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66 Cards in this Set
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Mechanisms producing glomerular disease |
Immunocomplexes (Type III hypersensitivity) - ICs circulate and deposit in glomeruli or they develop in situ, this includes DNA - anti DNA complexes in SLE - ICs activate the complement system. Complement 5a (C5a) is produced, which is chemotactic to neutrophils. These damage the glomeruli which primarily occurs in nephritic types of glomerulonephritis Antibodies are directed against GBM antigens - Goodpasture syndrome T-cell production of cytokines - Cytokines cause the GBM to lose its negative charge - Cytokines damage podocytes causing them to fuse - Example, minimal change disease (lipoid nephrosis) in the nephrotic syndrome |
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Clinical manifestations of glomerular diseases |
Nephrotic syndrome Nephritic syndrome Chronic glomerulonephritis |
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Nephritic syndrome |
Due to glomerular injury primarily as a result of neutrophils. Clinical and lab findings - Hypertension due to salt retention - Periorbital puffiness due to salt retention in the loose skin in that area, some cases oedema is more generalised and produces pitting oedema. Sodium retention increases plasma hydrostatic pressure. - Haematuria, dysmorphic RBCs are present with irregular membranes. Glomeruli become inflamed from IC deposition causing damage to RBC membranes. - Neutrophils are present in the urine sediment, particularly in IC types of nephritic glomerulonephrtis - RBC casts are a key finding, occasionally WBC casts are also present - Proteinuria is >150mg/day but <3.5 g/day - Azotemia is present with a BUN/Cr ratio >15, tubular function is intact in acute glomerulonephritis. |
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Nephrotic syndrome |
Glomerular injury due to cytokines - Cytokines damage podocytes causing them to fuse together - Cytokines destroy the negative charge of the GBM Clinical and lab findings - Key finding is proteinuria >3.5 g/24 hours - Generalised pitting oedema and ascites due to hypoalbuminaemia causing a decrease in oncotic pressure. Increased risk of developing peritonitis due to Strep. pneumoniae or E.Coli - Hypertension in some types due to sodium retention - Hypercoagulable state due to loss of antithrombin III, potential for renal vein thrombosis - Hypercholesterolaemia, hypoalbuminaemia increases synthesis of cholesterol - Hypogammaglobulinaemia due to the loss of gamma globulins in the urine - Fatty casts with maltese crosses and oval fat bodies - Key finding |
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Primarily Nephritic Types of glomerular disease |
IgA glomerulopathy (Berger disease) Post-streptococcal glomerulonephritis Diffuse proliferative glomerulonephritis Rapidly progressive (crescentic) glomerulonephritis |
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Primarily Nephrotic Types of glomerular disease |
Minimal change disease (lipoid nephrosis) Focal segmental glomerulosclerosis Diffuse membranous glomerulonephropathy Type I MPGN Type II MPGN |
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IgA glomerulonephropathy (Berger disease) |
Most common nephropathy (majority are nephritic, 5% of cases nephrotic) Affects children and adults, most common cause of chronic glomerulonephritis in children. Increased mucosal synthesis and decreased clearance of IgA; increased serum IgA (50% of cases) Focal proliferative glomerulopathy Mesangial IgA IC deposits with granular IF; ICs activate the alternative complement pathway Overlapping features with HSP may occur Episodic bouts of haematuria (microscopic or gross) usually occur following an upper respiratory infection; hypertension is common Slow progression to CRF (40-50% of cases) Treatment: corticosteroids decrease proteinuria; treat HTN |
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Poststreptococcal glomerulonephritis |
Most common type of post-infectious GN. Usually after Group A strep infection of skin (e.g. scarlet fever) or pharynx Sub-epithelial IC deposits with granular IF; ICs activate the alternative complement pathway Diffuse proliferative pattern with neutrophil infiltration Haematuria 1-3 weeks after Group A Streptococcal infection by a nephritogenic strain strain (never produces acute rheumatic fever; periorbital oedema (sodium retention); oedema can occasionally be more extensive and produce pitting in dependent areas (e.g. ankles); hypertension is usually transient; however, in some cases it is severe Increased anti-DNase B titers; ASO is degraded by oil in the skin and is not increased; streptozyme is positive because it detects anti-DNAase B antibodies. Usually resolves; CRF is uncommon in children but common in adults. Treatment: supportive; penicillin G or V is given if cultures are positive for Streptococcus pyogenes; treat hypertension |
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Diffuse proliferative glomerulonephritis |
Diffuse proliferative GN is the most common subtype of glomerular disease in SLE; one other type has a nephrotic presentation. Subendothelial IC deposits with granular IF; DNA-anti-DNA ICs activate the classical complement pathway "Wire looping" of capillaries corresponds with subendothelial ICs; neutrophil infiltration with hyaline thrombi in capillary lumens Kidneys are the major target organ in SLE (90% of cases) Serum ANA test usually has rim pattern, corresponding to presence of anti-dsDNA antibodies Evolves into CRF in most cases; common cause of death in SLE Treatment: corticosteroids + cyclophosphamide |
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Rapidly progressive crescentic glomerulonephritis |
Clinical syndrome that may be a primary or secondary type of glomerular disease Rapid loss of renal function progresses to ARF over days to weeks; very poor prognosis. May or may not be associated with crescent formation. Clinical associations: Goodpasture syndrome, microscopic polyarteritis (p-ANCA), Wegener granulomatosis (c-ANCA) Goodpasture syndrome: - Male dominant disease: 80% HLA-DR2 positive - Anti-basement membrane antibodies against collagen in glomerular and pulmonary capillaries (alpha 3, type IV) - Linear IF; EM has no electron-dense deposits crescentic GN (Goodpasture syndrome accounts for 5% of all cases) Begins with haemoptysis and ends with renal failure Treatment: plasma exchange; immunosuppressive therapy with corticosteroids and cyclophosphamide; renal transplantion |
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Minimal change disease (lipoid nephrosis) |
Most common cause of nephrotic syndrome in children; F>M; occurs in around 15% of adults with nephrotic syndrome T-cell cytokines cause the GBM to lose its negative charge selective proteinuria (albumin not globulins) Secondary cause: Hodgkin lymphoma Structurally normal glomeruli; positive fat stains in glomerulus and tubules Negative IF; EM shows fusion of podoytes and no electron-dense deposits Often preceded by an upper respiratory tract infection or routine immunisation Usually normotensive (90% of cases), unlike other types of nephrotic sydnrome Treatment: children respond well to steroid therapy; CRF is rare |
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Focal segmental glomerulosclerosis |
Primary or secondary disease; secondary causes - HIV (most common glomerular disease; mainly in young black males) and IV heroin abuse. Most common cause of nephrotic syndrome in adults Negative IF; EM shows focal damage of VECs (visceral epithelial cells) Nonselective proteinuria, microscopic haematuria (60-80%) Hypertension early (20%) Poor prognosis; commonly progresses to CRF Treatment - corticosteroids (only 15-20% response) |
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Diffuse membranous glomerulopathy |
Second most common cause of nephrotic syndrome in adults Highest incidence of renal vein thrombosis with pulmonary embolism most likely due to loss of antithrombin III in urine. Primary and secondary types, secondary causes: - Drugs: e.g. captopril, gold therapy - Infections: HBV, Plasmodium malariae, syphilis - Malignancy: carcinomas, Hodgkin lymphoma - Autoimmune disease: SLE (nephrotic presentation) Diffuse thickening of membranes; silver stains show "spike and dome" pattern beneath VECs (sub-epithelial deposits) Subepithelial ICs with granular IF Treatment: corticosteroids may slow progression |
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Type I MPGN |
Most common type of MPGN; nephrotic presentation (60% of cases); some cases have a nephritic presentation Associations: HBV, HCV, cryoglobulinaemia Subendothelial ICs with granular IF; ICs activate the classical and alternative complement pathways; EM shows tram tracks caused by splitting of the GBM by an ingrowth of mesangium. Hypertension (35% of cases), majority have haematuria Majority progress to CRF Treatment: response to corticosteroids not established |
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Type II MPGN |
Associated with C3 nephritic factor, an autoantibody that binds to C3 convertase, prevents degradation of it causing sustained activation of C3 and resulting in very low C3 levels. Diffuse intramembranous deposits (dense deposit disease); EM shows tram tracks. Hypertension (35% of cases); majority have haematuria Majority progress to CRF Treatment: response to corticosteroids not established |
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Diabetic glomerulopathy (nephrotic) overview |
Nodular glomerulosclerosis (Kimmelstiel-Wilson disease) Epidemiology - Occurs in T1 and T2 DM, more often in type 1 and is the most common cause of chronic renal failure. - Risk factors (poor glycaemic control, hypertension and diabetic retinopathy - correlation with coexisting glomerulopathy) Pathogenesis - Nonenzymatic glycosylation (NEG) of the GBM and tubular basement membrane, increases vessel and tubular basement membrane permeability to proteins. - NEG of afferent and efferent arterioles causing hyaline arteriosclerosis. This involves the efferent arterioles before the afferent. - Osmotic damage to glomerular capillary endothelial cells. Glucose becomes sorbitol, osmotically active, enters cells causing water entry and damages them. - Hyper-filtration damage to the mesangium due to selective hyaline arteriosclerosis of the efferent arteriole which increases the GFR and damages mesangial cells. - Diabetic microangiopathy - increased deposition of type IV collagen in the GBM, tubular cell basement membrane and mesangium |
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Diabetic glomerulopathy clinical findings |
Non-specific IF, EM shows fusion of podocytes Microscopic findings - Afferent and efferent hyaline arteriosclerosis, when afferent affected GFR decreases - Nodular masses develop in mesangial matrix due to increased type IV collagen synthesis and trapped proteins Clinical and lab findings - Microalbuminuria, initial lab manifestation begins around after around 10 years of poor glycaemic control. Dipsticks detect albumin levels in the range of 1.5 - 8 mg/dL Treatment - ACE inhibitor given when microalbuminuria is first detected as it slows progression of glomerulopathy. |
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Hereditary glomerular diseases |
Alport syndrome - X-linked recessive (most common) and autosomal dominant/recessive types due to mutations in alpha chain of type IV collagen in GBM - EM/monoclonal antibody studies to detect GBM defects are useful in confirming the diagnosis - Hypertension, gross/microscopic haematuria, RBC casts are common - Sensorineural hearing loss and ocular findings - End-stage renal disease more common in men Thin basement membrane disease (benign familial haematuria) - Autosomal dominant disorder. Extremely thin GBMs - Normal renal function with persistent microscopic haematuria |
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Chronic glomerulonephritis |
In order of incidence: - Rapidly progressive glomerulonephritis (RPGN) - Focal segmental glomerulosclerosis (FSG) - Type I MPGN - Membranous glomerulopathy - Type IV diffuse proliferative glomerulonephritis in SLE Gross and microscopic findings - Shrunken kidneys - Glomerular sclerosis and tubular atrophy |
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Acute renal failure overview |
Greater than 10% of intensive care unit patients develop acute renal failure. (ARF) Greater than 40% of hospital ARF is iatrogenic. Haemolytic uremic syndrome is the most common cause of intrinsic ARF in the US. ARF develops in 20% of patients with sepsis. ARF develops in >50% of patients with septic shock. Definition - Acute suppression of renal function developing in 24 hour - Accompanied by anuria or oliguria (around 400ml/24 hours) - ATN is the most common cause of ARF (ischaemic and nephrotoxic types) Other causes of ARF - Postrenal obstruction (BPH, invasive cervical cancer) - Vascular disease (malignant hypertension) - RPGN, drugs, DIC, urate nephropathy. |
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Ischaemic ATN pathogenesis |
Most often due to prerenal azotemia due to hypovolaemia Ischaemia damages endothelial cells - Causes decrease in vasodilators, increase in vasoconstrictors so the net effect is vasoconstriction of afferent arterioles decreasing GFR. Ischaemia damages tubule cells - Causes detachment of tubular cells into the lumen causing obstruction. Produces pigmented renal tubular cell casts. Coagulative necrosis of renal tubular cells. - Casts obstruct the lumen, causing an increase in intratubular pressure which decreases GFR, pushes fluid into the interstitium and leads to oliguria. Sites of tubular damage - Straight segment of proximal tubule which is most susceptible to hypoxia. - Medullary segment of TAL, location of the Na-K-2CL co-transporter - Tubular basement membranes are disrupted at these sites which interferes with renal tubular cell regenration |
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Nephrotoxic type ATN summary |
Causes - Aminoglycosides are the most common cause (e.g. gentamicin) - Radiocontrast agents - Heavy metals (e.g. lead, mercury) Microscopic findings - Primarily damages the proximal tubule cells, tubular basement membrane intact which allows renal tubular cells to regenerate properly Clinical and lab findings - Oliguria in most cases (around 400 ml/24 hours), some cases have polyuria (around 800ml/24 hours) - Pigmented renal tubular cell casts - Hyperkalaemia, increased anion gap (AG) metabolic acidosis - Increased serum BUN and creatinine (ratio <=15) - Hypokalaemia (diuresis phase) and infection are common problems |
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ATN: Treatment |
Treat prerenal azotemia - Volume expansion if hypovolaemic - Increase renal blood flow
Low dose dopamine (increases renal blood flow) Fenoldopam (dopamine alpha-1 receptor agonist) Dialysis |
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Tubulointerstitial nephritis (TIN) |
Definition - acute or chronic inflammation of tubules and interstitium Causes - Acute pyelonephritis (APN; most common) - Drugs - Infections (legionnnaires disease, leptospirosis) - SLE, lead poisoning, urate nephropathy, multiple myeloma |
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Acute pyelonephritis (overview) |
W>M as women have a shorter urethra E.Coli is the most common cause - Enterococcus second most Risk factors - Indwelling urinary catheter - Urinary tract obstruction - Medullary sponge kidney - Diabetes mellitus, pregnancy, sickle cell train/disease |
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Acute pyelonephritis: pathogenesis |
Vesicoureteral reflux (CUR) with ascending infection (most common) - Intravesical portion of the ureter is normally compressed with micturition which prevents reflux of urine into ureters. - In VUR, intravesical portion is not compressed and urine refluxes. - Corrected by reimplantation of the ureters or stents Ascending infection - Most common mechanism for lower and upper urinary tract infections (UTIs) in females. - Distal urethra and vaginal introitus normally colonised by E.Coli - Organisms ascend into the urethra and bladder causing urethritis and cystitis - If VUR is present, infected urine ascends to the renal pelvis and renal parenchyma Haematogenous spread to kidneys - Uncommon cause of APN - Suspect haematogenous spread if S.aureus is cultured in urine |
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Acute pyelonephritis: Clinical findings |
Gross and microscopic findings - Grayish-white areas of abscess formation are in the cortex and medulla - Microabscness formation occurs in the tubular lumens and interstitium Cliinical findings - Spiking fever, flank pain - Increased frequency of urination - Painful urination (dysuria) Laboratory findings - WBC casts (key finding) - Pyuria, bacteriuria (E.Coli) - Haematuria Complications - Chronic pyelonephritis - Perinephric abscess - Renal papillary necrosis - Septicaemia with endotoxic shock |
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Acute pyelonephritis: Treatment |
Ciprofloxacin given orally if uncomplicated Ciprofloxacin IV if hospitalised Repair VUR |
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Chronic pyelonephritis: Pathogenesis |
VUR starting in young girls Lower urinary tract obstruction - Produces hydronephrosis - Examples - BPH, renal stones |
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Chronic pyelonephritis: Clinical findings |
Gross and microscopic findings - Reflux type of CPN, U shaped cortical scars overlying a blunt calyx. Visible with an intravenous pyelogram (IVP). - Obstructive type of CPN, Uniform dilation of the calyces and diffuse thinning of cortical tissue. Microscopic findings - Chronic inflammation, secondary scarring of the glomeruli. - Tubular atrophy, tubules contain eosinophilic material resembling thyroid tissue Clinical and lab findings - Usually a history of recurrent APN - May cause hypertension, reflux nephropathy is a cause of hypertension in children - May cause CRF |
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Other causes TIN |
Acute drug induced TIN - Penicillin, Rifampin, sulfonamides, NSAIDs, diuretics - Type I and IV hypersensitivity, around 2 weeks after starting drug - Abrupt onset of fever, oliguria and rash - Withdrawal of drug reverses disease - Lab findings BUN/Cr ration <=15, eosinophilia and eosinophiluria (highly predictive) Analgesic nephropathy - Common cause of chronic drug-induced TIN, W>M, usually occurs in persons with chronic pain - Chronic use of acetaminophen plus aspirin for 3 or more years - Free radicals damage renal tubules in medulla, aspirin decreases renal synthesis of PGE2 leaving ATII unopposed which decreases blood flow to the renal medulla - Complications - renal papillary necrosis, HTN, CRF, Renal pelvic and bladder TCCs Urate nephropathy - Deposition of urate crystals in tubules and interstitium - Causes, massive release of purines (precursor of uric acid), usually occurs after aggressive treatment of disseminated cancer (e.g. leukaemia, lymphoma). Lead poisoning or gout. - Can produce ARF Chronic lead poisoning - Decreases renal excretion of uric acid and direct toxic effect Multiple myeloma - Bence Jones proteins are toxic to renal tubular epithelium - Casts obstruct the lumen and incite a foreign body giant cell reaction involving tubules and interstitial leading to renal failure Nephrocalcinosis - Hypercalcaemia secondary to lytic bone lesions produces metastatic calcification of the basement membrane of collecting tubules - Presents with polyuria and renal failure |
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Chronic Renal failure: Overview |
Definition: progressive irreversible azotemia that develops over months to years Culminates in end-stage renal disease - Characterised by inadequate kidney function to sustain life and GFR <10 mL/min Causes - Diabetes Mellitus - Hypetension - Chronic glomerulonephritis (RPGN, FSG) - Cystic renal disease (renal dysplasia in children, adult PKD) Gross appearance - Bilateral, small shrunken kidneys |
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Chronic renal failure: Clinical findings |
Haemotologic findings - Normocytic anaemia with corrected reticulocyte count <3%, primarily due to decreased EPO - Qualitative platelet defects that are corrected with dialysis Renal osteodystrophy - Osteitis fibrosis cystica, occurs secondary to hypovitaminosis D (loss of alpha hydroxylase in proximal renal tubules). This leads to secondary hyperparathyroidism which increases bone resorption causing cystic lesion in bone. - Haemorrhage into cysts causes a brown discolouration - Osteomalacia, decreased mineralisation of organic bone matrix (osteoid). In CRF, due to hypovitaminosis D producing hypocalcaemia, leading to decreased bone mineralisation. - Soft bone (increased osteoid) produces fractures and bone pain - Osteoporosis, loss of osteoid and mineralised bone which causes an overall reduction in bone mass. In CRF it is due to chronic metabolic acidosis. Excess H+ ions are buffered by bone. - Soft bone causes fractures and bone pain. Cardiovascular findings - HTN from salt retention - Haemorrhagic fibrinous pericarditis - Congestive heart failure, accelerated atherosclerosis Miscellaneous clinical findings - Hemorrhagic gastritis - Uremic frost (urea crystals deposit on skin) |
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Chronic renal failure: Lab findings |
Acid-base and electrolyte abnormalities - Hyperkalaemia and increased AG metabolic acidosis - Sodium is usually normal except in salt losing types Hypocalcaemia - Due to hypovitaminosis D - Hyperphosphataemia, excess phosphorus drives calcium into bone and soft tissue Normocytic anaemia - Decreased EPO Prolonged bleeding time - Defects in platelet aggregation Increased serum cystatin C - Cysteine protease inhibitor produced by all nucleated cells. Filtered by the glomerulus but not secreted. Level is less dependent on age, sex, race and muscle mass than creatinine. Serum value >1.3mg/L has a 88% sens and 96% spec for detecting renal dysfunction. Urinalysis findings - Fixed specific gravity, tubular dysfunction causes lack of concentration and dilution. Free water clearance is zero - Waxy/broad casts |
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Chronic renal failure: Treatment |
Nonpharmacologic - Restrict sodium - Low protein-diet - Adjust drug doses to the renal clearance - Kidney transplantation General treatment - ACE inhibitors to reduce proteinuria and disease progression and also treats hypertension - Dialysis - Erythropoiesis stimulating agents - Calcium supplementation and vitamin D (calcitriol) to treat renal osteodystrophy - Phosphate binder (sevelamer) |
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Vascular Diseases of the Kidney |
Benign Nephrosclerosis (BNS) Malignant hypertension Renal infarction Sickle cell nephropathy Diffuse cortical necrosis |
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Benign Nephrosclerosis |
Most common renal disease in essential hypertension. Pathogenesis - Hyaline arteriosclerosis of arterioles in the renal cortex - Causes tubular atrophy, interstitial fibrosis and glomerular sclerosis Small kidneys with a finely granular cortical surface. Lab findings - Mild proteinuria - Haematuria - Renal azotemia |
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Malignant hypertension overview |
Sudden onset of accelerated hypertension may occur: - Normotensive individuals - In those with BNS (most common) - As a complication of various disorders (systemic sclerosis) Risk factos - Preexisting BNS - HUS - TTP - Systemic sclerosis |
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Malignant Hypertension Pathogenesis |
Vascular damage to arterioles and small arteries. Gross and microscopic changes - Fibrinoid necrosis and necrotising arteriolitis and glomerulitis, manifested by pinpoint haemorrhages on the cortical surface (flea bitten kidneys) of both kidneys - Hyperplastic arteriosclerosis (onion skin lesion), smooth muscle hyperplasia and reduplication of basement membrane |
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Malignant hypertension: Clinical and Lab findings |
Clinical findings Rapid increase in blood pressure to >=210/120 mm Hg Hypertensive encephalopathy - Cerebral oedema - Papilloedema, loss of normal optic nerve disk margin - Retinopathy - flare haemorrhages, exudates - Potential for an intracerebral bleed Oliguric acute renal failure Lab finings - Azotemia with BUN/Cr ratios <=15 - Haematuria with RBC casts - Proteinuria Initial treatment is sodium nitroprusside |
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Renal infarction |
Causes - Embolisation from thrombi in the left side of the heart (most common) - Atheroembolic renal disease - Vasculitis, particularly polyarteritis nodosa Gross and microscopic appearance - Irregular, wedge-shaped pale infarctions occur in the cortex - Old infarcts have a V-shaped appearance due to scar tissue Sudden onset of flank pain and haematuria |
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Sickle cell nephropathy |
Occurs with sickle cell trait or disease Clinical presentations - Asymptomatic haematuria (most common) due to infarctions in the renal medulla - Loss of concentrating ability - Renal papillary necrosis, pyelonephritis |
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Diffuse cortical necrosis |
Complication of an obstetric emergency - Pre-eclampsia, abruptio placentae Due to a DIC limited to the renal cortex - Fibrin clots are present in arterioles and glomerular capillaries - Bilateral, diffuse, pale infarct of the renal cortex Anuria in a pregnant woman followed by ARF. |
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Hydronephrosis |
Definition - Distension and dilation of the renal pelvis and calyces due to obstruction of free flow of urine. Children - Usually have congenital malformations such as bladder neck obstruction, urethral valve Adults usually have acquired disease - Stone (most common), prostate hyperplasia Causes - Renal stone (most common) - Retroperitoneal fibrosis - Cervical cancer, BPH Gross findings - Dilated ureter and renal pelvis - Compression atrophy of renal medulla and cortex May produce postrenal azotemia Treatment is to relieve the obstruction - Catheter (most often), nephrostomy tube, cystoscopy |
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Renal stones (urolithiasis): Overview |
M>F Incidence greater in the summer due to decreased fluid intake Causes - Hypercalciuria in the absence of hypercalcaemia, most common metabolic abnormality producing stones and it is due to increased GI reabsorption of calcium - Decreased urine volume concentrates the urine, hydration important - Reduced urine citrate, normally chelates calcium - Urine pH alterations, alkaline urine favours calcium and phosphate containing stones, acidic urine favours uric acid, cystine stones - Primary hyperparathyroidism (10% cases) - Diets high in dairy products (contain phosphate) or oxalates - Urinary infections due to urease producers (Proteus; ammonia) |
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Types of renal stones |
Calcium stones (approx 80% of cases) - Calcium oxalate (>50%) is the most common type in adults. Increased incidence associated with pure vegan diet, vitamin C def, Crohn's disease - Calcium phosphate stones (10-20%) are the most common in children. Associated with dairy products and distal renal tubular acidosis. Magnesium ammonium phosphate - Staghorn calculus or struvite stones (15% of cases) - Associated with urease producers, urine is alkaline and smells like ammonia Uric acid (8%), cystine (3%) |
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Renal stones: Clinical and Lab findings |
Clinical findings - Sudden onset of flank tenderness - Nausea and vomiting - Colicky pain radiating into ipsilateral groin - Patient constantly moving to relieve pain - Gross haematuria may be evident Lab findings - Haematuria - Crystals may be present in the urine - Hypercalcaemia, consider primary hyperparathyroidism Diagnosis - Plain film (KUB), 80% are radio-opaque - Un-enhanced spiral (helical) CT, very high S+S - Ultrasound (sens 15%, specificity 90%) - Strain urine to collect stone, send for analysis, greater than 50% pass the stone within 48 hours. Recurrence occurs in around 50% |
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Renal stones: Treatment |
Treatment tailored to type of stone Calcium stone - Hydrochlorothiazide increases distal renal tubule reabsorption of calcium - Cellulose phosphate, binds calcium in intestine Uric acid stone - Allopurinol prevents synthesis of uric acid - Increases urinary pH, alkaline pH makes uric acid more soluble in urine Struvite stone - Surgical removal because of size - Antibiotic to eliminate urease producer Surgical removal - Extracorporeal shockwave lithotripsy - Ureteroscopic stone extraction |
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Angiomyolipoma |
Hamartoma composed of blood vessels, smooth muscle and adipose cells Associated with tuberous sclerosis - Mental retardation - Multisystem hamartomas |
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Renal cell carcinoma overview |
Sporadic (most common) and hereditary types M>W in the 6-7th decades Risk factors - Smoking (most common cause) - Von Hippel-Lindau disease, autosomal dominant, chromosome 3 relationship. Haemangioblastomas of cerebellum and retina. Bilateral renal cell carcinoma (50-60%) - Adult polycystic kindey disease - Obesity, asbestos exposure, lead exposure - Exposure to gasoline and petroleum products |
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Renal cell carcinoma: Pathogenesis and findings |
Cytogenetic abnormalities occur in sporadic and hereditary cancers, e.g. translocations with loss of vHL suppressor gene Cancer derives from proximal tubule cells Gross and microscopic findings - Clear cell carcinoma is most common (70-80%) - Most are sporadic, remainder associated with VHL - Upper pole mass with cysts and haemorrhage, tumour is bright yellow mass over 3cm (75-80%) - Composed of clear cells that contain lipid and glycogen - Tendency to invade renal vein (15-20%) Metastasis - Lungs are the most common site (50-60% cases), often haemorrhagic cannonball lesions appear on radiographs - Bone (lytic lesions; 30-40% of cases) - Regional nodes (15 - 30% of cases) - Haemorrhagic nodules in the skin due to increased vascularity in tumour Clinical findings - Haematuria (50-60%) - Adominal mass (25-45% of cases) - Flank pain (35-40% of cases) - Hypertension (20-40% cases) - Triad of haematuria, abdominal mass, flank pain (5-10% of cases) - Weight loss (30-35% of cases) - Fever (5-15%) - Left sided varicocele due to invasion of left renal vein blocking left spermatic vein drainage. |
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Renal cell carcinoma: Lab findings |
Lab findings Elevated ESR (non-specific finding) Normocytic anaemia Ectopic secretion of hormones - Produces secondary polycythemia - PTH related protein produces hypercalcaemia Diagnosis - Ultrasound, abdominal CT and MRI |
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Renal cell carcinoma: Treatment and Prognosis |
Treatment is nephrectomy Prognosis - Characteristically has late metastases and may recur 1-20 years after tumour has been removed - Average 5 year survival is 45% with mets and 70% in cases that don't - Poor prognosis associated with extension into the renal vein or through the renal capsule 10-15% 5 year survival |
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Renal pelvis cancer |
Transitional cell carcinoma (TCC) - Most common type, 50% have similar tumours elsewhere in the urinary tract - Risk factors are smoking, phenacetin abuse, aromatic amines (aniline dyes), cyclophosphamide Squamous cell carcinoma (SCC) - Risk factors are renal stones and chronic infection |
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Wilms tumour |
Accounts for around 5% of childhood cancer. Most common primary renal tumour in children, occurs between 2-5 years of age Sporadic type (most common) Genetic type - Autosomal dominant inheritance (chromosome 11) - WAGR syndrome, Wilms tumours, aniridia (absent iris), genitourinary, retardation (mental) - Beckwith-Wiedemann syndrome, Wilms tumour, macroglossia, enlarged body organs (liver, adrenal, pancreas), hemi-hypertrophy of extremities Morphology - Large, necrotic, grey-tan tumour derived from mesonephric mesoderm. - Contains abortive glomeruli and tubules, primitive blastemal cells and rhabdomyoblasts Clinical findings - Unilateral palpable mass in a child with HTN which is due to renin secretion - Lungs are the most common site of metastasis - With combined therapies 2-year survival is >90% |
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Haematuria |
Upper urinary tract causes (kidneys, ureter): - Renal stones (most common) - Glomerulonephritis, characterised by dysmorphic RBCs - Renal cell carcinoma (RCC) and Wilms tumour Lower urinary tract (bladder, urethra, prostate): - Infection (most common) - Transition cell carcinoma - Benign prostatic hyperplasia (most common cause of microscopic haematuria in adult men) Drugs associated with haematuria: - Anticoagulants (warfarin, heparin) - Cyclophosphamide (haemorrhagic cystitis, risk factor for TCC) |
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Bladder tumours |
Bladder papilloma (very uncommon benign tumour) Transitional cell carcinoma (>95%) Squamous cell carcinoma of the bladder Adenocarcinoma of the bladder Embryonal rhabdomyoscarcoma (most common in children) |
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Transitional cell carcinoma: overview |
Most common bladder cancer M>W Increased incidence with ageing Causes - Smoking cigarettes (most common) - Workers in dye, rubber or leather industries - Cyclophosphamide - Arsenic exposure - Beer consumption (nitrosamines) - S.haematobium (70% produce SCC, 30% TCC) |
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Transitional cell carcinoma: Pathogenesis |
Genetic factors - Numerous chromosomes implicated - Genes implicated: p53 and RB suppressor genes; HRAS proto-oncogene - Alteration in epidermal growth factor receptor Environmental factors Multifocality (field effect) and recurrence are the rule due to: - A common malignant stem cell abnormality - Reimplantation of the tumour from another site. |
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Transitional cell carcinoma: Gross, microscopic and clinical findings |
Gross and microscopic features - Low grade cancers, usually papillary and not usually invasive - High grade cancers, papillary or flat and usually invasive - Most common sites - lateral or posterior walls at the base of the bladder - Significance of blood group antigens (A, B or H), better prognosis if tumour has these antigens Clinical findings - Painless gross/microscopic haematuria is the most common sign - Dysuria, increased frequency of urination |
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TCC grading |
Grade I (well differentiated) - vast majority are papillary growths with no evidence of invasion. Grade II (moderately well differentiated) - usually papillary but many are either invasive at presentation or become so. Cells show significant atypicality and an increase in mitotic figures. Grade III (poorly differentiated) - mainly solid lesions which are extensively invasive. Cells are pleomorphic with numerous mitoses. |
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TCC: Treatment and prognosis |
Treatment - Surgical resection - Intravesical chemotherapy - Radiotherapy Prognosis - 5 year survival rate for all stages combined is 80% |
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Squamous cell carcinoma of the bladder |
Associated with S.haematobium, eggs located in the urinary bladder venous plexus Common cancer in Egypt 70% of cancers are SCC, 30% are TCC Pathogenesis - Eggs are surrounded by eosinophils, IgE antibodies are attached to the eggs - Eosiniphils have Fc receptors so they attach to IgE and release major basic protein which destroys the egg (Type II hypersensitivity reaction) - Chronic bladder irritation/infection causes squamous metaplasia which can progress to dysplasia and SCC |
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Adenocarcinoma of the bladder |
Causes - Ureachal remnants (most common cause) - Cystitis glandularis - Exstrophy of the bladder |
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Embryonal rhabdomyosarcoma |
Most commons sarcoma in children, accounting for approx 3% of childhood cancer Most common site for boys is the urinary system, presenting as grape-like masses protruding from the urethral orifice Most common site for girls is the vagina |
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Cancers invading the bladder |
Invasive cervical cancer and prostate cancer Obstruct the urethra and the ureters Produce hydronephrosis, postrenal azotemia and death by renal failure |
