Renal + urology Flashcards
Gitelman syndrome
Mutations in the thiazide-sensitive Na/Cl symporter
Autosomal recessive
Features:
- Normotensive
- Low Cl-, K+, Mg2+, Ca2+
- Metabolic alkalosis
- Raised urinary Na+ and K+
Investigations:
- Bloods
- 24h urinary Na+ and K+
Management:
- K+ and Mg 2+ supplementation
- Trial of aldosterone antagonists
Conn syndrome
Primary hyperaldosteronism
- Usually due to adrenal adenoma
Features:
- Hypertension
- Normal/raised Na+, low K+
Management:
- Aldosterone antagonists
- Adrenalectomy
Liddle syndrome
Pseudo-hyperaldosteronism due to mutations in the ENaC
- Autosomal dominant
- Increase ENaC activity = increased Na+ reabsorption
Features:
- HTN
- Hypokalaemia
- Metabolic alkalosis
- Low renin + aldosterone
Management:
- Potassium-sparing diuretics e.g. amiloride
Acute interstitial nephritis
Inflammation of the renal tubulointerstitium
Aetiology:
- Drug hypersensitivity
- Rifampicin, allopurinol, antibiotics, NSAIDs
- Autoimmune
- SLE, Sjogrens
- Idiopathic (rare)
- Viral
- Hantavirus
- Bacterial
- Leptospirosis, mycobacteria
Features:
- AKI
- Fever
- Eosinophilia
- Sterile pyuria
- Nephrotic syndrome if NSAID-induced
Management:
- Treat cause
- Steroids
Renal tubular acidosis
Type I - distal
- Failure of distal and collecting tubular cells to secrete H+ and reabsorb K+
- Features:
- Renal stones - due to urinary alkalosis +
increased secretion of Ca2+ in serum
acidosis
- Diabetes insipidus
- Salt wasting
- Severe metabolic acidosis + hypokalaemia
Type II - proximal
- Failure of proximal tubule cells to reabsorb HCO3
- Features:
- Mild metabolic acidosis +/- hypokalaemia
- Osteomalacia
- Rickets
Type III
- Combined type I and type II
Type IV
- Either low serum aldosterone or renal resistance to aldosterone activity
- Features:
- Hyperkalaemia
- CKD
Type 1 renal tubular acidosis
Failure of distal and collecting tubular cells to secrete H+ and reabsorb K+
Aetiology:
- Idiopathic or genetic
- Autoimmune disease
- Nephrocalcinosis
- Drugs incl. lithium
Features:
- Renal stones
- due to urinary alkalosis + increased secretion
of Ca2+ in serum acidosis
- Diabetes insipidus
- Salt wasting
- Severe metabolic acidosis + hypokalaemia
Type 2 renal tubular acidosis
Failure of proximal tubule cells to reabsorb HCO3
Aetiology:
- Idiopathic
- Fanconi syndrome
- Drugs incl. NSAIDs, heavy metals
Features:
- Mild metabolic acidosis +/- hypokalaemia
- Osteomalacia
- Rickets
Fluid requirements
Adult:
25-30 ml/kg/day
50-100g glucose
Child:
- 100ml/kg/day for first 10kg, then 50ml/kg/day for next 10kg, then 20ml/kg/day for the remainder
Central pontine myelinolysis (osmotic demyelination syndrome)
A disorder in which myelin +/- neuronal cells are damaged by rapid correction of hyponatraemia
- A rise of > 1 mmol/hr or >10 mmol/day
- Symptoms start 2-3 days after hyponatraemia
Features:
- Reduced GCS
- Confusion
- Limb weakness, paralysis, paraesthesia
- Dysphagia
- Dysphasia
- Impaired coordination
- Can progress to coma/death
Management:
- Supportive
- May recover over months or be left with permanent disability
Functional parts of kidney
Glomerulus
- Receives 600ml/min
- Filters (GFR) 120ml/min
- Filtration depends on molecular weight and charge of molecule
- Foot processes and BM are -ve charge
- Molecules > 4nm are completely blocked (e.g. cells, protein), 2-4nm partially blocked.
PCT
- 70% of reabsorption - esp. glucose, amino acids
- Completely permeable to water and glucose
- Secretes HCO3 to allow H+ reabsorption
- Can vary amount of isotonic reabsorption to modulate the ECF
- Contains a number of organic ion transporters which affect excretion of hormones, drugs, etc.
Loop of Henle
- Establishes the medullary concentration gradient to allow for later reabsorption
DCT
- Contains K+/H+ antiporters which help to maintain plasma K+ and pH
Collecting duct
- Site of ADH action -> aquaporin insertion allowing for reabsorption down the medullary concentration gradient
Afferent and efferent arterioles
Can be modulated by systemic NA/Adr or by local mechanisms to maintain GFR across a range of cardiac outputs
Afferent
- Constriction -> reduced rate filtration, same amount of filtrate
- Myogenic response
- Constricts when stretched due to stretch-
activated calcium channels
Efferent
- Constriction -> increased rate of filtration
- Dilation -> reduced rate of filtration
Renin-aldosterone-angiotensin system
Renin:
- Proteolytic enzyme
- Secreted by juxtaglomerular cells in the afferent arteriole in response to:
- NA action on beta-1 adrenoceptors
- Fall in afferent arteriole stretch
- Decreased Na+ load at the macula densa
- Catalyses cleavage of angiotensinogen to angiotensin - 1
Angiotensin:
- 2 step production:
- Angiotensinogen + renin -> angiotensin -1
- angiotensin-1 + ACE -> angiotensin-2
- AT1 stimulation
- Vasoconstriction - raises BP and GFR
- Increased Na+ reabsorption
- AT2 stimulation
- Increases thirst + Na+ appetite
- Stimulates aldosterone synthesis
Aldosterone:
- Acts on thick ascending limb + collecting ducts to promote Na+ reabsorption, H+ and K+ secretion
- Slowly increases expression of ENAC
Atrial and brain natriuretic peptides (ANP, BNP)
ANP
- Stored in atrial myocytes
- Released in response to atrial stretch (aka high BP)
- Stimulates Na+ and water loss, inhibits ADH and renin
BNP
- Cleaved from NT-proBNP
- Binds to ANP receptors although with reduced efficacy
- Found in brain and heart
ADH/vasopressin
Synthesised in the SON and PVN, stored in nerve terminals in the posterior pituitary
- Release dependent on osmoreceptors
Effects:
- V1
- Vasoconstriction
- V2
- Aquaporin insertion -> increased water
reabsorption
Hereditary angioedema
Mutation/deficiency in C1INH (C1 esterase inhibitor) leading to excessive bradykinin levels and episodes of painful swelling
- Similar mechanism can lead to angioedema
with ACEi use
Management
- Ecallantide - synthetic C1INH
Hypernatraemia
Aetiology:
- Diabetes insipidus
- HHS
- Dehydration
- ATN - early polyuric phase
- Diuretics
- Steroid excess - Cushing, Conn
- Salt poisoning - iatrogenic (NaCl, sodium bicarb), drowning in salt water, high sodium feed
Features:
- Mild (140-180)
- Can be asymptomatic
- Excessive thirst, confusion
- Severe (> 180)
- Ataxia, tremor, coma, seizures
- Raised ICP
Management:
- Aim reduction no greater than 10 mmol/day otherwise risk cerebral oedema
- Hypovolaemic
- Fluid resus + 5% dex
- Euvolaemic
- 5% dex
- Hypervolaemic
- 5% dex + loop diuretic
Hyponatraemia
Hypertonic
- Serum osmolality > 285
- Hyperglycaemia
- Mannitol infusion
Isotonic
- Serum osmolality 280-285
- Hyperlipidaemia or paraproteinaemia
Hypotonic
- Serum osmolality < 280
- Hypovolaemic
- Urine Na < 20
- Vomiting
- Diarrhoea
- 3rd spacing
- Urine Na > 20
- Diuretics
- Addisons’
- Salt wasting nephropathy
- Euvolaemic
- Urine osmolality > 100
- Primary polydipsia
- Beer potomania
- Ecstasy
- Urine osmolality < 100
- SIADH
- Hypothyroidism
- ACTH deficiency
- Hypervolaemic
- Urine Na < 20
- Heart failure
- Liver failure
- Nephrotic syndrome
- Urine Na > 20
- Kidney failure
Severe hyponatraemia management
aka symptomatic with seizures and drowsiness
Admit to ITU
- Aim initial rise of 1-2 mmol/hr over first 3 hr
- Can raise Na+ > 10mmol/day with care
Calculate sodium deficit:
Fluid [Na] - serum [Na]/1 + total body water
(1L 0.9% NaCl = 154 mmol)
Hypoalbuminaemia
Aetiology:
- Decreased production
- Chronic inflammation
- Severe malnutrition
- Liver cirrhosis
- Increased loss
- Renal - nephrotic syndrome
- GI - erosive (IBD, malignancy, PUD), non-
erosive (coeliac, sprue, SIBO, Whipples),
raised lymphatic pressure (CCF, mesenteric
TB)
- 3rd spacing
- Increased catabolism
- Prolonged severe illness e.g. ITU
Management:
- Mostly supportive + treat underlying cause
- HAS if cirrhosis or haemodynamic instability not responding to crystalloids alone
SIADH
Aetiology:
- Malignancy
- SCLC, pancreatic, prostate
- Infections
- TB
- Neurological
- Stroke, SAH, abscess
- Drugs
- SSRIs, Indomethacin, TCAs, thiazide diuretics,
antipsychotics, cyclophosphamide, vincristine
Investigations:
- Paired urine + serum osmolality
- Paired urine + serum sodium
- Water deprivation testing
Management:
- Fluid restriction
- Demeclocycline
Hyperkalaemia
Aetiology:
- Kidney failure
- Rhabdomyolysis
- Tumour lysis
- Metabolic acidosis
- Hypoglycaemia
Features:
- Muscle weakness
- Paraesthesias
- Palpitations
- Arrhythmia
Investigations:
- Bloods
- ECG - tall tented T waves, broad QRS
Management:
- Calcium gluconate 10ml over 10 mins, repeated
- Insulin/dextrose - 10 units in 250ml 10% dextrose
- Salbutamol nebs 5-10mg
Hypokalaemia
Aetiology
- Vomiting or diarrhoea
- Loop and thiazide diuretics
- Conn’s syndrome
- Laxative abuse
- Metabolic alkalosis
- Insulin therapy
- Refeeding syndrome
Features:
- Muscle weakness + myalgia + cramps
- Tremor
- Palpitations
- Constipation
Investigations:
- Bloods
- ECG - T wave flattening/inversion, U waves, QT prolongation
Management:
- Treat underlying cause
- Sando-K TT TDS
- IV KCl
Hypercalcaemia
Aetiology
- Malignancy
- Hyperparathyroidism
- Multiple myeloma
- Dehydration
- Paget’s disease
- Addison’s disease
- CKD
Features:
- Bone pain
- Fatigue, weight loss
- Constipation
- Kidney stones, kidney impairment
- Depression, psychosis
Investigations
- Routine bloods
- TFTs, PTH level, vitamin D
- ECG - shortened QTc
- Imaging of bones
Management:
- Acute:
- IV fluids
- IV bisphosphonates
Hypocalcaemia
Aetiology:
- Vitamin D deficiency
- Hypoparathyroidism (incl. post-surgical)
Features:
- Muscle cramps, twitching -> tetany
- Paraesthesias
- Carpopedal spasms
- Chvostek’s + Trousseau’s signs
- Risk of laryngeal tetany and asphyxiation
Investigations:
- Routine bloods
- PTH and vitamin D levels
- ECG - prolonged QTc
Management:
- Acute (calcium < 1.9, symptoms)
- IV calcium gluconate
- Chronic:
- Cholecalciferol (if vit D deficient)
- Calcitriol (if PTH deficient)
Calcium homeostasis
Absorption
- GIT
- Renal reabsorption
Storage:
- 99% calcium hydroxyapatite in the bones
- Remainin 1% in cells + serum
- Protein-bound
- Chelated - for transport
- Ionised - used in cellular signalling
PTH:
- Secreted in response to hypocalcaemia, from parathyroid glands (x 4)
- Stimulates bone resorption
- Increases renal calcium reasbsorption
- Increases renal vitamin D activation
Vitamin D
- Increases in response to hypocalcaemia
- Metabolised in two steps into 1,25-dihydroxyvitamin D
- Increased expression of GIT calcium-binding
proteins -> increased absorption
- Stimulates bone resorption
Calcitonin
- Secreted from parafollicular C cells (thyroid) in response to hypercalcaemia
- Inhibits bone resorption
- Inhibits renal reabsorption of calcium
Phosphate
Levels are usually inverse to calcium
High:
- Aetiology - CKD, acidosis, tissue lysis, tertiary hyperparathyroidism
Low:
- Aetiology - primary hyperparathyroidism, refeeding syndrome, ETOH, Cushing’s, alkalosis
- Features - muscle weakness, tremor, infection, confusion, respiratory depression
- Management - PO or IV replacement
Hypomagnesaemia
Aetiology:
- Malnutrition
- Medications - diuretics, PPIs, ciclosporin, cisplatin
- Osmotic loss - diabetes
- Malabsorption
- Prolonged GI suction, stoma, fistula etc.
Features:
- Fatigue
- Weakness
- Muscle cramps
- Spasticity
- Seizures
Investigations:
- U&Es + bone profile
- Leads to hypokalaemia
- ECG - prolonged QTc, tachy
Biochemical patterns:
Adrenal insuff (5)
Hyperaldo(3)
Phaeochromocytoma(1)
Sarcoidosis(2)
Carcinoid syndrome(3)
Refeeding syndrome(4)
Sequelae of parenteral nutrition(3)
Rhabdomyolysis (5)
Tumour lysis syndrome (6)
Toxic alcohols (ethylene glycol as eg)(3)
Lithium toxicity (2)
Salicylate toxicity (3)
Adrenal insufficiency
- Hyponatraemia
- Hyperkalaemia
- Normal anion gap acidosis
- Hypoglycaemia
- Hypercalcaemia
Hyperaldosteronism
- Hypernatraemia
- Hypokalaemia
- Metabolic alkalosis
Phaochromocytoma - beta-2 blockade
- Hypokalaemia
Sarcoidosis - ACE activity
- Hypercalcaemia
- Hypercalciuria
Carcinoid syndrome - secretory diarrhoea
- Hypokalaemia
- Hypomagnesaemia
- Normal anion gap acidosis
Refeeding sybdrome
- Hypophosphataemia
- Hypokalaemia
- Hypomagnesaemia
- Hyperglycaemia
Parenteral nutrition
- Hyperglycaemia
- Hyperlipidaemia
- Normal anion gap acidosis
Rhabdomyolysis
- Hyperkalaemia
- Hyperphosphataemia
- Myoglobinuria
- Raised CK, LDH
Tumour lysis syndrome
- Hyperkalaemia
- Hyperphosphataemia
- Hypocalcaemia
- Hyperuricaemia
- Raised anion gap acidosis
- Raised LDH
Toxic alcohols (e.g. ethylene glycol)
- Hypocalcaemia
- Raised anion gap acidosis
- Raised serum osmolar gap
Lithium toxicity
- Hypernatraemia
- Low anion gap acidosis
Salicylate toxicity
- High anion gap acidosis
- Hypokalaemia
- Hyperkaluria
Nephrotoxic drugs
Membraneous GN
- Pencillamine
- Gold
- Captopril
(Acute) interstitial nephritis
- Penicillins
- Cephalosporins
- NSAIDs
- Allopurinol
- Phenytoin
- PPIs
Renal tubular damage:
- Amphotericin
- Heavy metals - incl. mercury, lithium
- Cisplatin
- Aminoglycosides
- Vancomycin
- NSAIDs
- Aciclovir
Acute tubular necrosis
Renal tubular cell damage (+/- death) which initially causes AKI but can lead to strictural injury
Aetiology:
- Reduce renal perfusion e.g. hypovolaemia, sepsis
- Nephrotoxic medications
Pathology:
- Loss of brush border
- Tubular cell vacuolation and sloughing
- Typically Na+ wasting
Features - three phases:
- Initiation
- Oliguria
- Uraemia
- Maintenance
- Worsening oliguria and uraemia
- Hyperkalaemia
- Acidosis
- Fluid overload
- Recovery
- Polyuria - massive loss of Na+ and K+
- Hypokalaemia
Investigations:
- Urine analysis
- Urine Na+ > 40
- Urine osmolality < 350
- Microscopy - brown epithelial casts + free
epithelial cells
- Fluid balance
- Bloods
- Renal US normal
Acute interstitial nephritis
Aetiology:
- Infection
- Medications e.g. NSAIDs, PPIs, antibiotics
Features:
- AKI
- HTN
- Rash
- Eosinophilia
- Fever
- Flank pain - from swelling and stretch of the renal capsule
Chronic interstitial nephritis
Fibrosis and dysfunction secondary to chronic or repeated insults
Aetiology:
- Heavy metals
- Nephrocalcinosis
- Chronic hyperkalaemia
- Medication e.g. analgesics
Urea:creatinine ratio
Both freely filtered by the tubules but urea should be reabsorbed in a regulated fashion whereas creatinine is not
Normal ratio 40-110:1
Used to define types of AKI:
- > 110:1 = prerenal
- 40-110:1 = post-renal
- < 40:1 = intrinsic
