renal physiology Flashcards
What is the medullary interstitium
Space between nephrons and medulla of the kidney
What makes the medullary interstitium more concentrated
Sodium chloride urea
Which cells in the juxtoglomerular apparatus are responsible for sensing the conc. of sodium chloride in the distal convoluted tubule
Macula densa cells
What cells release renin
Granular cells (juxtoglomerular)
What cells make up the juxtoglomerular apparatus
Extraglomerular mesangial cells
Granular cells
Macula densa cells
How to differentiate between central diabetes insipidus and nephrogenis DI
Water deprivation test
Central = ADH deficiency
Nephrogenic = reduced ADH detection in the kidney
Urine osmolality will increase on administration of desmopressin in central DI but not in nephrogenic
What causes release of ADH
Increased plasma osmolality
what two structures make up the renal corpuscle
Bowman’s capsule + glomerulus
Which component of the nephron is responsible for reabsorption of sodium
Proximal convoluted tubule
why is creatinine a good measurement of GFR
It is freely filtered at the glomerulus and not reabsorbed
Therefore creatinine clearance rate is reflective of hoe well the kidney is working
How does renin-angiotensin correct a dehydrated state
Renin-angiotensin system stimulated
Sodium ion uptake in the distal convoluted tubule increased
Which ion provides the concentration gradient for the absorption of solutes ?
Sodium
What is the countercurrent system
What is the typical value of GFR in a healthy 20 year old
90-120mL/min
What helps differentiate between pre-renal AKI and acute tubular necrosis
Fractional excretion of sodium
*renal biopsy shows subepithelial immunoglobulin and complement deposits on the glomerular basement membrane , basement membrane is also thickened
Membranous nephropathy
Management of anti-GBM/ good pastures
High dose corticosteroids, cyclophosphamide and plasmapheresis
Treatment of HUS
Supportive with fluid rehydration
Haemofiltration
Steroids
Plasmapheresis
What is contained within the nephron
Glomerulus
Bowmans
Proximal con. Tubule
Descending l.o.h
Ascending ll.o.h
Distal convoluted. Tubule
Where are aquaporin 1 channels found
Descending loop
Features of aquaporin 1
These are always open in the descending limb
Allows for passive loss of water
What is the counter-current multiplier mechanism
Describes Na/K/2Cl co-transporter pumping solutes into the medullary interstitium and as a result the passive diffusion of water into the medullary interstitium via aquaporin channels
This mechanisms allows for the slow removal of sodium and chloride
What is the plasma osmolality at bowman’s and proximal convoluted tubule
300mosm
What’s is the plasma osmolality at the distal convoluted tubule / end of ascending limb
325 mosm
What is the plasma osmolality at the end of the descending limb
1200mosm
What is permeable at the descending limb
Water is the only permeable thing
What is permeable at the ascending limb
Only solutes
Water is impermeable here
What is the counter-current exchanger
Vasa recta
Where is glucose reabsorbed
100% is reabsorbed at the proximal convoluting tubule
90% of what is reabsored at the proximal convoluted tubule
Bicarbonate
Sodium is reabsored at 65% where ?
Proximal convoluted tubule this also means 65% of water is also reabsored
What is 100% reabsorbed at the proximal convoluting tubule
Glucose
Amino acids
Lactate
Is phosphate excreted or reabsorbed at the p.c.t ?
Excreted due to inhibition of transporter via binding of PTH
How do the other ions ie Cl, Ca, Mg, K get reabsorbed ?
Via Paracellular transport via tight junctions
About 50-55% reabsorbed
How are lipids reabsorbed into the blood ie urea
They can pass through the phospholipid bilayer - passive diffusion
what makes up the renal corpuscle ?
Glomerulus and bowman’s
What makes up bowman’s
Podocytes
What makes up glomerulus
Glom. Basement membrane. + endothelial lining
What charge is the GBM and why is this relevant to filtration
Negative charge on the GBM repels negatively charged particles ie plasma proteins (albumin IgG)
Acts as a filter in this way
What particles are attracted to the GBM
Na+
K+
(Positively charged -> attracted to negatively charged GBM)
So these particles will pass through the glomerular capsule
What’s gets through the GBM ?
Positively charged molecules of < 7.9nm
(Bicarbonate, glucose, insulin, haemoglobin, amino acids, creatinine, vitamins, sodium/potassium/chloride/magnesium)
What happens is macro-molecules manage to pass through the renal corpuscle ?
Mesangial cells phagocytose them
What do molecules have to pass through to make it into the proximal convoluted tubule ?
(In order)
Fenestrated capillaries
GBM
Filtration slit
Podocytes and nephrin
What is nephrin
A protein that sits in between Podocytes that allows only really small particles through (7-9nm)
What is the filtration slit
Space between nephrin proteins and GBM
What is the glomerular filtration rate ?
How much viscous plasma is passing through the glomerular to Bowman’s capsule every minute
What is the average GFR
125ml/min
What influences GFR
Permeability
NFR (net filtration pressure)
And surface area (of glomerulus)
What are the pressures (NFR) acting on GFR
- glomerular hydrostatic
- Colloid osmotic
- capsular hydrostatic pressure
(All these together = NFR = 10mmHg into Bowman’s)
What is glomerular hydrostatic pressure
Affected by blood pressure
Pushes things OUT of capillaries into Bowmans
At about 55mmHg
What is osmotic colloid pressure ?
Affected by proteins in blood ie myeloma increases proteins
This pressure tries to keep water in arterioles - so exerts a pressure of 30mmHg against Bowman’s capsule
Action is exerted by albumin
What is capsular hydrostatic pressure ?
Affected by calculi stuck in the nephron
This pressure is a back flow pressure , created when molecules pass from Bowmans -> prox. C.t. This creates a back pressure on capillary bed
Ie a car at 0mph has no air resistance but a car at 60mp will have air resistance (back pressure)
This pressure is about 15mmHg (acting against Bowmans)
Why does decreased surface area decrease GFR ?
What is KF
The filtration co-efficient
GFR = NFR + KF
What stimulates the secretion of potassium / K+
Aldosterone - otherwise all K+ would be reabsorbed via proximal and distal convoluted tubule
What is arterial natriuretic peptide
Produced by the heart and stored in atrial muscle cells
Released when the atrial cells are mechanically stretched due to an increase in the circulating plasma volume
What does ANP do ?
Promotes excretion of sodium and diuresis
What does PTH do ?
Increases calcium reabsorption
Decrease phosphate reabsorption
Which nephron structure is especially important in the kidneys ability to produce urine of varying concentration
Loop of henle
What is the GFR
A protein free plasma
Is formed as a result of passive forces acting across the glomerular membrane
When arterial BP is elevated above normal - what is a compensatory charge in renal function
Afferent arteriolar vasodilation
What is the renal threshold
Plasma concentration of a particular substance at which its Tm is reached and the substance first appears in the urine
Function of aldosterone
Stimulates sodium reabsorption in the distal and collecting tubules
Stimulates potassium secretion in the distal tubule
Where does water absorption occur to the greatest extent
Proximal convoluted tubule
Where is water reabsorption under the control of vasopressin
Distal and collecting tubules
What is plasma clearance
Volume of plasma that is completely cleared of a substance by the kidney in one minute of time
What establishes the medullary vertical osmotic gradient by means of counter-current multiplication
Loops of henle of juxtamedullary nephrons
Action of vasopressin
Activates cyclic AMP second-messenger system within the tubular cells
Nephrotoxic drugs
NSAIDs
Aminoglycosides
ACEi
ARBs
Diuretics
How to remove potassium from the body ?
Calcium resonium
Loop diuretics
Dialysis
What is oliguria
Urine output of less than 0.5ml/kg/hr
How to detect AKI
Urine output - oliguria
Fluid overload
Rise in potassium, urea, creatinine (normally excreted out)
KDIGO definitions on detecting AKI
- Rise in serum creatinine of 26 micro mol/litre or greater within 48 hours
- 50% rise in creatinine known or presumed to have occurred within past 7 days
- Call in UO to less than 0.5ml/kg/hr for more than 6 hours in adults
Diagnosis of AKI ?
All patient with suspected AKI need urinalysis done , also if there is no identifiable cause or at risk of UTI then do a renal USS within 24 hours of assessment
EGFR for kidney failure
Less than 15
*urine has brown granular casts
Acute tubular necrosis
Mechanism of action of spironolactone
Aldosterone antagonist
Common causative organism for post-strep. Glomerulonephritis in young kids
Strept. Pyogenes
*crescentic glomerulonephritis
GPA
What is renal papillary necrosis
Coagulative necrosis of renal papillae due to:
Pyleonephritis
Diabetic nephropathy
Analgesic nephropathy
Sickle cell anaemia
How does renal papillary necrosis present ?
Visible haematuria
Loin pain
Proteinuria
History of migraines
*tram-track appearance
Membranoproliferative glomerulonephritis (type 1)
*loss of subcutaneous tissue from patient face?
Type 2 membranoproliferative glomerulonephritis
What type of cells line distal convoluted tubule
Simple cuboidal cells
These allow for reabsorption via sodium-chloride co-transporter
Also found in thick ascending limb of the loop of Henle
Effect of alkalosis on potassium
A metabolic alkalosis causes the stimulation of beta-intercalated cells to re-absorb hydrogen ions in the kidney collecting ducts
Some hydrogen is re absorbed into co-transport with potassium —> therefore intracellular H+ and K+ within the intercalated cells will increase
This create a K+ concentration gradient that promotes passive transport of potassium from intercalated beta cells into tubule
This results in increased potassium excretion and therefore a transient hypokalaemia
What is the main osmotically active ion in the intracellular compartment
Potassium
Which cells sit between the glomerular capillary loops and binds them together
Mesangial cells
What is the specific component of the GBM that makes it negatively charged - and so able to repel plasma proteins of similar charge?
Heparin sulfate
What is the most accurate measure(r) of eGFR
Inulin
(It is freely filtered at the glomerulus and is not reabsorbed or secreted in the kidney tubules)
A decline in GFR = incline in inulin
Is the N/L/2Cl co-transporter found in the thick or thin ascending loop of henle
Thick
side effect of metformin
Compensated metabolic acidosis (lactic acidosis)
What is the active form of vitamin D
Calcitriol
What converts 25,hydroxyvitamin D3 into calcitriol
1-alpha-hydroxylase (in the kidney)
Function of calcitriol
Binds to vitamin D receptor for a variety of functions , including bone health , calcium regulation and immune function
Where are aqua-porin-2 channels
Distal convoluted tubule and collecting tubules (AV1 = descending loop of Henle)
Dysfunction of the proximal convoluted tubule results in what type of renal tubular acidosis ?
Proximal RTA type 2
Causes of RTA type II
Carbonic anhydride inhibitors ie acetazolamide
