Kidney, Urinary Tract, Prostate & Bladder

Pre-Renal:

- Shock - acute tubular necrosis, cortical necrosis

- Volume loss (Polyuria, diarrhoea, burns etc)

- Reduced cardiac output (heart failure etc)

- Systemic vasoconstriction (sepsis, anaphylx)

- Excessive constriction of afferent arteriole (NSAID, contrast, NA, hypercalcaemia)

Renal Injury:

- Glomerular - Severe GN (anti-GBM or vasculitis)

- Tubular

toxic acute tubular necrosis (gent'in)

myoglobinuria

crystal deposition e.g oxalate, urate

tubuloinerstitial nephritis

acute pyelonephritis

- Vascular

thrombo / atheroemboli

arteritis

accelerated hypertension, HUS

Post-Renal:

- Urinary tract obstruction e.g. tumours of bladder , prostate tumour

- Stones or crystals

- strictures, catheters blocked, increased inra-abdominal pressure

Glomerula:

Chronic glomerulonephritis

Diabetic Nephropathy

Acute glomerulonephritis - (e.g. vasculitic GN)

Whole Kidney:

Polycystic kidney disease

Hypertension - direct damage to kidneys or BP alone

Chronic Pyelonephritis

Targeting the Podocyte:

Minimal change disease

Primary Focal segmental glomerulosclerosis

Membranous Nephropathy

Others:

Other GNs - lupus, IgAN, MCGN (mesangiocapillary glomerulonephritis) etc

Diabetes

Amyloidosis

Myeloma Kidney

Lower UTI - stones, infection tumour

Glomerulonephritis - IgA nephropathy

Inherited abnormalities - thin membrane nephropathy

Rapidly progressive glomerulonephritis

=severe destructive glomerulonephritis

presents histologically as crescentic glomerulonephritis

Differential:

Vasculitic glomerulonephritis

Anti-GBM - goodpastures

severe immune complex glomerulonephritis

(lupus nephritis, IgA nephropathy)

Oliguria (urine output less < 400 mL/day)

or Anuria:

Presence of haematuria, proteinuria, leukocytes:

-

Large, painless bladder on abdominal palpation:

Purpura, petechial rash, bleeding:

Pericardial rub on auscultation:

Antibodies to type IV collagen - goodpasture Ag

Linear membrane staining for IgG on IHC

Goodpasture's disease =

- PULMONARY HAEMORRHAGE

& ACUTE RENAL FAILURE due to anti-GBM

- Lung Sx pre-date Kidney (usually)

(Haemoptysis, chest pain, Cough, SOB)

- Kidney Sx - haematuria, proteinuria, peripheral oedema (or face), uraemia, Hypertension.

Abs to ANCA (PR3 / MPO) = degranulation and fibrinoid necrosis

- focal segmental necrosis (grenades)

- arterial involvement in 20%

- NO IMMUNE DEPOSITS IN GLOMERULI

(pauci-immune)

- crescentic proliferation

MOST COMMON cause of tubular lesions

- NSAIDS - commonest

- Gentamicin

- Heavy metals

Ischaemic damage due to prolonged loss of BP.

Haemorrhage, cardiogenic shock

Proton pump inhibitors account for 50%

- Immune response to tubular epithelium Ags

- Interstitial inflammation

- LYMPHOCYTIC infiltrate

- Drug-induced - Abx, PPIs, NSAIDS

Severe, prolonged or recurrant injury

e.g. vasculitis, severe HTN, Tubulointerstitial nephritis

May be Insidious chronic injury

e.g. Diabetes, HTN, chronic GN, polycystic kidney, chronic pyelonephritis

Immune-mediated Glomerulonephritis:

- Complement mediated

- ANCA vasculitis

Genetic:

- Basement membrane disorders

- Lysosomal storage disorders

Non-immune deposits:

- Hyperlipidaemia

- Amyloidosis

- Deposition of light chains (myeloma)

Vascular:

- Diabetes mellitus thrombosis

- Fibrinoid necrosis in HUS

- accelerated Hypertension

Minimal Change disease or membranous nephritis

= podocyte injury, no proliferation

= PROTEINURIA

IgA nephropathy

Lupus nephritis

= Inflammation and/or mesangial proliferation

= HAEMATURIA / NEPHRITIC

Anti-GBM disease

Vasculitis

= necrosis, crescents (blown apart)

= Acute renal failure

Acute onset of nephrotic syndrome

Commonest in children (can occur any age)

STEROID RESPONSIVE

- Normal by light microscopy and IHC

- EM - podocyte foot effacement

Ideopathyic (80%)

- autoimmune to podocyte antigen (75% PLA2R)

Secondary (20%)

- Drugs

- SLE

- Malignancy (Ca lung or colon)

- Infections (HBV EBV, syphilis)

Nephrotic Syndrome

Sub-epithelial deposits of IgG and C3

Reactive new membrane formed between deposits - membranes spike on silver stain

- Podocyte produces NEW BM

- Dense deposits of Ag-Ab-Complement

Type of diabetic microangiopathy

- THICK LEAKY BASEMENT MEMBRANES

(T1DM w/ good glucose control prevents)

(T2DM irrelevant control, inevitably develops)

- Nodular glomerulosclerosis

(Kimmelstiel-Wlison Lesions)

Exudative Lesions (Fibrin caps)

Arteriolar hylinosis

(arteriole hyaline - sclerosis (nodular balls of collagen)

Presents:

Microalbuminuria -> Overt Proteinuria -> Chronic renal Failure

Commonest Glomerulonephritis

- IgG predominant deposits

(accompanied by IgG auto-Abs to IgA!)

Presentation:

- Variable

- asymptomatic haematuria

- proteinuria

- acute or chronic failure

Histology varies....

- Mesangial hypercellularity

- Segmental sclerosis

20-30% ESRF 20 yrs post diagnosis

Major cause of SLE morbidity and mortality

- Immune complexs, IgG, IgM, IgA, C3, C1q in mesangium +/- capillary wall

- variable clinical presentation

- variable histology - any glomerulonephritis

Nephrotic Syndrome:

- Protienuria

- Reduced blood protein = oedema

- May be increased fat in blood

(inflammation of podocytes, increases permeability - loss of protein/oncotic pressure = RAAS, Na+ retention)

Nephritic Syndrome:

- Haematuria

- Oligouria / Anuria

- Hypertension

(Inflammation of epithelial barrier = blood in urine, decrease in kidney blood flow = reduced urine output, RAAS = HTN)

INCREASED:

Salt - HTN

Water - Oedema, SOB

Potassium - Arrhythmia

Phosphate - Itching, contributes to bone disease

Waste (Urea/acid) - Sickness, anorexia, encephalopathy, SOB

DECREASED:

Vit D - Bone disease

EPO - Anaemia

Salt - Dehydration

Water - Thirst

Mild >30% function, no symptoms

Moderate 15-30% HTN, anaemia, lack Vit D

Severe - 5-15% progressively unwell, loss of appetite, nausea, tired, breathless

End-Stage <5% v. ill, death unless treat

- Proteinuria

- Haematuria

- Hypertension

- Altered urine output - oligouric/polyuric

- Uraemia (kidney failure) (commonly DM)

MULTISYSTEM:

SLE

hereditary renal disease - PKD, Alport's syndrome (kidney ear eye - collagen defect)

Triad of:

1. Proteinuria - >3.5g/day

2. Hypo-albumin-aemia - <25g/dL

3. Oedema

Associated:

- Hyperlipidaemia (CHOLESTEROL HIGH)

- Hypercoaguable (RISK VTE) *anticoagulate

Glomerular - increased permeability - albumin

Overflow - increased plasma conc exceeding re-uptake capacity of tubules (e.g. bence-jones - DIPSTIX NEGATIVE)

Tubular - Impaired reabsorption of normal filtrate - b2 microglobulin

Secreted - Tamm-Horsfall protein (part of renal matrix, decreased in urine when stones forming)

- Loss of concentrating power

- Inability to secrete molecules

- Inability to reabsorb = thirst (dehydration)

polyuria, nocturia (ADH doesn't work)

- Autoimmunity or allergic response to drugs (PPI, Abx, Anti-inflammatory) or infection

- ACIDOSIS and GLYCOSURIA

Pathologically:

PPI-induced interstitial nephritis

EBV / CMV / toxoplasma infection

Sarcoid

Sjorgen's

Presents with:

- Haematuria

- Reduced filtration = oliguria, uraemia, fluid retention (mild), HTN

Pathology:

- Post-strep glomerulonephritis (following sepsis)

- IgA nephropathy (most common)

- SLE

- Microscopic polyangitis

- Granulomatosis with polyangitis (Wegner's)

- Anti-GBM

RENAL CAUSES:

= Renal failure!

- Loss of renal function

- HTN

- Proteinuria

- Any Age

- No Evidence of Obstruction

- Occupation (solvents)

UROLOGICAL CAUSES:

MALIGNANCY

= pain free, renal function preserved (unless both obstructed), Older age, occurs late, aniline dyes exposure, drug exposure

STONES

= May be obstructed, Dehydration, Family Hx, PAIN, agonising renal colic

Biochemical presentation:

- Hyperkalaemia

- Metabolic acidosis

- Waste product accumulation

- High levels of renally excreted drugs

Brain - Strokes, lacunar infarcts

Eyes - Hypertensive retinopathy

Heart - Left ventricular hypertrophy, ECG/ECHO!

Kidneys - Haematuria and proteinuria -Urinalysis

EPO increases in AKI, not chronic kidney disease

Urea and creatinine - High in both

Potassium - High in both (academia)

pH - Low (academia) for both

Calcium - Low in chronic, not enough time to breakdown bone - precipitates in tissues - acute retention = normal acutely

Phosphate - High in chronic - PTH breaks down bone, phosphate precipitates calcium

PTH - High in chronic

Alk Phos - High in Chronic (bone turnover)

Bone Radiology - Loss in chronic

Hb - Low in chronic (loss of EPO)

Renal Size reduced in chronic (except PKD)

Immunology:

Immunoglobulins - monoclonal bands/myeloma

Bence Jones Protein - myeloma

Electrophoresis - free light chains/myeloma

ANA/DNA binding - SLE

Anti-GBM - goodpastures

ANCA - wegners/GPA

Cryoglobulins - precipitate on cold

Anti-streptolysin O antigen (ASOT)

Adults - renal cell carcinoma

Children - Wilm's Tumour (nephroblastoma)

- Usually small (<5mm)

- No clinical significance - papillary adenoma

HOWEVER:

Angio-myo-lipoma, Onco-cytoma

>5mm, clinically significant, mimics malignant

tumour on imaging

Oncocytoma = mahogany brown, central scar, nests of benign cells, round nuclei and eosinophilic cytoplasm

Angiomyolipoma = blood vessels, smooth muscle and fat - yellow fat - reddish vessels

FAT visible on radiology

RCC - 85% of adult malignant renal tumours

- 65% are >65 years

M>F

Smoking doubles the risk, VHL increases risk, end stage renal disease increases risk

clear cell often chrom 3 abnormalities (VHL 3p)

- CLEAR CELL is the commonest

- Epithelial cells of renal tubules, can be benign to v. agrressive, Often single mets - often lung

- Local Growth = renal capsule

- Vascular = renal vein and IVC

lymphatic = Para-aortic LN

PRESENTATION:

- May present with systemic symptoms, mets often to lungs and bones

TRIAD:

1.Haematuria 2.Loin pain 3.Mass (10% cases)

Commonest = haematuria

Paraneoplastic:

-Polycythemia

-Fever

SURVIVAL:

Age, Size (<7cm=>90% 5yrs, >7cm=<50% 5yrs)

Stage (10-30% 5 Yr survival w/ mets), grade

worse = collecting duct > clear cell > papillary

TREATMENT:

- Surgical - Nephrectomy +/- adrenal

- Partial nephrectomy and laproscopic

(nephron sparing)

- Tyrosine kinase inhibitor SUTITINIB

(resistance develops)

- High freq USS experimental treatment

Children <5 years, rarely older

(rare but commonest blastoma)

Presentation = Abdominal mass

Spread = direct, lymphatic, venous

Prognosis = >90% w/ aggressive chemo/radio

Appearance:

- large rounded mass, undifferentiated cells

- Blastoma recapitulates developing foetal cells

(tubules, glomeruli, stroma, deletion 11p)

Similar to transitional carcinoma of bladder

- urothelium (transitional epithelium) renal pelvis

- Difficulat to diagnose - hard to Bx, radiological

- Fills renal pelvis

Commonly intra-renal

- renal calyces or renal pelvis

Urinary bladder

CALCIUM (oxalate +/- phosphate) = 70%

TRIPPLE stones (magnesium, ammonium, phosphate) = 15%

Uric acid = 5-10%

Causes:

- Hypercalcaemia

- Dehydration

- Nidus of infection

- Obstruction - urinary stasis / infection

EFFECTS/PRESENTATION:

- PAIN!! urinary colic

- Haematuria (damage)

- Obstruction

HYDRONEPHROSIS

- Chronic infection

PYELONEPHRITIS

(STONES, STASIS, INFECTION contribute to one another)

Dilation of ureater (hydroureter)

Dilation renal pelvis+collecting (hydronephrosis)

CHRONIC OBSTRUCTION

Causes:

- PUJ obstruction

- Ureteric reflux (bladder valve abnormality)

- Tumours of lower tract

- Stones

- Prostatic enlargement / ureter compression

SECONDARY EFFECTS:

- Loss of renal parenchyma = chronic renal fail

- Urinary stasis=stones, infection, pyonephritis (frank pus), pyelonephritis (inflammation of renal parenchyma)

= Inflammation usually BACTERIAL affecting tubules, interstitium and pelvis

(glomerulonephritis= intrinsic of glomeruli)

ASCENDING - usually from UTI

- may be haematogenous spread

CAUSES:

- PREDISPOSED TO UTI

(diabetes, immunosuppressed, female)

- anatomical abnormality of tract

congenital ureteric or bladder abnormality

chronic obstruction due to stones/fibrosis

Simple = common, rarely symptomatic, thin walled cortical epithelial cyst filled with urine

-

PKD - Adult - Dominant

APKD1 - chrom 16

haematuria, hypertension, renal failure, bilateral massive kidneys.

Cysts in other organs - liver and pancreas

(ALSO Berry aneurysm - 30%)

5-10% of all end stage renal disease

-

PKD - Children - recessive

cysts and fibrosis in liver as well

Uncomplicated - E.coli in 80%

(rest-proteus, enterobacteriaceace, strep, chlamydia, adenovirus, ureaplasma, fungi)

Complicated - E.coli in 50%

(Klebsiella, Enterobacteriaceae, Pseudomonas)

HOST DEFENCES:

- Urine - osmolality, urea, organic acids, low pH, uromucoid = altered host defences

- Tamm-Horsfall Protein - mannose binding

- Mechanical - flushing, ureteric peristalsis, VUJ

- Prostatic fluid

HOST FACTORS:

- Age (increases with age)

- Gender (females at greater risk)

- Preganacy - 1-3%, dilated ureters, poor peristalsis, lower bladder tone, ureteric obstruction

- Obstruction - prostate, tumour

- Mechanical - sex, catheter, spermicides

- Genetic - blood group, immune response

- Neurological disease (MS, DM, Neuropathy)

- Reflux

- Stones

Sx:

- Dysuria, urgency, frequency

(50% of women have no bacteruria)

Culture negative-

30% = Chlamydia, candida

30% = low grade bacteruria

20% recurrant (post menopause, coital practice, genetic)

Acute pyelonephritis:

= Fever, loin pain, Rigors, Dysuria, Renal tender, 15-30% BACTERAEMIC = BLOOD CULTURES

Pregancy:

- Affect the outcomes of pregnancy

- asymptomatic bacteriuria in 5%

- 20-40% risk of pyelonephritis

UTIs in Men

- uncommon younger than 50 years

UTIs Children:

- Non-specific Sx

- Associated with reflux in 50% of children <5

CHRONIC Pyelonephritis

Chronic interstitial nephritis

- scarring from recurrent infection

Papillary Necrosis

- especially DM, sickle, obstruction, analgesic nephropathy

Abscesses:

uncommon - risk factor = DM / stones

- intrarenal / perinephritic

BACTERAEMIA - 30% mortality

- common cause of community bacteraemia

(gram -ve sepsis worsens the outcome)

Colonisation

- asymptomatic catheter-associated bactinuria should not be treated

- Risk about 5% per day

- 20% of catheterised patients develop bacteriuria, 6% develop symptoms of UTI

- Treat + remove catheter, + Gentamicin IM/IV

Urinalysis:

Leucocyte esterase:

- sterile pyuria: Treated UTI, fastidious organism, TB, foreign body, tumour

Nitrites:

- A bacterial metabolite

- Low sensitivity / high specificity

- FALSE NEG = Vit C, S.G.

Leukocytes + Nitrates both negative = 92% NPV

Urine culture:

- Pregnant women (first antenatal screen), after Rx screen monthly, treat on symptoms

- Elderly people with significant signs

- Recurrent cystitis

- Treatment failure

CULTURE IF SIGNS OF UTI AND....:

- immuncompromise (DM, drugs, HIV)

- indwelling catheter

- abnormal GI tract

Hydration - IV fluids if vomiting

Acidify urine (potassium citrate in cystitis)

Analgesia

Frequent voiding (forcefully)

Avoidance of risk factors

Antibiotics:

NITROFURANTOIN - 1st line

(also trimethoprim, cephalexin)

Co-Amox or Ceftriaxone - 2nd line

Uncomplicated - 3 days as good as 7

Complicated - imaging, 10-14 days, +/- IV Abx,

PREGNANCY:

- avoid Tetracycline, Ciprofloxacin

Urethral syndrome - no signif bacteriuria

Interstitial cystitis

Atrophic vaginitis / urethritis (lack of oestrogen)

Urethritis, vaginitis, cervicitis = chlamydia, gonorrhoea, herpes, other sexually transmitted

Drug-induced cystitis - allopurinol, NSAIDs

Pinworms / threadworms

- Renal pelvis to the urethra

- tough, protective layer from osmosis and pH

METAPLASIA - squamous metaplasia in repeated trauma, infection or inflammation (common but tumour as a result uncommon)

Carinoma of urinary tract common in bladder

>90% urothelial cancer

8% squamous cell carcinoma

1-2% adenocarcinoma

Age:

50-80 (rare<40)

M>F 3:1

Carinoma of urinary tract common in bladder>90% urothelial cancer

8% squamous cell carcinoma

1-2% adenocarcinoma

Age:50-80 (rare<40) M>F 3:1

RISKS:

- Aniline dye worker (rubber, plastic, benzidine)

- SMOKING (arylamines) biggest risk - @ 20yrs

- analgesic abuse (phenacentin - paracetamol)

- Cyclophosphamide (immunosuppressive)

- Chronic infection

(schistosomiasis = squamous cell carcinoma)

- Congenital defects (treated = increased risk)

Presentation:

- HAEMATURIA (20% with gross haematuria, 10% with microhaem have bladder Cancer)

- Dysuria

- LUTS (lower urinary tract symptoms)

- Pelvic pain (advanced disease)

Diagnosis:

- Urine cytology - picks up high grade, low grade doesn't shed as easily

- Cystoscopy + Bx

- Imaging - Uss, CT

UROTHELIAL CARCINOMA STAGING

-non-muscle invasive v.s. muscle invasive

- can be in situ

- papillary - exophytic into lumen

- Invasice through lamina propria or beyond muscle wall

-Grade 1-3 (WHO 2004 high/low/PNLMP)

- Low grade don't invade/progress but recur

- High grade often progress, invade - risk mets

PROGNOSIS:

well differentiated, non invasive = benign

poorly differentiated, solid, muscle invasion - poor prognosis

- Tend to be poor prognosis (far worse than urothelial)

- Often from metaplastic squamous epithelium

(Diverticula, stones SCHISTOSOMAL infection)

Uncommon:

Primary or CONSIDER SECONDARY - prostate or rectum

Risk:

- Urachal remnants (embryological), glandular metaplasia, bladder extrophy

INNER ZONE:

Glandular, muscular and fiberous

- Affects 75% men 70-80 years

- Complex hormonal dependance

- Outflow obstruction - LUTS

-

LUTS:

- Trouble starting (hesitancy)

- Decreased Flow

- Trouble stopping (terminal dribbling)

- Instability (nocturia, frequency)

-

COMPLICATIONS:

- Trabeculation

- Diverticula

- Acute retention

- Infection (due to stasis + ^ volume)

- Bladder and kidney stones

- Hydroureter +/- Hydronephrosis

- Renal impairment

1:9 lifetime risk, commonest UK male cancer

Most die with not from, 1/3 men >75yrs

1% cases in men <50yrs (BRCA2)

RISK:

-AGE!

- Heredity - BRCA2, commoner in afro-carribean

- ?hormones - castration protective

- ?diet - calcium + high animal fat bad; selenium and vit E protective

- IGF01, incidence lower in diabetes

PRESENTATION:

- often asymptomatic - PSA/DRE

when large = LUTS, haematuria

when advanced = Bone pain

DIAGNOSIS:

- DRE

- PSA

- Transrectal USS

- Needle Bx

- TURP - transuretheral resection of prostate

- MRI

GLEASON'S Grade= 5 patterns, architecture and degree of differentiation. Higher=worse

- Precursor lesion = DYSPLASIA

- Cell and nuclear pleomorphism

- loss of ordered maturation

- Mitotic activity

-HASN'T INVADED BEYOND BASAL CELL LAYER

GLEASON'S Grade= 5 patterns, architecture and degree of differentiation. Higher=worse

TNM stage

Localised - T1/T2 - remains in prostate

Local advanced - T3/T4 - beyond capsule

Metastatic - lymphatic spread to LNs

Distant Mets - Lytic lesions of bone

TREATMENT;

- age/stage dependant

- Active surveillance (repeated Bx)

- Watchful waiting

- Surgery (radical prostectomy)

- Irradiation (external/brachytherapy)

- Hormonal manipulation, androgen blockade

- Crytherapy