of the renal system that can go wrong?
Glomerular, tubular, interstitial, vascular
What is nephrotic syndrome?
Filter can leak - proteinuria, haematuria. Swelling due to low blood albumin. (O for oedema!)
What is nephritic syndrome?
Filter can block ‘renal failure’. Reduced renal function, acute kidney failure. Haematuria, hypertensive. Decreased eGFR
What is a primary kidney injury?
Just effects the glomerulus
What is a secondary kidney injury?
Systemic disease that effects kidneys, e.g. Diabetes
What are the sites within the glomerulus where immune complex deposition (antigen-antibody complex/circulating factors) may occur?
Subepithelial (podocytes)
Within GBM
Subendothelial
Mesangial (and paramesangial)
What is the likely site of kidney injury in nephrotic syndrome?
Podocytes/subepithelial damage
What are they common primary causes of podocytes/subepithelial damage (causing nephrotic syndrome)
Minimal change glomerulonephritis
Focal segmental glomerulonephritis
Membranous glomerulonephritis
What are they common secondary causes of podocytes/subepithelial damage (causing nephrotic syndrome)
Diabetes mellitus
Amyloidoses
What is minimal change glomerulonephritis?
Heavy proteinuria or nephrotic syndrome. No foot processes on podocytes (only visible under electron microscope). Unknown cause. No immune complex deposition. Responds to steroids. May reoccur. Usually no progression to renal failure. Incidence increases with increasing age (usually presents in childhood/adolescence). Circulating factor damaging podocytes.
What is FSGS spectrum (minimal change glomerulonephritis)?
More common in adults/older patients. Nephrotic. Less responsive to steroids. Glomerulosclerosis (scarring). Circulating factor damaging podocytes. Progressive to renal failure. Collagen deposition in glomerulus
Describe membranous glomerulonephritis
Immune complex deposits, probably autoimmune. May be secondary (associated with other pathologies e.g. Lymphoma). Immune complexes deposited near podocytes. Complex activation leads to cell injury IgG. Antigen either already on podocytes or gets there separately (complex can't get through BM!). Attracts antibody. Rule of 1/3s 1/3 Get better 1/3 Stay the same 1/3 Progress to renal failure
What is the commonest cause of nephrotic syndrome in adults?
Membranous glomerulonephritis
How does diabetes effect the kidneys?
Progressive proteinuria. Progressive renal failure. Microvascular. Mesangial sclerosis –> nodules. Basement membrane thickening.
Describe IgA Nephropathy
Commonest glomerulonephritis. Classically presents with visible/invisible haematuria. Relationship with mucosal infections. Variable histological features and course. +- proteinuria. Significant proportion progress to renal failure. No effective treatment (only ways to support renal function).
Is there a cure for IgA nephropathy?
No effective treatment (only ways to support renal function).
Does IgA progress to renal failure?
Significant proportion progress to renal failure.
Where is a particularly easy target, in the kidney, for IgA and antigen?
There is no BM/filtering system between the blood and mesangium
What might cause hereditary nephropathy?
Thin GBM nephropathy Benign familial nephropathy Isolated haematuria Thin GBM Benign course Alport syndrome X-linked Abnormal collagen 4 Associated with deafness Abnormal appearing GBM Progression to renal failure
What is the glomerular basement membrane primarily comprised of?
Collagen 4
Hence any abnormalities in collagen 4 will cause issues
What can you use to look for hereditary nephropathies?
Electron microscope
Describe goodpasture syndrome (anti GBM)
Relatively uncommon, though clinically important. Rapidly progressive GN. Acute onset nephritic syndrome. Classically described associated to pulmonary haemorrhage (smokers). Autoantibody to collagen 4 in BM, but BM is ubiquitous. Treatable by immunosuppression and plasmaphoesis if caught early. Replace patients plasma with donor - rapidly get rid of antibody. Cannot be seen on electron microscopy (just antibody)
What causes goodpasture syndrome?
Autoantibody (usually linked to collagen 4) suddenly starts to attack glomerulus
What is vasculitis?
A group of systemic disorders. No immune complex/antibody deposition. Associated with anti neutrophil cytoplasmic antibody (ANCA) - activates neutrophils, attack cells e.g. Endothelial cells as line blood vessels, inflammation of blood vessels. Nephritic presentation (RPGN). Treatable if caught early. Urgent biopsy service. Endothelial target.
What does ‘focal’ mean, with regards to kidney disease?
Involving <50% of the glomeruli on light microscopy
diffuse>50%
What does ‘diffuse’ mean, with regards to kidney disease?
Involving >50% of the glomeruli on light microscopy
Focal <50%
What does ‘segmental’ mean, with regards to kidney disease?
Involving part of the glomerular tuft
What does ‘global’ mean, with regards to kidney disease?
Involving the entire glomerular tuft
What does ‘membranous’ mean, with regards to kidney disease?
Thickening of the glomerular capillary wall
What does ‘proliferative’ mean, with regards to kidney disease?
Increased number of cells in glomerulus, cells can be either proliferating glomerular cells or infiltrating circulating inflammatory cells
What does ‘crescent’ mean, with regards to kidney disease?
Accumulation of cells (mostly mononuclear cells) within bowman space. Often compress capillary tuft, associated with more severe disease
What does ‘glomerulosclerosis’ mean, with regards to kidney disease?
Segmental or global capillary collapse - presumed there is little filtration across sclerotic area
What does ‘glomerulonephritis’ mean, with regards to kidney disease?
Any condition associated with inflammation in glomerular tuft
List some risk factors associated with malignancy of the urinary tract
Increased age, family history, BRCA 2 gene mutation, ethnicity (black>white>Asian)
What are the issues for PSA (prostate specific antigen) screening?
Over diagnosis, over treatment, quality of life (comorbidities of established treatments), cost effectiveness, other causes of raised PSA (infection, inflammation, large prostate)
What is the clinical presentation of urinary malignancy?
Usually asymptomatic, or urinary symptoms (benign enlargement of prostate/bladder overactivity +- CaP), bone pains. Sometimes haematuria (if advanced CaP)
What is the typical diagnostic pathway of a urinary malignancy?
Digital rectal examination, serum PSA (prostate specific antigen), TRUS (transracial ultrasound, guided biopsy of prostate), lower UTI symptoms, transurethral resection of prostate TURP
What factors would influence treatment of a urinary malignancy?
Age, DRE (localised, T1/T2), locally advanced (T3), advanced (T4). PSA level. Biopsies (Gleason grade, extent). MRI scan and bone scan (nodal and visceral metastases)
If a urinary malignancy is local, what treatment might you use?
Established Rxs. Surveillance. Robotic radical prostatectomy. Radiography. External beam, low dose brachytherapy.
What treatment might you use for metastatic CaP? With regards to urinary malignancy
Hormones +- chemotherapy. Surgical/medical castration, LHRH agonists. Palliation single dose radiotherapy. Bisphosphonates (zoledronic acid). Chemotherapy (docetraxel). New treatments?
Below what PSA (prostate specific antigen) level is bone metastases highly unlikely ?
<10ng/ml
How would bone metastases appear on a bone scan?
Sclerotic (osteoblasts) ‘hotspots’ on bone scan
How might you treat locally advanced CaP (with regards to urinary malignancy)?
Surveillance, hormones, hormones + radiotherapy
What are the classifications for haematuria?
Visible
Non-visible (symptomatic and asymptomatic)
What are the different types of cancer for urinary malignancies?
Renal cell carcinoma, upper tract transitional cell carcinoma TCC, bladder cancer, advanced prostate carcinoma
What might cause symptoms similar to a urinary malignancy?
Stones, infection, inflammation, benign prostatic hyperplasia (large)
What investigations might you do for a urinary malignancy?
Blood - FCB, U&Es
Urine - culture and sensitivity (cytology)
Radiology - ultrasound (tumour, stone, blockage)
Endoscopy - flexible cystoscopy
How does bladder cancer Presentation differ from men to women?
Less common in woman, but usually more advanced on presentation
What is the most common type of cancer in bladder cancer?
90% transitional cell carcinoma TCC
List some risk factors for bladder cancer
Smoking, occupational exposure, schistosomiasis
Exposure to what sort of occupational things might increase risk of bladder cancer?
Rubber/plastics manufacture, arylamines, carbon, crude oil, polyaromatic hydrocarbons, painter, mechanic, hairdresser ect….
Is chemotherapy alway systemic?
No, e.g. TUR bladder tumour treatment
What treatment might be used for bladder cancer?
Low risk non muscle invasive TCC (G1, G2, Ta) - check cystoscopies +- invasive chemotherapy
High risk non muscle invasive TCC (G3, Tis, T1) - check cystoscopies. Intravesical immunotherapy.
Muscle-invasive TCC. Neoadjuvant chemotherapy + radical cystectomy or radiotherapy
What sort of carcinoma are most upper urinary tract tumours?
Renal cell carcinoma RCC (95%)
What increases a persons risk of getting renal cell carcinoma?
Smoking, obesity, dialysis
Where does renal cell carcinoma frequently spread to?
Lymph nodes, IVC to right atrium, perinephric spread
30% metastases on presentation
What is the treatment for renal cell carcinoma?
Surveillance, radical nephrectomy, partial nephrectomy, developmental ablation.
Palliative - molecular therapies targeting angiogenesis (new 1st choice), poorly responsive to chemo/radiotherapies
Are upper urinary tract malignancies common?
No, only ~5%
What increases a persons likelihood of getting upper urinary tract malignancies?
Smoking, phenacetin abuse, balking nephropathy
What is the standard treatment for upper urinary tract malignancy ?
Nephro-ureterectomy (kidney, far, ureter, cuff of bladder)
What sort of cancer is in the upper urinary tract malignancies?
Upper tract transitional cell carcinoma
What initial inveatigations would you do for upper urinary tract malignancies?
USS, hydronephrosis, UT urogram, filling defects ureteric structure, retrograde pyelogram, ureteroscopy, biopsy, washings for cytology
What are the functions of the kidney?
Excretion - salt and electrolytes, water, acid, other metabolites, waste solutes
Glomerular permselectivity
Tubular functions - urine concentration/dilution, bicarbonate reclamation, NH4 secretion
Hormonal/vitamins - vitamin D, renin, erythropoietin
What might the symptoms of a failure of kidney excretion be?
Hyperkalaemia Na+ overload paralleled by H2O overload (oedema, peripheral and pulmonary, hypertension) Acidosis - acidotic breathing Lethargy and fatigue Uraemic syndrome
How might an error in glomerular permselectivity present?
Proteinuria
Haematuria
How might impaired tubular function present?
Impaired concentrating ability - frequency of urine, altered diurnal urine concentrating ability. Nocturia
Contributes to acidosis
May result in glycosuria with normal blood glucose
How might impaired kidney hormonal function present?
Metabolic bone disease
Anaemia
Hypertension
How is most kidney disease detected?
Opportunistically through screening at risk populations (hypertension, heart disease, diabetes, UT obstruction, systemic disease)
Describe asymptomatic microscopic haematuria
Common, may be due to urinary infection, polycystic kidneys, renal stones, renal/bladder tumours ect….
Increased likelihood of micro haematuria associated with proteinuria and/or hypertension of glomerular disease
Patients over 45yrs require cystoscopy alas first investigation
What colour is the urine in episodic macroscopic haematuria usually?
Brown/smokey rather than red
What might cause red or brown urine?
Haemoglobinurea, myoglobinuria, consumption of food dyes, macroscopic haematuria
What are the symptoms of (heavy) proteinuria?
Frothy urine, reduced plasma oncotic pressure (oedema), loss of immunoglobulins (infection), imbalanced regulators of the coagulation cascade (thromboembotic risk increased)
What is the normal urine protein excretion level?
Less than 150mg/24hrs (10-30mg albumin)
What is microalbinuria?
30-300mg albumininuria in 24hrs
Important prognostically in diabetes
What is non-nephrotic proteinuria?
Defined as protein excretion of less than 3.5g/24hrs
What sort of kidney disease is usually associated with proteinuria?
Glomerular
What is the classical triad of findings in nephrotic syndrome?
Proteinuria (usually over 3.5g/24hrs)
Hypoalbuminaemia
Oedema
+ hyperlipidaemia
Describe the clinical presentation of nephrotic syndrome
Muehrckes bands (fingernails)
Xanthelasma
Fat bodies in urine
Oedema
What does classical nephrotic syndrome accompany in children?
Post-streptococcal glomerulonephritis
Describe the manifestation of nephrotic syndrome
Rapid onset Oliguria Hypertension Generalised oedema Haematuria with smoky brown urine Normal serum albumin Variable renal impairment Urine contains blood proteins and red cell casts
Compare the onset of symptoms in nephrotic and nephritic syndromes
Nephrotic - insidious
Nephritic - abrupt
Compare the onset of oedema in nephrotic and nephritic syndromes
Nephrotic - ++++
Nephritic - +
Compare the BP in nephrotic and nephritic syndromes
Nephrotic - normal
Nephritic - raised
Compare the jugular venous BP in nephrotic and nephritic syndromes
Nephrotic - ++++
Nephritic - ++
Compare presence of haematuria in nephrotic and nephritic syndromes
Nephrotic - +/-
Nephritic - +++
Compare the presence of red cell casts in nephrotic and nephritic syndromes
Nephrotic - absent
Nephritic - present
Compare the serum albumin in nephrotic and nephritic syndromes
Nephrotic - low
Nephritic - normal/slightly reduced
What is rapidly progressive glomerulonephritis?
Describes a condition/clinical situation in which glomerular injury is so severe that renal function deteriorates over days. Patient may present as a uraemic emergency with evidence of extrarenal disease
When do symptoms of chronic kidney disease appear generally?
Once eGFR is over 30ml/min
Even then symptoms are mild and non-specific
Most patients start dialysis with eGFR 8-10ml/min
Describe some symptoms of advanced kidney disease
Tiredness and lethargy Breathlessness Nausea and vomiting Aches and pains Sleep reversal Nocturia Restless legs Itching Chest pains Seizures and coma
What is the clinical presentation of acute kidney injury ?
Abrupt decline in actual GFR (days-weeks). Upset of ECF volume, electrolyte and acid/base homeostasis. Accumulation of nitrogenous waste products.
What are the measurements that can be used to define acute kidney injury?
Increase in serum creatinine by >26.5umol/l within 48hrs
Increase in serum creatinine by >1.5 times baseline within 7 days
Urine volume <0.5ml/kg/h for 6hrs
What is the serum creatinine criteria for stage 1 AKI?
Increase of SCr >26umol/l
Increase of SCr >150-200% (1.5-2fold) from baseline
What is the serum creatinine criteria for stage 2 AKI?
Increase of SCr >200-300% (>2-3 fold) from baseline
What is the serum creatinine criteria for stage 3 AKI?
SCr >354umol/l with an acute rise of >44umol/l in less than 24hrs
Increase in SCr >300% (3 fold) from baseline or initiated on RRT (irrespective of stage at time)
What is the urine output criteria for stage 1 AKI?
<0.5ml/kg/hr for over 6hrs
What is the urine output criteria for stage 2 AKI?
<0.5ml/kg/hr for over 12hrs
What is the urine output criteria for stage 3 AKI?
<0.3ml/kg/hr for 24hr
Anuria for 12hr
What are the 3 types of AKI?
Pre-renal failure
Intrinsic renal failure
Post-renal failure
What is pre-renal AKI?
Actual GFR is reduced due to decreased renal blood flow.
No cell damage, so kidneys work hard to restore blood flow. Avidly reabsorption of salt and water (aldosterone and ADH release). Responds to fluid resuscitation
How does kidney autoregulation help prevent prevent pre-renal AKI?
Intrarenal prostacyclin high to reduce afferent tone. Effect tone high due to circulating vasoconstrictors. Of overwhelmed, AKI occurs.
What effect can NSAIDs have on kidney autoregulation?
Inhibit prostaglandins, so inhibit vasodilation of afferent artreriole
What effect can ACE inhibitors have on the kidney autoregulation?
Inhibit angiotensin 2 production, so inhibit vasoconstriction of efferent arteriole.
What are the 2 causes of pre-renal AKI?
Reduced effective extracellular fluid volume
Impaired renal autoregulation
What might develop if the causes of poor renal perfusion is not recognised and treated promptly?
Acute tubular necrosis
Why is ‘acute tubular necrosis’ a misnomer?
Generally not necrosis, but cells damaged therefore cannot be immediately reversed. The damaged cells cannot reabsorbed salt and water efficiently, or expel excess water
What might cause acute tubular necrosis?
Ischaemia (depletion of cellular ATP)
Nephrotoxins
Sepsis
Describe the sequence of blood vessels in renal bloodflow
Interlobar arteries - afferent arterioles - glomerular capillaries - efferent arterioles - peritubular capillaries - interlobar veins
List some endogenous nephrotoxins
Myoglobin, urate, biliruben
List some exogenous nephrotoxins
X-ray contrast
Assume every drug given to patient with ATN is nephrotoxic is until proven otherwise
Drugs e.g. ACE-I, aminoglycosides, NSAIDs, ect.
What is rhabdomyolosis?
Due to muscle necrosis - release of myoglobin ('crash injury e.g. Drug users/elderly who can't move, earthquakes/disasters ect). Myoglobin is filtered at the glomerulus and toxic to tubule cells, can cause obstruction. Very dark urine.
Give forced (alkaline) diuresisWhat is acute glomerulonephritis?
Immune disease affecting the glomeruli. Can be primary or secondary.
Describe primary acute glomerulonephritis
Disease only affects kidneys e.g. IgA nephropathy
Describe secondary acute glomerulonephritis
The kidneys are involved as part of a systemic process e.g. vasculitis
What is acute pyelonephritis?
Toxin induced - many drugs but commonest are antibiotics, NSAIDs, PPIs or bacterial infection that travels up the urinary tract.
Describe post-renal failure
5-10% AKI. More common in elderly. To cause AKI, obstruction must block both kidneys, or a single functioning kidney.
Obstruction with continuous urine production causes a rise in intraluminal pressure - dilation of renal pelvis (hydronephrosis) - decrease in renal function
How might the causes of post-renal kidney failure be grouped?
Within the lumen (kidney, ureter, bladder) e.g. Stones, blood, tumour
Within the wall (usually causes CKD, nor AKI) e.g. Congenital megaureter, stricture post TB
Pressure from outside e.g. Enlarged prostate, tumour, aortic aneurism
To cause AKI, what just stones be in?
Both renal pelvis or ureters
Obstruction of a single kidney
Neck of bladder
Urethra
Above what size will ureteric stones usually not be able to pass?
10mm
When might you use a USS for the urinary system?
Perform within 24hrs of presentation if obstruction is suspected as cause or AKI, or if cause is unclear
Do not need USS if cause is pre-renal/ATN unless not improving
When might you use a CXR for the renal system?
To look for fluid overload +- infection
When might you obtain a kidney biopsy?
Pre-renal and post-renal AKI ruled out
A confident diagnosis of ATN cannot be made
Systemic inflammatory symptoms/signs are present
How is AKI prevented?
Identify risk factors Monitor 'at risk' patients Ensure adequately hydrated Avoid nephrotoxins Detect early and identify cause
List some indications for dialysis
High K+ refractory to treatment
Metabolic acidosis where NaHCO3 not appropriate
Fluid overload refractory to diuretics
Presence of a dialysable nephrotoxin e.g. Aspirin OD
What are the signs of uraemia?
Pericarditis, reduced consciousness, intractable N&V
What is the prognosis of uncomplicated ATN?
Generally recovered within 2-3 wks if no superimposed insults. But hypertension on dialysis can cause additional ischaemic lesions and prolong recovery.
Mortality 30-80% (dependent on stage)
Define chronic kidney disease
The irreversible and sometimes progressive loss of renal function over a period of months to years.
Renal injury causes renal tissue to be replaced by extracellular matrix in response to tissue damage
Describe the parameters of GFR category G1
GFR >90
Termed normal or high
Describe the parameters of GFR category G2
GFR 60-89
Termed mildly decreased
Describe the parameters of GFR category G3a
GFR 45-59
Termed mildly to moderately decreased
Describe the parameters of GFR category G3b
GFR 30-44
Termed moderately to severely decreased
Describe the parameters of GFR category G4
GFR 15-29
Termed severely decreased
Describe the parameters of GFR category G5
GFR <15
Termed kidney failure
Define the parameters of ACR category A1
ACR <3mg/mmol
Termed normal to mildly increased
Define the parameters of ACR category A2
ACR 3-30mg/mmol
Termed moderately increased
Define the parameters of ACR category A3
ACR >30mg/mmol
Termed severely increased
At what point does does mortality start to increase with regards to normal renal function?
25% less than normal renal function
What is the normal range for GFR?
80-120ml/min
What is the normal range for serum creatinine?
80-120umol/l
What percentage of renal function can be lost, and still have creatinine levels within normal range?
Up to 60%
What determines creatinine conc.?
Renal function and muscle mass (age, sex, race)
If kidneys are normal in size and cause of CKD is not obvious, what should be considered?
A renal biopsy
What complications might acidosis have on CKD?
May affect muscle, bone, renal function progression (makes kidneys worse).
Not generally a problem until eGFR is <20, so only in serious kidney disease
How might you treat acidosis in CKD?
Oral NaHCO3 tablets
What are some complications of anaemia in CKD?
Decreased erythropoietin production, resistance to erythropoietin, decreased RBC survival. Blood loss.
Describe the effect of CKD on phosphate levels, and the consequences of this.
Decreased GFR causes an increase in blood phosphate levels (as phosphate is usually excreted at the kidney). This increase in phosphate leads to a decrease in serum calcium, thus causing an increase in PTH
What usually happens to phosphate at the kidney?
Excretion
What effect does an increase in phosphate in the blood have on serum calcium?
Decrease in serum calcium (stimulating PTH production)
What effect does decreased GFR have on active Vit D, and the consequences of this?
Decrease in levels of active Vit D, which can lead to osteomalacia
What are some signs of osteodystrophy found in an X-ray?
‘Rugger jersey’ spine (dark stripe in X-ray of vertebrae due to loss of Ca2+)
Erosion of terminal phalanges and bone cysts
Non bone calcification
How might you prevent or delay progression of mineral and bone disorders in CKD?
Lifestyle (smoking, obesity, lack of exercise) Treat diabetes (if present) Treat blood pressure ACE inhibitors/ARBs in proteinuria Lipid lowering
When is renal replacement therapy required?
When native renal function declines to a level no longer adequate to support health. Usually when eGFR 8-10ml/min (normal ~100ml/min)
Give some indications for initiating dialysis
Uraemic symptoms Acidosis Pericarditis Fluid overload Hyperkalaemia
What are the forms of renal replacement therapy?
Dialysis - haemodialysis, peritoneal dialysis
Renal transplant
When would you start renal replacement therapy?
When death is likely without it
eGFR <15mls/min
What are the symptoms of end stage renal disease
Tiredness - overwhelming fatigue. Physically and mentally incapacitated. Feelings of guilt and ineptitude at needing rest.
Difficulty sleeping
Difficulty concentrating
Symptoms and signs of volume overload (SoB, oedema)
Nausea and vomiting/reduced appetite (eat less meat)
Restless legs/cramps
Pruritus (itchy skin)
Sexual dysfunction/reduced fertility
Increased infections (reduced cellular and humoral immunity)
What does the amount of water produced depend upon?
GFR
ADH
What effect does reduced GFR have upon urine production?
Loss of the ability to maximally dilute and concentrate urine. Small glomerular filtrate but same solute load causes osmotic diuresis. Noctururia. Low volume of filtrate reduces maximum ability to excrete urine therefore maximum urine volume much smaller.
What bone diseases might occur as a result of kidney disease?
Hyperphosphataemia
Low 1-alpha-calcidiol
Generally asymptomatic in pre-dialysis patients (some have muscle and bone pains)
Why is there an increased tendency to bleed in anaemia?
Reduced platelet function
What effect does accumulation of waste products have in CKD?
Contributes to uraemia symptoms - reduced appetite, nausea and vomiting, pruritus
What might happen to dosing in a patient with ESRD/CKD?
Dose alteration required due to reduced metabolism/elimination. Drug sensitivity can be increased even if elimination is unimpaired, meaning side effects more likely e.g. Statins
Describe the passage of bloodflow in haemodialysis
Arterial blood - pressure monitor - pump - +anticoagulant - pressure monitor - dialyzer - airtrap & detector/pressure monitor - vein
What is the principles behind what goes on in a dialyzer?
Blood and dialysate move in opposite directions (countercurrent) to maximise clearance of solute through dialysis membrane
How often does a person on haemodialysis require dialysis?
3 times a week, 4hrs on the machine, in a designated slot.
What are some good points of haemodialysis?
Less responsibility than other renal replacement therapies
You get days off treatment
What are some not so good points of haemodialysis?
Travel time/ waiting
You’re tied to your allocated dialysis times
Big restrictions of food and fluid intake
Requires a fistula, which can be unsightly
~19 pills a day!
What are some contra-indications for haemodialysis?
Failed vascular access
Coagulopathy
Heart failure (can’t deal with loss of blood into machine)
What are some possible complications of haemodialysis?
Lines - infections, thrombosis, venous stenosis
AVF - thrombosis, bleeding, access failure, steal syndrome
CVS instability
Feel chronically unwell
Accumulate morbidity (CVS, bone ect.)
Describe the principles of peritoneal dialysis
Peritoneum is filled with dialysate fluid. Waste products cross the semipermeable membranes (from capillaries) into the perineal space. The fluid here is then replaced. Approx 4-5 bags throughout the day, but overnight dialysis is also an option.
Give some positives of peritoneal dialysis
Self-sufficient/independence
Generally less fluid/food restrictions
Fairly easy to travel
Renal function may be better preserved initially
Give some negatives of peritoneal dialysis
Frequent daily exchanges or overnight
You are responsible for your own care
Give some contraindications of peritoneal dialysis
Failure of peritoneal membrane
Adhesions, previous abdo surgery, hernia, stoma
Patient (or carer) unable to connect/disconnect
Obese or large muscle mass
~10 pills a day (significantly less than haemodialysis)
Give some possible complications of peritoneal dialysis
Peritonitis, exit or tunnel site infections Ultrafiltration failure Leaks (scrotal, diaphragmatic) Development of hernia ~10 pills a day
Talk about home dialysis
Allows more dialysis hours Better large molecule clearance Patients often feel better Patients often need fewer medications Home HD requires someone at home with you
What are the benefits of transplant?
Reduced mortality and morbidity compared to dialysis
Better quality of life
What are some drawbacks of transplant?
Peri-operative risk (mortality risk greatest for first 3 months)
Malignancy risk
Infection risk
Risk of diabetes/hypertension from meds
What are the different types of kidney transplant available?
Live donor (related or not)
Deceased after brain death (DBD)
Deceased after circulatory death (DCD) or non-heart beating
Is dialysis better for everyone?
No - patients who choose conservative care can survive a substantial length of time achieving similar numbers of hospital-free days to patients who choose haemodialysis.
Dialysis prolongs survival for elderly patients with ESRD and significant comorbidity by ~2yrs
Heart disease is especially associated with poor outcomes on dialysis
List some S ymptoms with ESRD with end of life care
Pain - related to ESRD (bone pain, dialysis-related pain). Not related (neuropathy, musculoskeletal) Constipation Fatigue Nausea/lack of appetite Pruritus Cramps/restless legs Sleep disturbance
