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Clinical Pathology > Kidney and Urinary Tract Pathology > Flashcards

Kidney and Urinary Tract Pathology Flashcards

1
Q

What is the function of the kidneys?

A

• Eliminate metabolic waste products
• Regulate fluid/ electrolyte balance- sodium
• Regulate acid-base balance
• Produces hormones;
o Renin: fluid balance (RAAS)
o Erythropoietin: stimulates erythrocyte production

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2
Q

Why is Renal Disease a Big Issue?

A
  • 26,000 patients- acute renal failure/year in England; 15% of all hospital admissions
  • Most recover, but 10,000 need dialysis (50% mortality)
  • 5,500 patients develop chronic renal failure/yr in England- 43,000 patients with CRF in England
  • 50% will have a transplant, 40% haemodialysis, 10% peritoneal dialysis (risk peritonitis)
  • 2010-2011; 1020 living donor renal transplants, 1667 deceased donor transplants, 7000 patients still on renal transplant waiting list
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3
Q

What are the Presentations of Renal Disease?

A
  • Acute renal failure; unwell, rapid rise in creatinine & urea
  • Nephrotic syndrome triad (loss of protein); oedema, proteinuria, hypoalbuminaemia
  • Acute nephritis (nephritic syndrome) (loss of blood): oedema, proteinuria, haematuria, renal failure
  • Chronic renal failure; slow decline in renal function
  • Heamaturia
  • Proteinuria
  • Progressive decline of renal function as age- accelerated in renal failure
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4
Q

What is the function of different parts of the kidney?

A
  • Afferent- vulnerable to damage
  • Bowmen’s capsule- big macromolecules remain in here, glucose & sodium pass through
  • So in descending loop of Henle- reabsorption
  • But in ascending loop- processes more based on secretion involved (getting rid of extra stuff don’t need)
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5
Q

What is Thrombotic Microangiopathy?

A

Renal Disease- Vascular Damage

  • Blocking blood flow into glomerulus
  • Thrombi in capillaries/ arterioles
  • Endothelial damage by bacterial toxins, drugs, complement or clotting system abnormalities
  • E.g. Haemolytic uraemic syndrome
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6
Q

What is Vasculitis ?

A
  • Acute/ chronic vessel wall inflamm with lumen obliteration
  • Various types affect diff calibre vessels
  • Vasculitis- small/ large vessels- e.g. Wegner’s granulomatosis (granulamotosis with polyangiosis)
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7
Q

How can an atheroma lead to kidney damage?

A

Atheroma- lumen narrowing- blood not getting through = ischaemic damage

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8
Q

What is Goodpasture’s syndrome?

A

autoimmune disease selectively damaging basement membranes= Glomerular Damage

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9
Q

What are the causes of Glomerular Damage ?

A

Immunological (autoimm destruct of kidney)
• Complexes made elsewhere in body- get stuck in kidney- cause effects (immune response)
• Goodpasture’s syndrome- autoimm disease selectively damaging basement memb

Non-immunological
• Abnormal basement memb- podocytes- abnormal collagen so abnormal basement memb
• Abnormal protein deposition- amyloid can have them with excess Ig’s, Rheumatoids etc- these being deposited continuously (fighting a losing battle)

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10
Q

What are the causes of Tubular Damage ?

A
  • Tubular component particularly vulnerable to ischaemic damage
  • Degree of renal tubule damage correlates with renal function

• Ischaemic (caused reduced perfusion= tubular damage);
o Hypotension e.g. shock
o Vessel damage e.g. vasculitis HTN
o Glomerular damage

•	Toxic (= tubular damage);
o	Direct toxins 
o	Hypersensitivity reacs- drugs 
o	Crystal deposits e.g. urate (gout) 
o	Abnormal protein deposition (direct tubular damage) e.g. Ig’s
  • NSAIDs Ace control hypertension- are on drugs that cause renal damage but hypertension also causes renal damage
  • Ethylene glycol (anti-freeze)- people drink
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11
Q

What does crescentic mean?

A

Rapidly progressive

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12
Q

What is Nephrotic Syndrome?

A

Always due to damage to glomerulus

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13
Q

What are the features of Nephrotic Syndrome?

A
  • Oedema (pitting) (fluid stays in circ- oncotic pressure unbalanced as lost proteins keeping fluid in)
  • Proteinuria (>3g in 24h)- loosing lots of protein in urea
  • Hypoalbuminaemia
  • +/- Hypertension (loosing fluid- renin agiotensin system kicks in= increases BP)
  • +/- Hyperlipidaemia
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14
Q

What are the complications of Nephrotic Syndrome?

A
  • Infection-pneumonia

* Thrombosis (in nephrotic syndrome antithrombin III filtered out- lost mechanism to stop forming clots)

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15
Q

What are the common causes of Nephrotic Syndrome in adults?

A
  • Membranous nephropathy (commonest); idiopathic primary glomerular disorder, usu. adults <60 yrs; M>F (20-30% progress to end stage renal failure)
  • Focal segmental glomerulosclerosis (FSGS); various possible causes (usu. idiopathic, but also genetic, heroin use, HIV); M>F
  • Minimal change disease; normal histology; M=F
  • Other causes: diabetes, lupus nephritis, amyloid
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16
Q

What are the common causes of Nephrotic Syndrome In children?

A

• Minimal change (commonest)- present with nephrotic syndrome triad; normal histology, usu. Excellent prognosis, give them steroids & they’ll be fine
• Focal segmental glomerulosis (FSGS)
• Other causes rare
Basement memb thickening, get holes punched through=progresses to end stage renal failure

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17
Q

What is Nephritic Syndrome?

A

Kidney disease involving inflammation

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18
Q

What are the features of Nephritic Syndrome?

A
  • Oedema
  • HAEMATURIA
  • Proteinuria
  • Hypertension
  • Acute renal failure
  • (Lots of overly with nephrotic syndrome)
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19
Q

What are the common causes of Nephritic Syndrome in adults?

A
  • Post-infective glomerulonephritis (happens after a primary infec)- weeks after Streptococcal throat infection, good recovery- then develop renal failure
  • IgA nephropathy (inappropriate IgA deposition in glomerulus)- common primary glomerular disease; usu. young adults (20-50% renal failure over 20 years)
  • Vasculitis; unwell, fever, rash, myalgia, arthralgia- spectrum of malaise with rash & renal failure
  • SLE (lupus nephritis); autoimmune disease; usu. young women, get full spectrum of immunoglobulins involved
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20
Q

What are the common causes of Nephritic Syndrome In children?

A

• Also post-infective glomerulonephritis & IgA nephropathy
• Henoch-Schönlein purpura;
o Specific IgA nephropathy (systemic vasculitis); often follows throat infection; most recover completely
o Usu. boys/teenagers with arthralgia, abdominal pain, purpuric rash (presentation- affects buttocks & legs- most kids recover from this), proteinuria/haematuria, acute renal failure
• Haemolytic-uraemic syndrome
o Typically children with E. coli 0157 enteritis- due to shegoli toxin made (damages glomeulus endothelium= becomes pro-thrmbotic= lumen narrowed = RBCs break open as trying to squeeze past & are depleting your platelets)
• With other GI toxins
• Get GI symptoms 1st e.g. diarrhoea then renal failure
• Acute nephritis, haemolysis, thrombocytopenia

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21
Q

What is the main difference between Nephrotic syndrome and nephritic syndrome?

A

Nephrotic syndrome loss of protein, nephritic syndrome loss of blood

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22
Q

What is Acute Renal Failure ?

A

Rapid loss of kidney function

  • Prognosis usually good if no underlying renal disease
  • Short term dialysis may be needed in some patients
  • Renal biopsy; UNHELPFUL if cause pre-renal or post-renal, HELPFUL if cause damage to kidney (renal)
  • Imaging helpful- see obstruc
  • All biopsies show acute tubular necrosis/injury/damage
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23
Q

What are the common causes of Acute Renal Failure ?

A 
o	Pre-renal (blood flow to kidney); severe dehydration, hypotension (bleed, septic shock, LVF), vol not reaching kidneys (oliguria)
o	Renal (in kidney); damage to kidney 
o	Post-renal (probs getting rid of urine- urinary tract obstruc); urinary tract tumours, pelvic tumour, calculi, prostatic enlargement
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24
Q

What are the features of Acute Renal Failure?

A

Anuria/oliguria (<400ml/24h)+(rapid increase) raised creatinine & urea– malaise, fatigue, nausea, vomiting, arrhythmias

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25
Q

What are the common causes of Acute Renal Failure in adults?

A

o Vasculitis
o Acute interstitial nephritis/tubulointerstitial nephritis (tubular damage with inflammation, usu. due to drugs); most recover

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26
Q

What are the common causes of Acute Renal Failure in children?

A

o Henoch-Schönlein purpura
o Haemolytic uraemic syndrome (from e.coli infec)
o Acute interstitial nephritis
• Beware (in books): rapidly progressive (crescentic) glomerulonephritis = acute nephritis with acute renal failure but is NOT a specific disease.

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27
Q

What are the complications of Acute Renal Failure?

A 
o	Cardiac failure (fluid overload)
o	Arrhythmias (electrolyte imbalance)- sodium &amp; K+ management 
o	GI bleeding (multifactorial)
o	Jaundice (hepatic venous congestion)
o	Infection, esp. lung and urinary tract
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28
Q

What is treatment of Acute Renal Failure?

A

o Depends on underlying cause! E.g. hypovolemic give fluids, obstruction- remove obstruc
o Short term dialysis may be needed

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29
Q

What is Chronic Renal Failure ?

A

loss of kidney function over time

Renal biopsy usu. unhelpful in established disease; kidney shows severe scarring with loss of glomeruli & tubules (doesn’t matter what original cause was), end-stage renal disease due to any cause is similar

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30
Q

What are the stages Chronic Renal Failure ?

A

• Permanently reduced GFR= reduced no. functional nephrons
o Stage 1: Normal/increased GFR (>90ml/min/1.73m2)
o Stage 2: Mild GFR reduc (60-89ml/min/1.73m2)
o Stage 3: Moderate GFR reduction (30-59ml/min/1.73m2)
o Stage 4: Severe GFR reduction (15-29ml/min/1.73m2)- need renal replacement theapy (dialysis/ transplant)
o Stage 5: Kidney failure (GFR <15ml/min/1.73m2 or dialysis)

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31
Q

What are the features of Chronic Renal Failure?

A

o Reduced excretion of water/electrolytes: oedema, hypertension
o Reduced excretion of toxic metabolites
o Reduced production of erythropoietin: anaemia
o Renal bone disease (kidneys excrete phosphate/calcium), kidney’s involved in vit D metabolism- active vit D3 promotes Ca reabsorption)- chronic disorder

loads of symptoms-systemic

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32
Q

What are the consequences of Chronic Renal Failure?

A

o In utero;
o Amniotic fluid in uterus is contributed by urine from foetus- so if foetus doesn’t have any kidney’s/ prob with kidneys then not enough aminotic fluid and lungs need amniotic fluid to develop so lungs will be affected
o If kidneys have posterior urethral valves stops urine being excreted =kidney damage & lung development affected

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33
Q

What is Isolated Proteinuria? What are the causes?

A

• Proteinuria BUT less than nephrotic range
• No allied haematuria, renal failure or oedema
• May be benign e.g. postural, related to pyrexia or exercise (change heamodynamic flow & cause temporary proteinuria)
• May be due to renal disease (need to be able to exclude these)
o Adults: FSGS, DM, SLE
o Children: FSGS, HSP
• Urine samples tend to be frothy- protein in urine creates bubbles

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34
Q

What is Isolated Haematuria? What are the causes?

A

• Haematuria +/- proteinuria with normal renal function: usu. renal
o IgA nephropathy
o Thin basement membrane disease: inherited condition causing abnormally thin glomerular BM; renal function usu. normal
o Alport hereditary nephropathy: inherited abnormalities of type IV collagen cause abnormal BM, sometimes with eye and ear problems - renal failure +/- deafness +/- ocular problems (as basement memb struc also involved in ear & eye)
• Cystoscopy/urological investigations needed to exclude malignancy (nephroscopy, CT KUB)

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35
Q

What is Pyelonephritis?

A
  • Kidney inflammation as a result of bacterial damage

* Infec; haematogenous spread, or ascends form urinary tract tracking back up into kidneys, structural abnormalities

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36
Q

What are the risk factors of Acute pyelonephritis?

A

o Risk factors; female (ascending infec), instrumentation, diabetes, urinary tract structural abnormalities

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37
Q

What are the complications of Acute pyelonephritis?

A

abscess formation

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38
Q

What are the risk factors of Chronic pyelonephritis?

A

Risk factors; urinary tract obstruc/ reflux

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39
Q

What are the complications of Chronic pyelonephritis?

A

scarring (=loss of functional renal tissue ), chronic renal failure

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40
Q

What is Renal Artery Stenosis? What are the causes? What are the complications?

A
  • Commonly due to atheroma (lumen narrowing in 1/ both renal arteries- downstream damage); also arterial dysplasia
  • Ischaemic injury of affected kidney
  • Renin-angiotensin-aldosterone system activation=HTN (hypertension- damages kidneys further)
  • Loss of renal tissue leads to reduced renal function
  • Inflammatory damage- proliferation in vascular wall
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41
Q

What is Vasculitis? What are the causes? What are the complications?

A
  • Various types affecting diff calibre vessels
  • Inflamm in glomerular vessels can cause clotting + obliteration of capillary lumena & glomerulus destruction
  • Inflammation of larger renal arterioles can cause tubule hypoxia
  • Often part of systemic disease – rash, myalgia, arthralgia, fever, weight loss (key diagnosis- not presented alone, has other symptoms)
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42
Q

What is Hypertension? What are the renal consequences?

A
  • Damages renal vessels - wall thickening + reduction in lumen size
  • This produces chronic hypoxia - loss of renal tubules + reduced renal function
  • Reduced renal blood flow activates renin-angiotensin-aldosterone system- exacerbates HTN
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43
Q

What is Diabetes? What are the renal consequences?

A

• Commonest cause of end-stage renal failure in developed world
• Hyperglycaemia causes 2 mechanisms of damage:
o Damaged basement memb thickens & glomerulus makes excess extracellular matrix (nodules)
o Small vessel damage causes ischaemia and tubular damage

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44
Q

What is Myeloma? What are the renal consequences?

A
  • Malignant tumour of plasma cells in bone marrow- causes abnormal proteins & antibodies to deposit in kidneys- cause obstruc
  • Plasma cell tumour; excess Ig’s deposit in tubules cause inflamm & fibrosis
  • Renal tubule loss causes irreversible decline in renal function
  • Elderly patient with acute renal failure; exclude drug reactions
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45
Q

What is Obstructive Uropathy?

A
  • Obstruction of urinary tract
  • Obstruction can occur anywhere in urinary tract from renal pelvis to urethral meatus
  • Onset may be chronic or acute
  • Unilateral or bilateral
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46
Q

What are Causes of Urinary Tract Obstruction?

A
  • Pelvis: calculi (get severe pain that comes & goes), tumors, uteropelvic stricture
  • Ureter intrinsic: calculi, tumors, clots, sloughed papilla (in diabetes papilla tips get necrosis & sloughed away), inflammation
  • Ureter extrinsic: pregnancy, tumours e.g. cervix, retroperitoneal fibrosis
  • Bladder: calculi, tumour, functional (neurogenic)
  • Prostate: hyperplasia, carcinoma, prostatitis (only in males
  • Urethra: posterior urethral valves stricture, tumours (rare)
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47
Q

What is a Stricture?

A

muscle wall thin so urine can’t flow down, proximal urethra distended

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48
Q

What can cause Obstruction within the lumen of the Urinary Tract ?

A
  • Urinary calculi
  • Strictures (post-procedure, post-infective, congenital)
  • Neoplasia
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49
Q

What can cause Abnormalities of the wall of the Urinary Tract?

A
  • Neoplasia (benign or malignant)

* Congenital anatomical abnormalities

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50
Q

What can cause External Compression of the Urinary Tract?

A
  • Tumour outside urinary tract
  • Inflammatory conditions e.g. retroperitonaeal fibrosis (idiopathic) both ureters obstructed by fibrosis (need surgical/ chemotherapy to release ureters)
  • Pregnancy
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51
Q

What can cause Functional Obstruction of the Urinary Tract?

A

• Neurological conditions
• Severe reflux
Bladder; functional stasis-
Urethra; abnormal valves in urethra, dysfunctional valve- urine tracts back up (reflux

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52
Q

What is Sequelae of Obstruction of the Urinary Tract?

A
  • Urinary infec- cystitis, ureteritis, pyelitis, ascending pyelonephritis
  • Stone/calculi formation
  • Kidney damage (acute or chronic)
Consequences of Urinary Tract Obstruction 
Depend on;
•	Site of obstruction
•	Degree of obstruction
•	Duration of obstruction
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53
Q

What is Detrusor hypertrophy & trabeculation?

A

obstruction at urethral level

• Hypertrophy of muscle of bladder as obstruc in ureter

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54
Q

What is Hydroureter ?

A

Chronic Uretic Obstruction can= Hydroureter
• Stones consequence of obstruc
• Dye in kidney not going completely down

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55
Q

What is Hydronephrosis?

A

Hydronephrosis- a result of chronic obstruction
• Non-functional kidney- chronic infec/ obstruc
• Need to remove obstruc
• If fills with pus- high mortality

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56
Q

What is acute complete obstruction?

A

Decreased glomerular filtration rate can = acute renal failure
mild dilation and mild cortical atrophy

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57
Q

What is chronic complete obstruction?

A

Partial/intermittent obstruction=
• Continued glomerular filtration=dilation of pelvis and calyces=
• Filtrate passes back into interstitium= compression of medulla=impaired concentrating ability=

Both eventually = cortical atrophy, fall in renal filtration and renal failure.

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58
Q

What are Clinical Features of Acute bilateral obstruction?

A
  • Pain

* Acute renal failure & anuria

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59
Q

What are Clinical Features of Chronic unilateral obstruction?

A
  • Suspect obstruct- recurrent UTIs
  • Asymptomatic initially
  • If unresolved cortical atrophy and reduced renal function
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60
Q

What are Renal Calculi/ Urotheliasis?

A
  • Affect 7-10% of the population - increasing
  • Male predominance
  • Peak onset 20 – 30
  • Can form anywhere in urinary tract but most commonly in kidney
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61
Q

What is the pathogenesis of Renal Calculi?

A
  • Either due to an excess of substances which may precipitate out e.g. Ca+
  • A change in urine constituents causing precipitation of substances e.g. change in pH
  • Poor urine output- superstauration (can also cause stones)
  • Decreased citrate levels- more likely to form stones
62
Q

What is the classification of Renal Calculi?

A

• Calcium stones (70%) - calcium oxalate +/- calcium phosphate
o Hypercalciuria main cause, due to: hypercalcaemia (bone disease, PTH excess, sarcoidosis), excessive intestinal Ca+ absorption, inability to reabsorb tubular Ca+, idiopathic
o Gout: forms a core for Ca+ crystal formation
o Hyperoxaluria: hereditary, excess dietary intake

• Struvite stones (15%) – magnesium ammonium phosphate
o Urease producing bacterial infection (proteus)
o Urease converts urea to ammonia rise in urine pH (pH changestones) precipitation of magnesium ammonium phosphate salts large ‘staghorn’ calculi

• Urate stones (5%) – uric acid
o Hyperuricaemia; gout, patients with high cell turn over e.g. leukaemia
o Idiopathic

• Cystine stones (1%)
o Rare
o Occur in presence of an inability of kidneys to reabsorb amino acids

• Diff stone types arise for diff reasons

63
Q

What are the investigations of Renal Calculi?

A
  • Non-contrast CT scanning is gold standard (sensitivity of >95%)
  • Ultrasound in pregnancy/ where CT not possible (30-67% sensitive)- CT detects most of stones
  • Intravenous urography (70% sensitive for stones)
64
Q

What are the Sequelae for Renal Calculi?

A
  • Obstruction
  • Haematuria
  • Infection
  • Squamous metaplasia +/- squamous cell carcinoma- ureter lined by transitional epithelium= squamous
65
Q

What is Renal Cell Carcinoma?

A
  • 3% of cancers
  • Vast majority of renal carcinomas are CLEAR CELL
  • Rarer variants include papillary and chromophobe
  • Peak (65-80)
  • Male > female (3:2)
66
Q

What are the Risk factors for Renal Cell Carcinoma ?

A
  • Tobacco (smoking)
  • Obesity
  • Hypertension
  • Oestrogens
  • Acquired cystic kidney disease (due to chronic renal failure)
  • Asbestos exposure
67
Q

What is Von Hippel-Lindau Syndrome ?

A
  • Most common of several cancer syndromes in RCC
  • Genetic disorder- protein usually breaks down oncogene
  • Need VHL gene for breakdown of Hypoxia Inducible Factor-1 (HIF-1) oncogene
  • Loss of gene function causes cell growth & increased cell survival
  • Tumours develop in kidneys, blood vessels, pancreas
  • VHL mutations also commonly identified in clear cell RCC
68
Q

What is the presentation of Von Hippel-Lindau Syndrome?

A
  • Local symptoms: hematuria, palpable abdominal mass, costovertebral pain (back ache)
  • Usually Incidental finding (rather than due to above symptoms)
  • Late presentation: systemic symptoms or metastases (25%) e.g. to skin (see skin nodules)
  • Paraneoplastic syndromes- tumour secrets certain substances
69
Q

What are Paraneoplastic Syndromes?

A
  • Clinical syndromes that result from substances produced by tumours
  • Not related to the tissue that the tumour arose from
  • Not related to invasion by the tumour itself or its metastases
70
Q

What are Paraneoplastic syndromes associated with RCC?

A
  • Cushing’s syndrome- as tumour secretes ACTH
  • Hypercalcaemia- parathyroid hormone related peptide
  • Polycythaemia- erythropoietin
71
Q

What is the morphology of Renal Cell Carcinoma?

A 
•	Clear cell renal carcinoma
o	Well defined yellow solid tumours
o	Often with haemorrhagic areas
o	May extend into perinephric fat 
o	Tendency to invade renal vein (staged depending on how much vein involved)
•	Papillary renal cell carcinoma
o	More cystic
o	More likely to be multiple (suspect papillary carcinoma)
72
Q

What is the microscopy of Renal Cell Carcinoma?

A
  • Clear cell has; clear cells, delicate vasculature, usually small bland nuclei
  • Papillary tumours; cuboidal, foamy cells, surrounding fibrovascular cores often containing foamy macrophages or calcium
73
Q

What is the prognosis of Renal Cell Carcinoma?

A
  • Overall 5 year survival ~45%
  • Organ confined > 70%, tumours extending into perinephric fat or renal vein ~ 50%
  • Distant metastases = very poor prognosis (<8%) as RCC tends to be chemo-resistant
74
Q

What is Urothelial (transitional) Cell Carcinoma?

A
  • 95% of bladder tumours
  • Arising from the specialised multilayered epithelium
  • Most common in bladder but may arise anywhere from renal pelvis to urethra
  • In collecting system; pelvis, ureter, bladder
75
Q

What are the risk factors of Urothelial (transitional) Cell Carcinoma?

A
  • Age (older)
  • Gender (male>female)
  • Carcinogens
  • Smoking
  • Arylamines (dyes)
  • Cyclophosphamide
  • Radiotherapy
76
Q

What is the presentation of Urothelial (transitional) Cell Carcinoma?

A
  • HAEMATURIA – most common
  • Urinary frequency
  • Pain on urination
  • Urinary tract obstruction
  • If urinary exam clear to cyscoscopy
77
Q

What are the Histological Patterns in Urothelial (transitional) Cell Carcinoma?

A

• Muscle- confined to mucosa & grows outwards
• 70% non-invasive if doesn’t grow into bladder wall
• But if grows into bladder wall- need to remove bladder (cystectomy)
• If flat- carcinoma in situ, can see cells in urine
• Flat invasive- cystitis (bladder infec) symptoms, if doesn’t respond to antibiotics suspect flat invasive carcinoma (flat can invade without forming a mass in the wall)
• Grade them;
o Low grade- all the cells look similar- large but uniform, see occasional mitosis
o High grade tumour- dark mucus, patient also gets intra cycle BCG (inject every 6 wks)- most patients respond to this

4 types:
Papilloma-papillary carcinoma
Invasive papillary carcinoma
Flat non-invasive carcinoma (CIS)
Flat -invasive carcinoma
78
Q

What is the Staging of Bladder Carcinoma?

A

Pathologic T (Primary Tumour) Staging of Bladder Carcinoma
• Ta: non-invasive papillary
• Tis: Flat non-invasive carcinoma (Carcinoma In Situ - CIS)
• T1: Lamina Propria invasion
• T2: Muscularis Propria invasion
• T3a: Microscopic extra-vesicle invasion
• T3b: Grossly apparent extra-vesicle invasion
• T4: Invades adjacent structures

79
Q

What is the prognosis of Bladder Carcinoma?

A
  • Recurrences are common (if non-invasive can keep taking them out)
  • Outcome depends on grade and stage (metastatic disease- poor prognosis)
  • Grade: low grade TCC 98% alive at 5 years
  • Stage: Muscle invasion (remove bladder)= 60% 5 year survival
  • TCC of bladder better than TCC of upper tract
80
Q

What are the Functions of the Kidney?

A

• Excretion (end products of metabolism) e.g. urea (a.a. breakdown), uric acid (purine (nucleic acid) metabolism), creatinine (catabolism of a.a. creatine in muscles)
• Regulation e.g. homeostasis; water balance (regulate urine vol, sodium, potassium), acid base balance (alter hydrogen ion excretion- compensatory mechanisms), sodium balance (alter rate of sodium reabsorption)
• Endocrine e.g. renin (secretion from JGA, influences aldosterone), erythropoietin (affects rate of RBC produc), 1,25 dihydroxycholecalciferol (active vit D, effects calcium homeostasis)
– Chronic renal disease/ impaired renal function- show defects in endocrine & excretory functions before loose homeostatic control
– When homeostatic functions cease=renal failure (need interventions or die)

81
Q

What are the Functions of the Kidney tests?

A

• Detect renal damage e.g. proteins, simple strip test for haematuria (important in screening for heavy metal poisoning)
• Monitor functional damage (how well is still working) e.g. serial plasma measurements monitor patient with renal disease
• Distinguish between impairment & failure
– Important to have test with these characteristics- none exist
– Lab tests help decide when to start dialysis in renal failure
– About a million nephrons in each kidney (represent functional reserve)- in renal disease ½ nephrons have to loose functioning before abnormality can detect abnormality by conventional lab tests

82
Q

What are the common causes of Kidney Failure ? (pre, renal and post)

A
  • Pre-renal e.g. decreased ECFV or MI (low BP- not enough input to kidneys)
  • Renal e.g. acute tubular necrosis (e.g. from road injury= ↓ BP= less blood supply= ischaemic= tubules necroes= tubule blockage)
  • Post-renal e.g. urethral obstruction (e.g. retroperitoneal fibrosis- sticks ureters to back of abdo wall- invades them, cancer can invade them, surgeons hit ureters with laproscope), urethral obstruct (e.g. enlarged prostate gland, bladder cancer)
83
Q

What is measure in common Lab Tests of Renal Function?

A

• Glomerular filtration rate
• eGRF - estimate
• Creatinine clearance
• Plasma creatinine
• Plasma urea
o Easy, quick, simple measurement
o Wide reference range 3-8mmol/L (value increases after a meal)
o Sensitive but non-specific index of illness (it’s conc increased in many diff conditions so is sensitive to presence of disease but is a non-specific test)
• Urine volumes
o 750 - 2000 mL/24h typical in health
o Oliguria 24hr vol < 400mL (minimum amount need to make to get rid of solutes & nasty substances from body)
o anuria (little/ no urine) < 100mL/ 24h
o polyuria > 3000mL (over 3L without taking 3L in e.g. in diabetes where no ADH)
o No absolute definition for polyuria e.g. drink lots- matched with high urine output, if vol greater than 3L per day & patient not drinking this is polyuria
o Depends on how much you drink & sweat, in health it’s closely matched to water balance by ADH or vasopressin (AVP)
• Urine urea & sodium
• Urine glucose (early renal damage indicator)
• Urine protein (important in diabetes)
• Haematuria (early renal damage indicator)

  • Plasma; creatinine (specific but insensitive), urea (subject to probs), sodium
  • Urine; volume (often forgotten), urea, sodium
  • Creatinine clearance (unreliable)
  • Urine dipsticks
  • Glomerular filtration rate (impractical)
  • Renal function & hydration status by plasma urea & urine vol
84
Q

What Factors Influencing Plasma Urea Concentration?

A
  • Lots of factors affecting urea- shows something going on GIT protein, Liver AAs, Tisue protein, Kidney filtration, Kidney reabsorption and excretion, distribution volume.
  • Urea produc- taking excess a.a. from proteins= deaminated in liver= deaminated constituents in urea e.g. end-product of nitrogen metabolism
  • So lots of proteins (e.g. steak)- more urea levels
  • Also if breakdown tissue protein e.g. post op muscle damage=breakdown protein goes to liver=raised urea
  • Affected by distribution vol (anything that changes water vol affect urea e.g. if over hydrated)
  • As slow renal reabsorption excretion down urea recovery increases
85
Q

What happens in Urea Excretion?

A
  • Filtered at glomerulus
  • About 40% filtered urea passively reabsorbed by renal tubules in health
  • More urea reabsorbed if rate of tubular flow is slow (more time for urea to diffuse into peritubular capillaries)
  • Tubular flow rate slow when there is renal hypoperfusion (decrease in renal blood flow (RBF) e.g. after MI)
  • More urea reabsorbed & plasma urea increases
  • Many conditions cause renal hypoperfusion e.g. fluid loss, circulatory insufficiency, renal artery stenosis
  • Early phase of pre-renal renal failure- early sign of high urea
86
Q

What are the Commonest Causes of Increased Plasma Urea?

A

Can be divided into prerenal, renal & post-renal)
• GI bleed e.g. hematemesis from gastric ulcer
• Trauma (e.g. accident, from surgeons0
• Renal hypoperfusion, decreased RBF, decreased ECFV
• Acute renal impairment
• Chronic renal disease
• Post-renal obstruction calculus tumour (slows filtration down by back pressure cause increased urea absorption)

87
Q

What is Plasma Creatinine?

A
  • 50 - 140 umol/L (wide reference range)
  • Increases in plasma creatinine concentration as GFR decreases (kidney function) (usually specific test of glomerular function)- but prob is GFR has to fall a lot before plasma creatinine conc reliably increases
  • Analytical interferences by other chemicals (acetoacetate - DKA)
  • NOT proportional to renal damage e.g. when creatinine changing need to know relationship with amount of renal damage (graph; as reduce GFR creatinine declines but non-linear)
  • Wide refereance range (reflects muscle mass) e.g. body builder at top end & old lady at lower end of range
  • E.g. if patient goes from high normal ref range to low- shows decline in function
  • Only measure 8hrs AFTER a meal as conc increases after eat meat
  • Check important analytical inferences with lab; patient with ketoacidosis, jaundice or infec might have plasma agents that invalidate creatinine measurement
88
Q

What is Plasma Creatinine like in Chronic Renal Disease?

A
  • Elevated, may increase up to 1000umol/L
  • Increases in exponential fashion
  • Plot of reciprocal plasma creatinine conc predicts when intervention needed (dialysis or transplant) in end stage renal failure (chronic renal prob)
89
Q

What is Glomerular Filtration Rate?

A
  • Seldom measured in clinical practise (needs patient to come into hospital)
  • Clearance of [99Tc]-Sn-DTPA (need radiolabeled chemicals to measure properly)
  • People considering donating their kidney whilst alive have GFR measured
  • Before administering drug with potentially toxic effects some patients need GFR measurement before chemo
  • This lets oncologists calculate exact drug dose after estimating it’s elimination rate
  • GFR measured by calculating insulin clearance; use radioactive substances (technetium labelled diethylenediaminetetra acetic acid DTPA or 51-chromium labelld EDTA ethylenediaminetetra acetic acid
90
Q

What is Creatinine Clearance?

A

• If you measure amount of creatinine excreted in fixed time period & use calculations knowing what plasma creatinine conc is can figure out what vol plasma goes through kidney to extract creatinine
• Do over 24hr time period
• Easy to get factors wrong by 1000x as urine creatinine in mmol/L & plasma creatinine conc in umol/L
• Probs;
o In health creatinine clearance 10-30% higher than GFR (as creatinine secreted by renal tubules)- so is an overestimation of GFR
o Tubular secretion increased in chronic renal disease (assumption no active absorption/ excretion- is all due to filtration, but with creatinine in this case this not true)
o As plasma creatinine increases, rate of creatinine secretion increases- so more creatinine gets in urine by tubular secretion rather than glomerular filtration
o So creatinine clearance not a reliable marker of GFR in chronic renal disease
o Tubular secretion inhibited by common drugs e.g. salicylate, cimetidine, aspirin
o Probs with incomplete collection (full 24hr sample) & patient compliance
o Unreliable test (don’t make requests for it’s measurement)
Ccreat= (Ucreat*V)/Pcreat. PR 10-130mL/min
Ucreat= urine creatinine conc mmol/L
V= urine vol mL collected in 24hrs
Pcreat= plasma creatinine conc umol/L

91
Q

What is the MDRD equation?

A

MDRD equation: 186 x (Creat / 88.4)-1.154 x (Age)-0.203 x (0.742 if female) x (1.210 if black)

eGFR calculation
Clinical Decisions from eGFR
Classifications- depending what grade you are, various intervention treatments
Grade 3 or 4- automatic referral to renal services
Look at eGFR table

92
Q

How does creatinine clearance correlate with Chronic Renal Disease?

A
  • Normal creatinine clearance (GFR marker) is about 120 in health
  • No increase in plasma creatinine conc until renal function halved
  • With creatinine clearance about 30-60mL/min we can measure increased creatinine & urea in plasma
  • With creatinine clearance about 20-30mL/- can detect hyperkalaemia & decreased bicarbonate (acidosis)
  • In addition to these plasma changes, we measure increased phosphate & uric acid when creatinine clearance very low (10-20mL/min)
93
Q

What is Pre-Renal Oliguria?

A

• GFR reduced
• If patient lost water from ECFV (extracellular fluid vol), ADH secretion increased (as they are dry)- concentrated urine/ low vol (urine osmolality over 500mmol/kg H2O)
• Urine urea conc high as increased urea reabsorption, plasma urea conc will also be elevated
• Increased renin & angiotensin & aldosterone
• Renal hypoperfusion causes to renin secretion;
o Functioning nephrons increase sodium reabsorption (aldosterone)
o So urine sodium concentration low in pre-renal oliguria (less than 20mmol/L)
• Diminished renal blood flow (RBF)= aldosterone secretion (2ndry hyperaldosteronism); increases sodium reabsorption (functioning renal tubules can respond to aldosterone by increasing sodium reabsorption)
• Give IV fluid- give saline (lots of water & sodium)- vol will increase & kidney’s start functioning

94
Q

What are the causes of Pre-Renal Oliguria?

A 
Low renal perfusion; 
•	Dehydration- sodium/ water 
•	Haemorrhage 
•	Renal artery damage 
•	Hypotension 
•	E.g. not given enough fluid post-op
95
Q

What is Renal Oliguria?

A 
•	GFR reduced/ normal 
•	Weak urine/ low vol
•	Renal renin secretion may be raised; 
o	Hypertension
o	But nephrons can’t reabsorb sodium 
o	Urine sodium conc >40mmol/L 
•	Need to cure hypertension by taking dead kidneys out- as excreting aldosterone so increasing BP
96
Q

What are the causes of Renal Oliguria?

A 
Intrinsic damage; 
•	Hypertension 
•	Diabetes
•	Tubular necrosis (reversible)  
•	Chronic infec 
•	Immunological damage- SLE 
•	Toxic damage- drugs, heavy metals (Hg, Ur), poisons (paraquat)
97
Q

What are features of renal failure?

A 
Oliguria
•	Anaemia 
•	Haematuria 
•	Proteinuria 
•	Urine casts 
Other probs;
•	Calcium/ phosphate metabolism disorders  
•	Bone disease
98
Q

How are causes of oliguria differentiated?

A
  • Can help differentiate between 2 causes of oliguria
  • Look at urine sodium & urine concentration rate
  • PRU (pre-renal uraemia)- conditions which produce renal hypoperfusion e.g. fluid loss & circulatory probs
  • ARF (acute renal failure with tubular necrosis)- nephrons damaged
  • Patients with ARF have nephrons that can’t respond to aldosterone or frusemide- urine sodium conc ususally >40mmol/L
  • Can be dangerous to infuse a ARF patient with a fluid- may be fluid overload with pulmonary oedema
  • Pre-renal renal failure- give fluids
  • Renal failure- if give fluids hasn’t got anywhere to go= cardiac overload & failure then need dialysis to get it out again
  • NEED to get this distinction between pre-renal & renal failure understood!
  • PRU: <20 Una mmol/L, >5 P/U Urea ratio
  • RRF: >40 Una mmol/L, <2 P/U Urea ratio
99
Q

What are the different zones of the prostate?

A

• Prostate has diff zones
o TZ- transition zone, TZ & central zone encapsulate urethra
o PZ- peripheral zone (most carcinomas develop here- can feel it here in rectal exam);
 Symptoms; heaviness, pain, asymptomatic
• Benign prostatic hyperplasia (prostate enlargement)- more common in central section
• Rectum posterior to bladder

100
Q

What is Benign Prostatic Hyperplasia?

A
  • Enlargement of the prostate (nodular hyperplasia or benign prostatic hyperplasia (BPH))- overgrowth of the epithelium and fibromuscular tissue of the transition zone and periurethral area.
  • Symptoms are caused by interference with muscular sphincteric function & by obstruction of urine flow through the prostatic urethra.
  • Enlarged prostate= compressed urethra
101
Q

What are the symptoms of Benign Prostatic Hyperplasia?

A

Lower urinary tract symptoms (LUTS);
o Diminished urinary stream, size & force
o Urgency
o Hesitancy (a while before flow comes out after have released)
o Increased freq
o Incomplete bladder emptying
o Nocturia

102
Q

What is the pathogenesis of Benign Prostatic Hyperplasia ?

A

o Normal prostate- several distinct regions; central zone (CZ), peripheral zone (PZ), transitional zone (TZ) & a periurethral zone
o Most carcinomas from peripheral glands of organ, may be palpable form digital rectal exam
o But nodular hyperplasia from more central situated glands & more likely to produce urinary obstruct early than is carcinoma- development has 3 pathogenic stages;
1. Nodule formation
2. Diffuse enlargement of transition zone & periurethral tissue
3. Nodules enlargement
 2. predominant among <70yr old men, 1. & 3. predominate among older men
• Benign prostatic hyperplasia (BPH) (adenofibromyohyperplasia)- see nodular hyperplasia
o Adeno- glands
o Fibro- mesenchymal between glands
o Myo- muscle
• Have big nodules expanding
• Hypothesis- accumulation of androgens but can happen to any man aging

103
Q

What is the histology of Benign Prostatic Hyperplasia?

A

o pure stromal hyperplasia, circumscribed nodule is uniform, nodule consists of stromal fibroblasts with scattered lymphocytes
o mixed epithelial- stromal nodule of nodular hyperplasia

104
Q

What is the aetiology of Benign Prostatic Hyperplasia

A 
o	Main component of hyperplastic process- impaired cell death 
o	Overall reduc of rate of cell death= accumulation of senescent cells in prostate 
o	Androgens (mainly DHT) which are needed for BPH development can increase cellular prolif &amp; inhibit cell death
105
Q

What is Adenocarcinoma of Prostate?

A
  • Most common malignancy of prostate

* Adeno= abnormal prolif of glandular epithelial cells

106
Q

What is the incidence of Adenocarcinoma of Prostate ?

A

o 95% of prostatic malignancies
o Rare in <40yrs, incidence rises quickly in over 40 (increases at age 40)
o Autopsy study- men no clinical evidence of cancer- high level of latent cancer
o More in people with African (100 per 100 000) rather than European ancestry (70.1 per 100 000)

107
Q

What are the risk factors of Adenocarcinoma of Prostate?

A

o AGING!!! (most important risk factor)
o Race
o Fam history (inherited polymorphisms);
 Men with 1 first degree relative with prostate cancer have 2x the risk, if 2 first degree relatives 5x risk
 Strong fam history also develop disease earlier
 Men with germline mutations of BRCA2 mutations- 20x increased risk
o Diet (increased fats)- env influence
o Chemicals (carcinognes, smokers)
o Hormones- androgens (maintain growth & survival of prostate cancer cells, anti-androgens treatment induce disease regression)

108
Q

What is the staging of Adenocarcinoma of Prostate?

A

o GLEASON scoring system only accepted GRADING system
o TNM Staging;
 T- extent of tumour (P stands for pathology)
• PT2- if tumour encased in prostate
• PT3- in adjacent strucs
 N- Nodes (lymph)
 M- metasteses
• Prostate does NOT have a capsule- look carefully at strucs around it to see if in adjacent strucs

109
Q

What is the Management & mortality of Adenocarcinoma of Prostate?

A

o Treat by surgery, radiation therapy & hormonal manipulations (>90% expected to live for 15 yrs after therapy)
o Most common treatment for clinically localized prostate cancer- radical prostatectomy (prognosis after this based on pathological state- pathological stage, margin status, Gleason grade)
o Alternative treatments for localised prostate cancer; external beam radiation therapy (also treats prostate cancer too locally advanced to be cured by surgery), interstitial radiation therapy (brachytherapy)
• Treatments; hormone therapy (prevents androgen impact on prostate or affects androgen produc), robotic surgery, bracket therapy (stick needles with radioactive isotopes around prostate cancer

110
Q

What is the screening practise for prostate cancer?

A

• Currently no screening programme
• Role of prostate specific antigen (PSA);
o Made by prostate gland
o Diff factors can cause it to be increased (e.g. inflamm)
o Not a specific correlation with prostate cancer- has false +ves & -ves
• Controversies;
o PSA test (false +ves & -ves 15%)- can find aggressive prostate cancer that needs treatment but can find slow-growing cancer (may never cause symptoms/ shorten life) difficult treatment decisions
o Treatment complications; impotence, incontinence, retrograde ejaculation (into bladder)
o Unnecessary treatments
o Limited benefits
o Consideration in high risk groups
o Reduced mortality vs. risks of overtreatment (ERSPC)
• ERSPC (European Randomized Study of Screening for Prostate Cancer)- screening signif reduces death from prostate cancer (man with high risk of dying from prostate cancer reduced by 29%)
• Has to be balanced against over-diagnosis (cancer that will never casue symptoms/ death in lifetime) & over- treatment (tumours unlikely to be harmful)
• To save 1 life from prostate cancer, 27 men diagnosed (recent American study- no reduc in deaths)

111
Q

What is the epidemiology of Testicular Cancer?

A

o Less in Africans & Asians (incidence), highest in Northern European men
o Germ cell tumours of testis (with exception of spermatocytic seminoma)- mostly in young males, incidence accelerates after puberty & peaks near 30 yrs.
o Small peak in early childhood, but many of cases in elderly men correspond to lymphomatous involvement or secondary tumours rather than germ cell tumours.

112
Q

What is the classification of Testicular Cancer?

A

• Classification (based on where arising from; glandular, mesenchymal component);
o Germ cell tumours (make sperm e.g. can form seminomas)
o Sex cord/ gonodal stromal tumours
o Miscellaneous tumours of testis
o Haematopoietic tumours
o Tumours of collecting ducts & rete
o Tumours of paratesticular strucs
o Mesenchymal tumours
o 2ndry tumours of testis (tumour metastised to testis)

113
Q

What are the risk factors of Testicular Cancer?

A 
o	Cryptochidism (3-14x)
o	Metachronous testis cancer (2-4x)
o	+ve family history (5x)
o	Diethylstilbestrol exposure (2.5-5x)
o	Gonadal dysgenesis (50x)
o	Androgen insensitivity syndrome (genetically male but phenotypically female- raised as female but don’t have ovaires) (15x)
114
Q

What are Pre-existing medical conditions associated with development of Testicular germ cell tumours?

A 
o	Prior TGCT in the contralateral testicle
o	Cryptorchidism
o	Impaired spermatogenesis
o	Inguinal hernia
o	Hydrocele
o	Disorders of sex development
o	Prior testicular biopsy
o	Atopy
o	Testicular atrophy
115
Q

What is a Seminoma?

A

Testicular tumours
o Most commonly in 35-45 years old, uncommon in men over 50 years of age, and rare in children.
o The clinical presentation includes testicular enlargement, with or without pain (>70%) and metastases (10%). Some patients with seminoma have no symptoms. Rare symptoms: gynecomastia, exophthalmos, and infertility
o Elevated serum PLAP and hCG seen in 40% and 10% of patients, respectively; the latter is the cause of gynecomastia.
o Macro: well-demarcated, cream-colored, homogeneous, and coarsely lobulated. Micro: Monotonous polygonal cells with mostly clear cytoplasm and central nuclei divided into lobules by thin bands of fibrovascular stroma.

116
Q

What is a Teratoma?

A

Testicular tumours
o Most common in the first and second decades of life.
o Presentation: gradual testicular swelling with or without pain. Although mature teratoma is almost always benign in prepubertal patients, it can pursue an aggressive clinical course after puberty (e.g. metastasis). Immature teratoma is a common component of NSGCTs but its pure form is very rare.
o Pure teratomatous tissues do not secrete tumour markers.
o Macro: well-demarcated solid or multicystic. Micro: an admixture of ectoderm, endoderm, and mesoderm.

117
Q

What is Acute & Chronic Epididymoorchitis?

A

Inflammatory Conditions of the Testis

ghostly outlines of infarcted seminiferous tubules, surrounded by purulent exudate containing neutrophils and other inflammatory cells

118
Q

What is Idiopathic Granulomatous Orchitis?

A

Inflammatory Conditions of the Testis
Typically in older adults, often with associated symptoms of UTI, trauma, or flu-like illness.
Testis becomes swollen, painful & tender initially but later may have a residual mass indistinguishable from a neoplasm, prompting orchiectomy
No granulomas present, but interstitial & intratubular aggregation of epithelioid histiocytes, lymphocytes & plasma cells= granulomatous appearance

119
Q

What is Sarcoidosis of the Testis?

A

Inflammatory Conditions of the Testis
Sarcoidosis can affect testis, & mimic malignancy, especially if with radiologic pulmonary abnormalities. Image shows non-necrotizing granulomas involving testicular parenchyma. Special stains for fungal organisms & acid-fast bacilli are -ve

120
Q

What is Myelofibroblastic Pseudotumour of Testis?

A

Inflammatory Conditions of the Testis
Atypical inflammatory & myofibroblastic reaction with fasciitis-like large cells. No malignancy features. Process regarded as a benign reactive & proliferative process of uncertain aetiology?

121
Q

What is Malakoplakia of Testis?

A

Inflammatory Conditions of the Testis
May affect only the testis, or less commonly, both testis & epididymis, forming soft yellow, tan, or brown nodules that replace normal testicular parenchyma.
The tubules and interstitium are extensively infiltrated by large histiocytes that have abundant eosinophilic granular cytoplasm (von Hansemann histiocytes)

122
Q

What is Sperm Granuloma?

A

Inflammatory Conditions of the Testis
Exuberant foreign body giant cell reaction to extravasated sperm. In up to 42% of patients after vasectomy & 2.5% of routine autopsies. Patients may have no symptoms, but often present with history of pain & swelling of upper pole of epididymis, spermatic cord, & rarely, the testis. Others have a history of trauma, epididymiditis & orchitis

123
Q

What is Tuberculous Orchitis?

A

Inflammatory Conditions of the Testis
Epididymis- reservoir for tuberculous involvement in male genital tract, with 2dry testicular involvement & other local sites of involvement in about 80% of cases; e.g. 40% of cases of renal TB with epididymal infec
Patients usually present with painless scrotal swelling, other signs & symptoms; unilateral/bilateral mass, infertility & scrotal fistula. Caseating granulomatous inflamm prominent, with fibrous thickening & enlargement of the epididymis & adjacent structures

124
Q

What is Cryptochordism?

A

• 1 or both testes fail to descend into scrotum
• Descend from abdo cavity starts in 3rd month of intro utero, by 7th month reaches inguinal canal, 1 month before birth- superficial inguinal ring, by birth should be down
• Normal testicular descent;
o Begins 2nd month of intrauterine life
o Reaches iliac fossa 3rd month
o Deep inguinal ring 4th-6th month
o Inguinal canal 7th month
o Superficial inguinal ring 8th month
o Scrotum 9th month (~ birth)
• 25% of cases of empty scrotum
• Undescended testes most freq in inguinal canal or upper scrotum; arrest in abdomen less freq
• Wait after a year from birth- if still undescended then diagnose
• More freq on R
• Most bilateral (18%)
• High scrotal (60%), Inguinal Canal 925%0, abdominal (15%)
• Risk factor of testicular cancer;
o Testes sensitive to heat, if undescended too hot in body (37 degrees)= atrophy

125
Q

What is the aetiology of Cryptochordism?

A

o CONGENITAL: anomalies in anatomical development or hormonal mechanisms involved in testicular descent
o ACQUIRED: post op or spontaneous ascent due to various mechanisms;
 Inability of spermatic blood vessels to grow adequately
 Anomalous insertion of gubernaculum
 Failure in reabsorption of vaginal process
 Failure in post elongation of spermatic cord

126
Q

What are the complications of Cryptochordism?

A

testicular atrophy, infertility, carcinoma (TGCTs)

127
Q

What is Hypogonadism?

A
  • Primary- undescended testis, Klinifelter syndrome, hemochromatosis, mumps, orchitis, trauma, cystic fibrosis, testicular torsion (if have one, other testicle more susceptible to torsion) & varicocele
  • Secondary- pituitary failure, drugs (glucocorticoids- steroids affect steroid produc of body (e.g. LH, GnRH), ketoconazole, chemo & opioids), obesity (adiposites take circulating androgens & turn them to female hormones) & aging
128
Q

What is Urinary Tract Flora?

A
  • Kidneys/ureters- sterile (no bacteria)
  • Bladder- usually considered sterile but this may not be the case (may have some non-pathogenic bacteria)
  • Urethra (non-sterile from here)- perineal flora (skin/ lower GI tract flora
129
Q

What is Perineal Flora?

A

• Skin flora- predominantly coagulase –ve staphylococci
• Qualitatively the bacteria on skin near any body orifice may be similar to those in orifice- lower GI tract flora;
o (Anaerobic bacteria- rarely cause UTI)
o Aerobic bacteria- more common cause of UTIs e.g. enterobacteriaceae (enteric gram -ve bacilli, coliforms)
o Gram +ve cocci e.g. Enetrococcus spp

130
Q

What are the terms used to Define Urinary Tract Infections?

A

Clinical terms; Cystitis (bladder inflamm), Pyelonephritis (upper urinary tract infalmm/ infec), Urethral syndrome
Microbiological terms; Significant bacteriuria, Asymptomatic bacteruria, Sterile pyuria

131
Q

What is Cystitis? What is the treatment?

A 
•	Lower urinary tract infection 
•	More common in women
•	Syndrome; 
o	Dysuria (burning pain) 
o	Urinary frequency 
o	Urgency 
o	Supra-pubic pain/ tenderness 
o	Polyuria, nocturia (get up in night to pass urine), haematuria

• Females;
o Treatment often pre-empts microbiology results
o Short course of antibiotics; 3-days
• Males/ recurrence of symptoms; longer course (7 days)

132
Q

What is Pyelonephritis ? What is the treatment?

A

• Upper urinary tract infec (infec of kidney &/or renal pelvis
• Symptoms of lower UTI
• Loin/ abdominal pain/ tenderness- usually unilateral
• Fever (>38°, pyrexia)
• Other evidence of systemic infec;
o Rigors, nausea, vomiting, diarrhoea
o Elevated CRP (inflamm markers), WBC

• Empiric therapy
o Cefuroxime, ciprofloxacin
o Piperacillin-tazobactam (if >65 yrs old)
• Targeted therapy- based on sensitivity results
• Duration- 7-14 days depending on antibiotic used

133
Q

What is Urethral Syndrome?

A
  • Controversial term- is abacterial cystitis, frequency-dysuria syndrome
  • Mostly affects 30-50 yr old women
  • Symptoms of lower UTI without demonstrable infec (theorized eitiologies; hormone imbalances, inflamm of skene glands & paraurethral glands (female prostate), reaction to certain foods, env chemicals (e.g. soaps, contraceptive gels, condoms), hypersensitivity following UTI & traumatic sexual intercourse)
134
Q

What is Kass criteria?

A

• Kass criteria;
o >105 cfu/mL = “significant” bacteriuria
o 104-105 cfu/mL = probable infection
o So if above a certain threshold then is due to a UTI not urethral contamination
• Limitations of criteria;
o Bacterial count is on a normal curve
o Many symptomatic females have bacterial counts of <105 cfu/mL & still have UTI
o Lower counts (103 cfu/mL) are significant in males
o Not relevant to catheter urine/ sterile-aspirated urine (in practical terms: similar testing/ reporting criteria used)
• Prob- urethra not sterile so urine won’t be sterile

135
Q

What is Asymptomatic Bacteriuria? What is the treatment?

A
  • Significant bacteriuria- with one organism (count over threshold, but no symptoms- patient says their well)
  • No symptoms of urinary tract infection
  • As get over age 65- wax & wane e.g. have a bacterial infec then it resolves itself, then get it again
  • Don’t expect catheter urine to have overgrown

Treat only specific groups;
• Pregnant;
o Association with upper UTI, pre-term delivery & low birth weight babies
o Confirm ‘genuine’ with 2nd sample if patient asymptomatic
• Infant- prevention of pyelonephritis & renal damage
• Prior to urological procedures- prevention of UTi/ bacteraemia
Elderly (male & female), catheterised etc do NOT need antibiotics

136
Q

What is Sterile Pyuria?

A
  • Pus cells in urine

* No organisms grown (with standard lab methods)

137
Q

What are the causes of Sterile Pyuria?

A

• Inhibition of bacterial growth;
o Patient taken antibiotics- collect sample before starting if possible
o Specimen contaminated with antiseptic
• ‘Fastidious’ (hard to grow on plates) organisms; e.g. Mycobacterium tuberculosis, Haemophilus spp, Anaerobes & cause UTIs
• Urinary tract inflammation (cause similar symptoms to UTI);
o Renal or bladder stones
o Other renal disease
• Urethritis (sexually transmitted pathogens)- urethra inflamm;
o Neisseria gonorrhoeae
o Chlamydia trachomatis

138
Q

What are the Predisposing Factors for UTI?

A
  • Female sex (10:1 female: male ratio)
  • Anything causing urinary stasis (affecting natural urine flow) e.g. pregnancy, prostatic hypertrophy, stones, strictures, neoplasia, residual urine
  • Instrumentation
  • Sexual intercourse (associated with recent sexual intercourse & commoner in sexually active women)
  • Fistulae (recto-vesical, vesico-vaginal- organisms can go through fistula & cause infec as lower GI has bacteria
  • Congenital abnormalities (veico-uteric reflux (VUR)- bowels at end of ureter into bladder, some of urine pushed back up ureter)
139
Q

What is an Complicated vs Uncomplicated UTI?

A

Complicated UTI
• Underlying abnormality (structural/ functional)
o Urinary stasis- obstruction/ retention
• Presence of ‘foreign body’
o Catheter/ other device/ renal calculi
o Biofilm (bacteria of matrix & protein mesh- hard for antibiotics to go through mesh)
• UTIs not usually in children <10-12, men <65, so if in them suspect complicetd UTI unless confirmed otherwise
Uncomplicated UTI - In absence of above

140
Q

What is the Pathology of a Urinary Tract Infection ?

A

• Perineum
o Movement of bacteria along a lumen
o Bacteria work up urethra & bladder, can go further up ureter & kidney
• Fistulae- movement of bacteria from genital/ GI tract to urinary tract
• Haematogenous
o Bacteria in blood, filtered (seeded) out by kidney- infec starts in kidney then works it’s way down
o Seeding of infection from blood (rare)- staphylococcus aureus (not usually in urine)

141
Q

What are Organisms that Cause UTIs?

A
  • Certain strains of E.coli more adapted to cause UTI e.g. have fimbri/ other adhesions so attach to cells
  • Coagulase –ve staphylococcus- usually causes UTI in young adult women
  • Proteus mirabilis- can be associated with renal calculi (stones0
  • Enyerococci- in hospital
  • Ecoli- most common, then Staphylococcus saprophyticus (CNS), Proteus mirabilis, enterococcus spp, Kiebsiella spp, Other coliforms, Pseudomonas aerugonosa.
142
Q

What is a catheter UTI?

A

• Catheter- leads to bacteria in urine
• Indwelling catheterisation causes bacteriuria- biofilm formation on plastic= colonisation
• Need to distinguish between colonisation & infection;
o Don’t expect ‘normal’/ ‘sterile’ results
o Clinical features (make sure correlates with this)
• Manipulation or catheter removal may result in bacteraemia (organisms get into blood stream)- at LTHT antibiotic prophylaxis may be used to prevent bacteremia;
o History of symptomatic urinary catheter associated infection with previous catheter changes
o Purulent urethral/ suprapubic catheter exit site discharge
o Catheter ot meatal/suprapubic catheter exit site colonisation with Staphylococcal aureus (including MRSA)
Other devices may also become colonised; urostomies, nephrostomies

143
Q

What is tested in Dipstick Testing?

A 
Dipstick Testing 
•	Blood
•	Protein
•	Nitrite- most specific for infec 
•	White blood cells (leucocyte esterase)
•	Dipstick testing no diagnostic value in patients with indwelling urinary catheters unless these been placed very recently.
144
Q

What are Microbiological Investigations for UTIs?

A

• Urine
o Mid-stream (MSU)- start of stream more likely contaminated with urethra contam, mid-stream is more bladder urine
o Catheter urine (CSU)
o “Clean catch”
o Supra-pubic aspirate (SPA)- wait till have a full bladder then aspirate through skin
• Blood- suspected pyelonephritis
• Tests- microscopy, culture (grow microoganism) and sensitivity testing

145
Q

What is Mid-Stream Urine Testing?

A

• Sample procurement- careful instructions
• Transport to laboratory- preservative e.g. boric acid
o “Red-topped” container
o Prevents “over-growth” of bacteria that might be in small numbers in urine
• Sample processing- semi-quantitative culture
• Interpretation of report- depends on clinical details and results

146
Q

What are special tests for UTIs?

A

Early morning urine (EMU) x 3
• If suspect urinary TB (better to get biopsy at site of suspected TB)
• Need to request Acid fast bacilli (AFBs) specifically (won’t grow on specific plates)
• (Poor sensitivity- tissue biopsy at site of suspected disease= better)

147
Q

What further infections may be needed for UTIs? What are the indications?

A 
•	Indications
o	Recurrent UTI
o	Any UTI in male patient
o	Any UTI in childhood
o	Pyelonephritis (e.g. if recurrent) 
•	Investigations 
o	Renal tract ultrasound scan
o	Specialised tests- isotope scans (DMSA, DTPA, MAG3), micturating cystourethrogram (shows urine flow- see if it’s flowing)
148
Q

What is the treatment for UTIs?

A

Non-antimicrobial management;
• Fluid intake (wash out bacteria)
• Anti-inflammatories (remove symptoms of cystitis) e.g. NSAID Ibuprofen
• Device removal if no longer indicated (e.g. catheter), if still needed- change (under prophylaxis) (e.g. change catheter)
• Drainage if obstruction/ abscess
• Recurrent UTIs;
o Re-infection or bacterial persistence (e.g. certain E.coli strains)- ‘significant’ recurrent UTIs > 3 episodes within 12 months.
o Cranberry juice (makes organisms less adherent to bladder wall)
UTI Antibiotics
• Requirements;
o Present in urine
o Minimally toxic
o Effective against likely organisms; increasing resistance, lack of ‘collateral’ damage (e.g. don’t want to treat with broad spectrum antibiotics- might get resistant to it in the future)
o Easily administrerd
o Cheap
• Examples to treat UTIs;
o Trimethoprim
o Nitrofurantoin
 Inadequate systemic conc (e.g. patient has a fever don’t treat with nitrofurantoin- as won’t treat systemic infec)
 NOT for upper UTIs
o Pivmecillinam
o Fosfomycin

149
Q

What are complications of UTI?

A

Abscess- site
• Perinephric (form around kidney)
o Uncommon complication; renal stones &/ or diabetics,2o to obstruction of infected kidney
o Gram –ve bacilli
• Intrarenal
o Haematogenous spread: unilateral, single, renal cortex- Staphyloccus aureus
o Can be associated with classic acute pyelonephritis- cortex or medulla.

Prostatitis
• Prostate inflamm (prevalence 2-16%)
• Acute bacterial
o Post procedure e.g. trans-urethral resection of prostate (TURP), trans-rectal ultr-sound guided (TRUS biopsy)
o Lower urinary tract symptoms
o Fever
o Tender tense prostate on PR (post-rectal) palpation
o Uropathogens- E.coli
• Chronic
o Recurrent UTIs with same organism (usually E.coli)
o Asymptomatic in-between
• Most antibiotics poor penetraition into prostatic tissue;
o (Better penetration of antibiotics in acute prostatitis)
o Fluoroquinolones: ciprofloxacin
o Trimethoprim/ co-trimoxazole

150
Q

What is the difference between features of a lower UTI vs upper?

A

o “Lower” UTI: dysuria, frequency,

o “Upper” UTI: Fever, flank / loin pain, +/- LUT symptoms.

Clinical Pathology (11 decks)

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