FUNCTIONS OF THE KIDNEY Flashcards
functions
-Removing metabolic waste from the extracellular fluid
(urea, acids)
-Controlling the volume of extracellular fluid (close link
to blood pressure)
-Maintaining optimal concentrations of vital solutes in
the extracellular fluid (Na, K, H, Ca, Mg, Cl, Phos)
How much of the cardiac output goes to the kidneys
20%
three basic processes of the nephron
glomerular filtration - filtering of blood into tubule forming the primitive urine (glomerular filtrate)
tubular reabsorption - selective absorption of substances from tubule to blood
tubular secretion - secretion of substances from blood to tubular fluid
what is the glomerular filtration barrier
A unique structure allowing extracellular fluid to be
filtered and to leave the body:
– Specialised capillary endothelium
– Glomerular basement membrane – collagen based
– Podocyte foot processes
Normal GFR approx
100ml/min = 144L per day
movement of solutes and water across membranes ..
diffusion
specific membrane channels
- energy dependent
- down a conc gradient
- down an electrical gradient
- down an osmotic gradient
controlled by systemic and local mediators
PCT cell features
basolateral membranes with infoldings for ATPase
apical membrane with microvillae and aquaporins .
cuboidal
how much sodium chloride is reabsorbed in PCT
approx 70%
nearly all amino acids and glucose is reabsorbed in PCT
what are the loop of henle rules
1. Thick ascending limb is impermeable to water, but actively transports sodium, potassium and chloride 2. Thick ascending limb provides the concentration gradient to promote water reabsorption from the thin DLH 3. Thin descending limb is freely permeable to salt and water 4. Vasa recta doesn’t wash away the gradient by using countercurrent exchange
what does the juxta-glomerular apparatus
maintains GFR in face of increases or decreases in blood flow to the kidney
macula densa senses tubular flow
what does the macula densa produce when there is an increase in tubular flow
adenosine which causes afferent arteriolar constriction
if there is a reduced tubular flow…
sensed by macula densa which causes granular cells to produce renin
reasons for reduced sensed volume
extracellular fluid depletion haemorrhage
vasodilation
pump failure
Kidney response to reduced sensed
volume
•Efferent glomerular arteriolar constriction preserves waste excretion • Avid tubular sodium and water re-absorption preserves extracellular fluid volume net effect - oliguria - concentrated urine - low urine Na concentration - high urine potassium secretion
what helps maintain extracellular fluid calcium concentration
sensing tissues - parathyroid gland
calciotropic hormones - parathyroid hormone , hydroxylated vitamen D
effector tissues - kidney , intestine and bone
equation for clearance
= number of particles in urine /concentration of particles in plasma
what is creatinine
normal product of muscle metabolism
plasma concentration is dependent on muscle mass and kidney function
incompletely filtered but some tubular secretion
creatinine clearance
= (urine volume x creatinine concentration in urine )/ conc of creatinine in plasma
effect of muscle ,mass on the serum creatinine levels leads to …
overestimation of function in women , elderly and other low muscle mass groups
what are the 3 concentric layers of connective tissue that protect and stabalise the kidnay?
fibrous capsule - layer of collagen fibres
adipose fat
renal fascia - dense fibrous outer layer that anchors the kidney into surrounding structures . the renal fascia also lines the renal sinus and internal cavity within the kidney
what is the hilum
is the entry of artery , renal nerves and exit of the vein and ureter
what is the difference between the cortical and juxtamedullary nephrons
85% Cortical nephrons & 15% Juxtamedullary nephrons
• Cortical nephrons are situated mainly in the cortex, they have a short loop that dips slightly into the medulla.
• Juxtamedullary nephrons have long nephron loops that extend deep into the medulla. The long loop plays a key role in water conservation and the formation of concentrated urine
the walls of the glomerular capillaries are covered in what?
podocytes which are specialised cells that create slits
what is the glomerular filtration barrier
endothelial cells
glomerular basement membrane
podocytes
what is autoregulation
is the process by which the afferent arterioles respond to changes in pressure in the glomerulus by dilating or constricting (myogenic reflexes). This maintains the local pressure constant between 60-70mmHg.
juxtaglomerular apparatus is made up of
macula dense (specialised part of the DCT ) juxtaglomerular cells (produce renin ) mesengial cells
RAAS system
when blood volume falls
juxtaglomerlar cells secrete renin into blood stream
renin converts angiotensin I
ACE from lungs converts angiotensin I to II
ANG II causes sytemic vasoconstriction . increasing BP . Acts on the adrenal glad to produce aldosterone
what is atrial natriuretic peptide ANP
hormone released from the atria when blood volume is high . the increased venous return stretches the walls of the atria and releases ANP
causes dilation of the afferent arterioles and constriction of efferent , thus increasing GFR.
there is decreased reabsorption of sodium in the tubules
where is the majority of bicarbonate absorbed
PCT
characteristics of the thin descending loop
permeable to water but impermeable to sodium and other salts
characteristics of the thick ascending loop
actively pumps out sodium and chlorine but is impermeable to water
what is the osmolarity of the loop
The osmolarity of the loop and the surrounding interstitial renal space increases deeper into the medulla. Therefore, the deeper medullary parts of the kidneys are saltier. The base of the loop has an osmolarity of 1200 mOsm/L • Countercurrent
what is an overview of the counter current multiplication
- Sodium and chloride are pumped out of the thick ascending limb and into the interstitial fluid.
- This pumping action raises the osmotic concentration in the interstitial fluid around the thin descending limb.
- This results in an osmotic flow of water out of the thin descending limb and into the peritubular fluid. This loss of water increases the solute concentration in the thin descending limb.
- The arrival of the highly concentrated solution in the thick ascending limb speeds up the transport of sodium and chloride ions into the interstitial fluid of the medulla.
what does a NK2CL co transport do?
located on the apical membrane of the thick ascending limb . it transports 2 chloride ions , 1 sodium ion and one potassium ion by active transport .
the potassium can be recycled as it passively moves back down the conc gradient to the tubular lumen. the positive charge created by the potassium drives other ions to pass through the intracellular gaps.
this is targeted by loop diuretics like furosemide
how much of the primary filtrate reaches the DCT
15-20%
what is an ENaC
epithelial sodium channel is unique protein that sits within the apical membrane of the principal cell and has affinity for sodium . sodium moves through the ENaC alone . the entry of sodium from the lumen creates a lumen negative voltage which stimulates the secretion of potassium ions into the lumen via apical channel
things to look out for in urinalysis
frothy urine - protein present concentrated urine - dehydration fishy smell - infection sweat smell - ketones (DKA) blood - visible haematuria and or non visible
what are the different types of calculi?
calcium oxalate (60%) calcium phosphate (15%) uric acid (10%)
symptoms of renal stones
continuous dull ache in loins
symptoms of ureteric stones
cause classic renal colic due to increase in peristalsis in ureters in response to passage of small stone - pain usually radiated from loin to groin
symptoms of bladder stones
cause strangury -urge to pass but cannot
recurrent untreatable UTIs , haematuria or renal failure
what are the different categories of transplant donation
directed donation - to a loved one or friend
non-directed - donor gives an organ the general pool of patients to be transplanted into the recipient and the top of the waiting list
where is erythropoietin made
in the kidney, the renal interstitial cells (fibroblasts) will sense hypoxia and are sensitive to low o2 levels and will start producing it
gold standard for measuring GFR
insulin is freely filtered by the glomerulus and neither reabsorbed not secreted by the tubule .
insulin clearance is the gold standard - but too expensive and cumbersome
why are creatinine and cystatin C used for measuring GFR
there is no such endogenous substance that is produced at a constant rate, that is freely filtered at the glomerulus , not reabsorbed and not secreted. but these two come very close
what is creatinine
• Normal product of muscle metabolism
• Daily production constant
• Plasma concentration dependent on muscle mass
and kidney function (and recent protein intake)
• Incompletely filtered but some tubular secretion
what is serum creatinine problems
exponential relationship leads to slow recognition of loss of the first 70% of kidney function . surprise at the sudden rise in creatinine
effect of muscle mass leads to ;
overestimation of fucntion in women and elderly and in other low musce mass groups
what is GFR measured in
ml/min/1.73m2
eGFR by MDRD formula is based on serum
creatinine, age, sex and black race
How can we tell kidneys are not
working?
• Low eGFR - <60ml/min
• Rise in serum creatinine within the
eGFR>60mL/min range
oliguria is a warning of what?
warning of impending acute
tubular necrosis
oliguria is a warning of what?
warning of impending acute
tubular necrosis
Kidney very sensitive to other ‘insults’ when
oliguric eg intravenous contrast, nephrotoxic
medicines, infection
causes of acute kidney infection or chronic kidney infection
ineffective blood supply
glomerular diseases
tubulo-interstitial diseases
obstructive uropathy
what threats are there to homeostasis
generation of CO2 from aerobic respiration
metabolism of foods generating acid or alkali
incomplete respiration - anaerobic - ketoacids and lactic acid
loss of alkali in stool or loss of acid in vomiting
acid base regulation has 3 major components
buffering
ventilation- control of co2
renal regulation of HCO3 and H+ secretion and reabsorption
change in H+ by factor of 2 leads to change in pH of
0.3
what are buffers
weak acids , partially dissociated in solution
what do buffers do?
buffers avoid big changes in hydrogen concentration
because co2 is highly diffusable and conc of co2 is regulated and controlled by respiration co2 conc is held constant
addition of H+ consumes HCO3 which generates co2 and water , the co2 is then exhaled and there is little h+.
loss of h+ leadz to the opposite , generating HCO3
WHAT IS A VOLATILE ACID
IT can be eliminated from the body as a gas
How do the kidneys Regulate AcidBase
Balance?
• Reabsorb filtered HCO3
• Secrete “fixed” acid
– Titrate non- HCO3 buffer in urine - primarily PO4
– Secrete NH4
into urine
• These goals are achieved by using selective permeability
of the luminal and baso-lateral cell membranes to match
transport of H+ and HCO3 in opposite directions
how is HCO3 reabsorbed
Active process largely in proximal tubule with
small contributions from TALH and DCT
• Inability to reabsorb filtered HCO3 is a cause of
metabolic acidosis
what does glutamate metabolism produce
bicarbonate and ammonia
excretion of acid in the kidneys
tubular cells generate new bicarbonate, which is absorbed, along with a hydrogen that binds ti a base other than bicarbonate . filtered PO4 or secretion of ammonia
excretion of ammonium is regulated by..
metabolism of glutamine . acidosis stimulates glutamine transport and oxidation .
metabolic acidosis
H+ increased
pCO2 decreased
HCO3 decreased
causes of metabolic acidosis
addition of extra acid - lactic acidosis , ketoacidosis
failure to excrete acid - renal tubular acidosis
loss of HCO3 - in stool or urine
* primary abnormality is fall in plasma HCO3
compensatory respinse is fall in pCO2 due to respiratory drive
Systemic effects of metabolic
acidosis
General – CVS • Arrythmias, ↓cardiac contractility, vasodilation – Resp • ↑ventilation (Kussmaul’s breathing) – Metabolic • Protein wasting, resorption of Ca from bone – Other • Neutrophilia
what is the main reason to calculate anion gap
is to identify likely cause
of metabolic acidosis – especially lactic acidosis, or
ingestion of acid
Normal AG: [Na+
] – {[Cl]
\+ [HCO3
-
] = 6-12 mmol/
Difference between major cation (Na) and major anions – Cl, HCO3 - - reflects presence of unmeasured anions
normal range of anion gap
9-16. BEWARE decrease in albumin can adjust anion gap by decreasing it by 2.5 for every 10g/L
metabolic alkalosis
decreased H+
increased HCO3
compensatory response increased pCO2
main causes of metabolic alkalosis
gastric acid loss - vomiting volume depletion hyperaldosteronism bartters cushings profound k depletion
respiratory acidosis
H+ decreased HCO3 increased pCO2 increased hypoventilation compensatory response to retain HCO3 most of the H+ is buffered intracellularly with later renal compensation
respiratory alkalosis
H+ decreased HCO3 decreased pCO2 decreased hyperventilation acute alkalosis increases the binding of Ca2+ to albumin thus inducing fall in ionised Ca2+ and tetany
venous a lymphatic drainage of bladder
surrounding bladder is a rich plexus of veins that ultimately empties into the internal iliac veins
lymphatics drain into vesical, external iliac , internal iliac and common iliac lymph nodes
bladder innervation - motor efferent parasympathetic fibres
SACRAL PREGANGIONIC nuclei in intermediolateral columns of S2,3,4
SYMpathetic motor innervation of bladder
pre ganglionic sympathetic nerve fibres arise from T10-12 and L1-2
travel in hypogastric nerves and innervate trigone /blood vessels of bladder and smooth muscle of prostate in men
gating theory
Afferent input into cord nullified by inhibitory
inter-neurones, restricting transmission to
preganglionic parasympathetic cell bodies
• Within parasympathetic ganglia inhibitory
effect of postganglionic sympathetic nerves
• Effect: Post-ganglionic parasymp fibres
‘protected’ from afferent input until
‘threshold’ reached
where does ONUF’s nucleus lie
medial part of the anterior horn of the spinal cord
where is pontine micturition centre located
dorsolateral region of pons
recieves projections from cortex , cerebellum , brainstem and extrapyramidal system
what does the PMC do?
PMC nuclei sends axons , via lateral columns , to sacral micturition centre (both interomediolateral nucleus and ONUF’s nucleus.
critical level of integration of storage and voiding
where is the PMC found (barringtons nucleus
found in dorsolateral region of pons
mechanism of Detrusor smooth muscle contraction
• NMJ transmission – increase in intracellular Ca++ :
• 1. Membrane depolarisation - voltage sensitive ion
channels – influx of extracellular Ca++
• 2. Ach binds to G-protein-linked (muscarinic) receptors
- release Ca++ from intracellular stores
• M2 receptors predominate in number, M3 in functional
importance
• ‘Regions of close approach’ - functional syncitium
examples of neurological conditions associated
with abnormal bladder and sphincter function
– Spinal cord injury – MS – Neuropathic detrusor hyperreflexia eg in patients with spina bifida – Parkinson’s disease
what is spinal shock
period of decreased excitability at and below spinal cord injury
- absent somatic reflexes and flaccid muscle paralysis
- autonomic activity decreased
- acontractile areflexic bladder
-spincter = functioning
- retention
lasts days to months
reflex recovery from spinal shock
1st - striated muscle of pelvic floor
- return of bulbocavernosus reflex
- s3,4 pinch glans /clitoris or pull catheter and anal sphicter contracts on your finger
if BCR present ; sacral micturition centre is intact
autonomic dysreflexia
spinal cord injury T6 or higher (splanchic circulation = t6-10)
exagerated sympathetic activity in response to a stimulus below level of sci
potentially fatal.
increased BP , Decreased HR , sweating, flushing above lesion, vasocontriction below.
detrusor hyperreflexia
this is bladder overactivity in a patient with an underlying neurological condition sucha as MS or parkinsons
occurs in 70% following a stroke.
if bladder is very high it can result in upper tract dilation . mainstay of treatment is anticholinerics - M3 receptor blockerz . cholinergic - parasympathetic control
adrenergic control - sympathetic
bladder outflow obstruction
principle cause in men is prostatic hypertrophy
women - pelvic organ prolapse
neurological disease can cause relaxation of external sphincter
tumours , stones, strictures
what is verumontanum a landmark for
TURP as lies just proximal to external urinary sphincter
the verumontanum leads into the prostatic utricle and on either side of V is the opening of ejaculatory duct.
chronic retention
• Painless retention of >300ml
• Broadly subdivided into 2 groups
– HPCR – residual volume remains at a pressure
higher than the intra-abdominal pressure after
micturition
– LPCR
• HPCR associated with bilateral hydronephrosis
Pathophysiology of upper tract
dilatation in chronic retention
Combination of diuresis and bladder filling causes upper tract pressures to rise Once ureters become dilated, co-aptive peristalsis is lost and ureteric drainage becomes dependent on gravity If end void pressure >25cm/H2O, deterioration in renal function ensues HPCR associated with hypertension (50%) Peripheral oedema CCF (20%)
what changes occur during the period of obstruction
reduction in GFR , secondary increase in the fractional excretion of solutes and water in an attempt to compensate.->
with extremes of dietry intake of salt and water and reduced ability of the nephron to compensate->
salt and water retentipn are common ->
hypertension , peripheral oedema , CCF
post obstructive diuresis
Refers to marked polyuria that occurs
after relief of BUO or obstructed single kidney
May be physiological - to excrete retained
water and solutes
Or pathological caused by impaired sodium
reabsorption or concentrating ability.
what are the two stages of post obstructive diuresis
tubular 0-14 days
reversal of tubular changes in obstruction - increased fractional excretion sodium leads to diuresis
glomerular 14-3month
gradual and more subtle
Why does diuresis occur
Patients with prolonged diuresis are unresponsive to ADH (acquired DI) Prolonged impairment of sodium reabsorption Elevated levels of ANP
Clinical management of post
obstructive diuresis
20% patients urine output > 4litres/day
10% patients develop thirst requiring oral fluids
5% patients require i.v replacement therapy
because of postural hypotension
1% patients prolonged POD/ chronic salt losers
management of post obstructive diuresis
Strict hourly urine output Daily weights, U+E’S BP - look for orthostatic hypotension Majority do not need volume replacement i.e. diuresis is physiological A minority of patients will show a UO of > 200ml/hr for 6 hours These patients need close observation and fluid replacement Aim to replace 1/2 hourly urine output with N. saline Also watch for postural hypotension and hyponatraemia
respiratory alkalosis
- ↓ CO2 due to Hyperventilation leads to ↓ [H+] • Compensatory Mechanism:
- Renal compensation - H+ ions are generated and HCO3- ions are secreted.
- Respiratory compensation - stimulation of arterial and CSF chemoreceptors causes a decrease in breathing rate
respiratory acidosis
• ↑ CO2 due to Hypoventilation leads to ↑ [H+] • Compensatory Mechanism: • Most of the increased [H+] is buffered intracellularly • Renal compensation - H+ ions are secreted and HCO3- ions are reabsorbed more. • Respiratory compensation - stimulation of arterial and CSF chemoreceptors causes an increase in breathing rate
sites of bicarbonate reabsorption
90% in PCT , 10% in intercalated discs of DCT / collecting duct
how is a fixed acid buffered
via the excretion of hydrogen ions in the form of ammonia and phosphate and subsequent absorption of bicarbonate
volatile acids
can be eliminated from the body as a gas
hydronephrosis.
Dilation of the renal pelvis and calyces - progressive atrophy of the kidneys, thus leading to kidney impairment
