RENAL Flashcards
definition of AKI clinical and laboratory
clinical = urine output below 0.5ml/kg/hr for over 6 hours
lab= serum creatinine rise of over 50% from baseline within 48 hours
Pre renal causes AKI
Pump failure:
- MI
- CHF
Leaky:
- Nephrosis, gasatrosis, cirrhosis
Hole:
- Diarrhoea, dehydration, diuresis, haemorrhage
Clog:
- Fibromuscular dysplasia, Renal artery stenosis
Intra renal causes AKI
Glomerulonephritis
acute interstitial nephritis
acute tubular necrosis
Post renal causes AKI
Cancer
stones
BPH
neurogenic bladder
Fluid status examination
eyes mucous membranes skin turgor respiratory rate and sounds heart rate and sounds oxygen sats urine output cap refill pulse BP JVP
AKI investigations
Urine dipstick MCS - infection
FBC - infection
CRP - infection
Blood cultures - infection
ECG - hyperkalaemia
U&E - hyperkalaemia
ABG - hyperkalaemia and acidosis
abdominal uss - obstruction
CK - rhabdomyolysis
LFTs - hepatorenalsyndrome
3 signs of hyperkalaemia ECG
tall tented t waves
widened QRS complexes
flattened P waves
Treatment for hyperkalaemia IV
10mls 10% calcium gluconate
10 units actrapid(insulin) in 50ml 50% glucose
Treatment for hyperkalaemia if no IV available
salbutamol neubliser
calcium resonium + laxatives po
Management of acute renal failure
fluids
ABx
calcium gluconate + actrapid
catheterise/nephrostomy
indications for dialysis
A - acidosis (pH < 7.1 HCO3 <12) E- electrolytes (K+ > 7 Na+) I - Intoxication O- Overload U - uraemia (urea >45)
Diagnosing cause of AKI
Pre: BUN:Cr - >20 Urine Na - <10 Fraction excreted Na - <1% Fraction excreted urea - <35%
Post:
USS
CT
Intra: diagnosis of exclusion use history and physical RBC casts likely glomerulonephritis WBC casts + WBC + eosinophils likely AIN Muddy brown casts likely ATN
Basics of the glomerulus
Epithelial pouch invaginated by capillary tuft
Semi-permeable filter
Endothelium
Basement membrane Epithelium
Mesangial cells are specialised smooth muscle cells that support the glomerulus and regulate blood flow and GFR
Filtration of blood in kidneys
Receive 25% CO
20% blood volume is filtered (250ml/min)
Basement membrane is negatively charged so anionic proteins are retained eg albumin
Filtration key to excrete waste and it remains constant over 80-200mmHg
Flow of filtrate will depend on Na and water reabsorption
Sodium reabsorption
Main factor for determining extracellular volume
Low BP and low NaCl at macula densa (DCT) ==> renin release ==> aldosterone release ==> upregulate Na/K pumps
Water reabsorption
Determines ECF osmolality
High osmolality or low BP ==> ADH release
Nephron PCT
reabsorption of filtrate
- Na/K pump basolateral keeps Na low
- Na can move in at apical membrane down conc gradient
- Can use secondary active transport to move AA, glucose, Cl-
- 70% total Na reabsorption
- Reabsorption of amino acids, glucose, cations
- Bicarbonate reabsorbed using carbonic anhydrase
- Water follows by osmosis
- Small proteins absorbed, lysed and back into circulation
Thick ascending limb
Creation of osmolality gradient
- 20% sodium reabsorption
- Na/K/2Cl triple symporter
DCT function
5% Na reabsorption
Apical NaCl co-transporter
Ca reabsorption under control of PTH
In very close opposition to the glomerulus
1st part is macula densa cells provides feedback for GFR and fluid flow, based on Na levels
2nd part overlap in function with ascending limb
Continues to dilute the fluid
IS susceptible to ADH action
ACID BASE regulation
Medullary collecting duct
Na reabsorption coupled to K or H excretion
Basolateral aldosterone sensitive Na/K pump
Intercalated cells - acidification of urine and acid base balance
Principal cells - role in Na balance and ECF volume regulation
ADH can act here
Also permeable to urea
Cortical CD
Water reabsorption controlled by aquaporin 2 channels
Endocrine function of the kidneys
- Secretion of renin by juxtaglomerular apparatus
- EPO synthesis
- 1 alpha hydroxylation of vitamin D controlled by PTH
Carbonic anhydrase inhibitor diuretics (acetazolamide)
MOA: inhibit carbonic anhydrase in PCT
Effect: ↓ HCO3 reabsorption → small ↑ Na loss
Use: glaucoma
SE: drowsiness, renal stones, metabolic acidosis
Loop diuretics (frusemide)
MOA: inhibit Na/K/2Cl symporter in thick ascending limb
Effect: massive NaCl excretion, Ca and K excretion
Use: Rx of oedema – CCF, nephrotic syndrome,
hypercalcaemia
SE: hypokalaemic met alkalosis, ototoxic, Hypovolaemia
Thiazide diuretics (bendroflumethiazide)
MOA: inhibit NaCl co-transporter in DCT
Effect: moderate NaCl excretion, ↑ Ca reabsorption
Use: HTN, ↓ renal stones, mild oedema
SE: ↓K, hyperglycaemia, ↑ urate (CI in gout)
K+ sparing diuretics ( spironolactone)
MOA
Spiro: aldosterone antagonist
Amiloride: blocks DCT/CD luminal Na channel
Effect: ↑ Na excretion, ↓K and H excretion
Use: used ̄c loop or thiazide diuretics to control K loss,
spiro has long-term benefits in aldosteronsim (LF, HF)
SE: ↑K, anti-androgenic (e.g. gynaecomastia)
Osmotic diuretics (mannitol)
MOA: freely filtered and poorly reabsorbed
Effect: ↓ brain volume and ↓ ICP
Use: glaucoma, ↑ICP , rhabdomyolysis
SE: ↓Na, pulmonary oedema, n/v
Renal causes of haematuria
Congenital: PCK Trauma Infection: pyelonephritis Neoplasm Immune: GN, TIN
Extra-renal causes of haematuria
Trauma: stones, catheter
Infection: cystitis, prostatitis, urethritis
Neoplasm: bladder, prostate
Bleeding diathesis (tendency)
Drugs: NSAIDs, frusemide, cipro, cephalosporins
Proteinuria classification
30mg/dL = 1+
300mg/dL = 3+
PCR < 20mg/mM is normal, >300 = nephrotic
Causes of proteinuria
Diabetes amyloidosis SLE HTN ATN fever
Microalbuminuria
albumin 30-300mg/24 hr
Causes DM, raised BP, minimal change glomerulonephritis
Causes of casts
RBC- glomerular haematuria
WBC - interstitial nephritis , pyelonephritis
tubular - ATN
Creatinine
synthesised during muscle turnover
freely filtered and small proportion secreted by PCT
take in to account, muscle mass, age, sex, race
Plasma Cr wont rise above normal until 50% decrease in GFR
Urea
Produced from ammonia by liver
Increased with protein meal
Decreased with hepatic impairment
10-70% is reabsorbed - depends on urine flow
decreased flow == increased urea reabsorption so high urea in dehydration
Interpreting urea and creatinine
Isolated increase urea = low flow (hypoperfusion / dehydration )
Increased urea and creatinine = low filtration = renal failure
Creatinine clearance
measuring creatinine clearance helps to give estimate of GFR
Modification of diet in renal disease equation (MDRD)
takes into account serum Cr, sex, age, race
elucidates need for urine collection
Presentation of renal failure URAEMIA (GFR<15ml/min)
Symptoms
- pruritus
- confusion
- lethargy
- paraesthesia
- bleeding
- hiccoughs
Signs
- pale
- striae
- pericardial rub
- fits
- coma
Presentation of renal failure PROTEIN LOSS and NA+ RETENTION
Symptoms
- polyuria
- polydipsia
- breathlessness
signs
- oedema
- raised JVP
- HTN
Presentation of renal failure ACIDOSIS
symptoms
- breathlessness
- confusion
signs
- kussmaul breathing
Presentation of renal failure hyperkalaemia
symptoms
- palpitation
- chest pain
- weakness
signs
- peaked T waves
- flattened P waves
- increased PR interval
- broad QRS complex
- can enter VF == death
Presentation of renal failure ANAEMIA
symptoms
- breathlessness
- lethargy
- faintness
- tinnitus
signs
- pallor
- tachycardia
- flow murmurs (mitral )
Presentation of renal failure vitamin D deficiency
symptoms
- bone pain
- fractures
signs
- osteomalacia
- cupped metaphyses
Presentation of renal failure overview
Uraemia Proteinuria + High Na+ Acidosis Hyperkalaemia Anaemia Vitamin D deficiency
Urine output
1ml/min
1.5L/day
0.5-1ml/kg/hr
2 types of nephron
Cortical - 85%
- short loop of henle
Juxtamedullary - 15%
- long loop of henle
- vasa recta develops alongside it
- able to reabsorb more water due to larger surface area
- these are the predominant nephrons in desert animals
Fanconi syndrome
All the normal PCT reabsorptive mechanisms are defunct
all solutes now found in urine, eg Na, glucose etc
Many causes
- inherited
- medications eg valproate
Medullary osmotic gradient
interstitium of the medulla becomes more hypertonic as you move down up to 1200mOsm/kg
this is created by countercurrent multiplier
this gradient helps as CD passes alongside and water is free to move out and dilute
Countercurrent multiplier
Thick ascending limb is impermeable to water but pumps out a load of solutes (Na/K/2Cl) especially lower down where it has more solutes to pump = (1200mOsmol)
Thin descending limb is permeable so water moves out in to interstitium to dilute, more water is lost at the superior aspect.
Tonicity of tubule fluid rises then falls, it is always 200 less in ascending vs descending.
Gradient is maintained by the vasa recta which is permeable to both
- absorbs solutes as it descends
- releases solutes as it ascends
GFR regulation
Intrinsic control
- autoregulation by vasoconstriction of afferent arteriole
- tubulo-glomerular feedback
Extrinsic control
- renal sympathetic vasoconstrictor nerve activity
autoregulation when we have high blood pressure get afferent vasoconstriction to prevent overload of DCT and CD due to too much fluid flowing through
if mean arterial pressure drops towards 70mmHg afferent vasodilation to encourage blood flow through kidneys
Calculating MAP
SBP + 2(DBP)/3
Glomerulus filtration sieve
fenestration of epithelia
negatively charged basement membrane
podocyte epithelium has filtration slits 4nm wide made up of protein rungs and if these rungs damaged == nephrotic syndrome
Measuring GFR with inulin
GFR = Uin x Flow rate / Pin
disadvantages of using inulin for gfr
prolonged infusion
repeated plasma samples
difficult for routine clinical use
advantages of using creatinine for gfr
intrinsic inert substance released at steady state from skeletal muscle no infusion needed freely filtered Not reabsorbed in the tubule
Disadvantages of creatinine for gfr
Some is secreted in to tubule
gives overestimate of gfr
also need to remember different muscle masses and MDMR score
Also trimethoprim acts as a competitive inhibitor of creatinine secretion
Glucose transport maximum in nephron
20mM
but can see glucose in urine from 10mM + due to different transport maximum values between the 2 million nephrons you have
PCT Na-Glucose co transporter
then GLUT2 on basolateral membrane
Familial renal glycosuria
SGLT2 protein mutation
also a drug target for T2DM treatment SGLT2 inhibitors help lower blood glucose levels
eg dapagliflozin
Dapagliflozin
SGLT2 inhibitor in PCT
Diabetes drug to increase glycosuria and lower blood glucose
Blood buffers
Bicarbonate buffers
Phosphate buffers
Protein buffers (inc Hb)
Using Henderson Hasselbach equation what is the normal clinical ratio of HCO3:CO2
20:1
Acid base control in PCT
In lumen brush border carbonic anhydrase creates CO2 + H2O
CO2 is reabsorbed and used to generate HCO3 and H+ in cell
H2CO3 moves into blood with Na symporter
H+ moves into filtrate with Na antiporter or via ATP H+ pump
Acid base control intercalated A cell
CO2 reabsorbed and used to generate HCO3 in the cell
HCO3 reabsorbed using Cl- antiporter
H+ out via ATP channel (this is upregulated by aldosterone)
or out via ATP and K+ antiporter
thus aldosterone helps lower blood acidity and increase pH.
Phosphate is also excreted into filtrate which buffers the excess H+ in the filtrate to keep pH above 4.5 whilst still secreting H+ ions
pH of urine cannot fall below 4.5 or gives lots of damage
Ammonia buffers
Glutamine breakdown on intercalated cells gives 2 x HCO3 and 2 x NH3
HCO3 is made de novo from glutamine and is reabsorbed using Na symporter
NH3 + H+ = NH4+ ammonium salts excreted into filtrate using Na antiporter
Intercalated B cells
Carbonic anhydrase in cell generates HCO3- and H+
HCO3- pumped out into filtrate with Cl antiporter
H+ back into blood using ATP pump
This cell type is upregulated during alkalosis in order to try and decrease the pH by reabsorbing H+
Role of aldosterone in kidney acid base
Aldosterone upregulates the function of the ATP H+ apical transport channel in intercalated A cells
Aldosterone also upregulates Na H+ antiporter in the PCT
Thus it acts to raise pH and remove acid
Medulla respiratory regulation
charged ions cannot cross BBB but CO2 does and is converted to H+ by CSF carbonic anhydrase
In acidotic times CSF pH decreases
Medulla recognises this and increases ventilation
The increase in ventilation can also be triggered by peripheral chemoreceptors in aortic arch and carotid bodies, and these detect H+ directly rather than CO2.
Increase ventilation helps blow off CO2 and return ECF pH to normal range.
Renal tubular acidosis
Caused by lack or fault in the acid- base regulating enzymes
type 1= Collecting ducts
type 2= PCT
type 4= deficiency of aldosterone
Respiratory acidosis causes
respiratory depression copd nm disorder airway obstruction restrictive lung disease
Respiratory alkalosis causes
anxiety hypoxaemia pneumothorax (causes hyperventilation) V:Q mismatch (hyperventilation) hypotension high altitude
Normal anion gap
cation = Na 140 anion = Cl- + HCO3 = 108 + 24 = 132
normal anion gap = 8-12
Non anion gap acidosis causes
this is when HCO3 drops but Cl- will increase so overall there is no change in the anion gap
causes
- renal tubular acidosis 1 and 2
- diarrhoea
- acetazolamide (CAi) therapy
all cause decrease of HCO3
causes of anion gap metabolic acidosis
MUDPILES or KARMEL Ketoacidosis Aspirin Renal failure Methanol Ethylene glycol Lactic acidosis (sepsis)
Glomerulonephritis definition
Group of disorders resulting from glomerular membrane damage
Can give proteinuria and haematuria
Can give AKI and ESRF
Glomerulonephritis causes
Immune - SLE, goodpastures, vasculitis Infection - Hepatitis , Streptococcus, HIV Idiopathic Drugs- penicillin, gold Sarcoidosis
Presentation glomerulonephritis
Asymptomatic haematuria
Nephrotic syndrome
Nephritic syndrome
Glomerulonephritis Ix
Bloods: Basic: FBC, U+E, ESR Complement (C3 and C4) Abs: ANA, dsDNA, ANCA, GBM Serum protein electrophoresis and Ig Infection: ASOT, HBC and HCV serology
Urine Dipstick: proteinuria ± haematuria Spot PCR MCS Bence-Jones protein
Imaging
CXR: infiltrates (Goodpasture’s, Wegener’s)
Renal US ± biopsy
3 causes of asymptomatic haematuria
IgA nephropathy
Thin BM disease
Alport’s disease
Features of IgA nephropathy
Young males with recurrent macroscopic haematuria
Often follows URTI (strep)
Rapid recovery between episodes
Can occassionally lead to nephritic syndrome
Diagnosing IgA nephropathy
Biopsy shows IgA in mesangium
Treatment IgA nephrop;athy
Steroids or cyclophosphamide if decreased renal function
Thin basement membrane disease features
Autosomal dominant condition
Commonest cause of asymptomatic haematuria
Persistent asymptomatic microscopic haematuria
Very small risk of ESRF
Alport’s syndrome features
85% X linked inheritance
Progressive proteinuria and haematuria ==> progressive renal failure
Sensorineural deafness
Lens dislocation and cataracts
Retinal flecks
Nephritic syndrome features
Haematuria (macro / micro) + red cell casts
Proteinuria → oedema (esp. periorbital)
Hypertension
Oliguria and progressive renal impairment
Causes of nephritic syndrome (acute GN)
proliferative - post strep
Crescenteric - RPGN
Proliferative nephritic syndrome
usually young child following URTI strep
malaise and smoky urine
Raised ASOT
Decreased C3
Biopsy proliferative nephritic syndrome
shows IgG and low C3
Prognosis proliferative nephritic syndrome
95% children will fully recover
minority go on to develop RPGN
3 types of RPGN (crescenteric nephritic syndrome)
Anti-GMN – goodpasture’s syndrome
Immune complex deposition
Pauci immune
Goodpastures syndrome features
5% of RPGN cases
Ab against collagen 4
Gives haematuria and haemoptysis
CXR shows infiltrates
Treat with plasmaphoresis and immunosuppression
Immune complex deposition RPGN
45% RPGN cases
Any predisposing condition to give immune deposition
eg SLE.. endocarditis
Pauci immune RPGN
cANCA: Wegener’s
pANCA: microscopic polyangiitis, Churg-Strauss Even if ANCA+ve, may still be idiopathic
i.e. no features of systemic vasculitis
Nephrotic syndrome features
Proteinuria – PCR >300mg/mM or >3g/24h
Hypoalbuminaemia: <35g/L
Oedema: periorbital, genital, ascites, peripheral
Often intravascularly depleted ̄c ↓ JVP (cf. CCF)
Nephrotic syndrome complications
Infection: ↓ Ig, ↓ complement activity
VTE: up to 40%
Hyperlipidaemia: ↑ cholesterol and triglycerides
Clinical assessment for AKI
acute or chronic?
volume depleted?
GU tract obstruction ?
Rare cause?
Mx acute renal failure
ABC
Treat life threatening states
- hyperkalaemia, pulmonary oedema, bleeding
Treat shock and dehydration
Monitor
- cardiac, catheter, fluid balance
Look for evidence post renal causes
Hx and Ix
Treat sepsis
Call urologists
Acute interstitial or tubulointerstitial nephritis
immune mediated hypersensitivity to either drugs or other haptens
Causes ATN
70% drugs
- NSAIDS
- ABx
- Diuretics
Infections 15%
- staph
Immune
- sle, sjogrens
ATN overview
People will come in with arthralgia, rash and oliguria and maybe uveitis
Ix
- look for raised IgE and eosinophilia
- also will have haematuria and proteinuria
Need to stop the offending drug
offer prednisolone
Analgesic nephropathy
Arises following chronic use of complex analgesia
gives mild proteinuria and slowly progressive CRF
Sloughed papilla can lead to obstruction of urinary tract
Ix- non contrast CT shows calcified papilla
Mx - stop analgesia
Rhabdomyolysis pathogenesis
Skeletal muscle breakdown gives release of K+, phosphate, urate, myoglobin and CK
Rhabdomyolysis clinical features
Red-brown urine
Muscle pain and swelling
AKI occurs 10-12 hours later
Rhabdomyolysis Ix
Dipstick: +ve Hb, -ve RBCs
Blood: ↑CK, ↑K, ↑PO4, ↑urate
Rhabdomyolysis Rx
Rx hyperkalaemia
IV rehydration: 300ml/h
CVP monitoring if oliguric
IV NaHCO3 may be used to alkalinize urine and stabilise a less toxic form of myoglobin.
Chronic renal failure features
Kidney damage for more than 3 months indicated by reduced function
Symptoms usually only seen at stage 4 <30ml
Stage 5 or need for RRT == ESRF
CKD classification
1- >90 2- 60-89 3a - 45-59 3b- 30-44 4- 16-29 5- <15
Ix CKD
Bloods:
↓Hb, U+E, ESR, glucose, ↓Ca/↑PO4, ↑ALP, ↑PTH
Immune: ANA, dsDNA, ANCA, GBM, C3, C4, Ig, Hep
Film: burr cells
Urine: dip, MCS, PCR, BJP
Imaging
CXR: cardiomegaly, pleural/pericardial effusion, oedema
AXR: calcification from stones
Renal US
Usually small (<9cm)
May be large: polycystic, amyloid
Bone X-rays: renal osteodystrophy (pseudofractures)
CT KUB: e.g. cortical scarring from pyelonephritis
Renal biopsy: if cause unclear and size normal
Complications CKD
CRF HEALS Cardiovascular disease Renal osteodystrophy Fluid oedema Hypertension Electrolyte disturbances Anaemia Leg restlessness Sensory neuropathy
Renal osteodystrophy mechanism
1 alpha hydroxylase deficiency less calcium so more PTH
Phosphate retention
- decreased calcium
- increased PTH directly
More PTH = bone resorption
this whole process gives acidosis
Management CKD
General
- stop toxic drugs
Lifestyle
- exercise
- stop smoking
- Na, fluid and PO4 restriction
CV risk
- statins
- low dose aspirin
HTN
- target 140/90
Oedema
- furosemide
Bone disease
- phosphate binders- calcichew
- alfacalcidol - (vit d analog)
- Cinacalcet - calcium analog
Anaemia
- EPO
Restless legs
- Clonazepam
Renal transplant assessment
Virology status: CMV, HCV, HBV, HIV, VZV, EBV
CVD
TB
ABO and HLA haplotype
Renal transplant CI
active current infection
cancer
severe heart disease or other significant co-morbidity
Renal transplant types of graft
LIVE
- related has best outcomes
- unrelated
CADAVERIC
- Deceased brain dead
- Deceased cardiac dead
Renal transplant pre-op immunosuppression
Alemtuzumab (anti CD52)
Renal transplant post-op immunosuppression
Short term
- prednisolone
Long term
- tacrolimus
- ciclosporin
Renal transplant prognosis
cadaveric graft
15 years
Renal transplant post-op complications
bleeding
graft thrombosis
infection
urinary leaks
Renal transplant hyperacute rejection
Occurs within minutes
due to ABO incompatibility
gives thrombosis and SIRS
- systemic inflammatory response syndrome
Acute rejection renal transplant
Occurs within 6 months
presents with increasing Creatinine
- with fever and graft pain
Cell mediated response
DOES respond to immunosuppression
Chronic rejection renal transplant
> 6 months
Interstitial fibrosis + tubular atrophy
Gradual increase in Cr
DOESN’T respond to immunosuppression
Ciclosporin and Tacrolimus nephrotoxicity
Acute
- reversible afferent arteriole constriction == decreased GFR
Chronic
- tubular atrophy and fibrosis
Immune complications of renal transplant
increased susceptibility to infection
- opportunists, fungi, warts
Increased risk of malignancy
- BCC
- SCC
- EBV
