Renal Pathology 1 to 10
What are the manifestations of nephrotic syndrome?
- Massive proteinuria
- Oedema (generalised)
- Bold to pass
What are the underlying processes responsible for these features?
- Derangement of glomerular capillary walls resulting in increased permeability to plasma proteins. Either structural damage or physicochemical alterations > massive proteinuria
- 1) secondary to above and
- 2) inability of liver to synthesise enough replacement albumin.
- 3) Additionally increased renal catabolism of filtered albumin
- Generalised oedema secondary to
- 1) loss of colloid osmotic pressure of blood.
- 2) Compounded by sodium and water retention due to activation of renin-angiotensin system, enhanced ADH secretion, stimulation of sympathetic system and reduction in natriuretic factors
- Hyperlipidaemia (complex causation). Causes include increased liver synthesis, abnormal lipid transport and decreased catabolism
- Lipiduria a combination of increased production (see point 4) and increased glomerular permeability (see point 1)
- Bold to pass
What are the causes of the nephrotic syndrome?
- Primary glomerular disease (95% kids and 60% adults)
- 60% minimal change, 10% each focal segmental, membranoproliferative and other, 5% membranous
- 35% focal segmental, 30% membranous, 10% minimal change 10% membranoproliferative, 15% other
- Systemic disease (mostly adults)
- diabetes, amyloidosis, SLE, drugs (NSAID’s, penicillamine), infections (malaria, hepatitis B&C, HIV), malignancies, other (bee-sting allergy, hereditary nephritis)
- PGN required to pass
- Should know difference in causation between kids and adults
What are the manifestations of the nephrotic syndrome?
- Massive proteinuria, with the daily loss of 3.5 gm or more of protein (less in children)
- Hypoalbuminemia, with plasma albumin levels less than 30 gm/L
- Generalized oedema
- Hyperlipidemia and lipiduria
- 3 out of 4
What are the mechanisms of the oedema?
- Loss of colloid osmotic pressure
- Loss of serum albumin
- Accumulation of water and sodium in tissues
- Due to compensatory secretion of aldosterone
- Mediated by
- Increased ADH
- Increased Sympathetic system
- 3 out of 4
What is the pathogenesis of post streptococcal glomerulonephritis?
- Initiated by Group A Beta-haemolytic streptococcal infection (commonly pharyngitis or impetigo), 90% due to types 1, 4 or 12 (cell wall M protein)
- Antibody and immune complex production over 1-4 weeks
- Immune complex deposition in glomeruli. (IGG and C3)
- Acute proliferative glomerulonephritis
- All 4
What is the clinical course of the disease in children?
- Recent streptococcal infection as above
- Abrupt onset of fever, malaise, nausea, oliguria and haematuria
- Mild to moderate hypertension
- Red cell casts in urine and mild proteinuria
- 95% fully recover (with complete resolution of glomerular lesions), 4% chronic GN, 1% rapidly progressive GN. Prolonged and persistent proteiniuria or abnormal GFR = poorer prognosis
How does the clinical course differ in adults?
- Less benign
- Sporadic cases @ 60% fully recover. (Better recovery rates in epidemic outbreaks)
- In the remainder glomerular lesions resolve less quickly or not at all. Prolonged proteinuria, haematuria and hypertension. Outcomes slow resolution, chronic GN or rapidly progressive GN
- Bold required
Describe the aetiology and pathogenesis of post streptococcal glomerulonephritis.
- Group A Beta-hemolytic streptococci (eg: 90% types 12, 4, and 1)
- Typically post pharyngeal/skin infections (impetigo) – sometimes epidemic, partic in overcrowded insanitary conditions
- An immunologically mediated disease Type 2/ or 3 type e.g. Circulating or antigen deposit disease.
- Granular immune deposits in the glomeruli (IgG & C3) – partic GBM- leading to leaking glomeruli.
- Streptococcal antigen found in the glomeruli.
- Complement activation – low serum complement
- Elevated titres of anti streptococcal Ab
- Nephritis associated streptococcal plasmin receptor NAPlr, Strep pyogenic exotoxin B (SpeB), zSPeb
- 2 x bold and 1 other
Describe the clinical features of post Streptococcal GN.
- 1 to 4 weeks after a streptococcal infection of the pharynx or skin (impetigo).
- Malaise, fever, nausea, oliguria, and haematuria
- Red cell casts, mild proteinuria (usually < 1 gm/day), periorbital and otheroedema, mild to moderate hypertension
- 95% will recover quickly in 1-3 weeks, 4 % chronic, 1% severe acute renal failure. Adult onset has worst prognosis
- Depleted C3 and almost always Strep Ags
- 2 x bold and 2 others
What are the types of urinary calculus?
1. Ca oxalate 70%
Idiopathic hypercalcuria 50%
Hypercalciuria & hypercalcaemia 5%
– (hyperparathyroid, bone diseases, Sarcoid)
Hypercalcaemia only 5%
– (increased absorption, renal, idiopathic, fasting)
– 4.5% enteric
– 0.5% Primary.
Pass: Bold plus 3 of 6 with examples
2. Magnesium ammonium phosphate (Struvite) (triple phosphate) 15%
– (staghom talc)
Urea splitting organisms….
– (proteus, some staph),
Pass: Bold plus 1 example
3. Uric acid
Raised uric acid
Over 50% normal uric acid and excretion (pH <5.5)
Pass: Bold plus 1 example
4. Cysteine 1-2%
What is the pathogenesis of renal stones?
Increased concentration of stone constituents
Change in urinary pH
Decreased urine volume
Infection — bacteria
Deficiency in inhibitors-pyrophosphates, Diphosphonates, Citrate, Glycosaminoglycans, Osteopontin, nephrocalcin-
Pass: 3 of 6
Infections by what types of streptococci can lead to glomerulonephritis?
Prompt: What groups of streptococci are there?
Strains of Group A beta haemolytic strep with M protein in wall
What is the cause of the glomerular damage?
Prompt: Do streptococci produce any harmful antigens?
1 Latent period of 1+ weeks
2 Immune complex disease
3 Several possible antigens involved
4 Antigens have affinity for glomeruli
5 Also activates alternative complement cascade
Pass: Immune complex plus 2 others
What abnormalities are seen in the urine in a patient with glomerulonephritis?
Prompt: What happens when glomerular membranes are damaged?
- Cellular casts
- Other debris
What different substances can renal calculi be composed of?
Prompt: What can become concentrated in the urine and crystallize?
- calcium (oxalate and/or phosphate) 80%
- struvate (magnesium/ammoninmlphosphate) 15%
- uric acid 5%
- cystine 1%
- Others (metabolic byproducts, drugs)
Pass: Calcium and one other
What factors may lead to formation of struvate calculi?
Prompt: Are there any general factors that could lead to formation of crystals?
- Anatomical: polycystic, horseshoe, sponge, diverticulae, reflux
- Concentration of urine
- Substrate formed by urea-splitting bacteria (proteus, klebsiella, pseudomonas).
- Metabolic causes
What are the potential complications of renal calculi?
Prompt: What can happen if urine flow is obstructed?
- 1 Infection
- 2 Renal parenchymal damage
- 3 Obstruction
- 4 Bleeding
- 5 Pain
- 6 Renal failure
What are the causes of acute tubular necrosis?
Prompt: What substances can damage the renal tubules?
- Ischaemic: hypotension, vasoconstriction, intracapsular pressure
- Direct toxic injury: aminoglycosides, amphotericin, sulfas Other substances: contrast, myoglobin, crystals, proteins
- 3. Acute tubulo-interstitial nephritis
- Urinary obstruction (post-renal)
- DIC, sepsis
Describe the phases of acute tubular necrosis?
Prompt: What is the first thing that happens in ATN?
- Initiation phase: decreased urine output, elevated urea, 36 hrs
- Maintenance phase: sustained decreased output, salt and water overload, uraemia, hyperkalaemia
- Recovery phase: increased output and possibly polyuria, hypokalaemia, vulnerable to infection
Pass: 1 and 3
What are the main types of renal calculi?
- Calcium oxalate and phosphate (70%)
- Struvite or triple (magnesium ammonium phosphate) (15-20%)
- Uric acid (5-10%)
- Cystine (1-2%)
- Calcium + 1 other to pass
What conditions in urine favour stone formation?
- Increased concentration of stone constituents
- Changes in urinary pH
- Decreased urine volume
- 2 to pass
What are the complications of ureteric calculi?
- Obstructive renal impairment
- 1 bold and 1 other
Define Acute Kidney Injury
- Clinico-pathological entity
- Acute reduction of renal function with morphologic tubular injury (usually)
- Bold to pass
What are the causes of AKI? (Please give examples)
- Ischaemia/abnormal blood flow
- Systemic – thrombosis (HUS, TTP, DIC) or hypovolaemia
- Intra-renal – angiopathies, malignant hypertension
- Toxic injury to tubules – drugs, radio-dye, myoglobin
- Acute tubulointerstitial nephritis – reaction to drugs
- Obstruction (“post-renal”) – tumour, clot
- Bold and 1 other category
- 1 example for each
Describe the typical clinical course of AKI.
- (1) – Initiation 36 hours: decreased urine output, increased urea
- (2) – Maintenance: oliguria, salt/water overload, incr urea/K/H
- (3) – Recovery: incrased urine volume (up to 3L/day), H2O/Na/K loss. Ur/Cr r/t normal.
- Oliguric phase
- Polyuric recovery
A 70 year old lady with a history of bipolar disorder is found on the floor many hours after a fall. On arrival in ED, she is tachycardic and complaining of severe thirst and thigh pain. On secondary survey, you suspect a fractured femur. What are the most likely causes in this 70 year old lady?
- Ischaemic injury from hypovolaemia/hypotension from femur fracture +/- inability to get to water
- Myoglobin deposition from rhabdo