Seminar 11 - Urosepsis Flashcards
The majority of mucinous carcinomas of the ovary are bilateral - true or false
False
Only 5% are
How is pyonephrosis managed
Antibiotics and nephrostomy
OR
retrograde stent drainage
These treatments usually result in the infectious process clearing up over 24-48hrs
What might a low urine output suggest in a septic patient
A low urine output may suggest intravascular volume depletion and/or acute kidney injury and is therefore a marker of sepsis severity.
What are the main locations for metastases from clear cell carcinoma
Lung
Bone
What is the most common route of infection in clinical pyelonephritis
From the lower urinary tract (ascending infection)
How does membranous nephropathy present on IF microscopy
Granular deposits contain both immunoglobulins + complement.
Immuno-stains also show PLA2R glomerular positivity in majority of patients
What is the most common cause of primary glomerulonephritis
Most cases are idiopathic
List the pathological features of endometrioid ovarian carcinoma
They have tubular glands that resemble benign or malignant endometrium - glandular patters that bear a strong resemblance to tumours of an endometrial origin
This is what distinguishes these tumours from serous and mucinous tumours
How does the endothelial injury in ATN lead to disruption of renal blood flow
Endothelial injury causes increased endothelin release (vasoconstrictor) and decreased release of vasodilators like NO
What is the lymph drainage of the kidneys
Lumbar nodes
Around the abdominal aorta and IVC
Which morphological changes occur in the urinary tract due to subtotal or intermittent obstruction
You have progressive dilatation which causes hydronephrosis
Pyelonephritis can be asymptomatic - true or false
True
30-50% pyelonephritis cases may be silent in men
How does anti-GBM antibody mediated GN present in IF microscopy
Linear GBM fluorescence for Ig and complement.
Also seen in Goodpasture’s as same cause
Type 1 primary membranoproliferative GN is most common in which group
Most present in adolescence or as YA with nephrotic syndrome + nephritic component
Which symptoms are seen in pre-renal AKI
Symptoms related to hypovolemia, including thirst, decreased urine output, dizziness, and orthostatic hypotension.
May have mental status change in elderly due to hypovolaemia.
What is Acute Kidney Injury
A syndrome of reduced renal filtration function where the reduction occurs over hours or days
Rapid decline in kidney function
It leads to dysregulation of both fluid and electrolyte balance and a retention of waste product
Glomerular filtration can continue for some time despite the obstruction - true or false
True
This is because the infiltrate can diffuse back into the renal interstitium and perirenal spaces from which it can return back to the lymphatic and venous systems
What controls resorption of Na in the distal convoluted tubules
Aldosterone
What is the definition of urinary tract obstruction
The inhibition of flow of urine due to a blockage in urinary tract
Any level of the urinary tract can be effected to cause an obstruction meaning the blockage can occur anywhere from the urethra to the renal pelvis
Septic shock is associated with a greater risk of mortality than with sepsis alone - true or false
True
What causes hypotension in sepsis
Persistent hypotension is often due to a combination of low systemic vascular resistance, hypovolaemia and reductions in cardiac output from myocardial failure
Describe the microscopic features of acute pyelonephritis
Will see numerous PMNs filing renal tubules which can then form into a cast within the tubule
In early stages, the neutrophilic infiltration is limited to the tubules
The tubular lumens are a conduit for the extension of the infection and the infection can extend to the interstitium and produces abscesses that destroy the involved tubules
Glomeruli are relatively resistant to infection
However, extensive disease and fungal pyelonephritis can eventually destroy the glomeruli
What causes post-renal AKI
Caused by obstruction of the renal and urinary tract, either within the tract or extrinsic pressure.
Within the tracts: stone, renal tract malignancy, stricture, clot
Extrinsic causes: pelvic malignancy, prostatic hypertrophy, retro-peritoneal fibrosis, ureter obstruction
Describe the microscopic appearance of PUNLMP
Singular core of loose fibrovascular tissue covered in thickened urothelium
What causes luteal ovarian cysts
These occur when the corpus luteum has filled with fluid and failed to regress
What are the functions of mesangial cells in the kidney
These cells of mesangial origin are contractile, phagocytic and capable of proliferation, of laying down matrix and collagen, and of secreting several biologically active mediators
Glomerulonephritis can have primary or secondary aetiologies - true or false
True
The larger the ovarian cyst, the more likely it will be symptomatic - true or false
True
In premenopausal women, every effort is made to preserve at least one ovary when cyst removal surgery is carried out - true or false
True
where possible only the cyst or the ovary that the cyst is in will be removed leaving either both ovaries or one remaining ovary to preserve fertility
Secondary membranoproliferative GN is invariably which subtype
Type 1
Though more common in adults
How can acute pyelonephritis lead to perinephric abscess formation
An extension of suppurative inflammation through the renal capsule into perinephric tissue
Nephritic syndrome is indictive of what
A proliferative process affecting endothelial cells.
How is AKI classified by type
Classed as pre-renal, renal (intrinsic) or post-renal
Ovarian cysts can be asymptomatic - true or false
True
They can be both symptomatic and asymptomatic but most tend to asymptomatic
Ovarian cysts are most common in which age group
They can occur at any age but are most common in women of reproductive age
Approx 4% of women will be admitted to hospital due to an ovarian cyst by age 65
What can cause recurrent UTIs
Unusually receptive uroepithelial cells
Colonization by ‘stick strains’ of E coli
Behavioural factors
Recurrent UTIs are mainly caused by reinfection by the same pathogen
What is the definition of a recurrent UTI
Infections within 3 months of the original infection
Which part of the kidney is clear cell carcinoma though to arise from
Proximal convoluting tubule
Pyelonephritis is more common in which sex
Women
Significantly more common
Pyelonephritis is more likely to occur via haematogenous spread in which patient groups
More likely to occur in the presence of ureteral obstruction and in debilitated patients
In patients receiving immunosuppressive therapy
Describe the macroscopic appearance of BPH
Well defined nodules compressing urethra to slit
What is azotaemia
A biochemical abnormality referring to elevated blood urea nitrogen (BUN) and creatinine levels, and is related largely to a decreased GFR
It is a consequence of many renal disorders (AKI, CKD), but it also arises from extra-renal disorders
How is targeted therapy used in the treatment of ovarian cancer
Targeted therapy can be given in some carcinomas and can also be used in some to treat recurrence
Describe the structure of the distal convoluted tubule
Has there are occasional microvilli, mitochondria, golgi apparatus, interdigitating processes (at base of cell) and a basal lamina
Smaller than PCT
More obvious luminal margin as apical microvilli are sparse - no brush border
Which symptoms suggest a ruptured ovarian cyst or ovarian torsion
Sudden onset of acute severe pain +/- nausea and vomiting
Describe the pathogenesis of an ascending urinary infection leading to pyelonephritis
Colonization of distal urethra & introitus (in the female) by coliform bacteria
From urethra to bladder: organisms gain entrance during urethral catheterization or other instrumentation
Or they can just spread up - more common in women
There are then many conditions that predispose to the movement of microbes from bladder to kidneys - obstructions (particualrly lower UT), vesicoureteral reflux and intrarenal reflux
Nephrotic syndrome is indicative of what
A non-proliferative process affecting podocytes
How can deposition of circulating immune complexes can lead to glomerulonephritis
Circulating Ag-Ab complexes can become trapped within the glomeruli and cause glomerular injury
Antigens which trigger formation of immune complexes can be endogenous (e.g., GN assoc. with SLE or in IgA nephropathy ) or exogenous (e.g., GN following infection).
Urological consultation should be considered for which acute pyelonephritis patients
Those whose condition does not respond rapidly to antibiotics
List risk factors for serous ovarian carcinoma
A family Hx of these tumours
Hereditable mutations Nulliparity
These tumours are also more frequent in women who have low parity
Describe the pathogenesis of nephritic syndrome
Proliferation of the cells within the glomeruli and an inflammatory leukocytic infiltrate severely injures the capillary walls
This allows blood to pass into the urine and induces haemodynamic changes
Leads to a overall reduction in GFR
What is meant by a relapsed UTI
Another infection with the same bacterial strain
Need to identify the cause of bacterial persistence in urinary tract e.g. stone, foreign body
Are most cases of membranous nephropathy primary or secondary
Most are primary -75%
This is the auto-immune form
The kidneys will become reduced in size due to urinary tract obstruction – true or false
False
They will me slightly or massively enlarged
Oncocytomas appear similar to which other renal pathology on imaging
Renal cell carcinoma
As a result they are resected when they are found to be safe
They also affect the same demographics
Describe the macroscopic appearance of BPH
Hyperplastic nodules composed of glands with infoldings of papillary epithelium
How do you treat sepsis
Begin treatment as soon as sepsis has been verified (NEWS2 of 5 or>5 in a patient with likely infection) by a senior clinician (ST3 or above)
Start the Sepsis 6 aka BUFALO
The critical care team may also adminisister corticosteroids, inotropes or vasopressors
Reassess and frequently monitor.
What determines the prognosis of ovarian carcinoma
How far it has spread outside the ovary and the extent of spread across the peritoneum
The histological appearance of serous carcinoma will also influence its prognosis
Acute proliferative GN can be caused by both exogenous and endogenous antigens - true or false
True
Post-infectious is the classic exogenous example
nephritis of SLE is an example of endogenous.
What is the most common subtype of bladder cancer
The vast majority (>90%) are urothelial
Squamous cell is associated with specific exposures - e.g. catheters
In the absence of vesicoureteral reflux, infection usually remains localized in the bladder - true or false
True
What are cystadenofibromas
They are rare benign tumours seen in the ovary
They can contain mucinous, serous, endometroid or transitional ( Brenner) epithelium.
What is the precursor lesion for high grade serous carcinoma
Serous tubal intraepithelial carcinoma
Can be the
precursor lesion fin both sporadic and familial cases (linked to BRACA mutations)
What causes the dilation of calyces and pyramids in hydronephrosis
The continued glomerular filtration on top of the obstruction
UTIs caused by S. saprophyticus are more common in which patient group
Young women
Which cells predominantely make up clear cell carcinoma of the ovary
Mainly made of epithelial cells that have abundant cytoplasms.
This makes the cells resemble hypersecretory gestational endometrium
Which types of glomerular injuries are caused by damage to mesangial or endothelial cells and nephritic syndrome.
Overall caused a proliferative glomerular injury which includes:
Acute proliferative - includes post-infectious (post-strep) and infection associated
Crescentic (Rapidly Progressive) GN (RPGN) - includes anti-GBM antibody mediated, immune complex deposition and Pauci-immune crescentic GN
Collapsing glomerulopathy is associated with prominent tubular interstitial inflammation - true or false
True
What is the most significant risk factor for death from AKI
Pulmonary complications
Describe type
2 endometriomas
Type 2 arise due to functional cysts being invaded by either ovarian endometriosis or type 1 endometriomas
How common are serous ovarian tumours
They account for 40% of cancers of the ovary and is the most common malignant ovarian tumour
What are the 3 most common toxic shock syndromes and how high are their mortalities
Meningococcal (Neisseria meningitidis) bacteraemic shock = Mortality of 10-20%
Staphylococcal (s.aureus) toxic shock syndrome = mortality of 5%
Streptococcal (group A) toxic shock syndrome - mortality of 50%
List risk factors for prostate cancer
Age – often described as a disease of advancing age and age is one of the strongest risk factors
Black ethnicity – Mortality is twice as high in the US
Family Hx
High dietary fat
The epidemiology of UTIs and pyelonephritis are similar - true or false
True
This is because they are related conditions
Data on pyelonephritis is however limited
List common clinical features of sepsis
Fever, tachycardia, and hypotension are common
Also have signs related to the sight of infection e.g. urosepsis flank pain and dysuria
What is Goodpasture’s syndrome
Caused by anti-GBM antibodies
They cross react with the BM in the alveoli and affect the GBM in the kidney
This leads to pulmonary haemorrhage associated with renal failure
What is the most typical histological feature of RPGN
Segmental glomerular necrosis and distinctive crescents (adjacent to glomerular segments uninvolved by inflammatory or proliferative change).
Which part of the kidney does ADH act on
The collecting ducts
It increases their permeability to water - more is resorbed
Describe the macroscopic appearance of bladder CIS/invasive carcinomas
Range from erythematous, slightly thickened bladder wall to large fungating tumours with areas of haemorrhage, necrosis and ulceration
Describe how renal infection occurs via haematogenous spread
Results from seeding of the kidneys by bacteria from distant foci during septicaemia or localized infections
What causes multi-organ failure in sepsis
The inflammatory response in sepsis causes widespread tissue injury.
Multi-organ dysfunction may be partly caused by apoptosis of immune, epithelial, and endothelial cells and a shift to an anti-inflammatory phenotype, compounded by impaired organ perfusion due to hypotension, low cardiac output states, circulatory microthrombi, a disordered microcirculation, and tissue oedema
How does Crescentic (Rapidly Progressive) GN present on electron microscopy
Shows deposits due to immune complex deposition.
Regardless of type, EM may show ruptures in the GBM, a severe injury that allows leukocytes, plasma proteins to reach the urinary space, where they trigger crescent formation.
In time, most crescents undergo organisation & foci of segmental necrosis resolve as segmental scars (type of segmental sclerosis).
Restoration of normal glomerular architecture may be achieved with early aggressive therapy.
Both high and low grade serous carcinoma of the ovaries commonly spread to which other areas
Both have a propensity to spread to the peritoneum and omentum and commonly cause ascites
What forms the glomerular basement membrane
It consists mostly of type IV collagen & several matrix proteins (incl. laminin, proteoglycans
List common causative organisms of sepsis
Of the 70% of infected patients with positive microbiology:
47% of isolates were gram-positive (Staphylococcus aureusalone accounted for 20%)
62% were gram-negative (20%Pseudomonasspecies and 16%Escherichia coli)
19% were fungal
What is endocapillary proliferation (glomerular injury)
The combination of infiltration of leukocytes and swelling and proliferation of mesangial and/or endothelial cells
Acute pyelonephritis is more common in men as their age increases - true or false
True
Due to prostatic hypertrophy & instrumentation
UTIs are most common in which patient group
Adult women
1 in 5 experience a UTI at some point
30x more likely than men to develop UTI
High rates in post-menopausal women
Prostate cancer is the most common cancer in men - true or false
False
It is second after lung cancer
Endometrioid carcinomas of the ovary are commonly accompanied by which other cancer
15-30% of endometroid ovarian carcinoma will be accompanied by carcinoma of the endometrium
In these cases the endometroid ovarian carcinoma is a result of metastasis of the primary endometrial cancer
Which symptoms are seen in renal AKI
nephritic syndrome of haematuria, oedema, and hypertension indicates a glomerular aetiology
Which species of bacteria produce superantigens
25 species known to date
Includes: Staphylococcus aureus(S. aureus)
Streptococcus pyogenes(S. pyogenes)
What causes membranous nephropathy
It is a chronic immune complex-mediated disease, primary form is an autoimmune disease caused mostly by antibodies to a renal autoantigen (PLA2R)
This is a membrane protein at the basal surface of glomerular epithelial cells
Also involves IgG4 deposition
How can infertility treatment increase risk of ovarian cysts
gonadotrophins and other ovarian induction agents can cause cysts as they can cause ovarian hyperstimulation syndrome
How is lactate used as an indicator in sepsis
Lactate is amarker of stressand may be a marker of a worse prognosis
Raised serum lactate highlights the possibility of tissuehypoperfusionand may be present in many conditions
Describe the structure of the renal capsule
It’s made of dense collagen fibres
Thin but strong
How would you treat fluid overload
Furosemide
What causes type one ovarian carcinoma
They arise in association with borderline tumours and endometriosis and are low grade.
This group includes endometrioid, mucinous and low grade serous carcinomas
Describe the pathogenesis of nephrotic syndrome
Derangement in glomerular capillary walls causes increased permeability to plasma proteins.
Describe the appearance of the GBM in membranoproliferative GN
They become thickened with a double-contour” or “tram-track” appearance on silver or PAS stains
This is caused by duplication of the BM (aka. splitting) usually as a result of new BM synthesis in response to subendothelial deposits of immune complexes
Describe the histological features of membranous nephropathy
Diffuse thickening of the glomerular capillary wall due to accumulation of deposits containing immunoglobulin along the subepithelial side of the BM
Epithelial cells of proximal tubules contain protein reabsorption droplets and there may be considerable mononuclear cell inflammation
List causes of LUT obstruction that can lead to pyelonephritis
Benign prostatic hypertrophy
Tumours
Calculi
Neurogenic bladder dysfunction caused by diabetes or spinal cord injury
How is very-low grade prostate cancer managed
Observation and active surveillance are both options
Especially in older patients
IC patients w/ pyelonephritis may exhibit few, if any, symptoms - true or false
True
Describe ovarian dermoid cysts
Also called mature cystic teratomas
They will contain elements from all three germ layers
Most will be benign but 1-2% can undergo malignant transformation
Can also become very large increasing the risk of ovarian
What is meant by reinfection with regards to UTI
New infection by a different organism/strain
List some risk factors for developing acute pyelonephritis
Urinary tract obstruction, either congenital or acquired
Instrumentation of the urinary tract, most commonly catheterization
Vesicoureteral reflux
Pregnancy - 4-6% of pregnant women develop bacteriuria during pregnancy
Pre-existing renal lesions, causing intrarenal scarring and obstruction
Diabetes
Immunosuppression & Immunodeficiency
List the main steps in the pathophysiology of sepsis
1 = Immune system activation
2= Activation of endothelium and alteration in the coagulation system
3 = Inflammation and organ dysfunction
4 = These abnormalities may lead to lactic acidosis, cellular dysfunction, and multi-organ failure
Describe the pathogenesis of minimal change disease
Current thinking is that there is some immune dysfunction and elaboration of factors that damage visceral epithelial cells
Ultrastructural changes point to a primary visceral epithelial cell injury
This leads to the proteinuria
What are the 2 subgroups of Membrano-proliferative GN
Type 1 - deposition of immune complexes containing IgG and complement
Type 2 - dense deposit disease, in which activation of complement appears to be crucial.
What are the most common mechanisms of death from ovarian cancer
Usually due to widespread metastasis and their effects on other organs causing ;
Bowel obstruction
Liver failure
Respiratory tract blockage leading to infection causing sepsis or respiratory failure
These patients have also been known to die from PE and infection - potentially due to chemotherapy or due to metastasis effecting the liver function and the lungs
List causes of UTIs in older men
Enlargement of prostate
Prostatism
Debilitation
Subsequent instrumentation of the urinary tract
The presence of polycystic ovaries is diagnostic of PCOS - true or false
False
Polycystic ovaries are found in 20-30% of women of a reproductive age so not all have PCOS
What can cause a mixed picture of ATN
Specific clinical settings such as a mismatched blood transfusion.
What causes ischaemic ATN
Caused by inadequate blood flow to the peripheral organs, hypotension and shock.
Seen in cases of severe trauma, pancreatitis and ones listed earlier all lead to these blood supply issues
Pyenephrosis can follow on from which condition
Pyelonephritis
What causes type two ovarian carcinoma
They tend to have come from serous intraepithelial carcinoma.
This group includes high grade serous carcinoma
Describe the macroscopic feature of follicular cysts
Often larger than 2cm in diameter
If >2cm can be detected by palpations and USS
Describe the initiation phase of AKI
Lasts about 36 hours
The main feature is the causative medical, surgical or obstetric event.
Only clue that renal system is affected is a slight decrease in urine output and rise in blood urea nitrogen.
Likely due to a transient decrease in blood flow and GFR
Which mechanism usually prevents the backflow of urine from the bladder
The normal ureteral insertion into the bladder is a one-way valve that prevents retrograde flow of urine when the intravesical pressure rises, as in micturition
How does kidney size change with urinary tract obstruction
The kidney can either be enlarged slightly or it can be enlarged massively. How enlarged it is will depend on the degree and the duration of the obstruction
Which genetic abnormalities are seen in clear cell carcinoma of the ovary
They include; aberrations in PIK3CA, KRAS, ARID1A, PTEN and TP53
Most of the genetic aberrations that are seen in clear cell carcinoma are shared with endometrioid carcinoma just in different frequencies
List the histological features of chronic pyelonephritis
Coarse, discrete, corticomedullary scars overlying dilated, blunted, or deformed calyces, and flattening of the papillae
Involve predominantly tubules and interstitium
Tubules show atrophy in some areas and hypertrophy or dilation in others
Thyroidization – Dilated tubules with flattened epithelium may be filled with casts resembling thyroid colloid
Varying degrees of chronic interstitial inflammation and fibrosis around the calyceal epithelium
Glomeruli may appear normal
Renal cell carcinoma is most prevalent in which age group
Tumours most commonly present in pts in their 60s and 70s
Median age of diagnosis is 64
Describe the normal histology of the renal pelvis, ureters and the bladder
Composed of basement membrane beneath transitional epithelium/ urothelium.
Most superficial layer of cells (“umbrella” cell layer) are very resistant to osmotic pressure and very distensible
They have rounded tops when the tissue not stretched
Why does ovarian cancer have a worse prognosis than endometrial and cervical cancer
The symptoms don’t appear until late stages of the disease so women often present much later than in cervical or endometrial
Describe the hyalinosis seen in glomerular injury
Hyalin is an extracellular, amorphous material composed of plasma proteins
It moves from the circulation into glomerular structures
When extensive, these deposits may obliterate the capillary lumens of the glomerular tuft
On light microscopy you see accumulation of material that is homogenous and eosinophili
How common are clear cell tumours of the ovary
These tumours collectively are rare with the benign and borderline forms being exceedingly rare and the clear cell carcinomas being uncommon
What is the most common cause of AKI in children
HUS - haemolytic uraemic syndrome
Also gastroenteritis can cause severe hypovolaemia and lead to an AKI
Which factors determine the treatment regime chosen for ovarian cancer
Treatment will depend on the patients health, whether they are post menopausal and how far the carcinoma has spread
Kidney cancers represent 3-4% of all newly diagnosed cancer in the US - true or false
True
Renal papillary adenomas are commonly found at autopsy - true or false
True
Incidence increases as age does
Up to 40% of overs-70s will have them
Describe how tubular injury occurs in ATN
The epithelial cells in the tubules are very sensitive to ischaemia and toxins
Ischaemia causes structural and functional changes such as redistribution of membrane proteins
This leads to abnormal ion transport and increased sodium in the distal tubules.
The rise in Na causes vasoconstriction via tubuloglomerular feedback which initially lowers the GFR to maintain distal blood flow.
The ischaemic tubular cells also release cytokines and adhesion molecules which recruit leukocytes to the area - contributes to injury
Can also be caused by urine backflow and intratubular obstruction.
You also get activation of the coagulation cascade and cell necrosis/apoptosis
Bladder cancer is more common in the older population - true or false
True
Over 70% of new cases in the over-65s
What are superantigens
Bacterial proteins that generate a powerful immune response by binding to Major Histocompatibility Complex class (MHC) II molecules on 1) antigen-presenting cells (APCs) and 2) T cell receptors on T cells
They are extremely potent
List the features of immune complex deposition GN
IF shows granular deposits of antibodies and complement.
Can be a complication of any of the immune complex nephritides, incl. post-strep GN, lupus nephritis, IgA nephropathy, and HSP
Which proportion of mucinous ovarian tumours are benign
The vast majority of these tumours will be benign and borderline with a smaller proportion being malignant
Angiomyolipomas are common in which patient groups
Occurs in up to 80% of pts w/ tuberous sclerosis
They also have a strong female predilection
Overall prevalence of 0.2-0.6% so rare in general population
List risk factors for sepsis
Age > 65 Immunocompromised Catheter Recent surgery Diabetes IV drug use
Describe the pulmonary complication of AKI
Seen in around 54% of patients.
Pulmonary oedema and hypoxia are common
Which type of ovarian cyst is present in the normal ovaries of women of a reproductive age
Luteal
Perirenal abscesses can form after pyonephrosis - true or false
True
Describe the action of aldosterone
It is secreted by the adrenal cortex
Acts on the DCT and results in greater Na+ and water retention
Therefore, increases BP.
What are the characteristics of polyomavirus nephropathy
infection of tubular epithelial cell nuclei, leading to nuclear enlargement and intranuclear inclusions visible by light microscopy
What is the principal immunoglobulin deposited in most cases of membranous nephropathy
IgG4
How do the glomeruli appear in membranoproliferative GN
They are large and hypercellular
Hypercellularity produced by proliferation of cells in mesangium and capillary endothelium + infiltrating leukocytes.
Accentuated “lobular” appearance due to proliferating mesangial cells & increased mesangial matrix.
The nephrons are structurally intact in pre-renal AKI - true or false
True
Which signs are typically abnormal in the NEWS score of a patient with sepsis
-RR and HR = tachypnoea and tachycardia Temp = high or low temp (+/- rigors) AVPU = Altered mental status O2 = low O2 sats BP = hypotension
List the main tests run in a patient with suspected sepsis
Blood culture - before antibiotics Serum lactate Hourly urine output Urea and electrolytes Serum glucose Clotting screen Liver Function Tests C-reactive protein Serum procalcitonin (new) Blood gas ECG
Which types of urinary obstruction typically cause pyonephrosis
The obstruction will either be a complete obstruction or an almost complete obstruction.
The obstruction also tends to be high in the urinary tract
How common are endometrioid carcinomas
They account for approximately 10-15% of ovarian cancer
Describe the macroscopic appearance of bladder papillary carcinomas
Lesions protruding into the lumen of the bladder
Non-enteric organisms such as staph are more likely to cause pyelonephritis in which patient groups
In patients receiving immunosuppressive therapy
Also more common for certain viruses and fungi to be involved
Which mutation is commonly seen in mucinous carcinoma of the ovary
KRAS proto-oncogene mutations are found in 85% of mucinous carcinomas and it is felt they are responsible for initiating the development of these tumours
KRAS mutations are also seen in benign and borderline forms of these tumours
What other diagnoses should be excluded in women with suspected pyelonephritis
Should exclude vaginitis, cervicitis or pelvic tenderness (suggests PID) in pelvic examination
BPH normally occurs in the peripheral zone of the prostate - true or false
False
This is where most cancers arise
BPH in more common in the transitional zone
List potential complications of salpingo-oophorectomy in the treatment of ovarian cancer
Vascular injury and bleeding Bowel, bladder or ureter damage Nerve damage Infection DVT Adhesion formation Ovarian remnant syndrome Anaesthetic complications
Endometrioid ovarian carcinoma can be bilateral - true or false
True
Can you get a malignant Brenner/TC tumour of the ovary
Yes
It is possible to get malignant Brenner tumours and transitional cell carcinomas.
The different is that malignant Brenner tumours are when are when there are benign Brenner nests mixed with malignant cells and transitional cell carcinoma is when >50% of the tumour is made of malignant transitional type epithelium
Describe the pathological features of a Brenner/TC tumour of the ovary
They are usually benign contained neoplastic epithelial cells that look like uroepithelium
What causes type 2 MPGN
Excessive activation of alternative complement pathway
How do women with pyelonephritis present
They appear uncomfortable but not toxic
Presence of toxic fever, chills, nausea and vomiting
May appreciate signs of dehydration e.g. dry mucous membranes & tachycardia
Clammy extremities & symptomatic orthostasis suggest poor vascular tone due to gram-negative bacteremia
How is lactate used as an indicator in sepsis
Lactate is amarker of stressand may be a marker of a worse prognosis
Raised serum lactate highlights the possibility of tissuehypoperfusionand may be present in many conditions
Describe the pathological features of serous tubal intraepithelial carcinoma
Made up of cells that are identical morphologically to high grade serous carcinoma.
The cells in this lesion do not invade the underlying stroma
List the microscopic features of high grade serous ovarian carcinoma
Have widespread infiltration or frank effacement of the underlying stroma and more complex growth patterns - distinguishes from low grade
Tumour cells have nuclear atypia, including pleomorphism, atypical mitotic figures and multinucleation
Sometimes of the tumours are so undifferentiated it may not be possible to recognise the serous feature
List the microscopic features of clear cell carcinoma
Tumours tend to be well-differentiated, but some cells may contain atypical nuclei
Cells are generally rounded/ polygonal with large amounts of clear cytoplasm
Vasculature is usually delicate and branching
How do you manage bladder cancer
For non-invasive cancers, transurethral resection is the treatment of choice with post-op intravesical chemotherapy +/- immunotherapy
Invasive cancer will usually require radical cystectomy +/- pelvic lymph node dissection +/- systemic adjuvant chemotherapy
List potential complications of targeted therapy in the treatment of ovarian cancer
Breathlessness
Nausea
Diarrhoea
Tiredness
Which drugs can increase the likelihood of complications from AKI
diuretics (especially K+ sparing), metformin and anti-hypertensives
They should be stopped in cases of AKI
Describe how the immune system is activated in sepsis
Pathogen successfully enters and survives in body
Innate immune system activated
Amplification of cellular and humoural response (cytokines, interleukins, ROS, complement system activate immune cells)
Describe the pathogenesis behind primary membranous nephropathy
Autoantibodies bind to the PLA2R membrane protein at the basal surface of glomerular epithelial cells
This triggers complement activation and shedding of immune aggregates from cell surface
Results in characteristic deposits of immune complexes along the subepithelial aspect of the BM.
Complement activation injures the capillary wall and causes increased protein leakage.
The incidence of UTI in women tends to increase with increasing age - true or false
True
What is the most common underlying infection in cases of post-infectious/infection associated GN
Streptococcal infection
Only certain group A b-haemolytic streptococcal strains are nephritogenic (>90% of cases due to types 12, 4 and 1).
How common is BPH
Seen in 30% of over 50s and 90% of over 80s
How does minimal change disease present on electron microscopy
GBM appears normal - no electron-dense material deposited
Principal lesion is in the podocytes: uniform + diffuse effacement of foot processes - reduced to a rim of cytoplasm with loss of recognisable intervening slit diaphragms
This change represents simplification of the epithelial cell architecture with flattening, retraction + swelling of foot processes
PT cells are often laden with lipid & protein, reflecting tubular reabsorption of lipoproteins passing through diseased glomeruli
How common are recurrent UTIs
Recurrent episodes afflict in 1 in10 women at some time in their life
How do you treat hypotension in sepsis
Fluid resuscitation is given with either colloids or crystalloids and vasopressors might be given
What are the three main phases of AKI development
initiation, maintenance and recovery
How does ischaemia cause a decrease in GFR in AKI
Leads to vasoconstriction which in turn decreases GFR
Bladder cancer may be multifocal at different stages of development/ invasion - true or false
True
At which point does the incidence of UTI in men approach that of women
When men reach the age of 60 and above
In glomerular injury how does the basement membrane thickening appear on electron microscopy
Takes 1 of 3 forms
Amorphous electron-dense material on the endothelial or epithelial side of the BM or within the GBM itself.
Increased synthesis of the protein components of the BM (e.g., diabetic glomerulosclerosis).
Formation of additional layers of BM matrices – most often occupy subendothelial locations; range from poorly organised matrix to fully duplicated lamina densa (e.g., MPGN).
Describe the maintenance phase of AKI
Get a sustained decrease in urine output (oliguria) of 40-400ml per day, salt and water overload, rising BUN, hyperkalaemia, metabolic acidosis and other symptoms of uraemia .
Can recover from this with appropriate treatment
How are microbes usually cleared from the bladder
Ordinarily, organisms introduced into the bladder are cleared by continual voiding and by antibacterial mechanisms
What are the most common neoplasms at each part of the urinary system - kidneys, ureters, bladder, prostate
Kidneys – RCC
Ureters – Urothelial carcinoma
Bladder – Urothelial carcinoma
Prostate – Adenocarcinoma
Which patients are more vulnerable to fluid overload
May be more likely in those with sepsis or pre-existing cardiac disease
What is the Sepsis 6
B - bloods U – urine output F – fluid resuscitation A – antibiotics L – lactate O – O2 judiciously
The majority of serous carcinomas of the ovary will be bilateral - true or false
True
66% are bilateral
List the histological features of FSGS
Epithelial damage = ultrastructural hallmark of FSGS
Circulating factors
and genetically determined defects damage slit diaphragms of epithelial
Causes hyalinosis + sclerosis from entrapment of plasma proteins in hyperpermeable foci + increased ECM deposition.
Describe the cardiovascular complication of AKI
Seen in 35% of cases and can include heart failure, MI, arrhythmia
Elderly with reduced cardiac reserve are high risk
Hyperkalaemia can lead to arrhythmia and cardiac arrest
How do endometriomas present on imaging
They appear as complex cysts on USS and have a ground glass appearance on internal echo
What causes cellular hypoxia in sepsis
Eventual hypoperfusion due to hypovolaemia
Impaired O2 delivery to cells due to peri-capillary oedema
Additional contributing factors: disordered blood flow at capillary level and increased blood viscosity
What are the characteristic histological features of type one MPGN
Discrete subendothelial electron-dense deposits between duplicated (split) BMs
IgG + C3 present in granular pattern along with early complement components (C1q & C4)
What are the most common systemic causes of nephrotic syndrome
Diabetes
Amyloidosis
SLE
What is micropapillary carcinoma of the ovary
This is when the epithelial cells in borderline serous tumours grow in a delicate papillary pattern.
This is thought to be the precursor lesion to low grade serous carcinoma
Describe the microscopic appearance of invasive urothelial carcinoma
Invasion in basement membrane associated with papillary urothelial cancers or adjacent CIS – overlying CIS destroyed by malignant invasion
How does minimal change disease present under immunofluorescence
no Ig or complement deposits
Urothelial carcinomas also affect which other body part beside the bladder
Also account for 5-10% of primary renal tumours
How does toxic injury cause a decrease in GFR in AKI
Contributes to tubular injury
This leads interstitial inflammation which directly decreases GFR
It also leads to sloughing of cells > obstruction and reduced GFR
What is considered to the be the precursor for endometrioid carcinoma of the ovary
Ovarian endometriosis
In some cases as the peak onset of endometrioid carcinoma is a decade earlier in endometriosis patients
Ascitic fluid in ovarian cancer cases typically contains what
Characteristically contains exfoliated tumour cells
Women with PCOS are at risk of which other conditions
Higher risk of endometrial hyperplasia and carcinoma
This is due to increased levels of free serum estrone (type of female sex hormone)
List the microscopic features of serous ovarian carcinoma
The cysts are lined with columnar epithelium Concentric calcifications ( psammoma bodies) are features that are common in all types of serous tumours however they are not specific to neoplasia
What is the main morphological feature of PCOS
The ovaries contain multiple cystic follicles which causes the ovaries to become enlarged
In which phase of the menstrual cycle to follicular cysts form
These cysts may form in the follicular phase due excessive FSH levels leading to a lack of ovulation or because of a lack of the LH surge
What are the 2 main patterns of ATN
Ischaemic
Nephrotoxic
Which endocrine syndromes can be caused by renal cell carcinoma
Cushing’s
Polycythaemia
Hypercalcaemia
Sex hormone disturbances
What is the main management for the majority of ovarian cysts
Watchful waiting
Serial ultrasounds to ensure that the cyst is regressing by itself
If the women is post menopausal they will have an ultrasound and a blood test every 4 months for a year
What is Collapsing glomerulopathy
A morphological variant of FSGS
It has a poor prognosis
List how pre-renal, renal, post-renal factors cause disrupted blood flow in ATN
Pre-renal causes = reduced perfusion.
Renal = disease of kidney itself causes ischaemic damage.
Post = obstruction causes an increase in pressure which interferes with the pressure gradients and reduces filtration driving force.
What is the 5-year survival for invasive mucinous carcinoma of the ovary
It has a 10yr survival rate greater than 90%
What are the 3 main complications of ovarian cysts
Rupture
Haemorrhage - can be severe and life threatening
Torsion - a surgical emergency
Does the severity of the microscopic features in ATN correlate to the severity of the clinical picture
NO
How are serous ovarian carcinomas subdivided
Into high and low grade forms
The difference between high and low grade is the degree of nuclear atypia
The grades will correlate with patient survival.
What forms the nephron
Renal corpuscle + tubule
This is the basic functional unit of the kidney
what is the source of pseudomyxoma peritonei
Originally thought it was mucinous carcinomas of the ovary but now believed to be the appendix
Define AKI (in terms of blood/urine results)
A rise in creatine >26 umol/L within 48hrs.
A rise in creatine >1.5x of the baseline for that patient within 7 days.
Urine output <0.5mL/kg/hr for more than 6 consecutive hours.
25% or greater fall in eGFR in children and young people within 7 days.
Can also stage AKI based on the highest creatine reading or longest period of oliguria
Mucinous ovarian tumours typically affect which age group
They mainly occur in the middle section of adult life and are rarer before puberty and after menopause
Endometrioid ovarian carcinoma can be bilateral - true or false
True
40% of these tumours are bilateral
How do you treat renal cell carcinoma
Usually radical nephrectomy
Nephron-sparing surgery may be possible for smaller masses - local ablation may be either cryoablation or radiofrequency ablation
Pharmacological treatment or chemotherapy typically not beneficial except in metastatic disease
What are the complications of radiotherapy in prostate cancer
Can lead to significant urinary complications
What is the 5-year survival for endometrioid carcinoma of the ovary
Approximately 75%
How can serous carcinoma of the ovary spread into the peritoneum
They can occur on the ovaries surface therefore if unencapsulated they can spread to the peritoneum easily
They can also originate from the fallopian tubes and from here they can also exfoliate into the peritoneum
Describe the clinical course of type 1 membranoproliferative GN
Slowly progressive but unremitting course
Some develop numerous crescents + clinical picture of RPGN.
~50% develop chronic renal failure within 10 years.
How does Pauci-immune crescentic GN present in IF microscopy
little/no deposition of immune reactants
Focal areas of carcinoma can be found within cystadenofibromas in the ovary - true or false
True
It is rare and metastatic spread from this is extremely uncommon
List potential treatment options for renal AKI
Renal causes may need referral for biopsy and specialist treatment of renal disease.
What is the biggest risk factor for developing a non-benign ovarian cyst
increasing age
Sepsis has a very high mortality - true or false
True
Sepsis is present in MANY hospitalisations that culminate in death
In 2015, 23,135 people in the UK died from sepsis, where sepsis was an underlying or contributory cause of death
How are the different types of ovarian carcinoma distinguished
They are distinguished by the differentiation of their neoplastic epithelium
Ascites is a common clinical sign of ovarian cancer - true or false
True
It occurs once the carcinoma has extended through its capsule and seeded into the peritoneal cavity
Fluid collection can be massive
What is hydronephrosis
The dilatation of the renal pelvis and calyces, that is associated with progressive atrophy of the kidney, due to the obstruction of the outflow of urine
Describe the structure of the loop of Henle
The thick ascending limb lined by simple cuboidal epithelium
The thin descending limb by simple squamous
Permeability to water and ions and active transport of ions varies in the different parts of the Loop
Which patient groups are more susceptible to urosepsis
women
children
older adults
people who have a compromised immune system
people who have existing wounds or injuries
people who have invasive devices, such as catheters or breathing tubes
Which morphological changes occur in the urinary tract due to sudden and complete obstruction
There will be mild dilatation of the calyces and pelvis and occasionally atrophy of the renal parenchyma will be seen
Acute tubular necrosis can follow which other conditions
Ischaemia - hypovolaemia, microscopic polyangiitis, microangiopathies such as HUS or TTP
Direct toxic injury, either from endogenous (myoglobin/haemoglobin/light chains) or exogenous sources (drugs or heavy metals)
Which AKI cases have the highest mortality
those with shock related to sepsis, extensive burns or multiorgan failure the mortality can be above 50%.
Describe the structure of the podocytes of the kidney
It’s a specialised visceral epithelium
It has interdigitating foot process, separated by 20-30nm wide filtration slits which are bridged by a thin diaphragm.
How does prostate cancer spread
Local invasion to eminal vesicles, periprostatic tissues and base of the bladder
Lymphatic spread through through the obturator nodes leading to the para-aortic nodes
Also mets to the axial skeleton - osteoblastic lesions suggest a prostatic origin
What causes hypercellularity in glomerular injury
Results from 1 or more of:
Proliferation of mesangial or endothelial cells
Infiltration of leukocytes (incl. neutrophils, monocytes, lymphocytes)
or
Formation of crescents
What signs would you look for in history and examination that may suggest sepsis
Presence of risk factors NEWS2 score of 5 or more Oliguria Poor cap refill / skin mottling Cyanosis Malaise Nausea/vomiting
Also have signs related to the sight of infection e.g. urosepsis flank pain and dysuria
List the main features/diagnostic criteria of septic shock
Persistent hypotension requiring vasopressors to maintain mean arterial pressure of ≥65 mmHg
Serum lactate >2 mmol/L (>18 mg/dL)
List some of the long term complications of sepsis
Neurological sequelae e.g. focal neurological deficits in patients with bacterial meningitis
What determines the prognosis of clear cell carcinoma and what is it’s 5-year survival
Prognosis largely depends on stage at diagnosis, but 5-year survival is approx. 75%
What is AKI treatment dependent on
The underlying cause
Need to diagnose and treat appropriately
List the macroscopic features of clear cell carcinoma
Thought to arise from PCT so most commonly originate in and are confined to the cortex
Most commonly solitary, well-circumscribed, unilateral, spherical mass which distorts the outline of the kidney
Usually yellow-grey-white, commonly with areas of necrosis and foci of haemorrhage
May show cystic changes
Can bulge and fungate into calyces and pelvis, and have been known to extend into the renal vein up to the IVC
List the risk factors for AKI
Pre-existing CKD
Male Sex
Age
History of AKI
Certain comorbidities – diabetes, CVD (heart failure), malignancy, chronic liver disease, complex surgery, connective tissue disease and autoimmune diseases
Certain drugs can also increase risk – NSAIDs
Some toxic substances too such as ethylene glycol, mercury vapour, heavy metal exposure
List common mutations in both ovarian endometrioid carcinoma and endometrial endometrioid carcinoma
Frequent alterations increasing PI3K/AKT signalling ( PTEN, ARID1A, KRAS and PIK3CA mutations)
DNA mismatch repair gene mutations
TP53 mutations are also common in poorly differentiated carcinomas in both locations
How does FSGS present under immunofluorescence
IgM and C3 present in sclerotic areas and the mesangium.
Focal sclerosis has possible pronounced hyalinosis and thickening of afferent arterioles
What causes staphylococcal (s.aureus) toxic shock syndrome
Menstrual - tampons
Skin wounds or surgical wounds
Pneumonia
Catheter infections
What causes the renal atrophy in hydronephrosis
The obstruction causes high pressure in the renal pelvis which is then transmitted through the collecting ducts into the cortex which will result in renal atrophy
What are the 2 key steps in the pathogenesis of ATN
Tubular injury
Disruption of blood flow
Post-strep GN occurs most frequently in which age group
Children ages 6-10
Usually after an infection of pharynx or skin (impetigo)
Which benign tumour of the ovary is also called a Brenner tumour
Transitional Cell Tumours
They account for 10% of ovarian tumours
Describe the link between COVID and AKI
COVID patients will often have kidney involvement with 20-40% having AKI on admission (Europe and US figures)
AKI in these patients is associated with a higher mortality
How do endothelial cells in the nephron respond to injury
Leads to vasculitis
This results in nephritic syndrome
What is requires for a diagnosis of minimal change disease
Only when podocyte effacement is associated with normal glomeruli by light microscopy that the diagnosis of MCD can be made.
Which proportion of endometrioid ovarian tumours are benign
The benign and borderline forms of this tumour are uncommon with the malignant form being more common
How does bladder cancer normally present
Patients most commonly present w/ painless haematuria, which may be associated w/ frequency, urgency and dysuria
What are the main factors determining whether management is required for an ovarian cyst
Its size and appearance
Whether it is symptomatic
If the women is post menopausal - as this carries a higher risk that the cyst is cancerous
What causes hyalinosis in glomerular injury
Consequence of endothelial or capillary wall injury
This is a typical end result of glomerular damage
Describe the microscopic feature of follicular cysts
If the intraluminal pressure has not been so high as to cause their atrophy, granulosa lining cells are present within them
Outer theca cells may be conspicuous due to luteinisation
If Luteinisation is pronounced there may be increased oestrogen production and endometrial abnormities
What causes urosepsis
Urosepsis starts with the development of a UTI and typically occurs if a UTI is left untreated
How does the body respond to the hypovolaemia and hypoperfusion in sepsis
It undergoes an initial increase in HR, but later hypoperfusion kicks in once heart is worn out
Describe the microscopic appearance of flat urothelial carcinoma (CIS)
May appear as scattered malignant cells in otherwise normal urothelium or full thickness atypia
May also see denuded basement membrane as malignant epithelium shed in urine
Describe the clinical course of a viral pathogen causing pyelonephritis in kidney allografts
Usually polyomavirus
Latent infection with polyomavirus is widespread in the general population and immunosuppression of the allograft recipient can lead to reactivation of latent infection and the development of nephropathy resulting in allograft failure in up to 5% of kidney transplant recipients
What is the 5-year survival for serous carcinoma of the ovary
The 5yr survival of serous carcinoma that is confined to the ovary is 70% however once it has spread to the peritoneum this becomes 25%
List some of the short-term complications of sepsis
High risk:
Renal dysfunction
Hypotension
Medium risk:
ARDS
Myocardial dysfunction and failure
Multiple organ failure
Low risk:
Hepatic encephalopathy
DIC
Dense deposit disease (T2 MPGN) typically affects which age group
Primarily children and YAs
Which proportion of serous ovarian tumours are benign
Of the serous ovarian tumours 70% will be benign and borderline and 30% will be carcinomas
Which type of cyst can lead to increased oestrogen production
Follicular
If lutenisation occurs in the outer theca cells
Which functional disorders can cause urinary tract obstruction
Either those are neurogenic - due to spinal chord damage or diabetic nephropathy
Or due to other functional abnormalities of the ureter or bladder
What can cause RPGN
May be a manifestation of renal or systemic disease
No single mechanism can explain all cases however, most cases have immunologically mediated glomerular injury
AKI related to sepsis is more common in which groups
It is more common in ICU and elderly
This accounts for 50% of ICU AKI cases.
Describe the normal structure and histology of the kidneys
Have a central glomerulus surrounded by Bowman’s capsule
Both PCT and DCT have cuboidal epithelium but PCT has taller cells with microvillae so appear more pink on histology
Superantigens have what effect on the body
They have been linked to the severe effects of bacterial infections, such as toxic shock syndrome
The shock state that these antigens induce is ultimately caused by a massive T cell proliferation and cytokine release (or cytokine storm)
List the main subtypes of glomerulonephritis caused by proliferative glomerular injury
Acute proliferative - includes post-infectious (post-strep) and infection associated
Crescentic (Rapidly Progressive) GN (RPGN) - includes anti-GBM antibody mediated, immune complex deposition and Pauci-immune crescentic GN
Where is ADH secreted from
Posterior pituitary
List potential complications of pyonephrosis
Urosepsis and septic shock
Kidney rupture resulting in peritonitis and death
Irreversible kidney damage
Fistula formation -renocolic, renocutanous and renoduodenal
List potential complications of hysterectomy in the treatment of ovarian cancer
Anaesthetic complications Bleeding Ureter, bladder or bowel damage Infection DVT Vaginal problems
Which symptoms are seen in post-renal AKI
urinary obstruction, flank pain, haematuria
Which type of ovarian cyst is always present in pregnancy
Luteal
They normally resolve after the first trimester
In hydronephrosis you get increased pressure within the renal pelvis, what effects does this have
It is transmitted through the collecting ducts into the cortex which will result in renal atrophy
It will also compress the renal vasculature in the medulla which reduces the inner medullary blood flow
These effects are reversible to begin with but eventually will progress to cause medullary functional disturbances
What are the histological characteristics of minimal change disease
Characterised by diffuse effacement of foot processes podocytes, detectable only by electron microscopy, in glomeruli that appear normal by light microscopy
Absence of immune deposits in glomerulus .
What is the latency period between between infection and nephritis onset in post-infectious cases of GN and why does this occur
Latency period of around 1-4 weeks
e.g. symptoms appear 1-4 weeks after the infection itself
This is due to time required to produce antibodies and form immune complexes
Intrarenal reflux is most common in which part of the kidney
The upper and lower poles of the kidney
The genetic alterations that are seen in ovarian endometrioid carcinoma are similar to ones seen in endometrial endometrioid carcinoma - true or false
True
Renal veins are posterior to renal arteries in hilum - true or false
False
Renal veins are anterior to renal arteries in hilum
Serous ovarian tumours typically affect which age group
The benign and borderline tumours are most common between the ages of 20-45 but the carcinomas tend to occur at older ages ( unless familial)
Which symptoms of AKI are suggestive of ATN
Acute tubular necrosis (ATN) should be suspected in any patient presenting after a period of hypotension secondary to cardiac arrest, haemorrhage, sepsis, drug overdose, or surgery.
What morphological changes are seen in advanced stage urinary tract obstruction
They kidney can become a cystic structure with thin walls and can have a diameter up to 15-20cm.
There will also be severe parenchymal atrophy
The pyramids will be totally obliterated and the cortex will be thinned
How does membranous nephropathy present on electron microscopy
Electron-dense deposits between the BM and epithelial cells with effacement of podocyte foot processes
BM material is laid down between these deposits forming irregular spikes protruding from GBM
Spikes thicken into dome-like protrusions; eventually, close over the immune deposits + bury them within a markedly thickened, irregular membrane
How are the microscopic features of UTI analysed
A “colony count” performed using a calibrated loop, with 0.001 mL of the urine sample plated onto culture media & incubated
Various tests can be performed to identify the causative organism
How does papillary necrosis (following acute pyelonephritis) present
The tips or distal 2/3 of the pyramids have areas of gray-white to yellow necrosis
Necrotic tissue shows characteristic ischemic coagulative necrosis, with preservation of outlines of tubules on microscopic examination
What is the purpose of the fenestrations and filtration slits in the capillary epithelium/endothelium
Makes it permeable to water and small solutes
The slit diaphragm -> acts assize-selective distal diffusion barrier to filtered proteins.
The collecting duct is not part of the nephron - true or false
True
How may a symptomatic ovarian cyst present
Pain – usually a unilateral pain that if felt low in the abdomen. It can either be intermitted or constant and it can also be either sharp or dull
Menstrual Changes – menstrual cycles can become irregular and abnormal vaginal bleeding can occur
Women may present with a feeling of fullness/pressure/ heaviness in the abdomen
Abdominal bloating may occur
What causes the HTN in nephritic syndrome
It is probably the result of both the fluid retention and renin release from the ischaemic kidneys
How does toxic injury cause a decreased urine output in AKI
Contributes to tubular injury
This causes tubular back leak which reduced urine output
It also leads to sloughing of cells > obstruction > decreased output
What is the glomerulus
A tuft of capillaries in the nephron
What is pyelonephritis
Inflammation affecting the tubules
Extrinsic obstruction to the renal/urinary tract is more likely to cause a bilateral obstruction than intrinsic - true or false
True
More likely to be bilateral and lower in tract
What causes AKI in sepsis cases
The underlying cause of AKI in sepsis is not completely understood.
It is likely multi-factorial and includes hemodynamic changes within the kidney, endothelial dysfunction, infiltration of inflammatory cells, intraglomerular thrombosis, and obstruction of tubules with necrotic cells and debris.
Arterial vasodilation with an associated decrease in SVR is a hallmark of sepsis, and until recently, it was believed that sepsis-induced AKI was mainly due to hypoperfusion of kidneys.
However, recent studies have shown that RBF is typically normal or increased in these cases.
What treatment is common to all cases of AKI
management of fluid balance, hyperkalaemia and acidosis.
Mainly want to restore renal blood flow - restore blood volume, remove obstructions.
May also need to correct blood abnormalities (e.g., anaemia, uremic platelet dysfunction) with measures such as transfusions and administration of desmopressin.
stop any nephrotoxic drugs (NSAIDs, ACEi etc), check dosages are suitable for renal impairment
Describe the microscopic features of mucinous carcinomas of the ovary
Characteristically demonstrate glandular growth that is confluent - flows together
This is not recognised as a form of ‘expansile’ invasion
what is the most common underlying mechanism of AKI
Acute tubular necrosis
Responsible for 50% of cases in hospitalized patients
What is the greatest risk factor for UTI
Presence of a catheter
80% of nosocomial UTIs are related to urethral catheterization
Urinary tract obstruction can be extrinsic or intrinsic - true or false
True
Can either caused by something extrinsic causing compression or by an intrinsic lesion in the urinary tract
Acute pyelonephritis is more common in adults of which sex
Women
What are the main complications of laparoscopy/ laparotomy to remove an ovarian cyst
Infection Bleeding Cyst recurrence Infertility - if both ovaries have to be removed Thrombosis Damage to surrounding organs Anaesthetic complications
Damage to endothelial or mesangial cells leads to what clinical picture
A proliferative lesion + red cells in urine.
How do you diagnose a urine infection
Established by quantitative urine culture
Low grade serous carcinoma arises in association with which lesions
Borderline serous tumours
Describe the macroscopic appearance of bladder papillomas and PUNLMP
Small finger-like protrusions which may be indistinguishable from papillary carcinomas at cytoscopy
What is the most common histological presentation of Crescentic (Rapidly Progressive) GN
The presence of crescents in most of the glomeruli
How does minimal change disease present
Massive proteinuria
However, renal function remains good
Often no HTN or haematuria
Disease sometimes follows a respiratory infection or routine prophylactic immunisation
Relatively benign condition
What is urosepsis
Urosepsis is just the development of sepsis from a UTI
How do angiomyolipomas present
Most are asymptomatic and found incidentally, but may present as fatal spontaneous retroperitoneal haemorrhage
What is the most common type of ovarian cyst
Most ovarian cysts are functional cysts ( Follicular and Luteal) and other forms of cysts are much less common
What are the pros and cons of the kidneys being near the ribs
The ribs offer some protection to the kidneys against penetrating trauma
“floating” ribs 11 and 12 are posteriorly related to the kidneys
However, if the ribs fracture the sharp displaced ends may bruise or lacerate the kidney.
Which organism is the most common cause of UTI
E. coli
70-95% of both upper and lower UTIs
List common clinical features of pyelonephritis
Fever
Tachycardia
Flank pain/costovertebral angle tenderness
Abdominal tenderness in suprapubic area
Often indications of bladder & urethral irritation e.g. dysuria, frequency and urgency
Describe the epidemiology of PCOS
It is a common condition effecting 6-10% of women of a reproductive age worldwide
Type one MPGN can be treated with steroids and immunosuppressants - true or false
False
Treatment with steroids, immunosuppressives, and antiplatelets have no proven benefit
How can intrarenal reflux be diagnosed
It can be demonstrated by voiding cystourethrography, in which the bladder is filled with a radiopaque dye and images are taken during micturition
How do you diagnose bladder cancer
Cystoscopy is gold standard for papillary tumours
CIS and invasive carcinomas may be more difficult to identify via cystoscopy – endoscopic resection may be an option here
Urine cytology can be a useful diagnostic tool, w/ up to 90% sensitivity
Membranous nephropathy can be associated with which other conditions (i.e. what are the secondary causes)
Underlying malignant tumours – esp. carcinoma of lung & colon
SLE
Infections (chronic hep B, hep C, syphilis, schistosomiasis, malaria)
Other autoimmune disorders e.g., thyroiditis.
Drugs (penicillamine, captopril, gold, NSAIDs)
What is the characteristic clinical feature of minimal change disease
A dramatic response to corticosteroid therapy.
How can the kidneys be used to identify someone at autopsy
Anatomical variation in the renal system can be used to identify someone if their abnormality is known
A solitary kidney might suggest agenesis or nephrectomy (pathology or donation).
A bifid renal pelvis is seen in 1 in 10 people and a bifid ureter and unilateral duplicated ureter can be seen in 1:25
Describe the clinical course of acute pyelonephritis in the presence of unrelieved urinary obstruction, diabetes mellitus, or immunodeficiency
Acute pyelonephritis may be more serious and can lead to repeated septicemic episodes
Secondary MPGN arises in which clinical settings
Chronic immune complex disorders (SLE, HBV, HCV, cryoglobulinemia, endocarditis, infected ventriculo-atrial shunts, chronic visceral abscesses, HIB, schistosomiasis.
Alpha1-antitrypsin deficiency
Malignant diseases, esp. lymphoid tumours such as CLL which are commonly complicated by autoantibody development.
How does cell-mediated injury occur in glomerulonephritis
Activation of alterative complement pathway.
Essentially, patients have persistent C3 activation and hypo-complementaemia
List the different terms used to classify urinary tract obstruction
sudden or insidious
partial or complete
unilateral or bilateral
What is the function of the loop of Henle
Creates a hyperosmotic environment in the medulla
How is sepsis identified
Identified by the NEWS score or SOFA/qSOFA criteria
SOFA = Sepsis-related Organ Failure Assessment
List symptoms of renal cell carcinoma
Often associated with systemic symptoms at presentation– fever, malaise, weight loss, weakness
Classic features are haematuria, costovertebral pain and palpable mass
All three are only seen in around 10%
Describe the normal histology of the prostate
Composed of roughly equal parts glands and fibromuscular stroma.
Concretions are normal and appear with increasing age
In type 1 membranoproliferative GN what are the deposits made of
Deposits made of immune complexes containing IgG and complement.
Mucinous carcinomas of the ovary rarely involve the surface of the ovary - true or false
True
How common are mucinous ovarian tumours
Collectively this group of tumours make up 20-25% of all ovarian tumours
Primary ovarian mucinous carcinoma is uncommon and only accounts for 3% of all ovarian cancers - most are instead benign
How common is bladder cancer
Ninth most common cancer worldwide
Incidence in the EU of around 20/ 100,000/ year
What are the two main forms of pyelonephritis
Acute and Chronic
What causes post-infectious GN
Exogenous antigens
Most commonly from a strep infection
Describe the pathological features of luteal cysts
A layer of bright yellow tissue that contains luteinized granulosa cells will line the rim of these cysts
It is common that they rupture which will then cause a peritoneal reaction
They may have old haemorrhage and fibrosis within them which makes it difficult to differentiate them from endometriomas
Renal cell carcinoma is more prevalent in which sex
Men
Male:female ratio is approx. 2:1
What is sepsis
Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to an infection
Basically, it’s the body having a massive overreaction to infection
Sepsis is more common in which sex
Males
What is the precursor lesion to prostatic carcinoma
Prostatic Intraepithelial Neoplasia (PIN)
Can be a significant predictor of the development of prostatic cancer, but this exact process has yet to be determined
List the features of nephritic syndrome
Acute renal failure Oliguria Mild-mod proteinuria ± oedema HTN Active urinary sediment (RBCs, red cell + granular casts)
Which mutations are seen in high grade serous carcinoma
A high frequency of TP53 mutations are seen in high grade serous carcinomas.
These tumours also lack either KRAS or BRAF mutations.
It is also common to see genomic imbalances in these tumours which may include amplifications of a number of oncogenes and deletions of tumour suppressor genes
List the potential complications of renal replacement therapy
RRT comes with the risk of catheter insertion, procedural hypotension, bleeding (raised by use of anticoagulants) and many more
By the time of presentation however the high grade serous carcinomas of the ovaries tends to have metastasised - true or false
True
Will usually have metastasized widely throughout the abdomen and causes rapid clinical deterioration
Why are tubular epithelial cells so vulnerable to ischaemia and toxins
large surface area, presence of active transport systems for ions and acids, high metabolism rate, high O2 consumption and the capability to resorb and concentrate toxins
all vital for their usual function of resorption but make them vulnerable
Most ovarian cysts will require some form of management - true or false
False
Most resolve themselves within a few months
Which physical findings of UTI may be seen in males
Scrotal hematoma, hydrocele, masses or tenderness
Meatal discharge
Prostatic tenderness
Inguinal adenopathy
What can cause streptococcal (group A) toxic shock syndrome
Deep seated infections
Necrotising fasciitis
Surgical operation sites
Puerperal sepsis
What is the most common cause of nephrotic syndrome in children
Minimal change disease
List the different classifications of FSGS
1 = Primary (idiopathic)
2 = Cases associated with other conditions e.g., HIV infection, heroin addiction, sickle cell, morbid obesity.
3= Secondary event reflecting scarring of previous active necrotising lesions (IgA nephropathy).
4 = Part of adaptive response to loss of renal tissue (congenital or acquired) or in advanced stages of other renal disorders.
5 = Uncommon inherited forms of nephrotic syndrome due to mutations in proteins found in slit diaphragm
Describe vesicoureteral reflux and how it causes pyelonephritis
Incompetence of vesicoureteral valve allows reflux of bladder urine into ureters
This allows bacteria to ascend the ureter into the renal pelvis
Describe the macroscopic and microscopic features of renal papillary adenomas
They are <15 mm discrete lesions arising from tubular epithelium
Histologically similar to low-grade RCC
Describe the classic pattern of ovarian cancer spread
First they seed into the peritoneum after breaking through their capsule
The serosa of the peritoneum becomes seeded with 0.1-0.5cm tumour nodules that do not, in most cases, invade deeply into the underlying parenchyma
After the peritoneum has been affected by the tumour ascites discussed will form
Metastasis will also travel to the regional lymph nodes, lungs, liver, Gi tract and elsewhere
Half of ovarian carcinomas will also spread to the other ovary.
List risk factors for bladder cancers
Tobacco smoking – Associated w/ 50-80% of bladder cancers in men
Workplace exposure – Aryl amines in rubber and dye industries, aromatic hydrocarbons in mining
Pelvic radiation and chemotherapy, particularly in relation to prostate cancer
Describe the appearance of FSGS as it progresses
An increased no. of glomeruli will be involved,
The sclerosis spreads within each glomerulus until there is total (global) sclerosis of glomeruli, with pronounced tubular atrophy + interstitial fibrosis
Describe the structure of the renal medulla
It is divided into pyramids (8-18/kidney) with apices pointing toward the hilum (papillae), ending on minor calyces
Each pyramid contains ~50,000 nephrons running axially towards the apex of each pyramid - looks striped
The stripes are called medullary rays and are composed of collecting ducts and straight segments of proximal and distal tubules
The superantigen response is much less specific than a normal antigen-specific immune response - true or false
True
They are not processed by the immune system as normal antigens are
List some of the complications of urinary tract obstruction
Obstruction increases risk of urinary tract infection and stone formation
If an obstruction is not fixed it will almost always result in permanent renal atrophy which is given the name hydronephrosis
An interstitial inflammatory reaction can also be caused by an obstruction which will eventually lead to interstitial fibrosis
The superimposition of papillary necrosis in cases of acute pyelonephritis can have what outcome
May lead to acute renal failure and then death
More than 50% of renal masses are identified incidentally - true or false
True
List the layers of the glomerular capillary wall
A thin layer of fenestrated endothelium
A GBM
The visceral epithelium (podocytes)
The entire glomerular tuft supported by mesangium.
When would an ovarian cyst be removed surgically
If it is large, symptomatic, persistent or there is concerns it either may become or already is cancerous
Why do you check U&Es in a septic patient
To evaluate the patient forrenal dysfunction-
Patients with acute kidney injury due to sepsis have a worse prognosis than those with non-septic acute kidney injury.
Determines whether the patient would benefit fromhaemofiltration or intermittent haemodialysis
Describe the microscopic appearance of high-grade papillary urothelial carcinoma
Nuclei may be hyperchromatic with prominent nucleoli
Cells will be dyscohesive with architectural disruption
List potential treatment options for pre-renal AKI
Correct the volume depletion and/or increase renal perfusion by circulatory or cardiac support
Treat hypovolaemia if present with fluid bolus (renal perfusion will improve as volume is replaced)
Describe the infectious complications of AKI
33% will develop infections, mostly pulmonary and urinary.
Infectious complications may have mortality of 11-72%.
What is the normal prognosis for an ovarian cysts
Most ovarian cysts are benign and will resolve spontaneously resulting in a very good prognosis and no requirement for surgical intervention
70-80% of functional cysts resolve spontaneously
However, if they malignantly transform (only occurs in certain types) the prognosis is poor as ovarian cancer presents late
List potential complications of acute pyelonephritis
Papillary necrosis – usually bilateral
Pyonephrosis
Perinephric abscess
What are three sub-groups of crescentic GN (RPGN)
Anti GBM antibody mediated - 1/5
Immune complex deposition - 1/4
Pauci-immune crescentic GN - the rest
Sepsis is very prevalent - true or false
True
Which types of renal dysfunction are common in septic patients
Transient oliguria (small output) is common - due to hypotension
Rarely, anuria occurs
AKI relatively common
Normal glomeruli are permeable to which molecules
highly permeable to water and small solutes - due to fenestrations
impermeable to proteins of the size of albumin or larger
Describe the pathogenesis of clear cell carcinoma in relation to the VHL genne
In 98% of clear cell carcinomas, there is loss of sequencing in the area of chromosome 3 which encodes the VHL gene (acts as tumour suppressor)
VHL protein is part of a ubiquitin ligase targeting HIF-1, a transcription factor which promotes expression of genes that trigger angiogenesis and cell growth
VHL gene becomes inactive which leads to high levels of HIF-1
This causes inappropriate expression of angiogenic and oncogenic genes which leads to tumour formation
Brenner tumours are usually an incidental finding in the ovary - true or false
True
Even if it is a large carcinoma they tend to behave in a benign way
Describe type 1 endometriomas
Type 1 are primary endometriomas.
They are small and develop from surface endometrial implants
What is the characteristic histological feature of collapsing glomerulopathy
Retraction and collapse of the entire glomerular tuft with or without additional FSGS lesions
Proliferation + hypertrophy of glomerular visceral epithelial cells is another characteristic
PSA can be used to diagnose prostate cancer - true or false
False - ish
It can be useful where there is high clinical suspicion but has limited use as a screening tool as sensitivity and specificity are suboptimal
List clinical differences between minimal change disease and FSGS
FSGS has a higher incidence of haematuria, reduced GFR, and HTN
Proteinuria is more often non-selective in FSGS
FSGS has a poor response to corticosteroid therapy;
There is progression to CKD in FSGS with at least 50% developing ESRD in 10yrs.
List different types of renal cancer
Renal cell carcinoma Rare ones: Papillary carcinomas Chromophobe renal carcinomas Collecting duct carcinomas
List potential treatment options for post-renal AKI
may need catheterisation, nephrostomy or urological intervention
What are the characteristics of the sclerosis seen in glomerular injury
Characterised by deposition of extracellular collagenous matrix.
May be confined to mesangial areas, involve the capillary loops, or both.
May also result in obliteration of some or all of the capillary lumens in affected glomeruli.
List the characteristic features of FSGS
Degeneration & focal disruption of podocytes with foot process effacement
List the features of post-strep GN
Pyogenic exotoxin B (SpeB) = principal antigenic determinant in most cases of post-strep GN.
Elevated antibody titres against 1 or more strep antigens is seen in majority of patients.
Serum complement levels are low - reflects activation of complement system + consumption of its components
List the potential complications of AKI treatment
Fluid overload - monitor fluid levels
Correction of acidosis with sodium bicarbonate can generate CO2 so ventilation may be required
Also comes with Na+ and a volume load which can precipitate fluid overload in vulnerable patients
Risks of RRT
Cystadenofibromas can form borderline tumours in the ovary - true or false
True
They can form borderline tumours with nuclear atypia
What are the initial morphological changes seen in urinary tract obstruction
The first features that are seen are simple dilatation of the pelvis and calyces.
There often is also significant interstitial inflammation even if no infection is present
What causes serous inclusion cysts of the ovary
The cause is unknown but may either arise due to invagination of the surface epithelium of the ovary followed by serous metaplasia or because of implantation of detached fallopian tube epithelium at areas where the ovaries surface has been disrupted by ovulation
Why are UTIs more common in females
Females have a shorter urethra
They lack the antibacterial properties in prostatic fluid
Hormonal changes affect bacterial adherence to the mucosa
Urethral trauma during sexual intercourse
Describe the pathogenesis of pyon ephrosis
Normally bacteria are cleared from the bladder due to voiding and antibacterial mechanisms.
If there is obstruction however incomplete bladder emptying occurs and residual urine is left where bacteria can multiply leading to infection which can effect the kidney - pyelonephritis
The pyelonephritis can then progress onto a pyonephrosis
Perirenal abscesses can then subsequently form
What happens to the injured tubular cells in ATN
With time they detach from the basement membrane and form casts which cause luminal obstruction, increased pressure within the tubules and a further decrease in GFR
What happens if RPGN is left untreated
Patients will die from renal failure within weeks to months
What are the most common sites of infection in sepsis cases
Lungs: 64%
Abdomen: 20%
Bloodstream: 15%
Renal or genitourinary tract: 14%
How does FSGS present on electron microscopy
Both sclerotic and non-Sclerotic areas show diffuse effacement of foot processes (resembling MCD)
May also be focal detachment of epithelial cells & denudation of the underlying GBM
How is radiotherapy used in the treatment of ovarian cancer
It is not often used in the management but can be used adjuvantly in early stage cancer or palliatively
When might fluid resuscitation be required in acute pyelonephritis cases
Fluid resuscitation is important if blood pressure is unstable or if the patient is very old
Which medical interventions increase the risk of UUTI
Catheterisation
Routine pelvic examinations - an increased risk of a UTI for 7 weeks post procedure
Renal transplantation - High susceptibility in the first 2 months following transplantation
What is Membrano-proliferative GN
Considered a pattern of immune-mediated injury rather than a specific disease
How can acute pyelonephritis recur
Bacteria may persist in the urine or there may be recurrence of infection with new serologic types of E. coli or other organisms
This infection can either disappear or may persist, sometimes for years
What are the 3 different forms of ovarian carcinoma
Serous, mucinous and endometroid carcinomas
Within each of these three groups it is also possible to get benign and borderline tumours
Describe the natural history and progression of urothelial bladder cancer
Most patients present with low-grade, non-invasive bladder cancers
These have a high risk of recurrence but low risk for disease progression and death
Once invasion has occurred, overall survival drops to around 50%
Up to a quarter of high risk patients will develop urothelial carcinoma of the prostate, which has >40% mortality rate
What is Bowman’s capsule
A cusp of simple squamous where the capillaries of the glomerulus invaginate into
Why might you need an amputation following sepsis
Sepsis can cause blood clots leading to limb ischaemia and amputation’s
How do podocytes respond to injury
They atrophy
Loss of size/charge specific barrier
Local invasion from prostate cancer typically affects which areas
The seminal vesicles, periprostatic tissues and base of the bladder
What’s the prognosis if ovarian cancer spreads’ to the second ovary
If this occurs most patients will only survive for a few months to a few years
Should you be concerned if an AKI patient’s creatine levels don’t drop in the first 24hrs of treatment
Not necessarily
Creatine will lag 24hrs behind the clinical response so give it time to drop
Which organ signs are sometimes used to identify sepsis at autopsy
Historical ‘diffluent’ or ‘septic’ spleen i- however this s a debatable gross entity so not used
‘Shock lung’ and ‘acute tubular necrosis’ are difficult to diagnose on gross examination alone
What are the primary causes of pyelonephritis in older men
Prostate enlargement along with delayed presentation
Thrombocytopenia may occur in patients who are severely ill with sepsis - true or false
Will be of non-haemorrhagic origin
Persistent thrombocytopenia is associated with an increased risk of mortality.
Lymphocytopenia is increasingly recognised as a useful sign in a patient with sepsis.
How does renal transplant increase risk of UTI
Triggering factors include vesicoureteral reflux and immunosuppression
List organisms which commonly cause UTIs
E.colii
S. saprophyticus
Proteus species, Klebsiella species, Enterococcus faecalis, other Enterobacteriaceae and Yeast
Candida - usually albicans
Mycobacterial & fungal organisms induce caseating & non-caseating granulomatous inflammation
Identifying prostate cancer by gross inspection alone can lead to false positives - true or false
True
They can be hard to accurately identify
Gross identification is only around 65% accurate with a 20% false positive rate
How is chemotherapy used in the treatment of ovarian cancer
Most women will have chemotherapy as well as surgery
Chemotherapy is used both neoadjuvatly and adjuvantly and is used for recurrence
Most people will have 6 cycles lasting 3 weeks each
Radiotherapy
Which gene is thought to be behind both familial and sporadic cases of clear cell carcioma
VHL gene
Acts as a tumour supressor
List the features of Pauci-immune crescentic GN
Defined by a lack of detectable anti-GBM antibodies or immune complexes by IF & EM
Most patients have circulating ANCAs - c-ANCA or p-ANCA staining pattern (thought to be related to vasculitis or polyangiitis)
Prognosis for patients with local or regional stage prostatic cancer at diagnosis is generally very good - true or false
True
Has an almost 100% 5-year survival rate in the US, but the treatment may cause significant morbidity
What is the main cause of acute pyelonephritis in the first year of life
Congenital abnormalities
Which part of the nephron is most vulnerable to necrosis
Straight portion of proximal tubule and ascending limb are very vulnerable
Proximal tubules most commonly affected by necrosis
If there has been malignant change in a dermoid cyst or endometrioma the prognosis is poor - true or false
True
This due to the fact that ovarian cancer tends to present in advanced stages
How does a reduced GFR manifest clinically
Oliguria
Fluid retention
Azotaemia - increased creatine and BUN
What are the risks of developing AKI after sepsis
It increases mortality and can lead to multi-organ effects.
Mucinous carcinomas of the ovary must be differentiated from which other cancer
Metastatic mucinous adenocarcinoma
Especially if they are bilateral as this is less common in the primary ovarian type
What is pyonephrosis
The infection is termed pyonephrosis when there is a suppurative exudate that is unable to drain so has filled the renal pelvis, calyces and ureters
Occurs due to superimposed infection on top of urinary tract obstruction
Bladder cancer is more common in which sex
Men
Male:female ratio is around 3:1
What is thought to cause prostatic adenocarcinoma
The exact pathogenesis is unknown
Thought to be a combination of inherited genetic factors, exposure to external carcinogens, and mutations within the androgen receptor gene
In type 2 membranoproliferative GN what are the deposits made of
Deposits made of unknown material
List the histological characteristics of membranoproliferative GN
Shows alterations in GBM Accumulation of mesangial matrix Proliferation of glomerular cells Leukocytic infiltration Deposits in mesangial regions and glomerular capillary walls. Crescents are present in many cases
What can cause vesicoureteral reflux
Most often due to a congenital absence or shortening of the intravesical portion of the ureter, such that the ureter is not compressed during micturition
It can be acquired from the infection itself or from persistent bladder atony caused by spinal cord injury
Biopsy in FSGS may miss the diagnosis - true or false
True
Focal and segmental lesions may involve only a minority of the glomeruli and therefore if a biopsy specimen doesn’t contain enough glomeruli, it can be missed
What are the 2 routes by which bacteria can reach the kidneys
Through the bloodstream (hematogenous infection) - less common
From the lower urinary tract (ascending infection) - more common
Why is it hard to identify sepsis at autopsy
There are no specific morbid anatomical features of ‘septicaemia’
The interpretation of pre-mortem, let alone post-mortem, blood cultures is not easy
There are no standard histopathological features that reliably point to ‘septicaemia’
There is no agreed case definition of ‘septicaemia’. It is more logical to consider ‘sepsis’: its local origins, systemic consequences and degrees of severity
The majority of angiomyolipomas occur spontaneously - true or false
True
Spontaneous in 80% of cases
What is asymptomatic bacteriuria
Bacterial infections of the lower urinary tract that are asymptomatic
IS ATN reversible
Yes
If detected and treated promptly
Why is little known about the prevalence of sepsis
there is a lack of reliable sepsis incidence and prevalence data due to the absence of a consistent definition for sepsis and differences in coding practices amongst professionals and organisations and different countries.
How can prostate cancer be managed
Radiotherapy can be given via external-beam or brachytherapy (a small radioactive source is implanted into the prostate)
Androgen deprivation therapy is increasingly being used at many grades
Radical prostatectomy +/- pelvic lymph node dissection is the first line treatment for high-risk disease, almost always in combination with radiotherapy
Foot process effacement is only a feature of minimal change disease - true or false
False
It is also seen in other protein-uric states such as membranous nephropathy and diabetic nephropathy
The symptoms of ovarian cancer tend to present early - true or false
False
Unfortunately they tend not to occur until later stages of disease meaning women don’t present until later stages of the disease
List treatment options for ovarian carcinoma
Surgery
Chemo
Radiotherapy
Targeted therapy
Ovarian endometriomas occur in which condition
They occur in endometriosis due to ectopic growth of endometrial tissue
List the characteristics of PCOS
Menstrual abnormalities
Decreased fertility
Chronic anovulation
Polycystic ovaries Hyperandrogenism.
List the potential outcomes of AKI
One outcome is that cells are repaired and function returns.
May see very mild renal impairment for some time after but most will recover with time.
However, those surviving severe AKI often have a worse health related QoL (worse with age and renal function).
May be left with impaired kidney function, CKD or requiring dialysis.
What glomerular changes may be seen in chronic pyelonephritis
Glomeruli may appear normal except for a variety of ischemic changes, including periglomerular fibrosis, fibrous obliteration and secondary changes related to hypertension
Which immune complexes, formed in situ, can lead to glomerulonephritis
Intrinsic tissue antigens, e.g., NCI domain of type IV collagen, PLA2R antigen, mesangial antigens, others.
Extrinsic antigens, including DNA/nucleosomes/other nuclear proteins, bacterial products, large aggregated proteins, and immunoglobulins themselves
What can determine the causative organism in sepsis
Causative agents vary significantly with region, hospital size, season and type of unit
What causes collapsing glomerulopathy
It is idiopathic but it has been associated with some drug toxicities (pamidronate) and it is the most characteristic lesion of HIV-associated nephropathy
How do men present with pyelonephritis
They appear ill and may have hypotension
Also have the fever, chills, flank pain/costovertebral angle tenderness that follow the symptoms of UTI
May also find prostate enlargement in older males with pyelonephritis
Combined with findings of pyuria and bacteriuria
What can cause intrarenal reflux
Vesicoureteral reflux also affords a mechanism to propel infected bladder urine up to the renal pelvis and deep into the renal parenchyma through open ducts at the tips of the papillae
How can diabetes cause acute pyelonephritis
Increases susceptibility to infection
Causes neurogenic bladder dysfunction
Undergo more frequent instrumentation
List the potential outcomes of a UTI
Minor, uncomplicated ones resolve on their own w/o the help of antibiotics
A more severe bladder infection left untreated can spread to kidneys and cause permanent damage
What is the function of the renal corpuscle
Production and collection of glomerular filtrate.
Which types of glomerulonephritis present with nephritic syndrome
Classic presentation of acute post-streptococcal GN
RPGN
Describe the recovery phase of AKI
Increase in urine output (up to 3L per day) as the damaged tubules lose a lot of water, sodium and K+ via the urine.
For some reason patients become vulnerable to infection in this stage .
With time, tubular function restored, and urine concentration returns to normal.
BUN and creatine return to normal
The symptoms will be the same across the different forms of ovarian carcinoma - true or false
True
Describe the pathological features of an ovarian dermoid cyst
They usually appear complex
They have a variety of appearances due to the different tissue types that can arise within them
What is meant by the term septicaemia
Usually implies that there was bacteraemia associated with one or more organ failures
Often used by pathologists as the final process causing death
What supports the glomerular tuft
The mesangium
A meshwork that mesangial cells are embedded in
Describe the appearance of oncocytomas
Well-circumscribed epithelial lesion made up of eosinophilic cells thought to arise from DCT
Most causes of urinary tract obstruction can be resolved either with surgery or medical management - true or false
True
Most ovarian cysts will not be fatal - true or false
True
Correction of volume depletion and hypotension generally reverses oliguria in sepsis - true or false
True
Describe how antibodies directed against normal components of the GBM lead to glomerulonephritis
You can get anti-GBM antibodies which bind to intrinsic antigens homogenously distributed along the entire length of the GBM
Causes a diffuse linear pattern of staining for the antibodies by IF techniques
Causes <5% of cases of human GN but is the cause of severe necrotising crescentic glomerular damage + clinical syndrome of RPGN
Describe the structure of solid clear cell carcinomas of the ovary
If they are predominantly solid the clear cells will be arranged in sheets or tubules
List risk factors for renal cell carcinoma
Tobacco smoking – smokers have 2x incidence of RCC
Obesity
HTN
Pre-existing renal disease, particularly CKD and some cystic disease
A strong family history of renal cancer – some autosomal dominant syndromes, particularly VHL (Von Hippel-Lindau Syndrome)
How is sepsis typically diagnosed at autopsy
In most cases, microbiology is used to diagnose
How would acute proliferative GN present on IF microscopy
Granular deposits of IgG and C3 (sometimes IgM) in the mesangium and along the GBM
What is the function of the distal convoluted tubule
Creates acid-base and water balance
Absorption of water, Na+ and bicarbonate, excretion of K+ and H+
What is the most common benign lesions of the ovary
Functional ovarian cysts
What is the most common cause of nephrotic syndrome in adults
Focal Segmental Glomerulosclerosis (FSGS)
What is thought to cause Pauci-immune crescentic GN
Thought to be a manifestation of small-vessel vasculitis or polyangiitis, which is limited to the glomerular and (possibly) peritubular capillaries.
List the parts of the nephron
Renal corpuscle
Proximal convoluted tubule
Loop of Henle
Distal convoluted tubule
What causes hypovolaemia in sepsis
Vasodilation + increased capillary permeability result in low circulating volume
Hypovolaemia is compounded by reduced LV contractility
This results in hypotension
How do you diagnose prostate cancer
Transrectal biopsy is needed to confirm diagnosis
List the common symptoms of ovarian cancer
Abdominal pain and distension - most common symptoms
Pelvic pressure
Vaginal bleeding
Urinary and GI tract symptoms due to compression or invasion by the tumour - urinary symptoms can include frequency and dysuria
Feeling full quickly
Progressive weakness, weight loss and cachexia can also occur
How do mesangial cells respond to injury
They proliferate
Releases angiotensin II, chemokines, attract inflammatory cells
List clinical features of prostatic adenocarcinoma
Localised disease is often asymptomatic
May be found on digital rectal exam - abnormal nodules felt
Urinary obstruction - may present in more advanced disease
Elevated PSA
What is the most common sites of infection in sepsis cases in those over 65
Genitourinary tract
Describe the structure of a angiomyolipoma
Neoplasm comprised of vessels, fat and smooth muscle
What is chronic pyelonephritis
A more complex condition that is a complication if UTIs
It can affect the bladder (cystitis), the kidneys and their collecting systems (pyelonephritis), or both
Which operations may be used in the treatment of ovarian cancer
A hysterectomy, salpingo-oophorectomy and omentectomy can all be carried out together
If the women is premenopausal and the carcinoma is confined to one ovary or both then the aim will be to only remove the effected ovaries and leave the uterus in place so they can still carry a pregnancy
How does immune complex mediated GN present in IF microscopy
granular deposits
Describe the pathological features of an ovarian endometrioma
They contain thick, gelatinous, dark, aged blood products and are therefore referred to as chocolate cysts
What form the renal corpuscle
The glomerulus and Bowman’s capsule
Which types of glomerular injury are caused by damage to podocytes and nephrotic syndrome
Overall causes non-proliferative glomerular injury which includes
Primary glomerular injuries such as: Membranous nephropathy Minimal change disease Focal Segmental Glomerulosclerosis (FSGS) Membrano-proliferative GN (MPGN) IgA nephropathy
Also the cause in cases secondary to systemic diseases such as diabetes and SLE
What are the morphological hallmarks of acute pyelonephritis
Patchy interstitial suppurative inflammation
Intratubular aggregates of neutrophils
Neutrophilic tubulitis
Tubular injury
How can acute pyelonephritis lead to pyonephrosis
Seen in those with total or almost complete obstruction - particularly when it is high in the urinary tract
Suppurative exudate is unable to drain and fills the renal pelvis, calyces and ureter with pus
What is the function of the proximal convoluted tubule
Reabsorption of water, proteins, amino acids, carbohydrates & glucose
Sepsis is common in which patient groups
Those with cancer or underlying immunosuppression
What is urosepsis
Sepsis caused by UTI
This can possibly lead to death
What causes type 1 MPGN
Immune complexes in glomerular and activation of both classical + alternative complement pathways
Indicative of an immune complex pathogenesis.
Sepsis is more common in which age groups
People over 65 years old are particularly susceptible
Describe the macroscopic appearance of prostatic adenocarcinoma
Can be difficult to identify Typically solid, white-grey lesion with gritty appearance
Poorly defined
Lesions may be easier to feel than see – will be gritty and firm compared to spongey feeling of normal prostatic tissue
What is the other name for type 2 MPGN
Dense Deposit Disease
What can the pattern of necrosis and casts in ATN tell you
Specific patterns are associated with each subtype - ischaemic and toxic
Tubular injury can have specific appearance in certain types of poisoning such as mercuric chloride or ethylene glycol
What is the most common treatment regime used for ovarian cancer
Most cases are managed with a combination of chemotherapy and surgery
Surgery is the main treatment
What is the main underlying cause of the symptoms of AKI
Electrolyte and fluid imbalances
How do you treat hyperkalaemia
Calcium chloride or gluconate for cardio protection
Insulin to trigger K+ uptake
Salbutamol again for K+ shift
Definitive is K+ removal by treating the underlying cause, if not quick may require renal replacement
What is acute proliferative glomerulonephritis
Cluster of diseases characterised histologically by diffuse proliferation of glomerular cells and associated with influx of leukocytes
Typically caused by immune complexes
Describe the epidemiology of AKI
Occurs in up to 18% of hospital patients and around 50% of ICU patients.
Post-op AKI develops in around 1% of general surgery cases.
Around 21% of solitary kidney recipients will develop AKI within 6 months.
A study in Wales found the incidence to be 577 per 100,000 population.
Describe the macroscopic appearance of serous ovarian carcinoma
Can either be a mass that project from the ovarian surface
OR
they can be a multicystic lesion where papillary epithelium is contained within fibrous walled cysts ( the latter being termed intracystic)
What symptoms can be caused by uraemia
neurological symptoms such as lethargy, reversal of the sleep-wake cycle, cognitive and memory issues
nausea, vomiting and anorexia
What is the prognosis for prostate cancer that has metastasized
survival rates drop to as low as 30%
List the main tests run in a patient with suspected sepsis
Blood culture - before antibiotics Serum lactate Hourly urine output Urea and electrolytes Serum glucose Clotting screen Liver Function Tests C-reactive protein Serum procalcitonin (new) Blood gas ECG
What are the complications of transrectal biopsy for prostate cancer
Can lead to infection and a raised PSA
May not correctly identify malignancy due to small tissue samples
How does dense deposit disease (T2 MPGN) present
Nephritic syndrome w/ haematuria ± nephrotic syndrome w/ proteinuria
Overlaps with that of MPGN
What causes pre-renal AKI
Due to decreased perfusion or volume depletion
Hypovolaemia – haemorrhage, diarrhoea and vomiting, burns and pancreatitis
Decreased cardiac output - shock, MI, heart failure
Systemic vasodilation - sepsis, drugs
Renal vasoconstriction - NSAID, ACEi, ARB, hepatorenal syndrome
What forms a lobe of the kidney
Each medullary pyramid + its associated cortical tissue
What is the definition of anuria
less than 100ml of urine per day
What causes follicular ovarian cysts
These occur either because the follicle has failed to rupture allowing ovulation or because the follicle has ruptured and then sealed immediately
What is the median age of diagnosis for prostate cancer
66
Which surgical techniques are used for ovarian cyst removal
Most are done laparoscopically but of the cyst is particularly large or there is chance that it is cancerous it will be removed via a laparotomy
Which types of glomerulonephritis cause nephrotic syndrome
Minimal change disease
Membranous nephropathy
FSGS.
What morphological changes are seen in chronic urinary tract obstruction
Cortical tubular atrophy with marked diffuse interstitial fibrosis.
Following this you will see progressive blunting of the apices of the pyramids which ultimately results in the pyramids becoming cupped
How common is prostatic adenocarcinoma
Seen in 20% of over 50s and 70% of over 70s
Which areas of the renal pelvis are affected by urothelial cancer?
When in renal pelvis, may be confined to the calyces or may begin to invade renal parenchyma
BRACA 1 or 2 mutations cause which type of ovarian carcinoma
It will almost always be a high grade serous carcinoma with TP53 mutations.
It is rare however to find BRACA 1 and 2 mutations in sporadic high grade serous carcinoma
How does AKI present
A rapid decline in GFR, raised serum creatine and/or decreased urine output
What causes acute pyelonephritis
Generally caused by bacterial infection
Associated with urinary tract infection
The infection can reach the kidney via hematogenous spread or through ureters in association with vesicoureteral reflux
What is the most common form of primary ovarian neoplasm
Ovarian carcinoma
What is the recommended antibiotic regime for acute pyelonephritis
Primary Care: Co-trimoxazole 960 mg bd or Co-amoxiclav 625mg tds (7 days)
Secondary Care: Amoxicillin IV 1g tds + Gentamicin IV (Total IV/PO 7 days)
If penicillin allergic: Co-trimoxazole IV 960mg bd + Gentamicin IV
Step down for all patients: Co-trimoxazole PO 960mg bd or as per sensitives
Where are the kidneys found
Upper retroperitoneal area
Right lies slightly inferior (L1-L3) to left (T12-L2) due to the liver
What are the most common malignant ovarian tumours
Serous carcinoma
List the pathological features of ATN
Membrane proteins redistributed from the basolateral to luminal surface of the tubular epithelial cells.
Patchy necrosis throughout the tubules - seen at multiple sites along the tubule with large skip areas in between.
Get a loss of brush border, flattening of the cells due to dilatation, detachment of cells and cast formation.
May be associated with rupture of the basement membrane and occlusion of the tubular lumen by casts.
May also see interstitial oedema and accumulations of leukocytes within dilate vasa recta
List the most common causes of urinary tract obstruction
Congenital anomalies Urinary Calculi Benign Prostatic Hypertrophy Tumours Sloughed papillae or blood clots Pregnancy Uterine Prolapse and Cystocele Functional Disorders
What is PUNLMP
Papillary urothelial neoplasm of low malignant potential
What happens to glomerular filtrate in ATN
It can leak into the interstitium - due to disruption of the tight junctions between cells
This causes oedema, increased pressure and further tubular damage
This contributes to the overall decrease in GFR
How would acute proliferative GN present on electron microscopy
Discrete, amorphous, electron-dense deposits on the epithelial side of the membrane, often having the appearance of “humps” - potentially Ag-Ab complexes at subepithelial cell surface
This is characteristic
Subendothelial deposits also commonly seen, typically early in disease course, and mesangial and intramembranous deposits may be present
List bacteria that commonly cause pyonephrosis
Escherichia coli Enterococcusspecies Candidaspecies and other fungi Enterobacterspecies Klebsiellaspecies Proteusspecies Pseudomonasspecies Bacteroidesspecies Staphylococcusspecies Salmonellaspecies Mycobacterium tuberculosis
What causes renal AKI
Intrinsic renal disease
Glomerular causes: glomerulonephritis and ATN (prolonged hypoperfusion causing intrinsic damage)
Interstitial causes: drug reactions, infections, infiltration from systemic diseases (e.g., sarcoidosis)
Vascular causes: renal artery or vein obstruction, vasculitis, HUS, TTP, DIC, transplant rejection
How does BPH present
Urinary symptoms – both storing and voiding
List risk factors for ovarian cysts
Infertility treatment
Tamoxifen therapy
Pregnancy – usually the cysts will form in the second trimester as this is when the HCG levels peak
Maternal Gonadotrophins – these lead to foetal ovarian cysts
Smoking
Tubal ligation – this leads to functional cysts
Endometriosis
Severe pelvic infection – if it spreads to the ovaries it can result in cyst formation
A previous ovarian cyst
How do you treat sepsis
Begin treatment as soon as sepsis has been verified (NEWS2 of 5 or>5 in a patient with likely infection) by a senior clinician (ST3 or above)
Start the Sepsis 6 aka BUFALO
What is the definition of oliguria
daily urine volume of less than 400mL
Which mutations are seen in low grade serous carcinoma
Mutations in KRAS, BRAF and EGFR2 oncogenes along with wild type TP53 genes are found
What determines the clinical course of sepsis
Depends on many factors like the type and resistance profile of infectious organism + the site and size of the infecting insult and the genetically determined or acquired properties of the host’s immune system
Why do you get a retention of waste products in AKI
Waste products normally excreted by the kidney but due to lack/loss of function they build up instead
What is the most common renal cancer
Renal cell carcinoma
Makes up 80-90%
Describe the microscopic appearance of low-grade papillary urothelial carcinoma
Orderly, cohesive cells w/ scattered nucleic changes and mitotic figures
What causes nephrotoxic ATN
caused by drugs, radiocontrast, heavy metals, poisoning etc.
Why is recovery from AKI thought to be possible
Because the necrosis is patchy and the basement membrane is usually maintained in other segments.
Therefore can be reversed if cause is removed/treated
cause is removed/treated Depends on the capacity of the injured epithelial cells to proliferate and differentiate
Describe the GI complications of AKI
GI complications such as nausea, vomiting and anorexia are very common (sign of uraemia).
1/3 of patients will have some form of GI bleed.
Also get pancreatitis ( AKI causes increased amylase) and jaundice (hepatic congestion and sepsis).
Lower urinary tract infection can potentially spread to the kidney - true or false
True
How can an ovarian cyst be fatal
If it is a dermoid cyst or endometrioma with malignant transformation it carries a poor prognosis and will likely be fatal due to the cancer
If the cyst causes a haemorrhage this can also be fatal
Which structural and functional changes can ischaemia cause in the tubular epithelial cells
An early effect is the loss of cell polarity due to redistribution of membrane proteins such as the sodium potassium pump
When might pyelonephritis present with a negative urine culture
When an obstruction of the upper urinary tract is present e.g. due to stone disease
List risk factors for death from AKI
Pulmonary complications Older age Multiorgan failure Oliguria Hypotension Number of transfusions AKI occurring alone
Describe the pathogenesis of urothelial cancer
Cells lining the urinary tract are exposed to carcinogens as they are concentrated and excreted in urine
This leads to a field effect’ with high proportion of multifocal or synchronous tumours
Tumours will develop following either a papillary or a CIS pattern
What causes PCOS
The aetiology is incompletely understood
They do however have excessive androgen production (central feature) and dysregulation of enzymes involved in androgen biosynthesis
Clear cell carcinoma of the ovary is thought to be a variant of endometrioid adenocarcinoma - true or false
True
This is due to the fact they sometimes occur alongside endometriosis or endometrioid ovarian carcinoma and look like clear cell carcinoma of the endometrium
Long-term catheterization carries a risk of urinary tract infection - true or false
True
Endometriomas have some risk of malignant transformation - true or false
True
There is a low risk of malignant transformation but they do increase the chances of malignancy in endometriosis
Describe lipiduria
Seen in nephrotic syndrome
The lipoproteins are resorbed by tubular epithelial cells and then shed along with injured tubular cells that have detached from the BM
Appears in the urine either as free fat or oval fat bodies
Dense deposit disease (T2 MPGN) has a good prognosis - true or false
False
Poor prognosis with >50% progressing to ESRD
Describe the clinical course of uncomplicated acute pyelonephritis
Usually follows a benign course and symptoms disappear within a few days after the institution of appropriate antibiotic therapy
What forms the crescents seen in glomerular injury
These are accumulations of cells composed of proliferating glomerular epithelial cells and infiltrating leukocytes
The proliferation occurs following an immune/inflammatory injury involving the capillary walls. This causes plasma proteins to leak into the urinary space where exposure to procoagulants is thought to cause fibrin deposition and triggers the crescents to form
List potential complications of omentectomy in the treatment of ovarian cancer - removal of part of the omentum
Pain
Lymphoedema
Potentially permanent nerve damage
List the different histological classifications of glomerulopathies
Focal - involves only a fraction of the glomeruli in the kidney
Diffuse - involving all of the glomeruli in the kidney
Global - involving the entirety of individual glomeruli
Segmental - affecting a part of each glomerulus
Crescentic - presence of crescents
Proliferative
Non-proliferative
- Usually refers to presence / absence of proliferation of mesangial cells
Capillary loop - predominately affects capillary regions
Mesangial - predominately affects mesangial regions
Describe the rate progression of low grade serous carcinomas of the ovary
The low grade forms of this tumours will often progress slowly even once they have spread outwith the ovary meaning that these patients can survive for long periods
List common sites of metastases in ovarian cancer
Regional lymph nodes Lungs Liver GI tract and elsewhere....
List the 4 main responses of the glomerulus to injury
Hypercellularity
Basement membrane thickening
Hyalinosis
Sclerosis
Which features of minimal change disease suggest an immunological basis to the condition
The clinical association with respiratory infections & prophylactic immunisation.
The response to corticosteroids ± other immunosuppressive therapy.
The association with other atopic disorders (e.g., eczema, rhinitis)
The increased prevalence of certain HLA halotypes in cases associated with atopy (suggesting genetic predisposition)
Increased incidence of minimal change disease in patients with Hodgkin lymphoma, in whom defects in & cell-mediated immunity are well recognised
However, the absence of immune deposits in glomerulus excludes immune complex-mediated injury
How do catheters cause UTIs
Catheters inoculate organisms into the bladder & promote colonization by providing a surface for bacterial adhesion and causing mucosal irritation
List the features of Anti GBM antibody mediated GN
Characterised by linear deposits of IgG and (in many) C3 in the GBM
The anti-GBM antibodies cross-react with pulmonary alveolar BMs in some patients
This leads to pulmonary haemorrhage associated with renal failure (Goodpasture syndrome).
What is the most common primary prostate neoplasm
Adenocarcinoma
Almost always the case
List the clinical features of AKI
High serum creatine
Rise in blood urea nitrogen (BUN)
Decreased urine output - in severe cases you get oliguria or anuria (gives worse prognosis)
Describe the macroscopic features of mucinous carcinomas of the ovary
Produce cystic masses
These masses are larger than the ones produced by serous tumours. Mucinous tumours have been know to form cystic masses up to 25Kg in weight
These tumours are multiloculated and are full of gelatinous fluid that is rich in glycoprotiens and is sticky
How does membranous nephropathy present on light microscopy
Glomeruli appear normal in early stages or show uniform, diffuse thickening of the glomerular capillary wall.
Immediately after the injury BUN and creatine can be normal - true or false
True
If you have a patient with a NEWS2 score of 5 or more how should you escalate
Arrange urgent assessment by a senior clinical decision-maker - CT3/ST3 or higher in the UK, or a trained nurse with prescribing rights in acute care If necessary (e.g. NEWS2 score of 7 or more) arrange an emergency assessment by a critical care specialist
List the main scoring systems for AKI
Kidney Disease: Improving Global Outcomes (KDIGO)
Acute Kidney Injury Network (AKIN) classification
RIFLE (risk, injury, failure, loss, end stage renal disease) system
Also have pRIFLE which is the paeds version
What is acute pyelonephritis
A suppurative inflammation of kidneys caused by bacterial and sometimes viral (polyomavirus) infection
List possible causes of the high rates of UTIs in post-menopausal women
Bladder or uterine prolapse causing incomplete bladder emptying
Loss of estrogen with attendant changes in vaginal flora - e.g. more gram-negative aerobes like E Coli
Higher likelihood of concomitant medical illness e.g. diabetes
How does hydronephrosis present clinically
Can remain clinically silent for long periods of time even when it is caused by complete obstruction if it is unilateral as the unaffected kidney can maintain adequate renal function
If the obstruction is relived within the first few weeks of hydronephrosis forming then the kidney function can return to normal
What is RPGN
A clinical syndrome assoc. with severe glomerular injury
However, does not denote a specific aetiology.
You get a relatively rapid + progressive loss of renal function - rapid decline in GFR (hrs-days)
Associated with severe oliguria and signs of nephritic syndrome.
How do the kidneys appear in Crescentic (Rapidly Progressive) GN
They are enlarged + pale
Often have petechial haemorrhages on cortical surface
How can bladder infection cause acquired vesicoureteral reflux
It is postulated that bacteria themselves or the associated inflammation can promote reflux by affecting ureteral contractility, particularly in children
Which congenital abnormalities can cause urinary tract obstruction
Posterior urethral valves Urethral strictures Severe vesicolurectal reflux Meatal stenosis Bladder neck obstruction - caused by ureteropelvic junction narrowing or obstruction
Which tumours can cause urinary tract obstruction
Bladder tumours
Prostatic carcinoma
Carcinoma of the cervix or uterus
Contiguous malignant disease -retroperitoneal lymphoma
What is the other name for acute tubular necrosis
acute tubular injury
List the clinical features of meningococcal (Neisseria meningitidis) bacteraemic shock
DIC is prominent
Haemorrhagic rash
Anuria in AKI is suggestive for what
bilateral obstruction or catastrophic damage
Describe the structure of the proximal convoluted tubules
Has very highly specialised cells Cuboidal epithelium Brush border - gives fuzzy border Microvillous apical surface Mitochondria are abundant Larger than the DCT
Podocyte changes are completely reversible after corticosteroid therapy - true or false
True
This is concomitant w/ remission of proteinuria
Describe the structure of cystic clear cell carcinomas of the ovary
If they are predominantly cystic the neoplastic cells will line the cystic spaces
Describe the role of the activated endothelium in the pathophysiology of sepsis
Activated endothelium allows adhesion and migration of stimulated immune cells & becomes porous to large molecules such as proteins, resulting in tissue oedema
List the histological features of type 2 MPGN
Many have a mesangial proliferative pattern of injury, in some, dense deposits can be seen permeating GBM
Permeation of lamina dense of GBM by ribbon-like, homogenous, extremely electron-dense material of unknown composition.
C3 in irregular granular or linear foci in BMs on either side of, but not within, dense deposits.
Also seen in mesangium in circular aggregates (mesangial rings).
Describe the macroscopic features of acute pyelonephritis
Will see suppuration – discrete focal abscesses or large wedge-like areas
Can involve one or both kidneys
Cortical surface shows grayish white areas of inflammation and abscess formation
List the histological features of acute proliferative GN
Enlarged, hypercellular glomeruli
Global, diffuse proliferation and leukocyte infiltration (i.e. involves all lobules of glomeruli).
Also swelling, which coupled with proliferation and leukocyte infiltration obliterates capillary lumens.
Crescents if severe
Which women are at higher risk of UTI
The elderly
Pregnant
Have pre-existing urinary tract structural abnormalities or obstruction
List causes of secondary glomerulonephritis
Infections or drugs associated with malignancies
Part of systemic disease (ANCA-associated vasculitis, SLE, Goodpasture’s, HSP).
Squamous cell bladder cancer is associated with exposure to what
Schistosomiasis
A history of chronic infection or irritation e.g. in frequent catheter use
What is the most characteristic lesion of HIV-associated nephropathy
collapsing glomerulopathy
How does FSGS present on light microscopy
In sclerotic segments you see collapse of capillary loops, increase in matrix & segmental deposition of plasma proteins along capillary wall (hyalinosis), which may occlude capillary lumens.
Lipid droplets and foam cells are often present.
However, the focal & segmental lesions may be missed on biopsy so may not be seen
Which other conditions are associated with PCOS
It is also associated with obesity, premature atherosclerosis and type 2 diabetes
How might the bladder appear macroscopically in UTI
There is no specific macroscopic appearance for UTIs.
However if UTI is due to chronic urinary tract obstruction, we can see the bladder become enlarged and hypertrophied and bladder wall thickened
What is the most common subtype of renal cell carcinoma
Clear cell carcinoma
Makes up 70-80% of newly diagnosed cases
Damage to the podocytes leads to what clinical picture
Non-proliferative lesion + protein in urine
What are the complications of androgen deprivation therapy in prostate cancer
Cognitive impairment
Gynecomastia
Metabolic disturbances
Erectile dysfunction
What is the leading cause of AKI
Septic shock
Even those with more minor infection are at higher risk of AKI.
High grade serous carcinoma arises in association with which lesions
In situ lesions on the fallopian tube fimbriae - serous tubal intraepithelial carcinoma
OR
Serous inclusion cysts in the ovary
Are most UTIs complicated or uncomplicated
Uncomplicated
In glomerular injury how does the basement membrane thickening appear on light microscopy
It appears as thickening of the capillary walls
Periodic acid-Schiff (PAS) stain is best.
Renal papillary adenomas are precursors to renal cell carcinoma - true or false
True - ish
Histologically similar to low-grade RCC but most do not appear to progress - potentially some act as a precursor
Bilateral endometrioid ovarian carcinoma suggests what
If the carcinoma is bilateral it suggests that the carcinoma has spread outwith the genital tract
What is septic shock
It is a subset of sepsis - indicates profound circulatory, cellular, and metabolic deterioration
List risk factors for candiduric UTIs
DM, indwelling urinary catheters and antibiotic use
Describe ovarian cystadenomas
Develops on the surface of the ovary
Can be serous or mucinous - filled with either watery or mucous material
Can become very large and increase the risk of ovarian torsion
List the most common causes of AKI
Sepsis Major surgery Cardiogenic shock Other hypovolaemia Drugs Hepatorenal syndrome Obstruction
In that order
Which part of the nephron is most vulnerable to apoptosis
Apoptosis more commonly seen in distal parts of the nephron
Normal human bladder & bladder urine are sterile - true or false
True
What is the function of the collecting tubules and ducts
Reabsorption of water under the control of ADH.
Describe how blood flow is disrupted in ATN
Intrarenal vasoconstriction leads to reduced glomerular blood flow and reduced oxygen delivery to the functionally important tubules.
The blood flow is the driving force behind renal filtration so if it reduces so does GFR.
This is caused by a variety of pathways including activation of RAAS by decreased Na due to lower pressure and endothelial injury
Which biochemical factors are monitored in AKI patients
Regular monitoring of fluid balance, K+, lactate if septic and creatine are important
How is a candiduric UTI defined
more than 1000 CFU/mL of yeast from 2 cultures
List the features of nephrotic syndrome
Proteinuria >3.5g/day (mostly albumin) Hypoalbuminemia (<3g/dL) Generalised oedema (most common PC) Hyperlipidaemia + lipiduria Usually normal renal function
Which AKI cases typically require renal replacement therapy
Fluid overload unresponsive to medical treatment
Severe or prolonged acidosis
Recurrent or persistent hyperkalaemia despite treatment
Uraemia
Pulmonary oedema
How is GFR affected in hydronephrosis
It is usually unaffected at the beginning but can fall later in the disease process
This is because the initial changes in hydronephrosis are mainly tubular not vascular
However, with time medullary functional disturbances occur due to reduced blood flow
Malignant Brenner tumours are the equivalent to which type of ovarian carcinoma
low grade ( type 1 ) ovarian carcinomas The Brenner tumours are usually in stage one when they present
Describe the role of the coagulation system in the pathophysiology of sepsis
Alterations in the coagulation systems include an increase in pro-coagulant factors and reduced levels of circulating natural anticoagulants (which also carry anti-inflammatory and modulatory roles)
Describe the pathological features of cystadenofibromas
These have pronounced proliferation of fibrous stroma that lies under the columnar lining epithelium
They tend to be small and multilocular with simple papillary processes that aren’t as complicated and branching as those in normal cystadenoma
How does advanced membranous nephropathy present histologically
With segmental sclerosis that can progress to total glomerular sclerosis
How does urinary tract obstruction predispose to the movement of microbes from bladder to kidneys
Causes incomplete emptying and stasis of residual urine
This stasis allows bacteria in the bladder to multiply unhindered
What pathological features may you see in healing ATN
May see signs of epithelial regeneration - flattened cells with hyperchromatic nuclei and mitotic figures
With time no evidence of damage is seen
What proportion of nephrotoxic AKI cases will recover
With treatment (removal of toxic cause) 95% will recover Nephrotoxic cases are likely to recover if the toxin has not damaged other organs.
Describe the microscopic appearance of prostatic adenocarcinoma
Form glands with a specific, defined pattern
Typically glands are smaller than benign glands without stroma/ epithelial infoldings/ outer basal cell layer
Will correspond to a Gleeson grade
Endometrioid ovarian carcinomas are low grade tumours - true or false
True
List the layers which separate the blood from the glomerular filtrate
capillary endothelium - simple squamous which is fenestrated
Capillary epithelium - made of podocytes (specialised visceral epithelium)
List histological features of Crescentic (Rapidly Progressive) GN
Presence of crescents in Most of the glomeruli
often show focal and segmental necrosis, and variably, endothelial proliferation, and mesangial proliferation
Prostatic Adenocarcinoma typically occurs in which part of the prostate
The peripheral zone
Papillary necrosis following acute pyelonephritis is usually seen in which patients
Seen in diabetes, sickle cell disease and those with urinary tract obstruction
What is the 5-year survival for clear cell carcinoma of the ovary
Although in advanced stages clear cell carcinoma has a poor prognosis, when it is confined to the ovary its 5yr survival is around 90%
What determines the prognosis of AKI
Dependent on the magnitude and duration of the AKI and the underlying cause
Clear cell carcinomas may not produce any identifiable symptoms until they are quite large - true or false
True
May not have symptoms until they are over 10cm
15% of newly diagnosed cases will already have mets
List some of the most common benign renal tumours
Renal papillary adenomas
Angiomyolipoma
Oncocytoma
Once mucinous carcinomas have spread outside the ovary they are usually fatal - true or false
True
However, they are uncommon tumours
