Renal Flashcards
What is the juxtaglomerular apparatus?
The region where the distal tubule passes in between afferent and efferent arterioles
How do glomerular capillaries differ from those in the rest of the body?
The pore sizes are 100x bigger - makes them very leaky
Where are macula densa cells located and what is their function?
Specialised cells found in the distal tubule at the region of the juxtaglomerular apparatus
Sensitive to salt - able to release vasoactive chemicals which can influence the SM in the wall of the afferent arteriole in order to achieve negative feedback
What is a typical GFR?
125 ml/minute
What are the four capillary pressures acting at the glomerulus?
Favouring filtration
- Glomerular capillary blood pressure (55 mm Hg)
- Bownman’s capsule oncotic pressure (0 mm Hg)
Opposing filtration
- Bowman’s capsule hydrostatic pressure (15 mm Hg)
- Capillary oncotic pressure (30 mm Hg)
How is autoregulation of GFR achieved?
Myogenic
- If vascular SM is stretched, it contracts to constrict the arteriole
Tubuloglomerular
- Involves juxtoglomerular apparatus
- If GFR rises, more NaCl flows through the tubule leading to constriction of afferent arteriole
What are the clearance values for:
- Glucose
- Urea
- H+
Glucose - 0
Urea - GFR
What is the difference between RPF and GFR markers?
A GFR marker should be filtered freely and NOT secreted or reabsorbed
A RPF marker should be filtered AND completely secreted
What is the rate of reabsorption of filtered fluid in the proximal tubule?
80 ml/min
What is the tonicity of fluid reabsorbed in the proximal tubule compared to the filtrate?
Isotonic
What path do H20 and Cl take when following Na reabsorption in the proximal tubule?
Paracellular route
Describe the process of glucose reabsorption in the proximal tubule
Glucose enters the tubular epithelial cell by secondary active transport through the Na+/glucose cotransporter at the apical membrane
This is an example of co-transport)
Glucose exits the tubular cell and enters the interstitial fluid at the basolateral membrane by facilitated diffusion
Where is the triple co-transporter found?
Thick part of the ascending limb in the loop on Henle
What is the tonicity of the tubular fluid on entering the distal tubule?
Tubular fluid entering the distal tubule is hypo-osmotic
What is the purpose of countercurrent multiplication?
To concentrate the medullary interstitial fluid
What happens to blood osmolality as it dips in and out of the medulla
Blood osmolality rises as it dips down into the medulla i.e. water loss, solute gained
Blood osmolality falls as it rises back up into the cortex (i.e. water gained, solute lost)
What makes up the countercurrent system?
The loop of henle with the vasa recta
What preserves the medullary osmotic gradient?
The countercurrent exchanger
What does a high medullary osmolality allow?
Production of hypertonic urine in the presence of ADH
What is meant by a compliant bladder?
Able to keep intravesicular pressure constant with an increase in volume of urine
What is the nervous supply to the bladder in the micturition cycle?
Filling phase is under sympathetic control from hypogastric nerves T10-L2
Voiding phase is under parasympathetic control form pelvic nerves S2-S4
How can you work out detrusor pressure?
Cystomethogram
Bladder pressure - abdominal pressure
List some causes of urge incontinence
Afferent overstimulation - source of irritation within the bladder e.g. stone, tumours
Paraplegia
Pelvic surgery or #
Surgery for urge incontinence?
Enterocystoplasty - cut the bladder in half and insert some small bowel in between
Treatment of stress incontinence?
Not much role for pharmacotherapy
Tape procedure - insert tape across urethra to pull it shut
Which part of the nephron is most important for salt balance?
Distal tubule
What is the main factor controlling Na and water regulation in the distal tubule?
Hormonal
Which parts of the nephron are under hormonal control?
Distal tubule + collecting duct
What can the collecting duct be divided up into?
What is the functional difference between the two?
Early + late
Early collecting duct is similar to late distal tubule
Late collecting duct has
- Low ion permeability
- Permeability to water and urea influenced by ADH
What is the stimulus for ADH and what is its purpose?
Stimulated by increased plasma osmolality
Promotes water reabsorption in the distal tubule and collecting duct
What are the two types of vasopressin receptor?
Type I - activation causes vasoconstriction of arterioles
Type II - causes increased aquaporin expression in renal tubular cells
How does ADH work in renal tubular cells?
Causes aquaporins in vesicles in the cytoplasm to migrate to the cell surface
This increases permeability of the tubular cell to water
When plasma ADH is low the aquaporins become internalized back into the cytoplasm, where they are stored
How does solute excretion change with ADH?
It doesn’t - ADH only works on water
How much of a change in ECF fluid volume do you need to stimulate left atrial volume receptors?
A LOT
Which drug is associated with diabetes insipidus?
Lithium
What is the relation of left atrial stretch receptors on ADH?
Decreased atrial pressure stimulates ADH release
How does stimulation of stretch receptors in the GI tract affect ADH release?
Feedforward inhibition of ADH
What are the two ways in which aldosterone can be stimulated?
- Indirectly - decrease in plasma concentration of Na activates RAAS
- Directly - increase in plasma concentration of K
What happens if you don’t secrete aldosterone?
You lose salt in the urine and you retain K
Describe the three modulators of renin release from the kidney
- Reduced pressure in afferent arteriole - sensed by granular cells
- Reduced NaCl in the distal tubule - sensed by macula densa cells
- Increased sympathetic activity (as a result of reduced MABP) - granular cells are directly innervated by the sympathetic nervous system
How does aldosterone work?
- Increases Na/K pump expression on basolateral membrane
- These pumps work at a higher rate
- Promotes apical expression of Na channels
What is the difference between water diuresis and osmotic diuresis
Water diuresis - increased urine flow but not an increased solute excretion
Osmotic diuresis - increased urine flow as a result of a primary increase in salt excretion
UTI foul smelling, like burnt chocolate = ?
Proteus spp
Organism in cathaterised patient with UTI = ?
Antibiotic?
Pseudomonas
Ciprofloxacin
When should you send a urine sample to the lab regardless of symptoms?
Male
Child
Pregnant
Immunosuppressed
Which UTI patients should you not dipstick?
CSU or elderly
Proceed by sending sample straight to lab and treat your top differential in the mean time
When is microscopy of urine done?
Only in selected urgent cases
Antibiotic for female lower UTI?
3 days of Nitrofurantoin or Trimethoprim
Antibiotic for Pyelonephritis or complicated UTI in GP?
Co-trimoxazole or co-amoxiclav (7 days)
Antibiotic for uncathaterised male UTI?
Nitrofurantoin or trimethoprim (7 days)
Antibiotic for prostatitis?
Ofloxacin or ciprofloxacin (28 days)
Antibiotic for epididymo-orchitis?
If suspect STI give doxycycline
If suspect UTI give ofloxacin or ciprofloxacin
Antibiotic for complicated UTI in hospital?
IV amoxicillin + gentamicin
if penicillin allergic give IV co-trimoxazole + gentamicin
Treatment of bacteriuria in pregnancy?
1st or 2nd trimester - Nitrofurantoin
3rd trimester - trimethoprim
Second line any trimester - Cefalexin
All 7 days
What should you be wary of in penicillin allergy?
Cephalosporins
Antibiotic for enterococci?
Vancomycin
What ENT problem can loop diuretics cause?
Hearing loss in high doses
Inner ear endolymph has the same co-transporter
Aside from mild heart failure and hypertension, what else can thiazides be used for?
Nephrolithiasis - hypercalciuria
Nephrogenic diabetes insipidus - along with NSAIDs can reduce urine output
Which renal disease are thiazides no good in
Renal failure with GFR <30
Name two thiazides and their uses
Bendroflumethiazide - mild-moderate heart failure, hypertension
Metolazone - additive diuresis with loop diuretics
List five side effects of thizides
- Postural hypotension
- Metabolic alkalosis
- Hypokalaemia, hyponatraemia, hypomagnesaemia, hypercalcaemia
- Hyperglycaemia, hyperlipidaemia
- Hyperuricaemia + gout
What does the risk of hypokalaemia when using diuretics vary with?
Duration of action of the drug - more risk with longer acting i.e. thiazides
Symptoms of hypokalaemia?
Weakness
Myalgia
Fatigue
Arrhythmias
What endocrine problem can loop and thiazide diuretics cause?
How can you treat this?
Secondary hyperaldosteronism
K sparing diuretic
How do spironoactone and eplerenone work?
Compete with aldosterone to reduce expression of Na channels by decreasing gene expression
The channel which is reduced is the Na/K ATPase which is in the basolateral membrane
Where in the nephron do amiloride and triamterene work?
Distal tubule and collecting tubules
What is spironolactone metabolised to?
Canrenone - accounts for up to 2/3 of the action of the drug
How do carbonic anhydrase inhibitors work?
In proximal tubule
Increase excretion of HCO3, Na, K and H20
Metabolic complications of CA inhibitors?
Alkaline diuresis
Hypokalaemia
Metabolic acidosis
If acidic drug poisoning, which type of diuretic should you give?
CA inhibitor
Which diuretic should you give a patient that is hyponatraemic?
Vasopressin
Which diuretic should you give in ascites?
Aldosterone inhibitor
When are aquaretics used?
SIADH
How do uricosurics work?
Block active transport of organic acids to reduce net reabsorption of urate
When are uricosurics contraindicated?
Renal impairment or history of renal stones
How do the kidneys control HCO3-?
What do these depend on?
- Variable reabsorption of filtered HCO3-
- Kidneys can add “new” HCO3-
Both depend on H+ secretion into the tubule - in orderr to reabsorb carbonate and make new, you need hydrogen ion secretion
How are H+, HCO3- and CO2 related in acid base balance?
Levels of CO2 drive H+ which in turn drives bicarbonate ion resorption
How is “new” HCO3- formed?
When buffer stores are depleted of HCO3- by a big acid load, secreted H+ combines with the next most plentiful buffer in the filtrate - phosphate
Acid phosphate is the excreted in the urine
In doing this you have gained a new HCO3- ion which can be added to the blood
How else can you add “new” HCO3- to the blood if severely acidotic?
You can combine ammonia with H+ to form ammonium, which is secreted
You have excreted acid as NH4+ and generated a new HCO3- in the process
What three things does tubular H+ secretion do?
- Drives reabsorption of HCO3-
- Forms “acid phosphate”
- Forms ammonium ion
What is the vast majority of H+ secretion used for?
HCO3- reabsorption to prevent generation of acidosis
What is normal HCO3- concentration?
23-27 mmol/l
What is normal arterial PCO2?
35-45 mmHg
What is compensation
Immediate restoration of pH irrespective of what happens to [HCO3-] amd PCO2
List some causes of respiratory acidosis
Failure of the respiratory system e.g. chronic bronchitis, emphsema, airway restriction
Respiratory depression - morphine, GA
Which direction is the equilibrium driven in respiratory acidosis?
CO2 retention drives it to the right
How do the kidneys compensate for respiratory acidosis?
Remember that blood PCO2 drives H+ secretion in the kidney
All filtered HCO3- is reabsorbed
H+ continues to be secreted and generated titratable acid and ammonium
What does correction of respiratory acidosis require?
Lowering of PCO2 by restoration of normal ventilation
List some causes of respiratory alkalosis
Low inspired PO2 at altitude
Hyperventilation
How do the kidneys compensate for respiratory alkalosis?
Excessive removal of PCO2 reduces H+ secretion in the kidneys
So HCO3- is secreted in the urine
What causes metabolic acidosis?
Excess H+ from any source other than CO2
Ingestion of acids
Lactic acid during exercise
Excess loss of base from the body e.g. diarrhoea
Why is HCO3- low in metabolic acidosis?
Depleted as a result of buffering excess H+
What senses a decrease in plasma pH?
Peripheral chemoreceptors in the aortic arch and carotid body
Why is respiratory compensation essential for metabolic correction?
Kidneys take a long time to catch up so you need the breathing to compensate while the kidneys catch up
List some causes of metabolic alkalosis
Excessive loss of H+ from the body
- Loss of HCl from vomiting
- Ingestion of alkali
- Aldosterone hypersecretion
