Nephrology Flashcards
Thiazide action
On distal convoluted tubule
Block NaCl symporter
Furosemide
On loop of Henle
Block NaK2Cl channel
Spironolactone
On collecting duct
Competitive antagonist of aldosterone
Amiloride
On collecting duct
Directly blocking Na channel
Glomerular filtraction rate
120mL/min
Renal autoregulation mechanisms
Myogenic mechanism: local release of vasoactive factors in response to perfusion (afferent arteriole)
Tubuloglomerular feedback: Na conc changes in macula densa lead to changes in afferent arteriolar tone
Renin
Released by JGA, converts angiotensinogen to angiotensin I.
Stimulated by:
Decrease stretch in afferent arteriole
JG cell B sympathetic nerve stimulation
Low Na at macula densa
ACE
Produced in the lungs, converts angiotensin I to angiotensin II
Angiotensin II effects
Vasoconstriction Increase vascular smooth muscle growth Increase Na reabsorption Increase aldosterone Increase bicarbonate products
Aldosterone
Minerocorticoid produced by the adrenal.
Acts on CT, stimulates Na retention and K excretion
Hypervolaemic hyponatraemia
Low urinary Na: CHF, cirrhosis, ascites, pregnancy
High urinary Na: ARF, CRF
Euvolemic hyponatraemia
High urine osmolality: SIADH, adrenal insufficiency, hypothyroidism
Low urine osmolality: psychogenic polydipsia
Hypovolaemic hyponatraemia
High urinary Na: diuretics, salt-wasting nephropathy
Low urinary Na: diarrhea, excessive sweating, third space
Iso-osmolar or Hyperosmolar hyponatraemia
Pseudohyponatraemia (severe hyperlipidaemia, paraproteinemia)
Hyperglycaemia
Mannitol
SIADH criteria
Urine inappropriately concentrated for serum osmolality
High urinary sodiem (>20mmol/L)
High FEna
SIADH disorders
Tumour: small cell Ca, bronchogenic Ca, pancreatic adenoca, Hodgkin’s disease, thyoma
Pulmonary: pneumonia, lung abscess, TB, acute respiratory failure, positive pressure ventilation
CNS: mass lesion, encephalitis, subarachnoid haemorrhage, stroke, head trauma, acute psychosis, acute intermittent porphyria
Drugs: antidepressants, antineoplastics, carbamazepine, barbituates, oxytocin
Diabetes insipidus
Deficit of ADH release or renal response to ADH. Acts on collecting tubules to reabsorb water.
Diagnosis: dehydration test, desmopressin test
Hypokalaemia ECG
U waves
Flattened or inverted T waves
depressed ST segment
Prolongation of QT segment
Hypokalemia (cellular redistribution)
Metabolic alkalosis (K/H exchange)
Insulin (Na/K/ATPase)
Catecholamines, beta agonists (Na/K/ATPase)
Tocolytic agents
New cellular growth (treatment of pernicious anaemia)
Hypokalemia (GI causes)
GI losses: diarrhea, laxatives, villous adenoma
Hypokalemia (hypertensive renal losses)
1* hyperaldosteronism: Conn’s syndrome,
2* hyperaldosteronism: Renovascular disease, renin tumour,
Non-aldosterone: Cushings’s
Hypokalemia (normotensive, based on pH)
Acidemic: DKA, RTA
Variable: hypomagnesium, vomiting
Alkalemic: diuretics, Bartter’s, Gitelman’s
Hyperkalemia ECG
Peaked and narrow T waves Decreased amplitude of P waves Prolonged PR interval Widening QRS and T wave merging AV block Ventricular fibrillation
Hyperkalemia causes
Increased intake: diet, KCl tablets, IV KCl
Cellular release: intravascular hemolysis, rhabdomyolysis, insulin deficiency, hyperosmolar, metabolic acidosis (except keto and lactic), tumour lysis syndrome, drugs (beta blockers, digitalis overdose, succinylcholine)
Decreased excretion: renal failure, hypovolaemia, NSAIDs in renal insufficiency, hypoaldosteronism.
Hyperkalemia - normal GFR with decreased K excretion
Decreased aldosterone stimulus (low renin, low aldosterone):
hyporeninemic, hypoaldosteronism, DM2, NSAIDs, chronic interstitial nephritis
Decreased aldosterone production (normal renin, low aldosterone):
adrenal insufficiency, ACEi, ARBs, heparin, congenital adrenal hyperplasia with 21-hydroxylase deficiency
Aldosterone resistance (decreased tubular response): K sparing drugs (spironolactone, amiloride), renal tubular disease, trimethoprim, cyclosporin, tacrolimus
Hyperkalemia treatment
Heart protection: Calcium gluconate
Intracellular K shift: insulin, NaHCOs, salbutamol
Enhance K removal: furosemide, dialysis
Anion gap
AG = Na - (HCO + Cl)
Osmolar gap
OG = measured osmolality - calculated osmolality CO = 2xNa + urea + glucose
Anion gap metabolic acidosis (KARMEL)
Ketoacidosis Aspirin Renal failure Methanol Ethylene glycol Lactic acid
Non-anion gap metabolic acidosis
Diarrhea
Renal tubular acidosis
Renal infarction
Acute renal artery occlusion - trauma, surgery, embolism, vasculitis
Renal artery stenosis
Atherosclerotic plaques (90%) - proximal 1/3 renal artery Fibromuscular dysplasia (10%) - distal 2/3 renal artery, in young females
Renal vein thrombosis
Hypercoagulable states (nephrotic syndrome), ECF depletion, malignancy, extrinsic compression
Small vessel renal disease
Hypertensive nephrosclerosis
Atheroembolic renal disease
Thrombotic microangiopathy (HUS, TTP, DIC, preeclampsia)
Calcineurin inhibitor nephropathy (cyclosporine and tacrolimus)
Nephrotic Syndrome
Proteinuria, hypoalbumina, oedema, hyperlipidaemia (raised LDL, fatty casts in urine), hypercoagulability (antithrombin III, protein C + S urinary loss).
Frothy urine
FSGS
Membranous glomerulopathy
Minimal change
Nephritic Syndrome (PHAROH)
Proteinuria Hematuria Azotemia RBC casts Oligouria Hypertension
Proteinuria - physiologic
Orthostatic Transient (exercise, fever)
Proteinuria - tubulointerstitial
Impaired resorption: Fanconi’s syndrome
Proteinuria - glomerular
Primary: minimal change, membranous, FSGS, mebrano-proliferative, PSGN, IgA nephropathy
Secondary: systemic (SLE, diabetes, vasculitis), infectious (HIV, Hep B/C, IE), herefitary (Alport’s, Fabry’s sickle cell, PCKD)
drugs (NSAIDs, gold, heavy metals), cancer (lymphoma, solid tumour), others (cryoglobulinemia)
Proteinuria - overflow
Overproduction of LMW proteins: multiple myeloma, amyloidosis, Waldenstrom’s macroglobinemia
RPGN I - anti-GBM mediated
Linear immunofluresence with IgG and C3 deposition along capillary loops:
Lung haemorrhage = Goodpasture’s disease
No lung haemorrhage = Anti-GBM disease
RPGN II - immune complex mediated
Granular pattern with subendothelial or subepithelial deposits of IgG and C3:
C3 normal = IgA nephropathy, HSP
Decreased C3 = membranoproliferative GN, SLE, IE, PSGN, cryoglobinemia
RPGN III - non-immune mediated
Pauci-immune, no immune staining, ANCA +ve:
c-ANCA = Wegener’s granulomatosis
p-ANCA = Churg-Strauss, microscopic polyangitis
Red urine
-ve dipstick, -ve RBC: beets, rifampicin
+ve dipstick, -ve RBC: myoglobin/rhabdomyolysis
+ve dipstick, +ve RBC: hemaglobin
Hematuria
Hematological: coagulapathy, sickle cell
Urologic: nephrolithiasis, trauma, tumour, prostatitis, urethritis
Renal:
Primary - membranoproliferative, PSGN, RPGN, interstitial nephritis, papillary necrosis, IgA nephropathy
Secondary - CTD (Wegener’s, Goodpastures, SLE, Churg-Strauss, HSP), infection (pyelonephritis), hereditary (Alport’s PCKD)
Acute nephritic syndrome
Subset of nephritic syndrome, proceeds over days
Clinical features: PHAROH
Rapidly progressive gomerulonephritis (RPGN)/ cresenteric glomerulonephritis
Subset of nephritic syndrome, proceeds over weeks to months.
Fibrous cresents typically seen on histology, RBC casts.
RPGN IV - double antibody positive
Has features of type I + III (anti-GBM + ANCA)
Asymptomatic urinary abnormalities
Isolated proteinuria - postural
Isolated hematuria - IgA nephropathy, Alport’s (X-linked), thin membrane disease (AD), exercise, febrile illness
Minimal change
2nd causes: Hodgkin’s lymphoma
Drug causes: NSAIDs
Rx: Steroids
Membranous glomerulonephropathy
2nd causes: HBV, SLE, solid tumours
Drug causes: gold, penicillamine
Rx: decrease BP, ACEi, steroids
Focal segmental glomerulosclerosis
2nd causes: reflux nephropathy, HIV, HBV, obesity
Drug causes: heroin
Rx: steroids, ACEi/ARB for proteinuria
Membranoproliferative glomerulonephritis
2nd causes: HCV, malaria, SLE, leukemia, lymphoma, infected shunt
Rx: aspirin, ACEi
Nodular glomerulosclerosis
2nd causes: diabetes, amyloidosis
Rx: treat underlying cause
Amyloidosis
Deposits of amyloid in mesangium (amyloid light chains). Presents as nephrotic proteinuria with progressive renal insufficiency.
Systemic Lupus Erythematous
Deposition of immune complex in glomerulus. Present with nephrotic syndrome/nephritis, low complement levels, ANA, RF and anti-dsDNA positive.
Henoch-Schonlein purpura
Commonly in children. Present with purpura on buttocks and legs, abdominal pain, arthralgia, fever. IgA and C3 staining.
Benign and self-limiting, 10% progress to CKD
Goodpasture’s disease
Antibodies against type IV collagen (lungs and GBM).
Present with RPGN I and hemoptysis.
Treat with plasma exchange, cyclophosphamide, prednisone.
Wegener’s granulomatousis
80% with renal involvement, c-ANCA positive. Treat cyclophosphamide, prednisone.
Cryoglobulinemia
Monoclonal IgM and polyclonal IgG. Presents with purpura, fever, Raynaud’s arthralgias, 50% Hep C.
Treat hep C, plasmapheresis
Infectious related renal disease
HIV Infective endocarditis Hep B Hep C Syphilis Malaria
Acute tubulointerstitial nephritis
Acute inflammatory infiltrates into renal interstitium, rapid (days to weeks) decline in renal function.
Present: AKI, hypersensitivity reaction, pyelonephritis
Etiology:
Hypersensitivity - antibiotics, NSAIDs, allopurinol, furosemide, thiazides, PPIs, phenytoin
Infection - bacterial pyelonephritis, strept, brucellosis, legionella, CMV, EBV, toxoplasmosis
Immune - SLE, acute allograft rejection, Sjogren’s, sarcoidosis
Chronic tubulointerstitial nephritis
Fibrosis of interstitium with atrophy of tubules, mononuclear cell inflammation. Slow progressive renal failure, moderate proteinuria and signs of abnormal tubule function
Etiology: UT obstruction, chronic pyelonephritis, nephrotoxins, vascular disease (ischemic, atheroembolic), malignancies (MM, lymphoma), granulomatous, immune (SLE, Sjogren’s, cryoglobulinemia, Goodpasture’s, amyloidosis, vasculitis), hereditary (PCKD, sickle cell)
Acute tubular necrosis
Abrupt and sustained decline of GFR within days after ischaemic/nephrotoxic insult.
Present: abrupt rise in urea and Cr after initial insult.
Complications: hyperkalaemia, metabolica acidosis, decreased Ca, increased PO, hypoalbuminemia.
ATN - toxins
Exogenous Antibiotics: aminoglycosides, cephalosporins, amphotericin B Antiviral Antineoplastic: cisplatin, methotrexate Contrast media Heavy metals
Endogenous
Endotoxins
Myoglobin
Hemoglobin
ATN - ischaemia
Decreased circulating volume: Hemorrhage Skin losses GI losses Renal losses
Decrease effective circulating volume: Heart failure Liver failure Sepsis Anaphylaxis
Vessel occlusion
Analgesic nephropathies
Vasomotor acute kidney injury - NSAIDs decrease prostaglandin, renal ischemia
Acute interstitial nephritis - fenopren, ibuprofen, naproxen causes nephrotic proteinuria
Chronic interstitial nephritis - excessive paracetamol + NSAID consumption, causes papillary necrosis (hematuria, flank pain, decrease GFR)
Acute tubular necrosis - paracetamol overuse, spontaneous recovery in 4 weeks
Other effects - Na retention, hyperkalemia, HTN, excess water retention
Diabetic renal complications
Albuminuria (ACR). Renal function declines once macroalbuminuria is established, progressing to ESRD in 50% by 7-10 years.
Progressive glomerulosclerosis: Kimmelstiel-Wilson nodular lesions, increase in mesangial matrix with diffuse glomerular sclerosis. Stage 1 - increased GFR, compensatory Stage 2 - microalbuminuria, ACR 2-10 Stage 3 - macroalbuminuria, ACR >20 Stage 4 - ESRD
Accelerated atherosclerosis:
Common finding
Autonomic neuropathy:
Bladder functional obstruction and urinary retention
Papillary necrosis:
Type 1 DM susceptible to ischaemic necrosis of meullary papillae
Scleroderma renal involvement
Mild proteinuria, high Cr, HTN
Rx: BP control with ACEi
Multiple myeloma nephropathy
Kidney damage mechanisms: Hypercalcemia Light chain cast nephropathy (LCCN - large casts light chains + Tamm-Horsfall protein) Hyperuricemia Infection Secondary amyloidosis Monoclonal Ig deposition disease (MIDD - nodular glomerulosclerosis) Diffuse tubular obstruction
Features: Bence-Jones proteins
Multiple myeloma (CARLI)
Calcium Anemia Renal failure Lytic bone lesions Infections
Malignancy - renal involvement
Solid tumours: mild proteinuria, membranous GN
Lymphoma: minimal change (Hodgkin’s), membranous (non-Hodgkin’s)
Renal cell carcinoma
Tumour lysis syndrome: hyperuricaemia, diffuse tubular obstruction
Chemotherapy (cisplatin): ATN or chronic TIN
Pelvic tumours: obstruction
Secondary amyloidosis
Radiotherapy
Hypertensive nephrosclerosis
Chronic nephrosclerosis: slow vascular sclerosis with chronic hypertensive disease.
Malignant nephrosclerosis: fibrinoid necrosis of arterioles, acute BP elevation, HTN encephalopathy
Adult polycystic kidney disease
AD involvement of PKD1, PKD2, PKD3.
Extrarenal manifestations: hepatic cysts, cerebral aneurysm, diverticulosis, mitral valve prolapse.
Common complications: UTI, HTN, CRF, nephrolithiasis, flank and chronic back pain
Medullary sponge kidney
AD multiple cystic dilitations in CT or medulla.
Complications: renal stones, hematuria, recurrent UTIs, nephrocalcinosis
Autosomal recessive polycystic kidney disease
Prenatal diagnosis by enlarged kidneys, perinatal death from respiratory failure.
Acute kidney injury
Abrupt decline in kidney function leading to increase urea.
AKI - prerenal causes
Disordered regulation:
NSAIDs, ACEi, Calcineurin inhibitors, hypercalcemia
Hypovolaemia:
Hemorrhage, GI loss, skin loss, renal loss, low CO, cirrhosis, sepsis, 3rd space
AKI - renal causes
Vascular: Vasculitis, malignant HTN, thrombotic microangiopathy, cholesterol emboli, large vessel disease Glomerular nephritis Acute interstitial nephritis Acute tubular necrosis
AKI - postrenal causes
Neurogenic
Anatomic
Chronic kidney disease
Progressive irreversible loss of kidney function
Stage 2 GFR
Renal failure
Volume overload
Electrolyte abnormalities: high K, PO, uric acid; low Na, Ca, HCO
Uremic syndrome: nausea, vomiting, anorexia, lethargy, muscle cramps, restless legs, prutitus, confusion, pericardial rub
Dialysis indications
Acidosis Electrolyte imbalance - K Intoxication Overload Uremic encephalopathy, pericarditis
Renal failure complications
CNS: decreased LOC, seizure
CVS: cardiomyopathy, CHF arrhythmia, pericarditis, atherosclerosis
GI: ulcers
Hematologic: anemia, platelet dysfunction, infection
Endocrine: decrease testosterone, estrogen, progesterone; increase FSH, LH
Metabolic: renal osteodystrophy, hypertriglyceridemia, insulin changes
Dermatologic: pruritus, ecchymosis, hematoma
Dialysis options
Peritoneal dialysis: slow, via peritoneum, multiple exchanges per day, will wear out.
Hemodialysis: fast, via artificial membrane, few exchanges per week.
Renal transplant complications
Interstitial fibrosis/tubular atrophy (graft loss)
Immunosupressant therapy (infections, malignancy)
Acute rejection
De novo glomerulonephritis (membranous)
New onset DM (prednisone)
Cyclosporin or tacrolimus nephropathy
Chronic allograft nephropathy (previous acute rejections, antibody injury)
CMV infection (1-6months)
