Lecture 9.1: Glomerular Pathology and Malignancies of the Urinary Tract Flashcards
What is Glomerulonephritis (GN)?
It is a renal disease characterised by inflammation and damage to the glomeruli
What is the effect of Glomerulonephritis?
This glomerular damage allows protein (with or without blood) to leak into the urine (proteinuria and haematuria respectively)
What can Glomerulonephritis present with? (5)
- Isolated Haematuria or Proteinuria
- Nephrotic Syndrome
- Nephritic Syndrome
- Acute Renal Failure
- Chronic Renal Failure (CKD)
What 2 categories can Glomerulonephritis (GN) can be broadly put into?
- Proliferative Disease
- Non-Proliferative Disease
Pathophysiology of GN
Increased permeability of the glomerulus leading to loss of proteins into the tubules
What does characteristics does Nephrotic Syndrome include (in terms of protein and albumin)?
- Loss of significant volumes of protein via
the kidneys (proteinuria) which results in
hypoalbuminaemia - The definition of nephrotic syndrome
includes both massive proteinuria (≥3.5
g/day) and hypoalbuminaemia (serum
albumin ≤30 g/L)
What are the other associated symptoms as a result of hypoalbuminaemia?
- Oedema (due to reduced oncotic pressure)
- Hyperlipidaemia
- Hypercoagulability
Clinical Symptoms of Nephrotic Syndrome (10)
- Peripheral Oedema (more common in adults)
- Facial Oedema (more common in children)
- Frothiness of Urine
- Fatigue
- Poor Appetite
- Recurrent Infections (due to immune dysfunction)
- Venous or Arterial Thrombosis (e.g. myocardial
infarction, deep vein thrombosis) due to
hypercoagulability - Oliguria
- Hypertension
Clinical Signs of Nephrotic Syndrome (4)
- Oedema (e.g. peri-orbital, lower limb,
ascites) - Xanthelasma and/or xanthoma
- Leukonychia
- Shortness of breath (with associated chest
signs of pleural effusion) - Uraemia (toxins in urine)
What are typical findings on Urinalysis in the context of Nephrotic Syndrome? (2)
- Proteinuria (protein ++++)
- Frothy appearance of urine
Pathophysiology of Nephrotic Syndrome
Thin glomerular basement membrane with pores that allow protein and blood into the tubule
What are some Red Flags of Malignancy in the Urinary Tract? (10)
- Abdominal Pain
- Fatigue
- Lower Back Pain
- Appetite or Weight Loss
- Iron Deficiency
- Haematuria
- Erectile Dysfunction
- Change in Bladder Habit
- Poor Stream
- Bone Pain
Renal Parenchymal Tumours (2)
- Renal Adenocarcinoma
- Nephroblastoma Tumour of Childhood
Known as Wilms’ tumour - Metastases
Renal Adenocarcinoma (RCC)
Most commonly clear cell cancer, incidental
findings
Risk Factors for RCC
- Smoking
- Obesity
Classic Triad of RCC
- Haematuria (may produce iron deficient
anaemia) - Loin Pain
- Palpable Flank Mass
What are Paraneoplastic Syndromes?
- Paraneoplastic syndromes are a group of
rare disorders that are triggered by an
abnormal immune system response to a
cancerous tumour known as a “neoplasm” - They are thought to happen when cancer-
fighting antibodies or WBCs (T-cells)
mistakenly attack normal cells in the
nervous system
What is Metastatic Disease/Metastasis?
- It is when cancer cells break away from
where they first formed (primary cancer) - Travel through the blood or lymph system
- Form new tumours (metastatic tumours)
in other parts of the body
How often does Paraneoplastic Syndromes occur in RCC?
<20%
How often does Metastasis occur in RCC?
15-20%
How common is RCC?
- 8th most common cancer in UK
- 95% of all upper urinary tract tumours
What is Von Hippel-Lindau Syndrome?
It is an inherited disorder characterised by the abnormal growth of both benign and cancerous tumours and cysts in many parts of the body
Risk Factors for developing RCC
- Smoking (2x↑)
- Obesity
- Dialysis
- Von Hippel-Lindau Syndrome
- Familial Inheritance
Mortality of RCC
- 8 in every 10 people live at least a year after
diagnosis - 5 in 10 live at least 10 years
What is Nephritic Syndrome?
- Nephritic syndrome is a condition
involving haematuria, mild to moderate
proteinuria (typically less than 3.5g/L/day),
hypertension, oliguria and red cell casts in
the urine - The patient usually has a more prominent
creatinine elevation and hypertension as
well which helps differentiate it from
Nephrotic Syndrome
What is Iatrogenic Cushing’s Syndrome?
It is usually related to prolonged and/or high-dose oral or parenteral steroid use
Iatrogenic Cushing’s Syndrome Signs and Symptoms (4)
- Moon-Face
- Odema
- Purple Stretch Marks
- Hair Thinning
- Hypokalaemia
- Hypernatraemia in blood (as cortisol can
mimic effects of aldosterone) - Initial weight-loss
- Then central weight gain
What is Intravesical BCG?
Chemotherapy injected directly into bladder
Why are people with Nephrotic Syndrome given corticosteroid?
In most children with nephrotic syndrome, this protein leak resolves with corticosteroid drugs (prednisone, prednisolone) reducing the risk of serious infection
What corticosteroids are prescribed for Nephrotic Syndrome?
- Prednisone
- Prednisolone
What is the difference between Prednisone and Prednisolone?
Prednisone must be converted by liver enzymes to Prednisolone before it can work
Paraneoplastic Syndromes (5)
1) Polycythaemia: due to secretion of erythropoietin
2) Hypercalcaemia: due to secretion of PTH-related
peptide
3) Hypertension: due to secretion of renin
4) Neuromyopathy
5) Feminising or masculinising syndromes
How is Diagnosis of RCC done? (5)
- Ultrasound
- CT scan
- MRI
- Cystoscopy
- Biopsy
Treatment of RCC
- Radiation Therapy
- Radical Nephrectomy
- Partial Nephrectomy
- Radio Frequency Ablation or Cryotherapy
- Embolisation
What is Embolisation?
Embolisation is a procedure to block the blood supply to the tumour, causing it to shrink
What is a Nephroblastoma/Wilms’ Tumour? What is it caused by?
- A rare kidney cancer that primarily affects
children - Caused by a Chromosome 11 abnormality
- 80% Present before 5 years of age
- Rarely seen after 10 years of age
What Symptoms does Nephroblastoma/ Wilms’ Tumour present with? (7)
- Large Abdominal Mass
- Abdominal Pain
- Anaemia
- Incidental Finding
- Hypertension
- Haematuria
- Weight Loss
Investigations for Nephroblastoma/Wilms’ Tumour (4)
- CT Scan
- Ultrasound
- MRI
- Kidney Biopsy
What is the Treatment for Nephroblastoma/ Wilms’ Tumour?
- Nephrectomy
- Chemotherapy
What is the Prognosis of Nephroblastoma/ Wilms’ Tumour?
- 80% Cured
What is another name for Ureteric (Urothelial) Cancer?
Transitional Cell Carcinoma (TCC)
Where does Urothelial Carcinoma arise from?
- Arise from the renal pelvis and resemble
bladder cancer cells - Urothelium
What is the Prevalence of Ureteric (Urothelial) Carcinoma?
- Only <5% of all malignancies of upper
urinary tract
What are Risk Factors for Ureteric (Urothelial) Carcinoma? (5)
- Smoking
- Phenacetin Abuse
- Being exposed to certain Dyes
- Chemicals used in making leather goods,
textiles, plastics, and rubber - Hereditary non-polyposis colorectal cancer
What Investigations are done for the Diagnosis of Ureteric (Urothelial) Carcinoma? (6)
- Ultrasound
- CT Urogram
- Retrograde pyelogram
- Ureteroscopy
- Biopsy
- Washings for cytology lkan’s nephropathy
What Key Factor about Haematuria makes it a Red Flag for Malignancy?
Painless haematuria must be treated as urinary tract malignancy until proven otherwise
What is the percentage of recurrence of bladder cancer?
50-75%
Low Grade Bladder Cancer (T1): How often do they recur? How many progress to invasive tumours? Percentage mortality? Treatment?
- Unlikely to spread further
- 70% recur
- 10-20% progress to more invasive
tumours - Mortality 1-15%
- Rx: TURBT + Intravesical cytotoxics (MMC –
60% effective,for high Grade BCG)
Moderately Invasive Bladder Cancer (T2-T3): Spread? Treatment?
- Spread to muscle layers
- Risk of cancer spreading further to rest of
body - Rx= Radical cystectomy +/- radiotherapy,
post op chemo or neo-adjuvant chemo
High Grade Invasive Bladder Cancer (T4): Spread? Treatment?
- Spread beyond bladder
- Mets – pelvic structures, local LN, liver and
lungs - Rx: Palliative chemo/radiotherapy
- Aim is pain relief and controlling
symptoms
Prevalence of Prostate Cancer? What type of cancer is it?
- It is the most common type of cancer in
men - Prostate cancer is the second most
common cause of cancer death in males in
the UK (after lung cancer), accounting for
13% of all cancer deaths - 95% are adenocarcinomas
What is the PSA Test? Is it good?
- Prostate Specific Antigen Test
- PSA is a protein (serine protease)
produced by normal and cancerous
prostate cells - Not very good as may things can give a
postive PSA Tests e.g. injured prostate,
benign prostatic hyperplasia, prostate
cancer, vigorous exercise, UTI ..etc
What are some Risk Factors for Prostate Cancer? (6)
- > 50
- Black
- Genetics
- Obesity or being overweight
- Migrants moving from low risk to high risk
areas acquire the local incidence rate - Incidence rates higher in more affluent
men
Where do Prostate Cancers most commonly metastasise? (2)
- Bone
- Lungs
What Signs and Symptoms can Prostate Cancer present with? (7)
- LUTS: nocturia, hesitancy, poor stream,
terminal dribbling - Asymptomatic
- Bone Pain
- Anaemia
- Weight Loss
- General Malaise
- Cachexia
What is Gleason Score/Grade?
It is the most common system doctors use to grade prostate cancer
Gleason Grading: Score 6 (Grade Group 1)
- The cells look similar to normal prostate
cells - The cancer is likely to grow very slowly, if
at all
Gleason Grading: Score 7 (or 3 + 4 = 7) (Grade Group 2)
- Most cells still look similar to normal
prostate cells - The cancer is likely to grow slowly
Gleason Grading: Score 7 (or 4 + 3 = 7) (Grade Group 3)
- The cells look less like normal prostate
cells - The cancer is likely to grow at a moderate
rate
Gleason Grading: Score 8 (Grade Group 4)
- Some cells look abnormal
- The cancer might grow quickly or at a
moderate rate
Gleason Grading: Score 9/10 (Grade Group 5)
- The cells look very abnormal
- The cancer is likely to grow quickly
Investigations to diagnose Prostate Cancer (4)
- PSA
- Digital Rectal Examination (DRE)
- MRI
- Biopsy (Transrectal ultrasoundguided
(TRUS)
is being replaced by Trans Perineal (Tp)
Prostate Biopsy)
How are Prostate MRIs Standardised
PI-RADS Scoring (Prostate Imaging-Reporting and Data System)
Complications of Transrectal Ultrasoundguided (TRUS) (4)
- Sepsis
- Acute Urinary Retention
- Haematuria
- Bleeding per rectum and blood on
ejaculation
Prevalence of Testicular Cancer
Commonest cancer in men between 15-35 yrs
Where do 95% of Testicular Cancers arise from?
Germ Cell
What does Testicular Cancer often present with? (8)
- Irregular, firm, fixed, no transillumination
- Dragging sensation
- Testicular/abdominal pain
- Lymphadenopathy
- Gynaecomastia (beta-hCG production)
- Back Pain (mets)
- Hepatomegaly (spread to liver)
- Neurological Disease
Prevalence of Penile Cancer
Very Rare
What does Penile Cancer present with? (2)
- Presents with non tender swelling of the
glans penis - Purulent and/or Bleeding from under the
foreskin
Risk Factors for Penile Cancer (4)
- Phimosis (inability to retract the skin
(foreskin or prepuce) covering the head
(glans) of the penis) - HPV
- Smoking
- Low Immunity
What type of cancers are Penile Cancers usually?
Squamous Cell Carcinomas
