GU Flashcards
Kidney function?
Filter or secrete waste/excess substances
- Retain albumin and circulating cells
- Reabsorb glucose, amino acids and bicarbonates
- Control BP, fluid status and electrolytes
- Activates 25-hydroxy vitamin D (by hydroxylating it to form 1,25 dihydroxy
vitamin D)
- Synthesis erythropoietin
GFR and eGFR??
The volume of fluid filtered from the glomeruli into Bowman’s space per unit
time (minutes)
- Normally this is 120ml/min = 7.2L/h, 170L/day
- Each kidney receives 20% of cardiac output
- eGFR predicts creatinine generation (produced by muscles and ONLY
ELIMINATED by the kidneys) from age, gender and race - Requires a steady state
what happens in proximal convoluted tubule?
Sugars, amino acid, POTASSIUM and bicarbonate get reabsorbed here
- Also absorbs the MAIN PORTION (70%) of Na+ and water follows
Vulnerable to ischaemic injury resulting in acute tubular necrosis
fanconi syndrome?
Rare
• Proximal tubular insult resulting in:
- Glycosuria (glucose in urine)
Acidosis with failure of urine acidification
- Phosphate wasting resulting in rickets/osteomalacia
- Aminoaciduria (amino acid in urine)
or can be caused by Wilsons and TENOFOVIR
what happens in loop on henle?
Reabsorbs 25% Na+ here and water follows
- Sodium potassium chloride (Na2KCl) transporters are more active in the
ascending loop
- Loop diuretics work here most, since 25% Na+ filtered here, so water
follows if can block here then can have a large effect
distal convoluted tubule, what happens here?
5% Na+ reabsorbed here and water follows
- Thiazide diuretics work here
what happens at collecting duct?
Does salt handling - by this point, most of the salt has been reabsorbed
- Tightly regulated by aldosterone (aldosterone increase the transcription of
eNac channels which absorb Na+ in exchange for K+)
- Secrete K+ and H+ into the urine
- Water handling is also done here and water is absorbed via aquaporin 2
channels (regulated by vasopressin)
renal potassium control?
- K+ is freely filtered and mostly reabsorbed in the proximal tubule/loop of
henle - Distal tubule secretion determines renal excretion
- Governed by:
• Distal delivery of Na+
• Aldosterone - Insulin and catecholamines drive cellular K+ uptake, buffering acute
changes
k+ modifying renal medications
K+ modifying renal medication:
• Cause hypokalaemia:
- Loop diuretics
- Thiazide diuretics
• Cause hyperkalaemia:
- Spironolactone (aldosterone antagonist)
- Amiloride (acts on eNac channels)
- ACE inhibitors
- Angiotensin receptor blockers (ARB)
- Trimethoprim (acts on eNac channels but milder)
diuretics?
Diuretics are NOT NEPHROTOXIC but hypovolaemia (which they can cause
e.g. loop & thiazide diuretics) IS
- In advanced kidney disease you require huge amounts of diuretics to do the
work
- Thiazide and loop diuretics are EXTREMELY POWERFUL & EFFECTIVE
TOGETHER resulting in profound diuresis
EPO?
Erythropoietin is hormone that produces haemoglobin, it is produced in
response to tissue hypoxia
- In advanced kidney disease and anaemia, erythropoietin will be given to
help increase O2 transport
vit d in kidnye?
Kidneys do vitamin D hydroxylation:
• It takes 25-hydroxy vitamin D and hydroxylates it to form 1,25-dihydroxy
vitamin D (calcitriol) - this is the active form of vitamin D
- In kidney failure the kidney cannot hydroxylate and thus there is a drop in
Ca2+
calictriol actions
Increases Ca2+ and phosphate absorption from the gut
• Increases phosphate absorption to a lesser extent
• Suppresses parathyroid hormone (PTH)
• Deficiency results in secondary hyperparathyroidism:
Low vitamin D results in low Ca2+ and phosphate resulting in
increased PTH which causes Ca2+ and phosphate leeching out of
the bones
- PTH also acts on osteoclasts by increasing their activity and thus
increasing their turnover resulting in reduced bone quality
upper urinary tract and lower urinarytract?
upper; kidney and ureters
lower; bladder, prostate gland, urethra
what happens during voiding?
Pontine micturition centre stimulates excitatory control to detrusor
nucleus and inhibits Onuf’s nucleus
• Signal is transmitted from spinal root S3,4,5 via the parasympathetic
nervous system and this results in contraction of detrusor muscles and
relaxation of the urethra
what happens during storage phase of urination?
Pontine storage centre stimulates and sends inhibitory signals to
detrusor muscles and excitatory signals to Onuf’s nucleus
• Signal is transmitted from spinal root T10, L1 & 2 via the sympathetic
nervous system and this results in the relaxation of the bladder and
contraction of the urethral sphincter
men v women bladder?
Men have a greater voiding pressure due to them having a longer urethra
• More likely to develop retention
- Women have a shorter urethra with lower resistance and thus higher flow
rates
• More likely to develop incontinence
renal stones?
• Renal stones (calculi) consist of crystal aggregates, stones form in collecting
ducts and may be deposited anywhere from the renal pelvis to the urethra
renal stones epidemiology?
Peak age is between 20-40 yrs
M>F
Most stones are composed of calcium oxalate and phosphate
risk factors and aetiology of renal stone?
Anatomical abnormalities that predispose to stone formation e.g. duplex,
obstruction or trauma
- Chemical composition of urine that favours stone crystallisation
- Dehydration resulting in a concentrated urine - seen particularly in those
working in hot climate
- Infection
- Hypercalcaemia, hyperoxaluria, hypercalciuria, hyperuricaemia
- Primary renal disease e.g. polycystic kidneys or renal tubular acidosis
- Drugs e.g. diuretics, antacids, acetazolamide, corticosteroids, aspirin,
allopurinol, vitamin C & D
- Diet e.g. chocolate, tea, strawberries, rhubarb - all increase oxalate levels
- Gout
- Family history
renal sones pathophysiology - crystals?
Stones form because solute concentrations exceed saturation, often in the
context of a trigger that starts crystallisation
- Renal stone/calculi form from crystals in SUPERSATURATED URINE:
• Calcium oxalate are the most common stones (60-65%)
• Calcium phosphate stones are uncommon (10%)
- Stones vary in size and may be single or multiple
- They may be located within the renal parenchyma or within the collecting
system
- Stones regularly cause obstruction, leading to hydronephrosis; a
combination of obstruction and dilation of renal pelvis that often causes
lasting damage to the kidney
renal stones pathophysiology - calcium stones?
Hypercalciuria (increased Ca2+ in urine) - causes:
- Hyperparathyroidism resulting in hypercalcaemia
- Excessive dietary intake of Ca2+
- Idiopathic hypercalciuria - increased absorption in gut
- Primary renal disease such as polycystic kidneys or medullary
sponge kidney
• Hyperoxaluria (increased oxalate in urine) - causes:
- High dietary intake of oxalate rich food e.g. spinach, rhubarb,
chocolate and tea
- Low dietary Ca2+ resulting in decreased binding of oxalate (by
Ca2+) so increase oxalate absorption and urinary excretion
- Increased intestinal resorption due to GI disease e.g. Crohn’s
renal stones pathophysiology, uric acid?
Associated with hyperuricaemia with/without gout
• Dehydration
• Patients with ileostomies are at particular risk, both from dehydration
and from bicarbonate loss from GI secretion resulting in the production of an acidic urine (uric acid is more soluble in alkaline than acidic) thereby
stimulating stone formation
renal stones pathophysiology infection?
Mixed infective stones are composed of magnesium ammonium
phosphate as well as calcium
• These are often large
• Usually due to UTI with organism such as Proteus mirabilis that
hydrolyse urea forming ammonium hydroxide
• The increased ammonium ions and the alkalinity both favour stone
formation
clinical presentation of renal stones?
- most are asymptomatic
- renal colic - pain from loin to groin
- dysuria
- recurrent UTI
- haematuria
investigations for renal stones?
KUBXR - Kidney Ureter Bladder X-ray:
• FIRST LINE INVESTIGATION
NCCT-KUB - Non-contrast Computerised Tomography:
• GOLD STANDARD
treatment for renal stones?
- Strong analgesic for renal colic e.g. IV DICLOFENAC
- Antibiotics if infection e.g. IV CEFUROXIME or IV GENTAMICIN:
- antiemetics
- Medical expulsive therapy:
• Stones larger than 5mm with pain and not resolving
• ORAL NIFEDIPINE or alpha blocker e.g. ORAL TAMSULOSIN can
promote expulsion and reduce analgesia requirements - If still not passing then:
• Extracorporeal shockwave lithotripsy (ESWL) - ultrasound fragments
stone
• Endoscopy (uteroscopy) with YAG - laser for larger stones
• Percutaneous nephrolithotomy (PCNL) - keyhole surgery to remove
stones that are large, multiple or complex
AKI?
An abrupt (over hours to days) sustained rise in serum urea and creatinine
due to a rapid decline in GFR leading to a failure to maintain fluid, electrolyte
and acid-base homeostasis - it is usually but not always reversible or self-
limiting
criteria for diagnosing AKI?
- Rise in creatinine > 26μmol/L in 48hrs
• Rise in creatinine > 1.5 x baseline (best figure in last 3 months)
• Urine output < 0.5mL/kg/h for more than 6 consecutive hours
epidemiology of AKI?
- common in elderly
- people with hypotension, diarrhoea, urinary retention, sepsis, heart failure
causes of AKI?
pre renal (most common) - hypo perfusion due to hypovolemia or sepsis or medications
intrinsic renal
- renal parenchyma damage due to acute tubular necrosis (NSAIDs, uric acid crystals) or vascular issues (SLE, thrombosis) or glomerular or intersistial (cancer)
post renal
- obstruction at ureter, bladder or prostate due to clots, malignancy, BPH
clinical presentation of AKI?
- palpable bladder and kidney
- oliguria
- arrthymia
- high urea
- SOB
- oedema
- thirst
investigations of AKI?
- urine dipstick
- FBC
- midstream specimen of urine
- ultrasound
- CT-KUB
- ECG
- renal biopsy
AKI treatment
Treat underlying cause:
• Pre-renal:
- Correct volume depletion with fluids
- Treat sepsis with antibiotics
• Intrinsic renal:
- Refer early to nephrology if concern over tubulointerstitial or
glomerular pathology
• Post-renal:
- Catheterise and consider CT of renal tract (CTKUB)
- If signs of obstruction and hydronephrosis then think cystoscopy
and retrograde stents or nephrostomy insertion - this buys time to
allows treatment of cause of obstruction e.g. stone or mass
- stop nephrotoxic drugs
- CALCIUM GLUTONATE or INSULIN for hyperkalaemia
- acidosis with SODIUM BICARB
indications for dialysis?
- Symptomatic uraemia including pericarditis or tamponade
- Hyperkalaemia not controlled by conservative measures
- Pulmonary oedema thats unresponsive to diuretics
- Severe acids
- High potassium
- Tall T waves, low flat p waves, broad QRS or arrhythmias on ECG
- Metabolic acidosis
- Fluid overload that is resistant to diuretics
glomerular diseases?
Glomerulonephritis is a broad term that refers to a group of parenchymal kidney
diseases that all result in the inflammation of the glomeruli and nephrons
acute nephritic syndrome; acute glomerulonephritis?
Haematuria - visible or non-visible (red cell casts seen on microscopy)
- Proteinuria (usually < 2g in 24hrs)
- Hypertension and oedema (periorbital, leg, or sacral)-
causes of acute glomerulonephritis?
IgA nephropathy:
• COMMONEST CAUSE of nephritic syndrome in the developed world
- treatment -> BP control
Post-streptococcal infection e.g. STREPTOCOCCUS PYOGENES:
- 2 weeks after tonsillitis
- treatment ANTIBIOTICS
- infective endocarditis
- SLE
- systemic sclerosis
- ANCA vasculitis
- good pastures disease; Antibodies against glomerular basement membrane
clinical presentation of glomerulonephritis?
- haematuria
- proteinuria
- hypertension
investigations of glomerulonephritis?
- Measure eGFR, proteinuria, serum urea & electrolytes and albumin - to
determine current status and monitor progress - Culture - swab from throat or infected skin
- Urine dipstick to detect proteinuria and haematuria
- Renal biopsy if necessary
nephrotic syndorme?
Proteinuria > 3.5g/24 hours
- Hypoalbuniaemia
- Oedema
- Severe hyperlipidaemia is often present:
- Liver goes into overdrive due to albumin loss and other protein loss which
increases risk of blood clots and produces raised cholesterol
epidemiology of nephrotic syndrome?
- diabetes secondary cause
- minimal change disease primary cause
aetiology of nephrotic syndrome?
PRIMARY
- minimal change disease is most common n children
- membranous neuropathy where there is asymptomatic proteinuria caused by drugs, autoimmune or infection is common in adults
SECONDARY
- diabetes
- amyloid
- SLE
pathophysiology of nephrotic syndrome?
Injury to podocyte appears to be the main cause of proteinuria
- Podocytes wrap around the glomerular capillaries and maintain the
filtration barrier - preventing large molecular weight proteins from entering
the urine
- Damage to podocyte foot processes or loss of podocytes can cause heavy
protein loss
clinical presentation of nephrotic syndrome?
Normal-mild increase in BP - Proteinuria > 3.5g/day - Normal-mild decrease in GFR - Hypoalbuniaemia - Pitting oedema of ankles, genital, abdominal wall and sometimes face (periorbital) - Frothy urine
investigations of nephrotic syndrome?
Establish cause - usually via renal biopsy
- Urine dipstick shows very high protein
- Serum albumin is low
- BP is usually normal or mildly increased
- Renal function is usually normal or mildly impaired
complications of nephrotic syndome/
Susceptibility to infection:
• Such as cellulitis, Streptococcus infections and spontaneous bacterial
peritonitis
• Due to low serum IgG, decreased complement activity and reduced T
cell function due in part to loss of immunoglobulin in urine and also to
immunosuppressive treatment
Thromboembolism:
• E.g. DVT, PE, renal vein thrombosis
• Hypercoaguable state due to increased clotting factors (produced by
liver due to low albumin since liver goes into overdrive) and platelets
abnormalities
Hyperlipidaemia:
• Increased cholesterol and triglycerides due to hepatic lipoprotein
synthesis in response to low oncotic pressure due to low albumin
treatment for nephrotic syndrome?
Reduce oedema:
• Loop diuretics e.g. IV FUROSEMIDE - IV since gut oedema may prevent
oral absorption
• Thiazide diuretics e.g. IV BENDROFLUMETHIAZIDE
• Fluid and salt restriction while giving diuretics
Reduce proteinuria:
• ACE inhibitor e.g. RAMIPRIL
• Angiotensin receptor blocker e.g. CANDESARTAN
• Eat normal rather than high protein diet
- Reduce risk of complications:
• Prophylactic anticoagulation with WARFARIN, especially when albumin
is low (<20g/l)
• Reduce cholesterol with statins e.g. SIMVASTATIN
• Treat infections promptly and vaccinate
minimal change disease?
Disease of the kidney that can cause nephrotic syndrome
epidemiology of minimal change disease?
Commonest cause of nephrotic syndrome in children
- Occurs most commonly in BOYS under the age of 5
risk factors and aetiology of minimal change syndrome?
Can be idiopathic - Atopy is present in 30% of cases and allergic reactions can trigger nephrotic syndrome - Drugs: NSAIDs, lithium - Hodgkin's
pathophysiology of minimal change syndrome?
- Glomeruli appear normal on light microscopy, but on electron microscopy,
FUSION of the FOOT PROCESSES of the PODOCYTES is seen, consistent
with a disrupted podocyte actin cytoskeleton - Immature differentiating CD35 stem cells appear to be responsible for the
pathogenesis
clinical presentation of minimal change disease?
Proteinuria
- Oedema, predominantly around the face
- Fatigue
- Frothy urine
minimal change syndrome investigations and treatment?
Biopsy:
• Normal under light microscopy
• Electron microscopy shows FUSED PODOCYTE FOOT PROCESSES
treatment
High dose corticosteroids e.g. PREDNISOLONE - can reverse proteinuria in
95% cases - however the majority relapse
CKD?
CKD is longstanding, usually progressive, impairment in renal function
(haematuria, proteinuria or anatomical abnormality) for more than 3 months
• Defined as a GFR < 60mL/min/1.73 m2 for more than 3 months with/without
evidence of kidney damage (haematuria, proteinuria or anatomical abnormality)
epidemiology of CKD?
- increasing age
- F>M
aetiology of CKD?
Diabetes mellitus - Type II > Type 1
- Hypertension
- Atherosclerotic renal vascular disease
- Polycystic kidney disease
- Tuberous sclerosis
- Primary glomerulonephritides e.g. IgA nephropathy
- SLE
- Amyloidosis
- Hypertensive nephrosclerosis (common in black africans)
- Small and medium-sized vessel vasculitis
- Family history of stage 5 CKD or hereditary kidney disease e.g. polycystic
kidney disease
- Hypercalcaemia
- Neoplasma
- Myeloma
pathophysiology of CKD?
CKD tends to progress to end-stage kidney disease (ESRF), although the
rate of progression may be slow
- Speed of decline tends to depend on the underlying nephropathy and on
blood pressure control
- Each kidney has roughly a million nephrons
- In CKD, where many nephrons have failed, and scarred, the burden of
filtration falls to fewer functioning nephrons
- Functioning (remnant) nephrons experience increased flow per nephron
(hyperfiltration), as blood flow has not changed, and adapt with glomerular
hypertrophy and reduced arteriolar resistance
- Increased flow, increased pressure and increased shear stress set in
motion a VICIOUS CYCLE of raised intraglomerular capillary pressure and
strain, which accelerates remnant nephron failure
- This increased flow and strain may be detected as new/increasing
proteinuria
clinical presentation of CKD?
- early stages asymptomatic as kidney has a lot of reserves
- malaise
- anorexia
- itching
- polyuria
- pulmonary oedema
complications of CKD?
Anaemia - normochromic normocytic anaemia:
• Due to reduced erythropoietin production by diseased kidney
- Bone disease:
• Bone pain - Renal osteodystrophy - osteomalacia, osteoporosis,
hyperparathyroidism
Neurological:
• Occurs in almost all patients with severe CKD
• Autonomic dysfunction presents as postural hypotension and
disturbed GI motility
Cardiovascular disease:
• Highest mortality in CKD is from CVD particularly MI, cardiac failure,
sudden cardiac death and stroke
Skin disease:
• Pruritus due to nitrogenous waste products of urea - may be scratch
marks
investigations for CKD?
ECG for high potassium signs
- Urinalysis:
• Haematuria - indicates glomerulonephritis
- urine microscopy
Bloods:
• Raised phosphate
• Low Ca2+
• Hb low - normochromic normocytic anaemia
Immunology:
• Auto-antibody screening for SLE, scleroderma and Goodpastures
• Hep B, C, HIV and streptococcal antigen tests
- Imaging:
• Ultrasound to check renal size and exclude hydronephrosis
(obstruction & dilation of renal pelvis):
- In CKD kidneys tend to be small
treatment of CKD?
- Identify & treat reversible causes: • Relieve obstruction • Stop nephrotoxic drugs • Stop smoking and achieve healthy weight to deal with cardiovascular risk • Tight glucose control in diabetes
BP
- target <130/80 -> RAMIPRIL
bone disease
- CALCITRIOL
CVD
- SIMVASTATIN
- ASPIRIN
renal cystic disease?
Solitary or multiple renal cysts are common,
especially with advancing age; 50% of those over 50
have one or more such cysts
• These cysts are often asymptomatic and are found
incidentally on ultrasound examination
types of kidney cysts?
Simple cysts - most common form - benign
- Polycystic when lot of them can be bad -
- Hydronephrosis is when ureter blocked
and kidney dilates and gets bigger
- Dysplasia – when not formed properly
- Medullary sponge – dilation of collecting ducts
ADPKD?
Multiple cysts develop, gradually and progressively, throughout the kidney
eventually resulting in renal enlargement and kidney tissue destruction
epidemiology of ADPKD?
COMMONEST INHERITED KIDNEY DISEASE
- Autosomal dominant inheritance with high penetrance
- Usually presents in adulthood (20-30)
- M>F
aetiology of ADPKD?
- Mutations in PKD1 (85%) gene on chromosome 16
- Mutations in PKD2 (15%) gene on chromosome 4
pathophysiology of ADPKD?
PKD1 encodes polycystin 1 which is involved in cell-cell and/or cell-matrix
interactions - regulates tubular and vascular development in kidneys
- PKD2 encodes polycystin 2 which functions as a calcium ion channel
- The polycystin complex occurs in cilia that are responsible for sensing flow
in the tubule
- Disruption of the polycystin pathway results in reduced cytoplasmic Ca2+,
which, in principal cells of the collecting duct, causes defective ciliary
signalling and disorientated cell division resulting in cyst formation
- Progressive loss of renal function is usually attributed to mechanical
compression, apoptosis of the healthy tissue and reactive fibrosis
- Rate of renal function decline is dependent on the growth and size of cysts;
patients with rapidly growing cysts on MRI lose renal function more rapidly
clinical presentation of ADPDK?
Can be clinically silent for many years, so family screening is essential
- loin pain
- haematurnia
- renal colic
investigations of ADPKD?
Family history of ADPKD, ESRF, hypertension
- BP may be raised
- Ultrasound
- exclude ADPKD if >40 <2 cysts
treatment of ADPKD?
No treatment shown to slow disease progression
- Blood pressure control with ACE-inhibitor e.g. RAMIPRIL
- Treat stones and give analgesia
- Laparoscopic removal of cysts to help with pain/nephrectomy (remove
entire kidney)
- renal replacement therapy
ARPKD, epidemiology?
- rarer
- recessive
- infants
aetiology of ARPKD?
PKHD1 mutation on long arm (q) of chromosome 6
clinical presentation of ARPKD?
Variable - Many present in infancy with multiple renal cysts and congenital hepatic fibrosis - Enlarged polycystic kidneys - 30% develop kidney failure
investigations of ARPKD?
Diagnosed antenatally or neonatally
- Ultrasound - to see cysts
- CT & MRI to monitor liver disease
- Genetic testing
treatment of ARPKD?
Currently no treatment available
- Genetic counselling for family members
- Laparoscopic removal of cysts to help with pain/nephrectomy (remove
entire kidney)
- Blood pressure control with ACE-inhibitor e.g. RAMIPRIL
- Treat stones and give analgesia
- Renal replacement therapy for ESRF
