Renal pathology Flashcards
1
Q
State the functions of the kidney.
A
- Endocrine function - prod of erythropoietin, renin, active 25-hydroxy vitamin D
- Reabsorb glucose, amino acids and bicarbonates
- Maintain balance of electrolytes, water & pH
- Control BP
- Excrete waste/excess products
(2,3,4,5 = homeostasis)
2
Q
Define GFR.
What is the average GFR for a 70kg person?
A
The volume of fluid filtered from the glomeruli into Bowman’s space per unit time (minutes).
90 - 120 ml/min.
3
Q
Why can albumin not pass through the filtration barrier?
A
The barrier is negatively charged, as is albumin.
4
Q
What is creatinine? Define eGFR.
A
Creatinine = waste product of muscles. eGFR = Estimate of creatinine generation based on a patient's serum creatinine level, age, sex and race. Likely to be inaccurate in people at extremes of muscle mass e.g. severely malnourished, amputees, body builders, morbidly obese.
5
Q
What area of the kidney is most vulnerable to ischaemic injury and what does this often result in?
A
PCT. Acute tubular necrosis.
6
Q
What % of cardiac output does each kidney receive?
A
20%
1L/min.
7
Q
Why does water flow out of the blood into Bowman’s space?
A
The afferent arteriole has a wider diameter than the efferent, thus pressure in glomerulus is high & water and solutes are forced out.
8
Q
Why is potassium and hydrogen ion excretion imparied in hypotensive or hypovolaemic patients?
???
A
Renal perfusion is low thus glomerular filtration is also low, which means reabsorption of water and sodium by PCT increases so minimal fluid reaches DCT.
9
Q
List some causes and signs of Fanconi syndrome.
A
A disorder of the PCT.
Causes: cytinosis, Wilson’s, Tenofovir drug (HIV)
Signs: aminoaciduria, glycosuria, phosphate wasting (resulting in rickets/osteomalacia), bicarbonate wasting/acidosis with failure of urine acidification.
10
Q
What is the effect of hyperaldosteronism on electrolyte balance?
A
Excessive Na+ reabsorption resulting in a negative tubular fluid, K+ and H+ rush in to lumen = hypokalaemic alkalosis
11
Q
What is the effect of Addison’s on electrolyte balance?
A
Hyperkalaemic acidosis. Corrected by giving sodium bicarb.
12
Q
What 2 factors govern potassium reabsoprtion?
A
Distal delivery of Na+, aldosterone.
13
Q
State 2 hormones that drive cellular K+ uptake.
A
Insulin, catecholamines (epinephrine). Do so by activating Na/KATPase pumps. Diabetic ke
14
Q
State two types of medication that can cause hypokalaemia and the mechanism by which this occurs.
A
Loop diuretics (inhibit NKCC2 in thick ascending limb), thiazide diuretics (inhibit NCC in distal tubule). The inhibition of Na reabsorption results in greater delivery of sodium to the collecting duct, where enhanced Na influx through epithelial Na channels (eNac) results in potassium efflux, which can result in the development of hypokalemia. “Increase in distal tubular sodium concentration stimulates the aldosterone-sensitive sodium pump to increase sodium reabsorption in exchange for potassium and hydrogen ion, which are lost to the urine. The increased hydrogen ion loss can lead to metabolic alkalosis. Part of the loss of potassium and hydrogen ion by loop and thiazide diuretics results from activation of the renin-angiotensin-aldosterone system that occurs because of reduced blood volume and arterial pressure. Increased aldosterone stimulates sodium reabsorption and increases potassium and hydrogen ion excretion into the urine.”
15
Q
List types of medication that can cause hyperkalaemia.
A
Spironolactone (aldosterone antagonist) Amiloride (acts on eNac channels) ACE inhibitors Angiotensin receptor blockers (ARB)
16
Q
Define acute kidney injury.
A
An abrupt (1-7 days) & sustained (>24 hrs) deterioration in renal function, usually reversible over days - weeks. Often recognised by a falling urine output and rising serum urea and creatinine, or both.
17
Q
Briefly describe the pathophysiology of AKI.
A
Rapid decline in GFR, often due to decreased renal perfusion, leading to a failure to maintain fluid, electrolyte and acid-base homeostasis
18
Q
Who is typically affected by AKI / how common is AKI?
A
Elderly, sepsis (25%), septic shock patients (50%).
18% of hospital patients and ~50% of ICU patients.
Incidence of community acquired AKI is 5% in UK.
Severe AKI affects 130-140 per million population per year.
Mortality rates for uncomplicated sepsis 5-10%, for severe 50-70%.
19
Q
What 3 categories are the causes of AKI divided in to?
A
- Pre renal (40-70%) - reduced kidney perfusion leads to falling GFR.
- Renal (10-50%) - injury to glomerulus, tubules or vessels.
- Post renal (10-25%) - functioning kidneys cannot excrete urine due to urinary tract obstruction
20
Q
What is the RIFLE criteria and what does it stand for?
Old system
A
Describes 3 levels of renal function (RIF) defined by serum creatinine or urine output, and 2 outcome measures (LE) defined by the duration of loss of fxn. Indicates an increasing degree of renal damage and mortality value as you go down the letters.
Risk, Injury, Failure, Loss, End stage renal disease.
21
Q
What is the system currently used to diagnose AKI?
A
KDIGO system. Like RIFLE criteria it uses serum creatinine and urine output to assess severity. Only one criterion (SCr or urine output) has to be fulfilled to qualify for a stage
Stages 1-3. Stage 1:
• Rise in creatinine >1.5x baseline* within 7 days or >26.5μmol/L in 48hrs
• Urine output < 0.5mL/kg/h for >6 consecutive hours
*Baseline = best fig in last 6 months.
22
Q
State the causes of prerenal AKI.
A
Hypoperfusion either due to falling circulating volume:
- Hypovolaemia (e.g. due to dehydration, haemorrhage)
- Hypotension without hypovolaemia e.g. cirrhosis, septic shock
- low cardiac output e.g. cardiac failure, cardiogenic shock
or intrarenal vasomotor changes that drop glomerular perfusion pressure:
-NSAIDs (inhibit production of renal prostoglandins by COX 1 & 2, pglandins dilate afferent arteriole)
-ACE inhibitors
(nephrotoxins)
23
Q
State the causes of intrinsic/renal AKI.
A
Renal parenchyma damage due to:
- 80-90% due to acute tubular necrosis (e.g. due to prerenal damage & nephrotoxins like NSAIDs, uric acid crystals, myeloma, increased Ca2+, also due to
- Vascular damage: renal artery/vein thrombosis, emboli, vasculitis, haemolytic anaemia, haemolytic uraemic syndrome (HUS)
- Glomerular damage: glomerulonephritis, SLE
- Interstitial damage: infiltration with lymphoma, infection, tumour lysis following chemo
24
Q
State the causes of post renal AKI.
A
Urinary tract obstruction at ureter, bladder or prostate due to
- Luminal: stones, clots
- Mural (wall): malignancy, BPH
- Extrinsic compression from malignancy esp from pelvis or retroperitoneal fibrosis
25
How can pre renal AKI be distinguished from renal AKI using biochemical markers?
Prerenal AKI shows higher urine osmolality and lower urine sodium due to salt retention.
Renal AKI may be indicated by immunoglobulins, paraproteion, autoantibodies.
26
What are the risk factors for AKI?
-Age>75yrs
-Male sex
Comorbidities:
-Cardiovasc disease (heart failure, peripheral vascular disease)
-Chronic liver disease i.e. cirrhosis
-Diabetes M
27
How does AKI present clinically?
- On examination there may be palpable bladder, palpable kidneys (polycystic disease)
- Loin & groin pain
- Oliguria
- Symptoms of uraemia: weakness, fatigue, anorexia, nausea, vomiting, mental confusion, seizures, coma
- Breathlessness from a combination of anaemia and pulmonary oedema secondary to impaired fluid excretion/volume overload
- Pericarditis occurs with severe untreated uraemia and may be complicated by a pericardial effusion, tamponade or pericardial rub
- Impaired platelet function causes bruising and exacerbates GI bleeding
- Infection due to immune suppression
28
How does AKI present biochemically?
- hyperkalaemia --> arrhythmias
- metabolic acidosis (unless H+ ions are lost by vomiting which itself can be caused by acidosis)
- hyponatraemia (due to water overload from continued drinking in response to oliguria)
- hypocalcaemia (due to reduced vit D prod)
- hyperphosphataemia
29
State the 3 aims of investigation in AKI.
1. To differentiate acute from chronic uraemia.
2. To establish whether AKI is prerenal, renal or post.
3. To establish the degree of renal impairment and obtain baseline values so that response to treatment can be monitored - measurement of serum urea and creatinine.
30
What investigations might you perform for suspected AKI?
1. Blood count - anaemia & high ESR suggest myeloma or vasculitis
2. Mid stream urine & blood cultures to exclude infection
3. Urine dipstick - can suggest infection (leucocytes + nitrites) and intrinsic renal disease, spec glomerular disease (Haematuria/
proteinuria)
4. Urinary electrolytes to determine prerenal vs renal
5. Serum Ca, Pi, and uric acid.
6. Ultrasound - detect obstruction, assessment of renal size (very small indicates CKD), corticomedullary differentiation (reduced in CKD). CT is useful in detecting retroperitoneal fibrosis & other causes of obstruction (post renal.)
7. Histological investigation: renal biopsy should be performed in every patient with unexplained AKI and normal sized kidneys.
31
How is AKI managed?
-In prerenal, treat hypovolaemia with fluids
-In postrenal, catheterise or if still obstructed consider cystoscopy and retrograde stent or nephrostomy insertion (buys time to allow treatment of cause of obstruction)
Common to all aetiologies of AKI:
-Fluid balance
-Hyperkalaemia:
• Insulin & glucose - drives K+ into cells
• Calcium gluconate - no effect on K levels but reduces the excitability of cardiomyocytes, lowering likelihood of cardiac arrhythmias (cardio protective)
-Treat acidosis with sodium bicarb
-Treat pulmonary oedema with diuretics e.g. furosemide or dialysis/
haemofiltration
-Diet: Na+ & K+ restriction, supply vitamin D
-Dialysis or haemofiltration
nephrotoxins
32
How is fluid balance optimised in hypovolemia?
- Examine before and after all fluid given to ensure an adequate response and to reduce the risk of overload.
1. Give 500mL crystalloid over 15 min.
2. Reassess fluid state. Get expert help if unsure or if patient remains shocked.
3. Further boluses of 250–500mL crystalloid with clinical review after each.
4. Stop when euvolaemic or seek expert help when 2L given.
33
State some causes of hypervolaemia and describe treatment?
Aggressive fluid resuscitation, oliguria, and in sepsis due to increased capillary
permeability.
-Monitor weight daily in patients receiving IV fluids. Treat with:
• Oxygen supplementation if required.
• Fluid restriction. Consider oral and IV volumes. Give antibiotics in minimal fluid
and consider concentrated nutritional support preparations.
* Diuretics. Only in symptomatic fluid overload. They are ineffective and potentially harmful if used to treat oliguria without fluid overload.
* Renal replacement therapy (p306). AKI with fluid overload and oligo/anuria needs urgent referral to renal/critical care.
34
Which ECG changes indicate hyperkalaemia?
Tall ‘tented’ T waves; increased PR interval; small or absent P wave; widened QRS complex; ‘sine wave’ pattern; asystole.
35
When is hyperkalaemia treated and how?
Treat K+ >6.5mmol/L or any with ECG changes (ECG for all K+ >6.0mmol/L)
1. Calcium chloride/calcium gluconate) IV via a
big vein over. This is
cardioprotective (for 30–60min) but does not treat K+
level.
2 IV insulin in glucose - stim intracellular uptake. Monitor hourly for hypoglycaemia which may be delayed in renal impairment.
3. Salbutamol also causes an intracellular K+ shift but high doses are required
(10–20mg via nebulizer) and tachycardia can limit use (10mg dose in IHD, avoid
in tachyarrhythmias).
4 Definitive treatment requires K+ removal. If the underlying pathology cannot
be corrected renal replacement may be indicated. Safe transfer to an off site
renal unit requires K+ <6.5mmol/L—discuss with renal team and critical care.
36
What are the indications for RRT in AKI?
* Persistent fluid overload or hyperkalaemia unresponsive to medical treatment.
* Refractory pulmonary oedema
* Severe/prolonged acidosis.
* Uraemic encephalopathy or pericarditis
* Drug overdose – BLAST ( Barbiturate, Lithium, Alcohol-ethylene glycol, Salicylate, Theophylline)
Haemofiltration is most commonly used but haemodialysis is also an option.
37
What are some risks of RRT?
Risks of dialysis catheter insertion and mainte-
nance: infection procedural hypotension, bleeding due to the requirement for anticoagula-
tion, altered nutrition and drug clearance.
38
When might you refer to a nephrologist?
- Hyperkalaemia or fluid overload unresponsive to medical treatment.
- Urea > 40mmol/L +/- signs of uraemia
- No obvious cause
- Creatinine > 300 or rising > 50micromol/L per day
39
Define acidosis in terms of pH levels.
Mild = pH 7.30–7.36 (~bicarbonate >20mmol/L).
• Moderate = pH 7.20–7.29 (~bicarbonate 10–19mmol/L).
• Severe = pH <7.2 (~bicarbonate <10mmol/L): refer to renal/critical care.
40
How is acidosis treated?
Treatment is of the underlying disorder which will stop acid production. Where effect of treatment may be delayed, acidosis will persist and RRT may be indicated.
Medical management is controversial: giving sodium bicarbonate will generate CO2. Adequate ventilation is therefore needed to prevent respiratory acido-
sis worsening the clinical picture. Sodium bicarbonate also represents a sodium and
a volume load which can precipitate fluid overload in the vulnerable patient.
41
Differential diagnosis of AKI?
Abdominal aortic aneurysm (AAA), alcohol toxicity, alcoholic & diabetic ketoacidosis, chronic renal failure, dehydration, GI bleed, heart failure, metabolic acidosis.
42
What is the prognosis for AKI?
Most common cause of death: sepsis as a result of impaired immune defence (from uraemia and malnutrintion) and intrsumentation (dialysis and urinary atheters and vascular lines).
AKI is irreversible in a few patients probably bc of cortical necrosis which heals with formation of scar tissue, unlike tubules that can regenerate.
43
Define chronic kidney disease.
Longstanding, usually progressive impairment in renal function (haematuria, proteinuria or anatomical abnormality) for more than 3 months, with health implications.
GFR < 60mL/min/1.73 m2 for more than 3 months with/without evidence of kidney damage (haematuria etc)
44
How common is CKD in the general population?
6-11%
45
Describe the epidemiology of CKD.
- risk increases with age thus incidence is rising as we are living longer
- more common in females
46
Why is screening recommended for patients at risk of CKD?
Early intervention can reduce progression to end-stage renal failure.
47
List some of the causes of CKD.
- Idiopathic – 20%
- Congenital/inherited:
- Polycystic kidney disease/any hereditary kidney disease
- Tuberous sclerosis
Glomerular:
-Primary glomerulonephritides e.g. IgA nephropathy
Primary glomerular disease: DM, amyloidosis, SLE
Vascular:
- Hypertensive nephrosclerosis (common in African black ppl)
- atherosclerotic renovascular disease
- Small and medium sized vessel vasculitis
Other:
- Diabetes M – type 2>type 1
- Hypertension
- Neoplasma
- Myeloma
- any causes of chronic urinary tract obstruction
48
What are the risk factors for CKD?
- Smoking
- Old age
- Hypertension
- Diabetes Mellitus
- CVD .e.g ischaemic heart disease
- AKI
- Renal stones
- BPH
- Recurrent UTI’s
- African, Afro-Caribbean or Asian origin
- Chronic use of NSAIDs
49
Why is CKD often asymptomatic in early stages?
The kidney has a lot of reserve capacity - each kidney has roughly 1 mil nephrons.
50
What are some clinical complications/signs & symptoms of CKD?
Renal:
- nocturia
- polyuria
- salt and water retention leading to odeoma
Anaemia (normochromic normocytic) due to reduced EPO prod:
-Pallor, lethargy, breathlessness on exercise. Increased blood loss from gut during haemodialysis may contribute.
```
Bone pain/disease due to renal phosphate retention and impaired vit D prod lead to fall in serum Ca thus increase in parathyroid (secondary hyperparathyroidism) --- skeletal decalcification.
"Renal osteodystrophy" =
-Osteoporosis
-Osteomalacia
-hyperparathrydoisim
-Osteosclerosis
```
Neurological complications.
- CNS: advanced uraemia (toxic metabolic accumilation) causes depressed cerebral function e.g. confusion, fits, coma
- PNS:
- polyneuropathy manifests as peripheral parasthesia / weakness.
- autonomic dysfunction presents as postural hypotension and disturbed GI motility
- median nerve compression in carpal tunnel syndrome caused by amyloidosis (complication of dialysis).
- Several mechanisms involved include toxic metabolic accumulation, hyperkalemia, hypercoagulability, immunologic disturbances, and acid base disequilibrium.
CVS:
-pericarditis and pericardial effusion due to secer uraemia
-MI, cardiac failure, stroke due to hypertension, hyperlipidaemia and vascular calcification
Other:
-anoreixia and weight loss (GI)
-nausea, vomiting, diarrohea (GI)
-insomnia
-itching
-Pruritus due to nitrogenous waste products of urea
51
How can CKD be differentiated from AKI?
| differential diagnosis
- history
- duration of symptoms
- normochromic anaemia, small kidneys and presence of renal osteodystrophy favour CKD.
52
Briefly describe the progressive nature of the pathophysiology of CKD.
In CKD, where many nephrons have failed, and scarred, the burden of filtration falls to fewer functioning nephrons.
These remnant nephrons experience increased flow per nephron (hyperfiltration), as blood flow has not changed, and adapt with glomerular hypertrophy and reduced arteriolar resistance.
Increased flow, increased pressure and increased shear stress set in motion a VICIOUS CYCLE of raised intraglomerular capillary pressure and strain, which accelerates remnant nephron failure.
-each kidney has roughly 1 mil nephrons.
53
What role does the RAAS play in CKD pathophysiology?
Reduced renal perfusion leads to decreased transglomerular pressure and decreased GFR.
The response is intrarenal activation of RAAS:
Angio 2:
-efferent arteriolar/postglomerular arteriole vasoconstriction to increase transglomerular pressure. GFR increases
-increases pore size between mesangial cells and podocytes thus impairing the size-selective function of the basement membrane for macromolecules e.g. protein - resulting in increased proteinuria
-modulates cell growth directly and indirectly by upregulating transforming growth factor-beta (TGF-Beta), a potent fibrogenic cytokine, increasing collagen synthesis and epithelial cell transdifferentiation to myofibroblasts that contribute to excessive matrix formation
-up regulates plasminogen activator inhibitor-1 (PAI-1), which inhibits matrix proteolysis by plasmin - resulting in the accumulation of excessive matrix and scarring in both the glomeruli and interstitium
54
What investigations would you perform in a case of suspected CKD?
Urinalysis:
- Early morn sample for (ACR)/(PCR)
- dipstick analysis for haematuria (indicated glomerulonephritis), proteinuria (if heavy suggests glomerular disease, can be caused by infection)
• Mid-stream urine sample sent for microscopy and sensitivity???
```
- Urine microscopy:
• White cells - bacterial UTI
• Eosinophilia - allergic tubulointerstitial nephritis/cholesterol emboli
• Granular casts - active renal disease
• Red cells - glomerulonephritis
```
-Bloods:
- Serum biochemistry
• Urea, electrolytes, bicarbonate and creatine - HIGH UREA & CREATININE, LOW Ca2+
• Low Hb
• Low eGFR
• Raised alkaline phosphatase (renal osteodystrophy)
• Raised PTH if CKD stage 3 or more
Immunology:
• Auto-antibody screening for SLE, scleroderma and Goodpastures • Hep B, C, HIV and streptococcal antigen tests
maging:
• Ultrasound to check renal size and exclude hydronephrosis
(obstruction & dilation of renal pelvis):
- In CKD kidneys tend to be small
- Can be large in infiltrative disorders e.g. amyloidosis
• CT:
- Detect stones, retroperitoneal fibrosis and other causes of urinary
obstruction and maybe cortical scarring
-Biopsy and histology to diagnose condition causing renal failure
55
What are the aims of treatment in CKD?
1. Specific therapy aimed at underlying cause of renal disease
2. Slow the deterioration of kidney function (renoprotection)
3. Reduce cv risk
4. Treat complications e.g. anaemia
5. Dose adjustment of prescribed drugs based on national formulary guidance.
56
Describe how you would treat CKD in terms of renoprotection.
-goal is to maintain bp less than 12/80mmHg & urinary conc less than 0.3g/24 hrs
-stop smoking, weight loss
Patients with CKD and proteinurea > 1g/24 hrs:
-ACE inhib e.g. ramipril
-Angiotensin receptor agonist e.g. Candesartan if goals not achieved/if diabetic
-diuretic e.g. ORAL BENDROFLUMETHIAZIDE to prevent hyperkalaemia and help BP control
-calcium channel blocker e.g. verapamil if goals not achieved
57
Describe how you would treat CKD in terms of CVD.
- Control bp and proteinurea as described in renoprotection
- smoking cessation, weight loss
- normal protein diet (0.8-1g/kg body weight/day)
- Statins e.g. simvastatin to lower cholesterol
- give aspirin
- optimise diabetic control: HbA1c 53mmol/mol
58
Describe how you would treat CKD in terms of bone disease.
-check PTH, if raised:
Treat hyperphosphataemia:
-restrict diet to low phosphate e.g. avoid milk, cheese, eggs
-phosphate binders e.g. calcium carbonate to decrease gut absorption
-vitamin D analogues e.g. calcitriol and Ca2+ supplements
This will also treat hyperkalaemia.
59
How would you treat anaemia in CKD?
- iron/folate/folic acid
| - recombinant human erythropoeitin (expensive, may lead to hypertension)
60
If a patient fails to respond to treatment for anaemia in CKD, what might this be due to?
- haematinic deficiency
- bleeding
- malignancy
- infection
61
What does acidosis in CKD contribute to and how would you treat acidosis?
- increased serum potassium, dsypnea, lethargy
| - sodium bicarbonate
62
How would you treat oedema in CKD?
Furosemide.
63
What protective measures should be taken in patients with CKD?
Influenza and pneumococcal vacination bc more at risk of infections.
64
When might you refer a patient with CKD to a nephrologist?
- severe CKD: GFR<30mL/min/1.73m2
- rapidly deteriorating kidney function: fall in eGFR> 5mL/min in 1 yr or >10mL/min/year in 5 years
- high levels of protein urea: ACR ≥ 70mg/mmol or PCR ≥ 100mg/mmol
- Proteinurea & haematuria: proteinurea with ≥ +1 blood on urine dipstick
- Poorly controlled hypertension despite use of antihypertensives
- Suspected rare or genetic cause of CKD
65
How does haemodialysis work?
Blood in an extracorporeal circulation is exposed to dialysis fluid separated by an artificial semi permeable membrane. Uraemic toxins diffuse down the conc gradient from blood to dialysis fluid. The gradient is maintained by replacing 'used' dialysis fluid with fresh fluid.
Patients are anticoagulated with heparin bc contact of blood w foreign substances activates clotting cascade.
66
What are the requirements for haemodialysis?
Blood flow must be at least 200ml/min and is achieved by arteriovenous fistula which also provides permanent and easily accesible site for needle insertion.
Patient must be haemodynamically stable, not atherosclerotic, can't have many fistulas.
67
What are some advantages and disadvantages of haemodialysis?
-good clearance of solutes in short periods
-time consuming
Complications may occur:
-hypotension
-nausea
-chest pain
-infected dialysis catheter
68
How does peritoneal dialysis work?
A permanent tube (Tenckhoff catheter) is placed into the peritoneal cavity via subcut channel. Bags of dialysite are connected and fluid runs into peritoneal cavity. Urea, creatinine, phosphate & other uraemic toxins pass into fluid down their conc gradients and fluid is drained out.
P dialysis is done at home.
69
What are some advantages and disadvantages of peritoneal dialysis?
More convenient than haemodialysis bc can be done at home without need for nurses.
Complications:
-infection e.g. peritonitis often with S. epidermidis
-abdominal wall herniation
-intestinal perforation
-loss of membrane function (peritoneum fxn) over time
70
How does haemofiltration work?
Plasma water is removed along with its dissolved constituents (Na, K, urea, phosphate) through a highly permeable membrane, and replaced with solution of desired biochemical composition.
71
What form of dialysis is most commonly used for treatment of CKD?
Peritoneal
72
What form of dialysis is most commonly used for treatment of AKI in the ICU setting?
HaemoFILTRATION.
73
What are some complications of all long term RRT?
- CVD (as a result of atheroma)
- Sepsis due to peritonitis complicating p dialysis, S.aureus infection including endocarditis complicating access to indwelling devices for haemodialysis
- Amyloidosis due to accum of beta 2 microglobulin which is normally removed by kidneys but not by dialysis membranes, can cause carpal tunnel syndrome, arthalgia, fractures.
- malignancy
74
What are the advantages and disadvantages of renal transplant?
- chance of complete rehabilitation
- doubles life expectancy, improves quality of life
- more cost effective than dialysis in long term
-donor must be ABO compatible
-long term immunosuppression e.g. corticosteroid such as prednisone + azathioprine + ciclosporin
Complications:
-opportunistic infection
-hypertension
-tumour developement
-recurrence of renal disease
75
What are renal caliculi (nephrolithiasis) and ureteral stones (urolithiasis) composed of?
Most stones: calcium oxalate (60%) and/or calcium phosphate (10%).
Also uric acid (10%), magnesium ammonium phosphate/struvite (10%), cystine (1%).
76
Which 3 narrowings are renal and ureteral stones most often found?
- pelviureteric junction
- pelvic brim
- vesicoureteric junction (where ureter meets bladder)
77
Describe the epidemiology of renal/ureteral stones.
- incidence is increasing
- 10% lifetime risk
- peak age 20-40
- male:female 2:1
- higher in middle east due to higher oxalate and lower ca diet, also increased risk of dehydration in hot climate
78
Why do renal/ureteral stones form?
The solute concentrations of normally soluble material e.g. calcium exceeds saturation, beginning the process of crystal formation.
79
What are some causes of renal/ureteral stone formation?
- Anatomical abnormalities e.g. horseshoe, duplex, spina bifida
- Hypercalcicuria/hypercalcaemia
- Polycystic kidney disease
- Hyperoxaluria
80
What are some causes of hypercalciuria leading to calcium stone formation?
- Hypercalcaemia (most commonly caused by hyperparathyroidism)
- Excessive dietary intake of calcium
- Excessive resorption of calcium from bone e.g. with prolonged immobilization
- Idiopathic hypercalcaemia: increased absorption of Ca from gut and in turn increased urinary excretion with normal serum calcium levels.
- Primary renal disease e.g. polycystic renal disease or renal tubular acidosis -- alkaline urine favours precip of stones??
81
What are some causes of hyperoxaluria leading to calcium oxalate stone formation?
Increased oxalate excretion favours formation of calcium oxalate even if calcium excretion is normal.
- High oxalate dietary intake: e.g spinah, rhubarb, tea. Or low Ca dietary intake results in hyperoxaluria via decreased intentinal binding of oxalate by Ca thus increased oxalate absoprtion and urinary excretion.
- Enteric hyperoxaluria: chronic intestinal of any cause leads to reduced intestinal Ca for oxalate binding
- Primary hyperoxaluria: rare AR enzyme deficiency
82
What are some causes of uric acid/urate stone formation?
Hyperuricaemia e.g due to impaired excretion (CKD, hypertension) or increased production (increased purine turnover, myeloproliferative disorders e.g. polycythaemia vera).
83
Who is at risk of uric acid stone formation?
Patients with ileostomies bc loss of bicarbonate from GI secretions results in acidic urine and reduced solubility of uric acid.
84
Which UTI causing organisms are associated with struvite stones and how?
Proteus, Klebsiella and Pseudomonas.
They produce enzyme urease which hydrolyses urea to ammonia, raising urine pH. Alkaline urine and high ammonia favour stone formation.
85
What causes cystine stones?
Cystinuria due to AR conditon affecting cystine and other basic aa transport (lysine, arginine, ornithine) across luminal membrane of PCT and small intestine.
86
How do stones present clinically?
- Mostly asymptomatic
- Pain (loin, groin)
- Haematuria
- UTI
- UTO
87
Where are the stones that often cause renal colic found?
Ureteric stones - upper urinary tract obstruction.
88
How do ureteric stones often present?
Renal colic - a severe intermittent (comes and goes in waves as ureters peristalise) pain lasting for hours.
- Rapid onset
- Felt anywhere between loin and groin, may radiate to scrotum or labium or tip of penis.
- Associated w nausea, vomiting
- Haematuria
- Often can't lie still (differentiates from peritonitis)
89
How do bladder stones often present?
Increased urinary frequency and haematuria.
90
How do urethral stones often present?
Bladder outflow obstruction resulting in anuria and painful bladder distension.
91
If infection is present in UTO what may this present as?
Acute pyelonephritis: fever, rigors, loin pain, nausea, vomiting.
92
What are some differentials for renal/ ureteric stones?
- Vascular accident e.g. rupture aortic abdominal aneurysm (AAA) if over 50
yrs - until proven otherwise
- Bowel pathology e.g. diverticulitis or appendicitis
- Ectopic pregnancy or ovarian cyst torsion - do uric pregnancy test
- Testicular torsion - can present with loin pain and nothing else
-Bleeding within kidney e.g. after biopsy can prod clots that temporarily lodge in ureter causing ureteric colic
93
How would you take a history for a patient presenting with renal colic?
SOCRATES.
| Site, onset, character, radiation, associated features, timing, exacerbating/relieving factors, severity.
94
What investigations would you do in a case of suspected renal/urinary tract stones?
-Detailed history - vit D consumption (leading to hypercalcaemia), recurrent UTI's, intestinal resection, gout.
BOXES.
B: Serum urea, electrolyte, creatinine and calcium. FBC.
O: Chemical analysis of any stone passed. Urine dipstick to check for blood, red cells, protein etc. Mid stream urine specimen for culture. Urine preg test to exclude ectopic pregnancy.
X: NCCT-KUB is the 1st line and best diagnostic test available - no contrast so no renal damage, but gives high radiation dose. KUBXR may show radiopaque stones.
95
Why is an ultrasound not used in the investigation of renal/ureteric stones?
Shows kidney stones well ish but poor at visualising ureteric stones.
Useful in pregnant and younger recurrent stone formers (no radiation risk).
96
How would you initially treat renal/ureteric stones?
- strong analgesic to relieve renal colic e.g. IV 75mg diclofenac
- antiemetic to prev vomiting
-most small ureteric stones (≤5mm) will pass spontaneously
97
How would you treat renal/ureteric stones if infection is present?
Antibiotics e.g. IV cefuroxime or IV gentamicin.
| To prevent pyonephrosis
98
What are some indications for intervention in renal/ureteric stones?
- persistent pain
- infection above the site of obstruction
- failure of stone to pass down ureter
99
If a stone does not pass naturally what can be done?
-Extracorporeal shockwave lithotripsy (ESWL) - x ray/ultrasound fragments stone with shockwaves
-Endoscopy (ureteroscopy) with a YAG - laser for larger stones
-Percutaneous nephrolithotomy (PCNL) - keyhole surgery to remove
stones that are large, multiple or complex
-Open surgery as a last resort
100
How is recurrence of renal/ureteric stones prevented?
- for prev of all regardless of cause: high fluid intake (mainstay when no metabolic or renal abnormality can be identified "idiopathic stone formers"), reduce BMI
- Idiopathic hypercalciuria: Normal low calcium diet, avoid high oxalate foods, thiazide diuretics e..g bendroflumethiazide 2.5mg daily to reduce Ca excretion if persists.
- Struvite stones: low-dose long-term prophylatic antibiotics
- Uric acid stones: xanthine oxidase inhib allopurinol which allows excretion of precursor hypoxanthine. Oral sodium bicarb supplements to maintain alkaline urine thus increased solubility of uric acid if unable to tolerate allopurinol.
- Cystine stones: very high fluid intake (5L/24hrs) to maintain solubility of cystine in urine. Urine alkalisation. ACE inhib captopril (binds to cystine, makes more soluble molecule)
101
What are some causes of pyelonephritis?
KEEPS
- Klebsiella pneumoniae
- E.coli (80%)
- Enterococci
- Proteus mirabilis
- Staphylococcus spp. - coagulase negative
102
What are some risk factors for pyelonephritis?
- Mechanical: vesicoureteral reflux, stones
- Diabetes Mellitus
- Immunocompromised states
- Sexual intercourse/change in sexual partner
- Frequent UTIs (most nephritis cases start off as cystitis or prostatitis)
- Pregnancy
- Menopause
103
Who is most at risk of developing pyelonephritis?
- More common in women bc urethra is shorter
| - Young women bc more sexually active
104
How does pyelonephritis often present?
| Differentiate between acute and chronic.
Acute:
Triad of loin pain, fever and pyuria. Also pain on passing urine, and abdominal pain that radiates along the flank towards the back. S&s develop rapidly over a few hours/a day.
Chronic: Persistent flank or abdominal pain, signs of infection (fever, unintentional weight loss, malaise, decreased appetite), lower urinary tract symptoms and blood in the urine. Inflammation-related proteins can accumulate in organs and cause the AA amyloidosis.
105
What would indicate pyelonephritis on urinalysis/blood tests?
-Nitrites (bacteria breakdown nitrates to release nitrites)
-WBC
-FBC might show neutrophilia
CRP & ESR may be raised in acute infection.
106
What is the gold standard for diagnosis of pyelonephritis?
Midstream urine microscopy, culture and sensitivity.
107
Describe the main inflammatory feature of acute pyelonephritis.
-purulent exudate (pus) consisting of
| neutrophils, fibrin, cell debris
108
Describe the main inflammatory feature of chronic pyelonephritis.
-scarring of renal parenchyma
109
What are some differentials of pyelonephritis?
AAA, appendicitis, diverticulitis, endometriosis, pelvic inflammatory disease, kidney stones
110
How is mild pyelonephritis treated?
Oral fluoroquinolone e.g. ciprofloxacin
-If this doesn't work, single IV dose of a long-acting antibiotic e.g. ceftriaxone.
Should improve in 48-72 hrs,
In pregnant women who do not require hospital admission: oral cefalexin
111
How is moderate - severe acute pyelonephritis treated?
| e.g. acute pyelonephritis accompanied by high fever and leukocytosis
- IV fluids to compensate for increased insensible loss due to fever, also to encourage vasodilation and optimise urine output
- broad-spectrum antibacterial such as a cephalosporin (e.g. cefuroxime) or a quinolone if the patient is severely ill; gentamicin
112
In a GP setting, in which cases would you refer patients with pyelonephritis to hospital/a urologist?
-if they have severe systemic infection (signs of sepsis)
-are significantly dehydrated or unable to take oral fluids and
medicines
-are pregnant
-if they are a man?
-have a higher risk of developing complications e.g.
people with structural or functional
abnormality of the GI tract or have underlying diseases e.g. diabetes, immunosuppression
-refer children and young people
113
Define UTI.
The inflammatory response of the urothelium to bacterial invasion, often associated with bacteriuria and pyruia.
Defined as >10^5 organisms/ml of fresh mid-stream urine.
114
What does it mean if a UTI is "uncomplicated"?
UTI in healthy non-pregnant woman with normally functioning urinary tract
115
What does it mean if a UTI is "complicated"?
Infection in patients with abnormal urinary tract e.g. stones, obstruction or systemic disease involving the kidney e.g. diabetes mellitus, sickle-cell, or virulent organism e.g. Staphylococcus Aureus
- men
- pregnant
- immunosupressed
116
What features of E.coli make it apt at sticking to urothelium?
surface attachment molecules: --FIMBRIAE/PILLI
- Afimbrial attachments e.g. glycocalix
- Acid polysaccharide coat that resists phagocytosis
117
Why does menopause make you more susceptible to UTI?
In post-menopause when oestrogen depletes there is loss of lactobacilli and pH rises thus there is increased colonisation by colonic flora & redution in vaginal mucus secretion.
118
What are some features of UTI microbes that make them effective infective agents?
- Capsule to reist phagocytosis
- E.coli release cytokines that are directly toxic
- Release of urease that increases risk of stone formation: Gram-negative; Proteus, Klebsiella & Pseudomonas. Gram-positive; Staphylococci & Mycoplasma
119
What are some host defence mechanisms involved in UTI?
- Antegrade flushing of urine
- Tamm-Horsfall protein - has antimicrobial properties
- Low urine pH and high osmolarity
- Urinary IgA
120
What is pyelonephritis?
Infection of the renal parenchyma and soft tissues of renal pelvis and upper ureter
121
What is cystitis?
Urinary infection of the bladder.
122
What are the risk factors for cystitis?
- Urinary obstruction resulting in urinary stasis
- Previous damage to bladder epithelium
- Bladder stones
- Poor bladder emptying
123
How does cystitis usually present?
- Dysuria
- Frequency
- Urgency
- Suprapubic pain
- Haematuria
- Offensive smelling/cloudy urine
- Abdominal/loin tenderness
124
How is cystitis treated?
```
Antibiotics:
• First-line:
-Nitrofurantoin or
TRIMETHOPRIM
• Second-line:
- CIPROFLOXACIN or CO-AMOXICLAV
```
125
Describe the epidemiology of prostatitis.
- more common in men
- most common UTI in men <50
- associated with LUTS
126
What are some causes of prostatitis?
- E.coli
- Streptococcus faecalis
- Chlamydia
- Elevated prostatic pressure, pelvic floor myalgia
127
What are the risk factors for prostatitis?
- STI
- Indwelling catheter
- Post-biopsy
- Increasing age
128
How does prostatitis often present?
- systemically unwell ?
- fevers, rigor, malaise
- pain on ejaculation
- significant voiding LUTs e.g. poor intermediate stream, hesitancy, incomplete emptying, post micturition dribbling, straining, dysuria
129
What are some differentials for prostatitis?
Cystitis, BPH, calculi, bladder neoplasia, prostatic abscess
130
How would you investigate prostatitis?
- on examination prostate is tender/hot/hard (from calcification)
- urine dipstick - positive for leucocytes and nitrites
- mid stream urine microscopy and sensitivity
- blood cultures
- STI screen for chlamydia
- TRUSS trans urethral ultrasound scan
131
How would you treat acute and chronic prostatitis?
Acute: If severe: IV broad spectrum cephalosporin e.g. cefuroxime, plus gentamycin
If normal: 2-4 weeks on a quinolone e.g. CIPROFLOXACIN (antibiotic) TRUSS guided abscess drainage if necessary.
If allergic/ intolerant of quinolones an alternative is Trimethoprim.
Chronic: 4-6 week course of quinolone e.g. CIPROFLOXACIN. +/- Alpha-blocker e.g. TAMSULOSIN. NSAIDs e.g. IBUPROFEN
132
What is a complication of prostatitis?
Urinary retention.
133
Who is most often affected by urethritis?
- young people aged 15-24 yrs
| - men
134
What is more common, non-gonococcal urethritis or gonococcal?
Non
135
What are the causes of urethritis?
Non-gonococcal:
- Chlamydia trachomatis (most common)
- Myoplasma genitalium
- Ureaplasma urealyticum
Gonococcal: Neisseria gonorrhea
Non infective:
- Trauma
- Urinary caliculi
- Urethral stricture
136
What are the risk factors for urethritis?
- Sexually active
- Unprotected sex
- Male to male sex
137
How does urethritis typically present?
- asymptomatic (90-95% with gonorrhoea, 50% of patients with chlamydia)
- dysuria +/- discharge, blood, pus
- urethral pain
- penile discomfort
- skin lesions
- systemic symptoms
138
What are some differentials for urethritis?
-candida balantis, epididymitis, cystitis, urethral malignancy
139
How is urethritis diagnosed?
| Urethritis = sti's
```
Nucleic acid amplification test (NAAT):
• Female - self collected vaginal swab (best), endocervical swab, first void urine
• Male - first void volume
• High specificity and sensitivity
- Microscopy of gram-stained smears of genital secretions
-Blood cultures
- Urine dipstick to exclude UTI
- Urethral smear
```
140
How is chlamydia treated?
| What about in pregnant women?
ORAL DOXYCYCLINE 100mg bd 7 days or if contraindicated (liver disease, renal disease, lupus)
ORAL ERYTHROMYCIN 500mg bd 14 days.
Pregnant women: ORAL AZITHROMYCIN 1g followed by 500mg daily 2 days
-test for other STIs
141
How is gonorrhoea treated?
IMI 1g CEFTRIAXONE with ORAL AZITHROMYCIN
- partner notification
- patient education
- test for other STIs
142
What is the aim of primary secondary & tertiary prevention of STIs?
Primary: reduce risk of acquiring STI
Secondary: find and treat undetected cases of infection, thereby removing from community pool
Tertiary: reduce morbidity/mortality
143
Describe 3 primary prevention strategies for STIs.
-STI awareness campaigns that aim to reduce personal risk behaviour ( eg “Sex. Worth talking about”)
-One to one risk reduction discussion (NICE 2007)
15-20 minute structured discussion
Based on a behaviour change theory
-Vaccination: Hepatitis B; HPV.
Pre and post exposure prophylaxis
144
Describe some secondary prevention strategies for STIs.
- Easy access to STI / HIV tests / treatment
- Partner Notification: prevent reinfection of index patient, prevent complication in asymptomatic contacts
- Targeted screening: IVDUs, sexually active ppl under 25 esp females, msm.
- Antenatal screening for HIV and syphilis
- National Chlamydia Screening Programme
- National HIV testing week
- HIV home-testing: ‘It start’s with Me’ Terrence Higgins Trust
145
Describe some tertiary prevention strategies for STIs.
Anti-retrovirals for HIV
Prophylactic antibiotics for PCP
Acyclovir for suppression of genital herpes
146
What is partner notification?
“A public health activity that aims to control infection by identifying key individuals and sexual networks,
warn the unsuspecting and attempt to break the chain of infection”
147
What are the complications of Chlamydia?
Male: epididymo-orchitis, reactive arthritis
Female: -Pelvic inflammatory disease: (Infection spreads up to the fallopian tube leading to inflammation
and scarring)
Tubal factor infertility
Ectopic pregnancy
Chronic pelvic pain
-Neonatal transmission
148
A recent change in sexual partner is common in diagnosis of a) Gonorrhoea or b) Chlamydia
Gonorrhoea bc chlamydia is often asymptomatic so often diagnosed in established relationships.
Also gonorrhoea more common in men.
149
What are some causes of syphilis?
Treponema pallidum
150
Describe some s&s of primary, secondary and tertiary syphilis.
Primary: 2 or 3 weeks after infection. Chancre (small painless sore on genitals or anus, fingers, lips.) Any genital ulcer is syphilis until proved otherwise!!
Swollen neck glands.
Secondary: Blotchy red rash, generalised lymphadenopathy, systemic symptoms, small skin growths like genital warts.
Latent syphilis is when these symptoms pass.
Tertiary/Late: Over 2 yrs since infection. CNS: meningitis,
strokes, dementia symptoms
loss of co-ordination,
vision problems or blindness. CVS.
151
What form of sex is syphilis commonly passed on by?
Oral sex.
152
How is syphilis diagnosed?
```
Enzyme immunoassay (EIA) test (screens for antibodies IgM and IgG)
Microscopy of early lesions. Mainstay = Serology of genital ulcer. Treponema pallidum particle agglutination test (TPPA).
-Non specific high sensitivity tests to assess disease activity/stage: Rapid Plasma Reagin test (RPR) and the Venereal Disease Research Laboratory (VDRL)
```
153
How is syphilis treated?
Penicillin IM or oral.
| Follow up testing and partner notification.
154
Define epididymo-orchitis.
Pain, swelling and
| inflammation of the epididymis that can extend into the testis
155
What are the main causes of epidydmo-orchitis?
```
Under 35: Chlamydia trachomatis, neisseria gonorrhoea.
Over 35: UTI extending from urethra/bladder. KEEPS.
Klebsiella
E.coli - most common
Enterococci
Pseudomonas
Staphylococcus - coag neg
Mumps (viral)
```
156
What are the risk factors for epidydmo-orchitis?
- indwelling catheter
- structural/functional abnormality of the urinary tract
- anal intercourse
157
How does epidydmo-orchitis clincally present?
- subacute onset of unilateral scrotal pain and swelling
- in STD epidydmo-urethritis there may be urethritis or urethral discharge
- Mumps usually presents with headache, fever and unilateral or bilateral parotid swelling
- Sweats/fever
- On examination there is tenderness and palpable swelling of the epididymis and also testicles
158
What are some differentials for epidydmo-orchitis?
-Testicular torsion (twisting of the spermatic cord) - urological emergency!! Suggestive features: short duration sudden onset pain, nausea, abdo pain, high riding/bell-clapper testis. Treatment is immediate SURGICAL SCROTAL EXPLORATION.
- Hydrocele
- Trauma
- Abscess formation
159
How is epidydmo-orchitis diagnosed?
- Nucleic acid amplification test (NAAT):
• Female - self collected vaginal swab (best), endocervical swab, first void
urine
• Male - first void volume
• High specificity and sensitivity
• If intracellular gram-NEGATIVE DIPLOCOCCI are present, then this is suggestive of GONORRHOEA
- Mid-stream urine dipstick for UTI symptoms - Ultrasound to rule out abscesses
- STD screening
- Urethral smear and swab
160
How is epidydmo-orchitis treated?
Chlamydia: Oral doxcycline or erythromicin.
Gonorrhoea: IM ceftriaxone + oral azithromycin.
UTI: Oral ciprofloxacin.
Analgesia: NSAIDs e.g. ibuprof
-Partner notification
-Abstain from sexual intercourse
161
Define glomerulonephritis.
A group of parenchymal kidney diseases that result in the inflammation of the glomeruli and nephrons.
162
What are the complications of glomerulonephritis?
-Damage to the filtration mechanism resulting in HAEMATURIA and
PROTEINURIA
- Damage to the glomerulus restricts blood flow, leading to compensatory HYPERTENSION
- Loss of the usual filtration capacity leads to ACUTE KIDNEY INJURY
• end stage kidney failure (25% cases caused by gn)
163
What 4 conditions does glomerulonephritis present as?
- Acute Nephritic Syndrome (Acute glomerulonephritis)
- Nephrotic syndrome
- Asymptomatic urinary abnormalities e.g. haematuria, proteinuria or both
- Chronic kidney disease (CKD)
164
What are some typical s&s of acute nephritic syndrome (acute glomerulonephritis)?
Haematuria - visible or non-visible (red cell casts seen on microscopy). Commonly caused by IgA nephropathy.
- Proteinuria (usually < 2g in 24hrs)
- Hypertension and oedema (periorbital, leg, or sacral)
- Oliguria
- decrease in gfr
- signs of uraemia e.g. anorexia, lethargy
165
What are the causes of acute nephritic syndrome?
Primary: IgA nephropathy. Commonest cause in developed world. IgA deposition in mesangium is attacked. "Mesangial proliferative GN"
- Bacterial infection e.g. MRSA, typhoid
- Hep B & C
- Malaria
- Post-streptococcal infection e.g. STREPTOCOCCUS PYOGENES. Presents 1-3 weeks after strep infection e.g. pharygnitis, tonsilitis
- ANCA associated vasculitis
- SLE
166
What is goodpastures disease and how is it treated?
The co-existence of acute glomerulonephritis and pulmonary alveolar haemorrhage due to the presence of circulating antibodies directed against an intrinsic antigen to the basement membrane of both kidney and lung
• Rapidly progressive kidney failure
• Treatment:
- Remove antibody via plasma exchange - Immunosuppression
- Steroids/cyclophosphamide
167
How is acute nephritic syndrome diagnosed?
- history
- Measure eGFR, proteinuria, serum urea & electrolytes and albumin - to determine current status and monitor progress
- Culture - swab from throat or infected skin
- Urine dipstick to detect proteinuria and haematuria
- Renal biopsy if necessary
168
How is acute nephritic syndrome treated?
- antibiotics to treat infection
- immunosuppression, steroids, cylophosphamide, rituximab, plasma exchange if caused by goodpastures, anca, SLE etc
- BP control in IgA nephropathy - ACE inhib/antiotensin receprot blocker. Also diet, low cholesterol.
- treat hypertension with loop diuretics e.g. ORAL FUROSEMIDE and calcium channel blockers e.g. AMLODIPINE
169
Define nephrotic syndrome.
Kidney damage characterised by triad of:
- Proteinuria >3.5g/24hrs
- Hypoalbuminaemia
- Oedema
- Protein:Creatinine ratio of 300mg/mmol on spot urine
-Also sever hyperlipidaemia is often present as liver goes into overdrive due to albumin loss which increases risk of blood clots and results in raised cholesterol
170
What are some causes of nephrotic syndrome?
Primary:
-Minimal change disease (commonest cause in children)
```
-Membranous neuropathy - Thickening of glomerular capillary wall. IgG & complement C3 deposit along outer aspect of glomerular basement membrane causing leaky glomerulus. Podocyte dysfunction.
MN also caused by
-drugs e.g. NSAIDs, gold.
-infection e.g. hep B, C
-neoplasia e.g. lung, colon
```
-Focal segmental glomerulosclerosis. CD80 in podocytes resulting in increased permeability in glomeruli
and thus proteinuria and haematuria.
Secondary:
- DM most common
- Amyloid
- Infection e.g. hep B, C
171
How does nephrotic syndrome often present?
- increased bp
- proteinuria >3.5g/day
- decrease in gfr
- hypoalbuminaemia
- pitting oedema of ankles, genital, abdominal wall
- frothy urine
172
What are some differentials for nephrotic syndrome?
Congestive heart failure: oedema and raised JVP. In nephrotic syndrome normal/low JVP unless there is renal failure and oliguria.
Cirrhosis: where there is hypoalbuminaemia and oedema but will also be signs of chronic liver failure e.g. jaundice, fever, loss of body hair.
173
How is nephrotic syndrome diagnosed?
B: serum creatinine, eGFR, lipids and glucose. Serum albumin = low.
O: urine dipstick will show proteinurea
X: chest xray for pleural effusion or ascites
S: renal biopsy = diagnostic. antibody screening.
-serum Antiphospholipase A2 receptor antibody indicates membranous
nephropathy
174
What is the treatment for nephrotic syndrome?
Reduce oedema:
Loop diuretics e.g. IV FUROSEMIDE - IV since gut oedema may prevent oral absorption
Thiazide diuretics e.g. IV BENDROFLUMETHIAZIDE. Fluid and salt restriction while giving diuretics
- Reduce proteinuria:
• ACE inhibitor e.g. RAMIPRIL
• Angiotensin receptor blocker e.g. CANDESARTAN • Eat normal rather than high protein diet
- Reduce risk of complications:
• Prophylactic anticoagulation with WARFARIN, especially when albumin
is low (<20g/l)
• Reduce cholesterol with statins e.g. SIMVASTATIN
• Treat infections promptly and vaccinate
175
What are the complications of nephrotic syndrome?
Thromboembolism:
• E.g. DVT, PE, renal vein thrombosis
• Hypercoaguable state due to increased clotting factors (produced by liver due to low albumin since liver goes into overdrive) and platelets abnormalities
- Hyperlipidaemia:
• Increased cholesterol and triglycerides due to hepatic lipoprotein
synthesis in response to low oncotic pressure due to low albumin
- Susceptibility to infection:
• Such as cellulitis, Streptococcus infections and spontaneous bacterial peritonitis
• Due to low serum IgG, decreased complement activity and reduced T cell function due in part to loss of immunoglobulin in urine and also to immunosuppressive treatment
176
What is minimal change disease? (pathology)
- Glomeruli appear normal on light microscopy, but on electron microscopy, FUSION of the FOOT PROCESSES of the PODOCYTES is seen, consistent with a disrupted podocyte actin cytoskeleton
- Immature differentiating CD35 stem cells appear to be responsible for the pathogenesis
177
What are the causes of minimal change disease?
Primary idiopathic
Secondary:
-Drugs e.g. NSAIDs, antibiotics e.g. cephalosporins, rifampicin. Biphosphonates.
-Infection: syphilis, HIV, hep B & C
178
How is minimal change disease treated?
- High dose corticosteroids e.g. PREDNISOLONE - can reverse proteinuria in 95% cases - however the majority relapse
- Frequent relapse or steroid-dependent disease is treated with CYCLOPHOSPHAMIDE or CICLOSPORIN/TACROLIMUS
179
If a urine dipstick shows haematuria+/-proteinuria but kidney fxn and bp are normal, what is the most likely cause?
(asymptomatic urinary abnormalities)
IgA nephropathy:
• Abnormality in IgA glycosylation leads to deposition in mesangium (provides structural support for glomerulus)
• Can present as nephritic, nephrotic or asymptomatic or as progressive chronic kidney disease
• COMMONEST CAUSE OF GLOMERULONEPHRITIS WORLDWIDE
• Associated with tonsillitis and macroscopic haematuria
• Treated with BP control e.g. ACE inhibitor e.g. RAMIPRIL,
180
How does a genetic mutation lead to congenital renal cysts?
Genetic mutation leads to predisposition for cyst formation. Increased abnormal cell hyperproliferation → loss of planar polarity →
cyst initiation → fluid secretion by epithelial cells → cyst
181
What are some causes of acquired renal cysts?
- CKD
- lithium (used to treat depression)
- tuberous sclerosis
182
What is autosomal dominant polycystic kidney disease?
Gradual and progressive development of multiple cysts throughout the kidney eventually resulting in kidney enlargement and tissue destruction.
183
Describe the epidemiology of AD polycystic kidney disease.
- commonest inherited kidney disease
- males>females
- family history
Risk factors also include family history of ESRF or hypertension.
184
What is the cause of AR polycystic kidney disease?
Mutations in PKD1 (85%) gene on chromosome 16
| Mutations in PKD2 (15%) gene on chromosome 4
185
Describe the pathophysiology of AD polycystic kidney disease.
PKD1 encodes polycystin 1 which is involved in cell-cell and/or cell-matrix interactions - regulates tubular and vascular development in kidneys
PKD2 encodes polycystin 2 which functions as a calcium ion channel
The polycystin complex occurs in cilia that are responsible for sensing flow
in the tubule
Disruption of the polycystin pathway results in reduced cytoplasmic Ca2+, which, in principal cells of the collecting duct, causes defective ciliary signalling and disorientated cell division resulting in cyst formation
Progressive loss of renal function is usually attributed to mechanical compression, apoptosis of the healthy tissue and reactive fibrosis
Rate of renal function decline is dependent on the growth and size of cysts; patients with rapidly growing cysts on MRI lose renal function more rapidly.
186
How does AD polycystic kidney disease present clinically?
- symptoms from 20yrs onwards
- loin and abdo pain
- haematuria from haemorrhage into a cyst
- excessive water and salt loss
- nocturia
- renal colic due to clots
- hypertension
- uric acid stones
- progressive renal failure
187
What are some extrarenal complications fo AD polycystic kidney disease?
- subarachnoid haemorrhage associated w berry aneurysm rupture
- polycystic liver disease (70%)
- pancreatitis
- ovarian cysts
188
What are some differentials for AD polycystic kidney disease?
- AR PKD
- acquired and simple cysts
- medullary sponge kidney (congenital disorder characterised by cystic dilatation of the collecting tubules)
189
How is AD polycystic kidney disease diagnosed?
- history & fam history
- Ultrasound (enlarged)
- - Genetic testing for PKD1 (however its a huge gene and there are many
mutations) and PKD2
190
How is AD polycystic kidney disease treated?
Blood pressure control with ACE-inhibitor e.g. RAMIPRIL
- Treat stones and give analgesia
- Laparoscopic removal of cysts to help with pain/nephrectomy (remove entire kidney)
- Disease progression monitored by serial progression of serum creatinine
191
What are some implications for genetic testing for AD polycystic kidney disease?
Individual older case with no family history • Atypical cystic disease
• Very early onset (<2 yrs)
• Prenatal/Pre-implantation genetic diagnosis
To facilitate life choices/reproduction decisions
192
What is the cause of AR PKD?
PKHD1 mutation on long arm (q) of chromosome 6.
| Disease of infancy.
193
How would you diagnose a scrotal mass?
- Can you get above it? Cannot: inguinoscrotal hernia or proximally extending hydrocele.
- Is it separate from the testis?
Separate & cystic (soft) =epidydmal cyst
Separate & solid = epididymitis or varicocele
Testicular & cystic = hydrocele
Testicular & solid = tumour, haematocele.
A testicular lump is CANCER until proven otherwise.
194
Describe the pathophysiology of an epididymal cyst.
- contains clear and milky fluid (spermatocele)
| - lies above and behind testis
195
How do epididymal cysts often present?
- lump
- will transilluminate since fluid filled not solid
- Testis is palpable quite separately from the cyst (unlike hydrocele where the testis is palpable within the fluid filled swelling)
196
How do you diagnose a epididymal cyst? Can it be differentiated from a spermatocele?
Scrotal ultrasound.
• Can be differentiated as sperm are present in the milky fluid aspirate of
a spermatocele
197
Define hydrocele.
Abnormal collection of fluid within the tunica vaginalis
198
What are some causes of hydrocele?
Secondary: testis tumour, trauma, infection, TB, torsion
199
What is the pathophysiology of a simple and communicating hydrocele?
Overproduction of fluid in the tune vaginalis (simple hydrocele)
Processus vaginalis fails to close, allowing peritoneal fluid to communicate
freely with the scrotal portion (communicating hydrocele)
200
How do hydrocele clinically present?
- Scrotal enlargement with a non-tender, smooth, cystic swelling
- Pain is not a feature unless the hydrocele is infected
- Lie anterior to and below the testis and will transluminate
201
Define varicocele.
Abnormal dilation of the testicular veins in the pampiniform venomous
plexus, caused by venous reflux
202
Describe the epidemiology of varicocele.
- Left side MORE COMMONLY AFFECTED
- Unusual in boys under 10 yrs
- Incidence increases after puberty
- Associated with sub fertility
203
What are the causes of varicocele?
Increased reflux from compression of renal vein where testicular vein enters renal vein.
Lack of effective valves between the testicular and renal veins
204
How does varicocele present clinically?
Often visible as distended scrtoal blood vessels that feel like ‘a bag of worms’
- Patient may complain of a dull ache or scrotal heaviness
- Scrotum hangs lower on the side of the varicocele
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How is varicocele diagnosed?
Venography
| - Colour doppler ultrasound (see blood flow)
206
Define testicular torsion.
Torsion (twisting) of the spermatic cord resulting in occlusion of the testicular blood vessels - which can rapidly lead to ischaemia and infarct and thus the potential loss of the testis (GERM CELLS are the MOST SUSCEPTIBLE CELL LINE TO ISCHAEMIA)
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What is a cause of testicular torsion?
Underlying congenital malformation - belt-clapper deformity - where the testis is not fixed to the scrotum completely, allowing for free movement leading to twisting
208
How does testicular torsion present?
Any boy presenting with abdominal pain - the testes should be checked
- SUDDEN onset of pain in one testis - makes walking uncomfortable
- Pain often comes on during sport or physical activity
- Pain in abdomen, nausea and vomiting are common
- Inflammation of one testis - it is very tender, hot and swollen
- Testis may lie high and transversely
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How would you diagnose testicular torsion?
- Doppler ultrasound may demonstrate lack of blood flow to testis - Urinalysis to exclude infection and epididymis
- DO NOT DELAY SURGICAL EXPLORATION
210
What is the cause of stress incontinence?
Sphincter weakness due to birth trauma, neurogenic, congenital, in men post-prostatectomy.
211
How is stress incontinence treated?
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Pelvic floor exercises
- DULOXETINE (Centrally acting serotonin and norepinephrine reuptake inhibition)
- Surgery:
• Sling
• Artificial sphincter
```
212
What is urge incontinence caused by?
Detrusor overactivity - rise in detrusor pressure on filling associated with urgency -
213
How is urge incontinence treated?
Bladder exercises - gradually increasing the interval between voids
• Behavioural therapy - controlling caffeine, alcohol and frequency volume charts
Anticholinergic agents:
• Act against the cholinergic system (parasympathetic) e.g. OXYBUTYNIN - decreases detrusor excitability
- Beta 3 agonist - e.g. MIRABEGRON
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What area of the brain controls micturition?
Pontine-micturition centre/periaqueductal grey.
215
What is the bladder contraction reflex?
Parasymp reflex from sacral micturition centre s3 to bladder and back. Initiates micturition.
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What is the guarding reflex?
sphincter senses urine and sends impulse to spinal cord to tell Onuf’s nucleus to store urine
217
What are the effects of a supraconal (high in spinal cord) lesion on bladder control?
- spinal cord damage above T12
- "Spastic spinal cord injury"
- Involuntary intermittent destrussor contraction (overactivity)
- Detrusor sphincter dyssynergia : retention
- urge/stress incontinence : nocturia, leaking of urine
- puts kidneys at risk
218
What are the effects of a conus (low in spinal cord) lesion on bladder control?
-spinal cord damage s2-s4
"Flaccid spinal cord injury"
- Absent detrussor contraction (underactivity): constant dribble
- Lost bladder contraction & guarding reflex (areflexic bladder): overflow incontinence
- kidneys at risk
219
How would you investigate neuropathic bladder problems?
cystography, cystoscopy, with urodynamic testing.
220
How are neuropathic bladder problems such as spastic and flaccid bladder treated?
Patients who can retain normal volumes can use techniques to trigger voiding by stimulating symp system (eg, applying suprapubic pressure, scratching the thighs); anticholinergics may be effective. For patients who cannot retain normal volumes, treatment is the same as that of urge incontinence.
-permanent catheterisation
221
What are the symptoms of LUTs?
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Storage symptoms:
- Urgency
- Nocturia (> 30% voided volume @ night)
- Frequency
- Overflow incontinence (leaking urine during day/wetting bed)
• Voiding:
- Poor intermittent stream
- Hesitancy
- Incomplete emptying
- Post micturition dribbling - Straining
- Haematuria RED FLAG
- Dysuria (painful urination) RED FLAG
```
RED FLAGS = infection, stones, cancer
222
How would you diagnose LUTs?
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Serum prostate specific antigen (PSA):
- PSA is a glycoprotein that is expressed by normal and neoplastic prostate tissue
- Produced by the prostate in semen
- Small amounts in bloodstream normally
- Raised in:
• BPH
• Prostate cancer
• Perianal trauma and mechanical manipulation of the prostate e.g. in cytoscopy (endoscopy of bladder), prostate biopsy or surgery
• BMI<25
• Taller men
• Recent ejaculation
• Black africans
• Prostatitis
• UTI
- PSA > 1.4ng/ml confers an increases risk of LUTS progression e.g. acute urinary retention etc.
```
Flow rates & residual volume:
Max flow rate < 10ml per second is suggestive of bladder outflow obstruction due to BPH
223
Define acute urinary retention and list some causes.
Sudden onset of painful inability to pass urine usually with over 500ml in the bladder.
- Prostatic obstruction e.g. due to BPH or prostate cancer - Urethral strictures
- Anticholinergics
- Alcohol
- Constipation
- Neurological (spinal compression - cauda equina syndrome)
224
How would you investigate/diagnose acute urinary retention?
- Examination of abdomen, prostate, perineal sensation (to check for cauda equina syndrome
- PSA test
-AUR will show normal U&Es
225
How would you treat acute urinary retention?
Catheter relieves pain
- Alpha-1 blocker e.g. TAMSULOSIN which relaxes smooth muscle in bladder neck to aid voiding
- Prevent by giving 5-alpha-reductase inhibitor e.g. FINASTERIDE which reduces testosterones conversion to dihydrotestosterone and thus reduces prostate size
226
What are some causes of chronic urinary retention?
Prostatic enlargement due to BPH/prostate cancer
- Pelvic malignancy or rectal surgery
- Diabetes
227
How does chronic urinary retention present?
Overflow incontinence - leaking urine during the day/wetting bed - Loss of appetite, constipation, distended abdomen, UTI
228
How would you treat chronic urinary retention?
If painful: intermittent bladder catheterisation should be offered before an indwelling catheter. Catheters may be used as a long-term solution where persistent urinary retention is causing incontinence, infection, or renal dysfunction and a surgical solution is not feasible. Their use is associated with an increased risk of adverse events including recurrent urinary infections, trauma to the urethra, pain, and stone formation.
229
What are the implications for surgery for LUTS?
```
RUSHES.
Retention
Utis
Stones
Haematuria
Elevated creatinine due to bladder outflow obstruction
Symptom deterioration.
```
230
What are the causes of urinary tract obstruction, divided in to mural & extra mural?
- Luminal: stones, blood clot, sloughed papilla, tumour
- Mural: stricture, neuromuscular dysfunction
- Extra mural: abdominal or pelvic mass, pregnancy, BPH, retroperitoneal fibrosis, inflam e.g. peritonitis
231
How does acute and chronic upper (kidney & ureter) tract obstruction present?
Acute upper: loin pain radiating to groin
| Chronic upper: flank pain, renal failure, polyuria
232
How does acute and chronic lower (bladder to urethra) tract obstruction present?
- Acute lower: acute urinary retention, severe suprapubic pain, bladder outflow obstruction
- Chronic lower: urinary frequency, hesitancy, overflow incontinence
both: distended, palpable bladder
233
How is urinary obstruction diagnosed?
BOXES
B: U&Es & creatinine will be raised
O:mid stream urine sample for culture and sensitivity
X:ultrasound
234
How is upper urinary tract obstruction treated?
Nephrostomy - artificial opening created between the kidney and the skin which allows for the urinary diversion directly from the upper tract i.e. renal pelvis
- Alpha-1 antagonist e.g. TAMSULOSIN (bladder neck smooth muscle relaxer) - improves flow
- 5-alpha reductase inhibitor e.g. FINASTERIDE - inhibits conversion of testosterone to active form and thus reduces prostate size
235
How is lower urinary tract obstruction treated?
Urethral catheter
- Suprapubic catheter:
• Less risk of urethral damage and thus UTI
• Requires general anaesthetic for insertion
• Small risk of bowel injury during insertion
• Less likely to be colonised by bacteria than a long term urethral catheter
• Long term urethral catheter can leaf to urethral erosion and damage to the urethral sphincter
- Beware of large diuresis (large amount of urine) after obstruction relief as can result in a temporary salt losing nephropathy resulting in weight loss - monitor weight and maintained fluid balance
236
Define benign prostatic enlargement/hyperplasia and describe the epidemiology.
Increase in the size of the prostate WITHOUT the presence of malignancy.
- men over 60
- afro caribbean
237
Who can not suffer from BPH?
those with castration prior to puberty or genetic disease that inhabit androgen (testosterone) action or production
238
Descrive the pathophysiology of BPH.
Benign nodular or diffuse proliferation of musculofibrous and glandular layers of the prostate
Inner (transitional) zone enlarges in contrast to peripheral layer expansion seen in prostate carcinoma
As the prostate gets bigger, it may squeeze or partly block the urethra (narrows the urethra)
239
What does BPH not cause?
- infertility
- prostate cancer
- erection problems
240
What are some differentials for BPH?
Bladder tumour, bladder stones, trauma, prostate cancer, chronic prostatitis, UTI
241
How would you diagnose BPH?
-Digital rectal exam - feel prostate and would feel enlarged but SMOOTH
-Serum electrolytes and renal ultrasound - to exclude renal damage caused
by obstruction
-Transrectal ultrasound - to see size of prostate
- Serum prostate specific antigen (PSA): • May be raised in large BPH
- Biopsy and endoscopy
- Mid-stream urine sample - to exclude infection - Flow rates and residual volume:
• Max flow rate < 10ml per second is suggestive of bladder outflow obstruction due to BPH
- Frequency volume chart:
• Measure volumes voided and time over MINIMUM of 3 days • Calculates whether nocturic (>30% voided volume at night)
242
How is BPH treated?
If symptoms are minimal then watchful waiting
- Lifestyle:
• Avoid caffeine and alcohol to reduce urgency and nocturia • Relax when voiding
• Void twice in a row to aid emptying
- Drugs:
• Useful in mild disease or those awaiting surgery • FIRST LINE:
- Alpha 1 antagonists e.g. ORAL TAMSULOSIN:
• Which relax smooth muscle in the bladder neck and prostate thereby producing increase in urinary flow rate and improvement in obstructive symptoms
• Side effects; drowsiness, dizziness, depression, ejaculatory failure (since its a vasodilator), extra-pyramidal signs, weight increase and nasal congestion
• AVOID in postural hypertension
• 5-alpha-reductase inhibitor e.g. ORAL FINASTERIDE:
- Blocks the conversion of testosterone to dihydrotestosterone (active form) - the androgen responsible for prostatic growth
- Alternative to alpha-antagonist especially in men with very large prostate
- Side effects; impotence, decreased libido
-Surgery as a last resort but gold standard: Transurethral resection of prostate (TURP)
243
What complications can BPH lead to if untreated?
- Bladder calculi
- UTI
- Haematuria
- Acute retention
