Week 1 - Renal disease

Question 1

Identify the clinical syndromes of kidney disease.

Answer 1

• Azotemia - increased BUN (blood urea nitrogen), pre-renal, renal and post renal. Acute, chronic kidney disease.
- Increased BUN. When it is with clinical disease → known as uraemia.

• Uraemia - increased BUN + clinical features - gastroenteritis, neuropathy, pericarditis etc.

• Nephritic syndrome - oliguria, haematuria, proteinuria (non selective).
- Non selective proteinuria - all proteins get leaked out - due to severe damage to basement membrane.

• Nephrotic syndrome - massive, selective, albuminuria, lipiduria, oedema.

• Minimal damage - only affecting podocytes → results in massive albuminuria. Only albumin as it is the smallest protein. Also have lipiduria and oedema due to decreased protein.
• In nephritic syndrome, oedema is due to cardiac failure, hypotension. In nephrotic syndrome, oedema is due to hypoproteinaemia.
• ARF - acute decreased GFR within hours/days, oliguria/anuria.
• CRF - chronic decreased GFR (<60mL/min > 3months - clinical diagnosis).
• ESRD - decreased GFR (<5%), terminal stage (patients need dialysis to survive).

• ATN - tubular defects ischaemic/toxic. Polyuria, metabolic acidosis.
- Acute renal failure due to tubular damage. 2 types - ischaemic and toxic.

• Nephrolithiasis - stone - spasmodic, severe pain, renal colic.
- Stone formation in the kidney.

• UTI, urinary tract obstruction and pyelonephritis.

Question 2

Describe the anatomy of the kidney.

Answer 2

• Left kidney located higher.
• Renal pain typically presents in the loin region.
• Blood supply - arcuate arteries.
• Lobulations are prominent in foetal kidney. Less common in adult kidney.

Cut section:
• Outer cortex - glomeruli.
• Inner medullary pyraminds - location of collecting ducts, DCT, loop of Henle.
• Renal papilla - tip of pyramid, most distal part of nephron.

Nephron:
• Blood supply enters glomerulus and the efferent arteriole then supplies all of the tubules.
• Any damage e.g. glomerulonephritis or block in capillary → affects the whole tubule (distal portion affected first).
• Glomerular damage results in tubular atrophy.

Ultrastructure of glomerulus. The capillary has 3 layers:
• Inner endothelium.
• Basement membrane.
• Outer epithelial cells known as podocytes - foot processes.
• Filtration of blood plasma to glomerular filtrate.

Question 3

Outline the juxtaglomerular apparatus.

Answer 3

• Specialised cells in JGA (endocrine gland) → secretes hormones.
• Label structures A-F - exam.
• Decreased GFR → renin → aldosterone, angiotensin BP, Na/K/H+

See renal CLIX notes.

Question 4

Describe normal kidney histology.

Answer 4

Microscopic image of glomerulus:
• Patent glomerular capillaries.
• PCT - large cells, enzymatically active, rough ER - prominent cells.
• DCT - thinner, flatter cells - only reabsorb.
• Efferent arteriole.
• JGA.

Question 5

Identify the components of the filtration membrane.

Answer 5

Filtration membrane:
• Endothelium has large holes that only stop cells - everything else is filtered out.
• Basement membrane stops all the larger proteins (globulins).
• Foot processes stop the smallest proteins (albumin).
- Foot processes are nephrin molecules - stop smallest proteins.
- Nephrin molecules from adjacent foot processes forming slit diaphragm.
• Therefore, only water and solutes pass out renal filtration membrane.

• When the damage is minor - usually only damages podocytes → all things stopped except albumin → goes out into urine → severe albuminuria. Although damage is less, there is too much loss of albumin. Patients develop hypoalbuminaemia and oedema.
• When the damage is severe - total destruction of podocytes, BM, endothelium → everything leaks out - patients will have all proteins, RBCs leaking into glomerular filtrate. Will also have oliguria as the inflammation blocks the capillaries.

Question 6

Differentiate between nephrotic and nephritic syndrome.

Answer 6

Nephrotic:
• Patent glomerular capillary.
• No inflammation.
• Albuminuria.
• Lipiduria.
• Polyuria.

Nephritic:
• Obstructed glomerular capillary.
• Inflammation.
• Proteinuria.
• Haematuria.
• Oliguria.

• Nephrotic - damage is minor → no inflammation, capillaries still patent and the blood is flowing through. Too much albumin has leaked out along with it osmotically, more fluid. Patients will have albuminuria, lipiduria and polyuria. No oliguria.
• Nephritic - inflammatory cells, neutrophils, lymphocytes all blocking capillaries. Few patent capillaries. Little urine produced - but will contain RBCs, WBCs and protein. Non selective proteinuria.

Question 7

Describe the pathogenesis of renal symptoms and signs.

Answer 7

• Uraemia (disease) - fatigue, nausea, vomiting, encephalopathy → renal failure.
• Azotemia (lab) - increased BUN (uraemia is clinical manifestations of azotemia).
• Fatigue/malaise - renal failure - azotemia/uraemia.
• Headache - fluid retention, acidosis, uraemia.
• Flank pain - ureteric colic - stones.
• SOB, pallor - anaemia - decreased EPO.
• Nausea/vomiting - renal osteodystrohphy - renal failure.
• Pruritis - uraemic neuropathy.
• Pigmentation - endocrine abnormality in uraemia.
• Smoky urine - microscopic haematuria (glomerular, RBC casts - nephritic syndrome).
• Haematuria - UTI, glomerulonephritis, tumour or glomerulonephritis.
• Painless haematuria - DM, IgA neuropathy, TB, cancer.
• Proteinuria - with casts (glom) and without casts (UTI). Selective (albumin - nephrotic), non selective (nephritic).
• Oliguria <500mL or anuria <50mL/day - dehydration, nephritic syndrome, renal failure, obstruction.
• Polyuria >3L - increased fluid, osmotic, nephrotic syndrome, tubule dysfunction (D. insipidus).
• Dysuria (pain) - inflammation, obstruction, stone, tumour, stricture.
• Renal colic - calculus, blood clot or tumour in ureter.
• Haematuria - infection, stones, tumour, glomerulonephritis (red cell casts).
• Casts - tubule/glom injury - coagulation of proteins in renal tubules.
- Hyaline/Gr. casts - protein loss from glomeruli or necrotic cells.
- RBC, WBC, Ep. - protein with cell loss from glomeruli/tubules.
- Waxy casts - degenerated cast following prolonged retention (chronic RF).
• Hypertension - renal ischaemia, decreased GFR → renin* aldosterone*
• Oedema - hypoalbuminaemia.

Question 8

Outline glomerulonephritis.

Answer 8

• Glomeruli - microscopic structures with large function.

1. Large quantity blood filtration
   • 1.2L/min = 1,728 L/day (25% cardiac output).
   - 1.2L of blood flows through them per minute.
   • Glomerular filtrate 180L/day (most reabsorbed), urine 1-2L/day.
   - 180L of glomerular filtrate per day, most of which is reabsorbed leaving 1-2L of urine per day.
2. Trap large proteins - Ag, Ab, Ig complex, toxins.
   • Due to its filtration capacity - traps large proteins particularly antigens, antibodies, immune complexes, toxins - glomerular injury is common, also due to drugs.
3. Activation of complement system.
   • Whenever Ag:Ab complexes are deposited → activates complement system.
4. Inflammation - cytokines and inflammatory cells.
   • Activation of complement → inflammation → damage.
5. Glomerular damage:
   • Minor podocyte injury → no inflammation → albuminuria → nephrotic syndrome.
   • Major filter damage → inflammation → oliguria, haematuria → nephritic syndrome.
   - Oliguria as inflammation compresses capillaries (decreased blood flow).
   - Haematuria - leakage of blood.

Question 9

Identify the systemic effects of glomerulonephritis.

Answer 9

• Increased JGA → renin (angiotensin, aldosterone - BP, water, electrolytes).
• Decreased EPO - anaemia.
• Decreased vitamin D - bone demineralisation.

Question 10

Describe the classification of glomerular disorders.

Answer 10

Aetiological:
• Primary - damage to glomerulus.
• Secondary - damage in other diseases.

Immunological:
• Glomerular Ag (anti GBM) - commonest cause.
• Non glomerular Ag - sitting on glomerulus forming complexes.
• Immune complex - secondary damage to glomerulus from entrapment of Ag:Ab immune complexes circulating in blood.

Morphological:
• Diffuse - all glomeruli are affected.
• Focal - involvement of some glomeruli but not others.
• Global - whole of glomerulus.
• Segmental - part of glomerulus (portion or one of the capillary tufts).

Clinical:
• Most important - clinical features of glomerular disease classified into 2 major syndromes. Also acute/chronic renal failure.
• Nephritic.
• Nephrotic.

Pathologic:
• Minimal change - normal appearing.
• Proliferative - increased cells, inflammation.
• Membranous - thickening of BM.
• Membranoproliferative - combination.
• Crescentic - FSGS/rapidly PGN.

Question 11

Explain the pathogenesis of glomerulonephritis.

Answer 11

• Commonest cause of glomerular disease is immune. Antigen antibody immune complexes get deposited in the filtration membrane.
• Immune complexes causing minimal damage sit under the podocytes (sub-epithelial) or within the basement membrane. Large deposits sit throughout membrane and cause major damage by activating inflammation.
• Deposition can be linear or lumps (assists in classifying glomerulonephritis).
- When linear - usually in-situ - formation of Ag:Ab complexes or antibodies against the whole BM. Linear positivity in immunofluorescence.
- When granular/lumpy (more common) - the depositions will be irregular.

1. Circulating immune complex deposition e.g. SLE, infections.
2. Ab against Ag in glomerulus e.g. in-situ (most common), SLE, Strep. A.
3. Anti GBM Ab - autoimmune, crescentic, GP sy.

Question 12

Describe the classification of nephrotic syndrome.

Answer 12

AGN: Nephrotic syndrome (non inflammatory)
- massive albuminuria, hypoalbuminaemia, hyperlipidaemia.

Primary glomerular diseases:
1. Minimal change disease (MCD).
2. Focal Segmental Glomerulosclerosis (FSGS).
3. Membranous GN (MGN).
• Membrano-proliferative GN (MPGN subtype 1 and 2).

Inherited disease:
• Congenital nephrotic syndrome (Alport’s).

Secondary glomerular disease:
• SLE (membranous).
• Henoch-Schönlein purpura.
• Malignancy, tumours, infections, HIV, drugs (gold, penicillin, phenytoin etc.)
• SBE, Diabetes mellitus* (covered previously - microalbuminuria).
• Amyloidosis.
• Bee sting.

Question 13

Outline minimal change glomerulonephritis.

Answer 13

• Synonyms - nil disease, lipoid nephrosis.
• Incidence - 80% of nephrotic syndrome in children.

Aetiology:
• Idiopathic, destruction of podocytes (EM - loss of foot processes).
- Only seen under electron microscopy (EM). No change under normal routine microscopy - looks like normal glomerulus.

Morphology:
• Normal routine microscopy.

Lab:
• Albuminuria.
• Lipiduria.
• Polyuria.

Clinical features:
• Nephrotic syndrome, recent URI in 30%.
- Nephrotic syndrome usually following a recent upper respiratory tract infection in 30% of children.
• Spontaneous remission in majority.
• Some may progress to chronic renal failure, Focal Segment Glomerulosclerosis (FSGS).

Question 14

Outline Focal Segmenal Glomerulosclerosis (FSGS)

Answer 14

Aetiology:
• Primary - unknown aetiology.
• Secondary - HIV, Hodgkins, IgA.
- 20-30% nephrotic syndrome in adults (primary). Secondary (HIV, Hodgkins, IgA).
• Can also occur in children however rare.

Morphology:
• Segmental collapse sclerosis. IgM deposit, podocyte damage (like MCD).

Lab:
• Nephrotic.
• Albuminuria.

Clinical features:
• Nephrotic sy, following URI - 30% associated with Hodgkins lymphoma, overlap with MCD FSGS.

Prognosis:
• Spontaneous resolution (30%), chronic renal failure (50%) or rapidly progressive renal failure (20%).
- Majority end up in chronic renal failure.
• Where severe, global sclerosis - known as collapsing glomerulopathy. HIV, drugs etc.
- When sclerosis extensive, most of glomeruli involved → collapsing glomerulopathy - seen in HIV, drugs.

Question 15

Outline membranous glomerulonephritis.

Answer 15

Epidemiology:
• Incidence - 50%, 50 years, adult nephrotic syndrome.
- More common in adults.

Aetiology:
• Primary - auto Ab to podocyte Ag.
• Secondary - HBV, SLE, malignancy, gold, mercury poisoning, drugs (anti inflam).
- Autoimmune disorders.

Pathogenesis:
• Ab against podocyte Ag, directly activating complement (C3, C5b-C9). Only proteinuria, no inflammation.
- Deposition of Ab is so strong, whole glomerular capillaries appear like thick wires - wire loop nephropathy.

Morphology:
• Wireloop thick BM. Sub epithelial humps of IgG and C3, effacement of foot processes.
- Effacement/loss of foot processes → proteinuria. Also some damage to BM - globulins leak out.

Lab/clinical features:
• Nephrotic syndrome 80%, non selective proteinuria and haematuria. No response to steroids.
- Non selective - both albumin and globulin will be there due to slightly increased damage (unlike childhood type).
- May have haematuria. Do not usually respond to steroids.

Prognosis:
• Adults 40% CRF. Good recovery in children.
- 40% lead to chronic renal failure.

Question 16

Describe the classification of nephritic syndrome.

Answer 16

Nephritic syndrome (inflammatory) - oliguria, haematuria, azotemia, HPTN and non selective proteinuria.

Primary glomerular diseases:

1. Post strep proliferative GN.
2. IgA nephropathy (Berger’s disease).
3. Rapidly progressive GN.

Inherited disease:
• Hereditary nephritis - Alport’s.

Seconary glomerular disease:
• SLE.
• Wegener’s.
• Henoch-Schonlein purpura.

Question 17

Outline acute post streptococcal diffuse proliferative GN.

Answer 17

• Synonyms - post infectious GN.
- Autoimmune disease induced by streptococci (like rheumatic fever).

Epidemiology:
• Incidence - children, commonest nephritis.
- Most common in children.

Aetiology:
• Autoimmune GABH strep (type 12 nephritogenic species). Other bacteria, virus etc.
- Can be caused by other bacteria and viruses - rare.

Pathogenesis:
• 1-4 weeks after infection, in-situ immune complex - C3 and IgG coarse deposits subepithelial, GBM and sub endothelial humps → injury and inflammation.
- 1-4 weeks after infection, in-situ immune complexes are formed in the glomeruli. C3 and IgG coarse deposits → activates inflammation - neutrophils come in, proliferation of mesangial cells → becomes inflamed glomeruli → compresses blood vessels - little urine produced (oliguria). Also major damage - leakage of blood, patients present with haematuria.

Morphology:
• Diffuse hypercellular glomeruli with neutrophils, collapsed capillaries.

Lab:
• Oliguria, haematuria, RBC casts, non selective proteinuria, decreased serum complements (decreased C3).

Clinical features:
• Children, post infectious period, fatigue, headache, oedema.

Question 18

Outline IgA nephropathy (Berger’s disease).

Answer 18

Epidemiology:
• Common cause of recurrent haematuria in young, males, Asia-Pacific. Infections*
- Congenital disease. Usually following infections.

Aetiology:
• Abnormal IgA, Ab against glycosylated IgA.
• Genetic, familial, twins, coeliac and liver disease (secondary IgA nephropathy).
- Immune complexes get deposited in the mesangium.
- In case of coeliac and liver disease (lack of removal of IgA in liver) - known as secondary IgA nephropathy.

Morphology:
• IgA containing immune deposits and C3 in mesangium. High serum IgA1.
• Immune deposits in the glomerulus leading to thickened larger glomeruli with more protein in the mesangium.
• IgA deposition shown on immunofluorescence.

Clinical features:
• Episodic, asymptomatic, haematuria. Following episode of infection.
• Microscopic (haematuria) 40% or massive haematuria 40%.
- Nephritic or Nephrotic (rare).
- Renal failure (10%).
- Slowly progressive CRF in 1/3 patients.

1. Focal - 60% of cases are partial and improve.
2. Diffuse - 30%
3. Total destruction of glomerulus - 10%
   40% of cases go into chronic failure.

Question 19

Identify other causes of asymptomatic haematuria.

Answer 19

1. Systemic Lupus Erythematous (SLE).
2. Vasculitis-polyarteritis.
3. Henoch-Schönlein purpura.
4. Bacterial endocarditis.
5. Exercise haematuria.

Question 20

Outline rapidly progressive/crescentic GN.

Answer 20

• AKA Crescentic GN
• Not a separate disease, any GN may result in RPGN (when the inflammation becomes severe).
• Acute, severe rapidly progressive, renal failure - weeks.
- Severe inflammation in glomerulus - inflammatory cells and fluid get excreted out from the glomerulus and it gets deposited in the Bowman’s capsule → leads to crescentic formation of inflammatory exudate. Poor prognosis.
• Bowman’s space - fibrin, epithelial and infl. cells matrix → form crescents.
• Compress glomerulus.
• Many types:
- Type I - anti GBM Ab.
- Type II - immune complex.
- Type III - idiopathic, ANCA.
• Progress to CGN → end stage kidney → renal failure - poor prognosis.
- Progress to chronic glomerulonephritis and ESKD very quickly.

• Crescent of inflammatory cells compressing the glomerular capillaries - blood doesn’t flow through - glomerulus becomes non-functional.

Question 21

Differentiate between nephrotic and nephritic syndrome.

Answer 21

Nephrotic:
• Proteinuria (nephrotic range >3.5g/24h) - albumin.
• Oedema (hypoalbuminemia).
• Hyperlipidemia.
• Lipiduria.
• Protein casts.

Nephritic:
• Oliguria.
• Haematuria - RBC casts.
• Non-selective proteinuria. Protein casts.
• Decreased GFR, increased creatinine and BUN.
• Oedema (due to salt and water retention and activation of renin).
• Hypertension.

Question 22

Describe the progression of glomerulonephritis.

Answer 22

Progression to chronic GN:
• Post-streptococcal GN → 1% (99% heal).
• IgA nephropathy → 40%
• Membranous GN
• Membranoproliferative GN → 50%
• FSGS → 70%
• Crescentic GN → 90%

Question 23

Outline acute renal failure.

Answer 23

• Acute deterioration of renal function, usually presenting with oliguria/anuria and uraemia.
• Decreased GFR (<20mL/min) → BUN and creatinine increase (serum).
• Common, 1% of inpatients to 20% in intensive care patients.
• Blood supply - glomerular function - tubular and collecting system.
- 3 major targets of acute renal injury.

Question 24

What are the 3 types of acute renal failure?

Answer 24

Pre-renal:
• 60% (if blood supply is decreased - pre-renal). Pre-renal is most common.
• Decreased blood supply → decreased urine.
• Causes:
- Hypovolemia, shock, dehydration, cardiac failure.
- Microangiopathy - DIC, HUS, TTP etc. - arterial block emboli (microscopic block in blood vessels).
• Increased U/C ratio, FENa <1%, UNa <20mmol/L.

Renal:
• 30%
• ATN, AGN, ATIN (acute tubulointerstitial nephritis).
• Infiltrations, malignancy, tubular obstructions - drugs, HB, myoglobin, myeloma proteins etc.
- Can all block tubules and cause acute renal failure.
• Decreased U/C ratio, FENa >1%, UNa > 40mmol/L

Post-renal:
• 10%
• Urinary tract obstruction - stones, UTI, tumours, bladder, prostate.
• Increased U/C ratio, FENa >4%, UNa >40mmol/L

Question 25

Outline acute tubular necrosis.

Answer 25

• Acute Tubular Injury (ATI).
• Necrosis of tubular epithelium - fall of as casts.
- Epithelial cells fall off as casts in urine.
• Common cause of renal ARF - 50%.
- Commonest cause of renal ARF.
• 2 types - ischaemic (due to obstruction to blood vessels), toxic (due to toxins).

• Ischaemic (patchy PCT and DCT) - can involve any part of tubule. Length varies according to amount of obstruction.

• Hypovolemia, shock.
• DIC, HUS, TTP etc.

• Toxic (PCT only) - toxins first come into contact with cells in the PCT → only PCT affected.

• Drugs, toxins, mercury, CCL4, radiocontrast.
• Haemoglobin, myoglobin, bilirubin, immunoglobulins.

• Reversible*
- If patient gets immediate attention and dialysis.

Question 26

Explain the pathogenesis of acute tubular necrosis.

Answer 26

Ischaemic:
• Ischaemia → vasoconstriction* → decreased GFR.
* vasoconstriction can also lead to tubular injury.

Toxic:
• Toxic injury → tubular injury:
- Tubular backleak → decreased urine output.
- Sloughed cells → obstruction*
- Interstitial inflammation → decreased GFR.
* Obstruction leads to decreased urine output and GFR. See diagram.

Question 27

Outline benign nephrosclerosis.

Answer 27

• Vascular disorder, common in hypertension.
• AKA hypertensive nephropathy/vascular nephrosclerosis.
• Arteriolosclerosis (hyperplastic and hyaline).
- Due to thickening of small blood vessels - arterioles - due to chronic hypertension.
• Pathogenesis - increased hydrostatic pressure.
• Glomerulosclerosis → atrophy → fine granular surface (orange peel) - cortex atrophy (glomerulosclerosis).
- Narrowing of vessels → atrophy of glomeruli predominantly in cortex → leads to fine granular surface (orange peel) - cortical atrophy → chronic renal failure.
• CRF stages 1-5 → ESRD.
• African race - Apoliproprotein L1 mutation - Trypanosoma resistance.
- More common in African race, mutation gives resistance against Trypanosoma. Patients with mutation more prone to developing benign nephrosclerosis.
• Leathery granularity (orange peel) appearance due to glomerular scarring in the cortex.

Question 28

Outline malignant hypertension.

Answer 28

• >200/120 mmHg.
• 5% of hypertensive patients (rare).
• Renal ‘arteriolar fibrinoid necrosis’
• Petechial haemorrhages - flea bitten kidney.
- Arteriolar fibrinoid necrosis leading to petechial haemorrhages → flea bitten kidney.
• Severe stimulation of renin-angiotensin mechanism leading to increased BP.
• (Also in microangiopathy - DIC, TTP, HUS etc*) - similar feature seen but it is due to thrombi obstructing the small arterioles.
• Microscopy - total necrosis of blood vessel with fibrin leakage forming a thick fibrin ring. Blocked by embolus because no blood supply to dead blood vessel - fibrinoid necrosis of arteriole.

Question 29

Explain the development of secondary hypertension due to renal artery stenosis.

Answer 29

• Renal artery stenosis for different reasons - congenital, atherosclerosis of aorta - the renal artery can be blocked - when there is a block in one of the renal arteries - that particular kidney undergoes total atrophy. Ischaemia of kidney → release of renin → RAAS → benign nephrosclerosis of normal kidney.
• Secondary HT due to block in renal artery.

Question 30

Outline analgesic nephropathy.

Answer 30

• Tubulointerstitial nephritis:
• Progressive chronic use of analgesic (Phenacetin*)
- Excessive use of analgesics. Phenacetin in old days, not common now.
• Chronic eosinophilic interstitial inflammation with tubular injury.
• Renal papillary necrosis, sloughing and calcification progress to CRF.
- Calcification characteristic feature on imaging. On specimen as well.
• Clinical - haematuria, renal colic, mild proteinuria and leukocyturia (predominantly eosinophils).
- Leads to total renal failure in long term. Also cancer of the renal pelvis - transitional carcinoma.
• Rare urothelial cancer of renal pelvis.
• Cut section - necrosis with calcification in all the renal pyramids.

• NSAID nephropathy - different to analgesic nephropathy. COX inhibition leading to decreased prostaglandins → leads to vasoconstriction → ischaemic damage → interstitial nephritis (acute or chronic) or minimal change disease or membranous GN.
• Multiple types of renal damage can occur with over use of NSAIDs.

Question 31

Outline chronic renal failure.

Answer 31

• Progressive scarring of the kidney from any cause, resulting in chronic renal failure eventually terminating in end-stage kidney disease (dialysis/transplantation).

• All primary kidney disorders e.g. infection, GN can result in chronic renal failure. Hypertension and diabetes most common clinically.
• Eventually terminates in ESKD - kidneys cannot sustain life.

2 major types:
• End stage of several types of GN/kidney injury.
• Primary (De novo) presentation.
- No previous history of kidney disease. Idiopathic chronic renal disease.

Question 32

What are the clinical features of chronic renal failure?

Answer 32

• Uraemia (lack of kidney function resulting in increased BUN, creatinine and urea causing) - nausea, vomiting, GI bleeding, anaemia, itching.
• Metabolic - acidosis (Kussmaul breathing - deep breathing), increased K, increased BUN, increased creatinine.

• Osteodystrophy - decreased vitamin D - decreased calcium absorption - increased PTH - bone lysis.
- Bone lysis - due to decreased vitamin D conversion in the kidney → decreased calcium absorption in the intestine, resulting in increased PTH → activates osteoclasts and bone lysis.

• Endocrine - hyperparathyroidism.
• Bleeding - platelet dysfunction due to uraemia (toxins).

• Anaemia - decreased EPO (separated by kidney), bleeding, RBC lysis (uraemia).
- RBCs get deformed in uraemia due to toxins in the blood.

• Nausea and vomiting, pruritis, skin pigmentation, pericarditis, myopathy, neuropathy, osteodystrophy, coma.

Question 33

Outline GFR/eGFR.

Answer 33

• Single most important test for CKD. Normal ~120mL.
- Most important investigation for CKD.
- Normal GFR ~120mL.
• eGFR (estimated) using MDRD formula = (140-age) x Wt/(0.81 x SCr) [x 0.85 if female].

CRF staging: (mL/min/1.73m2)
• Stage 1: GFR > 90mL - asymptomatic.
• Stage 2: GFR 60-89mL - asymptomatic.
• Stage 3: GFR 30-59mL - mild kidney failure.
• Stage 4: GFR 15-29mL - moderate.
• Stage 5: GFR <15mL - severe → ESRD (patients require dialysis or transplantation).

Question 34

Describe the morphology of endstage renal disease.

Answer 34

Microscopy:
• Scarred glomeruli.
• Atrophic tubules with casts.
• Interstitial inflammation.

• Total destruction of the glomeruli resulting in rounded scars and all the tubules are atrophied - epithelium is gone and there are only casts. The interstitum is full of inflammatory cells.
• Special stain for collagen showing that all the glomeruli are scars.

Question 35

Outline pyelonephritis.

Answer 35

• Suppurative tubule interstitial inflammation (pus formation).
• Acute/chronic. Unilateral*
- Usually unilateral.
• Secondary to UTI/UTO (obstruction), DM (immunosuppression), pregnancy.
• Vesicoutereral reflux - defective sphincter.
- Due to defective sphincter - commonest cause (deranged vesicoureteral junction).
• Papillary necrosis (rare) - poor prognosis.
- When there is papillary necrosis, it carries a very poor prognosis.
• Abscess pus → atrophy scarring → ESRD.
- Grossly, multiple abscesses leading to atrophy and scarring → resulting in end stage renal disease.
• Clinical - fever, loin pain, pyuria (pus in urine).
• Microscopy - plenty of acute inflammatory cells (neutrophils). WBC cast within tubule.
• End result is very large irregular scarring - typical of pyelonephritis.

Haematogenous infection:
• Staphylococcus.
• E. coli

Ascending infection:
• E. coli.
• Proteus.
• Enterobacter.
Bacteria colonisation → bacteria enter bladder → deranged vesicoureteral junction → vesicoureteral reflux (ascending infection).