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.
