Kidney and urinary tract pathology Flashcards
What is pathogenisis
What is the mechanism causing the disease
What is aetiology
What causes the disease
What is epidemiology
Who gets the disease
What is renal cell carcinoma
Cancer of the kidney that arises from the renal tubular epithelium
What are the most common types of renal cell carcinoma
Clear cell (75%) Papillary (10%)
What is the epidemiology of renal cell carcinoma
60yo+ Male > female Family history PMH of: -Obesity -Smoking -NSAID use -ESRF and on dialysis
What are paraneoplastic syndromes
Signs and symptoms that are not related to local effects of the primary or metastatic tumours
Develop as a result of either:
-proteins/ hormones secreted by tumour cells
-immune cross reactivity between tumour cells and normal tissues
What are the clinical features of renal cell carcinoma
Local primary tumour effects:
- Haematuria
- Abdominal pain
Effects of distant metastases:
- Lung mets-> SOB etc
- Bone mets -> bone pain etc
Paraneoplastic syndromes:
- PNS are common in RCC and include:
- weight loss (cancer cachexia)
- Hypertension (renin)
- Polycythemia (EPO)
What is Wilms’ tumour and who gets it
Nephroblastoma
Cancer of the kidney that arises from the nephroblasts (cells that develop into the kidney in embryological development)
Children under 5
What are the clinical features of Wilm’s tumour
Abdominal distention
Haematuria
Mets are rare
PNS are rare
What is urolithiasis
Urinary tract calculi/ stones
Stones forming in the lumen of the urinary tract, anywhere from renal calyx to bladder
What are the types of urolithiasis
Calcium stones (70%) Urate stones (5%) Cystine stones (1%) Struvite stones (15%) (magnesium ammonium phosphate)
What causes each type of urolithiasis
Too high a concentration of a solute in the urine
Calcium: hypercalcemia
Urate: gout, malignancy (high cell turnover)
Cystine: congenital cystinuria (kidneys unable to reabsorb amino acids)
Struvite: urinary tract infection
What are the clinical features of urolithiasis
Pain: -Ureter: loin to groin -Bladder: lower abdominal -Urethra: dysuria Haematuria (blood in urine) Symptoms of complications Obstruction leads to renal impairment Urinary stasis leads to infection Local trauma leads to squamous metaphase and then SCC risk
What is dysuria
Painful urination
What is vesicoureteral reflux (VUR)
When urine flows backwards from the bladder to the ureter rather than from the bladder to the urethra
What is the epidemiology of VUR
Young people especially <2yo
Those with family history of VUR
What is the aetiology of VUR
Congenital abnormality of vesicoureteric junction
Shorter intramural ureter
What is the pathogenesis of VUR
Ureter enters bladder at abnormal angle -> dysfunction of vesicoureteric junction -> when voiding, urine flows the wrong way
What are the clinical features of VUR
Usually asymptomatic
Only symptoms of complications
Stasis: UTI
Back pressure and ascending infection - renal damage
What are the clinical features of urothelial carcinoma
Haematuria Frequency, urgency, dysuria, urinary obstruction Lung mets - SOB Bone mets - bone pain Liver mets - jaundice PNS are rare
What is urothelial carcinoma
Transitional cell carcinoma
Cancer of urothelial epithelium
Accounts for >90% of bladder cancer
What is the epidemiology of urothelial carcinoma
Adults aged >60yo M>F Smokers Exposure to certain industrial chemicals Family history Treatment for other Cancer (pelvic radiotherapy, cyclophosphamide)
What is a neurogenic bladder
Inability to properly empty the bladder due to neurological damage
Two types:
-Spastic if damage to brain or spinal cord (UMN)
Flaccid if damage to peripheral nerves (LMN)
What causes neurogenic bladder
UMN damage:
- stroke
- MS
- Spinal injury
LMN damage:
- Pregnancy
- Diabetes
- Alcohol
- B12 deficiency
What are the clinical features of neurogenic bladder
Symptoms of lack of control of bladder emptying:
- Urinary retention
- Abdominal distention
- Incontinence
- Urge
- Frequency
Symptoms related to complications:
-Stasis -> UTI -> dysuria
-Stasis -> urinary stones -> haematuria
Inability to empty bladder -> bladder distention -> hydroureter -> hyronephrosis -> renal function impairment -> oedema
What is benign prostatic hyperplasia
Increased number of both stroll and glandular cells in the prostate
Know by patients as an enlarged prostate
What is the epidemiology of benign prostatic hyperplasia
Old men
Obesity
Diabetes
Family history
What are the clinical features of benign prostatic hyperplasia
Lower urinary tract symptoms:
- Hesitancy or urgency
- Poor/ intermittent stream
- straining
- prolonged micturition (peeing)
- Incomplete bladder emptying
- Dribbling
- Frequency
- Incontinence
- Nocturia (waking in night to pee)
What is prostatic adenocarcinoma
Cancer of the glandular epithelium in the prostate
What is the epidemiology of prostatic adenocarcinoma
Old men
Black men
Family history (inc BRCA1 /2)
Pesticide exposure
What are the clinical features of prostatic adenocarcinoma
Lower urinary tract symptoms
Bone mets -> bone pain
PNS are rare
What is cryptochidism
Undescended testis where the testis is not in the scrotum
Types based on site of testis
Who gets cryptorchidism
Premature babies
What are the clinical features of cryptorchidism
Empty scrotum May resolve spontaneously or may develop complications: -infertility -hernias -testicular cancer risk -testicular torsion
What is seminoma
Malignant neoplasm of the testis arising from the germ cells in seminiferous tubules
Most common type of testicular cancer
Which forms of primary testicular tumour have a bad prognosis and so need more aggressive treatment
Teratoma Choriocarcinoma Yolk sac Embryonal Lymphoma
Which forms of primary testicular tumour have a good prognosis and so need less aggressive treatment
Classic seminoma
Spermatocytic seminoma
Leydig cell tumour (usually benign)
Sertoli cell tumour (usually benign)
What is the epidemiology of seminoma
Young men 25 - 45 yo
family history
Crytorchidism regardless of whether it was surgically corrected or only affected the other testis
What are the clinical features of seminoma
Testicular lump, swelling, pain
Lung mets - SOB
LN mets - back pain
Gynecomastia (BHCG)
What are the complications of Urinary tract obstruction
Irreversible renal impairment and secondary VUR due to back pressures
Infection and calculi formation due to urinary stasis
What are the renal functions
Eliminate metabolic waste products
Regulate fluid/electrolyte balance
Regulate acid-base balance
Produce hormones
What hormones are produced by the kidneys and what do they do
Renin: fluid balance (RAAS)
Erythropoietin: stimulates erythrocyte production
How does acute renal failure present
Unwell
Rapid rise in creatinine and urea
How does nephrotic syndrome present
Always due to damage to glomerulus Oedema Proteinuria Hypoalbuminaemia \+/- hypertension \+/- hyperlipidaemia
How does acute nephritis (nephritic syndrome) present
Oedema Proteinuria Haematuria Hypertension Renal failure
How does chronic renal failure present
Slow decline in renal function
How is renal pathology diagnosed
Renal physician: clinical history, examination
Biochemist: Blood tests (urea, creatinine), Urine analysis (Protein, blood, electrolytes)
Pathologist: Renal biopsy (Light microscopy, immunofluorescence, electron microscopy)
Urologist: Cytoscopy (obstruction, haematuria)
Radiologist: Radiology (obstruction, kidney size, structural abnormalities)
What is the blood flow of renal system
Branches of renal artery Afferent arteriole Glomerulus (capillary bed- network of capillaries) Efferent arteriole Branches of renal vein
What is thrombotic microangiopathy
Thrombi in capillaries/arterioles
Endothelial damage by bacterial toxins, drugs, complement or clotting system abnormalities
What is vasculitis
Acute/chronic vessel wall inflammation with lumen obliteration
Various types affect different calibre vessels
What causes vascular damage
Hypertension Diabetes Atheroma Thrombotic microangiopathy Vasculitis
What are the complications of nephrotic syndrome
Infection
Thrombosis
What are the common causes of nephrotic syndrome
Adults:
- Membranous nephropathy
- Focal segmental glomerulosclerosis (FSGS)
- Minimal change disease
- Diabetes
- Lupus nephritis
- Amyloid
Children:
- Minimal change disease (commonest)
- Focal segmental glomerulosclerosis
- Other causes are rare
What are the various possible causes of FSGS
Idiopathic or genetic
Heroin use
HIV
Male more than female
What are the causes of acute nephritis
Adults:
- Post infective glomerulonephritis
- IgA nephropathy
- Vasculitis
- SLE
Children:
- Post infective glomerulonephritis
- IgA nephropathy
- Henoch-Schönlein purpura (specific IgA nephropathy)
- Haemolytic-uraemic syndrome
How does acute renal failure present
Anuria/oliguria (<400ml/24h) Raised creatinine and urea Malaise Fatigue Nausea Vomiting Arrhythmias
What are the causes of acute renal failure
Pre-renal: reduced blood flow to kidney (severe dehydration, hypotension (bleed, septic shock, LVF)) (renal biopsy unhelpful)
Renal: damage to kidney (renal biopsy can be helpful)
Post-renal: urinary tract obstruction (urinary tract tumours, pelvic tumour, calculi, prostatic enlargement) (renal biopsy unhelpful)
What are the adult causes of acute renal failure
Vasculitis
Acute interstitial nephritis/ tubulointerstitial nephritis (tubular damage with inflammation usually due to drugs)
What are the children causes of acute renal failure
PIGN
Henoch-Schönlein Purpura
Haemolytic uraemia syndrome
Acute interstitial nephritis
What are potential complications of acute renal failure
Cardiac failure (fluid overload) Arrhythmias (electrolyte imbalance) GI bleeding (multifactorial) Jaundice (hepatic venous congestion) Infection (especially lung and urinary tract)
What is chronic renal failure
Permanently reduced GFR
Reduced number of functional nephrons
What are the stages of chronic renal failure
Stage 1: Normal/increased GFR (>90ml/min/1.73m2)
Stage 2: Mild GFR reduction (60-89ml/min/1.73m2)
Stage 3: Moderate GFR reduction (30-59ml/min/1.73m2)
Stage 4: severe GFR reduction (15-29ml/min/1.73m2)
Stage 5: Kidney failure (GFR <15ml/min/1.73m2 or dialysis)
What chronic conditions cause chronic renal failure
Adults:
-Dibetes
Children:
-Developmental abnormalities/ malformations
Both:
- Glomerulonephritis
- Reflux nephropathy (repeated infections/scarring)
What is isolated proteinuria and what causes it
No allied haematuria, renal failure or oedema May be benign May be due to renal disease: Adult: FSGS, DM, SLE Children: FSGS, HSP
What causes isolated haematuria
IgA nephropathy
Thin basement membrane disease
Alport hereditary nephropathy
What are the mechanisms of damage to kidneys due to hyperglycaemia in diabetics
Damaged basement membrane thickens and glomerulus produces excess extracellular matrix (nodules)
Small vessel damage causes ischaemia and tubular damage
What is a myeloma
Plasma cell tumour
Excess Ig deposit in tubules cause inflammation and fibrosis
Renal tubule loss causes irreversible decline in renal function
What is a UTI
An infection of any part of the urinary system
What is an infection
The invasion of body tissues by a pathogenic organism which causes an immune response, giving rise to symptoms
What causes a UTI
Usually an endogenous bacteria which has got in the wrong place and invaded
Who are at higher risk of UTIs
Female Pregnant Patients with: -Prostatic hypertrophy -Stones -Strictures -Neoplasia -Residual urine Urological instrumentation (including catheters) Sexual intercourse Fistulae: Recto-vesical, vesico-vaginal Congenital abnormalities: vesico- ureteric reflux
Which areas of the Urinary tract have bacteria and which are sterile
Sterile: kidney, ureter and usually the bladder (sometimes not though)
Colonised: urethra (perineal flora)
What makes up perineal flora
Skin flora: mainly coagulase negative staphylococci
Lower GI tract flora:
-internal colonising bacteria found on skin around relevant orifice
-Anaerobic bacteria
-Aerobic bacteria
–Enterobacterales (coliforms, enteric gram negative bacilli)
–Gram positive cocci
—Enterococcus spp
What is asymptomatic bacteriuria
No symptoms of a urinary tract infection but cultured urine sample grows a single organism in significant numbers
What are the symptoms of cystitis (lower UTI) and who is most likely to contract it
Dysuria Frequency Urgency Supra-pubic pain or tenderness Polyuria, nocturne, haematuria More common in women
What are the symptoms of an infection of the kidney or renal pelvis
Dysuria Frequency Urgency Supra-pubic pain or tenderness Polyuria, nocturne, haematuria More common in women Loin/abdominal pain or tenderness Fever Signs of systemic infection: -rigors, nausea, vomiting diarrhoea -Elevated CRP, WBC
What is a complicated UTI
Underlying abnormality to structure or function Urinary stasis Presence of foreign body: -catheter/other device/renal calculi -biofilm -Children <10-12 -Men <65
What is Urosepsis
Systemic signs of infection related to any underlying urinary source of infection
What are other causes of urethritis
STIs (gonorrhoea)
Thrush can cause irritation and symptoms such as dysuria
Urethral syndrome
What is urethral syndrome
Symptoms of Lower UTI without infection
What are the types of Urinary tract abscesses
Perinephric
Intra-renal
What is prostatitis
Inflammation of prostate
How does acute bacterial prostatitis present
Lower urinary tract symptoms
Fever
Tender tense prostate on PR palpation
Acute retention
What are the risk factors for acute bacterial prostatitis
Procedures involving the prostate:
-Trans-urethral resection of prostate (TURP)
-Trans-rectal ultra-sound guided (TRUS biopsy)
Indwelling urinary catheter
Which pathogens usually cause acute bacterial prostatitis
Typically normal urinary pathogens (E.coli)
Can be caused by S. aureus
How does chronic prostatitis present
Pain inland around the perineum and genitalia
Lower urinary tract symptoms
Enlarged or tender prostate on examination
What causes chronic prostatitis and how are the causes distinguished
> 90% due to chronic pelvic pain syndrome:
- Negative urinary culture
- Non-bacterial
Chronic bacterial prostatitis:
- Recurrent UTIs with the same organism
- Asymptomatic in-between
What are the points of clinical tests
To confirm clinical suspicion
To find out the pathogen and how best to treat it
Monitor response
What is imaging used for in UTIs
Is the Urinary tract anatomically normal?
Are there stones?
Is there an abscess
What are the microbiological investigations available for UTIs
Dipsticks/Ward tests? Urinalysis
Laboratory testing of urine samples
What do the ideal renal function tests do
Detect renal damage
Monitor functional damage
Distinguish between impairment and failure
How is it known when the kidney functioning system is broken
No urine output
Clinical symptoms
Tests
What is the flow for kidney function
Input arterial-> filter -> processor -> output venous/ output urine
What are the lab tests for renal function
Glomerular filtration rate eGFR creatinine clearance plasma creatinine plasma urea urine volume urine urea urine sodium urine protein urine glucose haematuria
What is Oliguria
Abnormally low urine volume
24 hour volume less than 400ml
When is a patient considered anuric
No or little urine, less than 100ml/24hr
When does a patient have polyuria
Urine volume greater than 3 litres per day and not drinking.
Which factors influence plasma urea conc
GIT protein Liver amino acids Tissue protein Distribution volume Kidney reabsorption excretion Kidney filtration
What does urea excretion show
60% of urea is usually excreted with the rest being absorbed passively by the renal tubules
Rate of reabsorption depends on rate of tubular flow
More urea is reabsorbed if the flow rate is slow as there is more time for urea to diffuse into the peritubular capillaries
Tubular flow rate is slow when there is renal hypoperfusion
What causes increased plasma urea
GI bleed Trauma Renal hypoperfusion Decreased RBF Decreased ECFV Acute renal impairment Chronic renal disease Post-renal obstruction calculus tumour
What is the normal range of plasma creatinine and when should it be measured
50-140 umol/l
8 hours after a meal as evidence of increased conc after meat ingestion
What does an increase in plasma creatinine mean
GFR decreased a large amount
In chronic renal disease it may increase to as high as 1000umol/l
How do physicians predict when a patient will require dialysis or transplantation
Plot the reciprocal of the plasma creatinine conc which is linear and then extrapolate
When is Glomerular filtration rate measured
No often as requires patient to come to hospital
People considering donating a kidney whilst alive
Before administering a potentially toxic drug before chemo
How is GFR measured
Used to be by calculating the clearance of insulin but now radioactive substances are used
How is creatinine clearance measured
(Urine creatinine conc m/mol/l x urine volume)/ plasma creatinine conc umol/l
