Genitourinary Clinical

Clinical Problems – Kidney failure

• Acute renal failure: rapid deterioration of kidney function over a short period of time. Its often reversible and associated with other illness
• Clinical example: 68 year old lady
• Sign of failure: unwell, nausea, vomiting, loss of appetite, reduced urine output and itchiness (pruritis)
• Clinical examination:
- Raised serum urea and creatinine
- Decreased serum albumin
- Decreased red blood count
- Increase white blood count (neutrophils and basophil)
- eGFR was 6ml/min (very low)
• Blood tests: used to test for acute or chronic
- Haemoglobin is low in chronic renal failure. This is because healthy kidney sends hormone called erythropoietin to bone marrow to produce blood cells but fails to do so in CRF.
- PTH also assess difference between chronic and acute
• Ultrasound:
- Kidney size: a kidney that’s less than 8cm (normal 11) is likely to be due to CRF
- Obstruction: acute
• Other indicators:
- Proteinuria and haematuria supports CRF
- Fast onset and not passing urine is ARF

Chronic Renal Failure

• Features of the kidney: major role of kidney is to remove waste products and maintain the balance of internal solute concentration.
- Rate at which blood is cleared of waste product is defined as GFR. The normal rate is usually above 120 ml/min giving a daily rate of above 170 L.
• Chronic kidney disease: permanent reduction in the glomerular filtration rate
- Severity of the CKD is classified into 5 classes depending on GFR with lowest class >90 ml/min and highest class <15 ml/min
• Calculation of GFR: clearance of artificially injected substance or creatinine can both be used.
- Inulin clearance: a sugar that is filtered by the glomerulus and is neither reabsorbed or secreted in the tubule. The GFR is then measured by product of volume of urine per time (collected) times concentration of inulin urine over the concentration of inulin in blood.
- Isotope clearance: examples include 99mTc-DTPA (diethylenetriaminepentaacetic acid), 125I-IOT (lothalamate)
• Creatinine clearance: freely filtered at the glomerulus but it is also secreted slightly in the tubules so results tends to over-estimate GFR. But error in estimating serum creatinine usually balances this.
- Role in CKD: moderate to severe CKD can confound the interpretations of creatinine clearance. With the loss of muscle mass from muscles mass and extra-renal excretion of creatinine, clearance will decrease while secretion continues giving an overestimation
• Estimated GFR: calculated using creatinine clearance
• The Cockcroft and Gault formula: used to estimate creatinine clearance for an individual based on their ideal body weight, age and serum creatinine.
CrCl = IBW × (140-Age)/72SCr, if female multiply by 0.85
• Causes of chronic kidney disease:
- Diabetic nephropathy
- Glomerulonephritis
- Hypertensive nephrosclerosis
- Polycystic kidney disease
• Anatomical causes of CKD:
- Renal: renal artery, intra-renal vasculature, glomerular, tubular interstitial space, intra-renal obstruction, renal vei
- Pre-renal: not enough BP or flow and damaging drugs
- Post-renal: blockage of renal to outside
• Risk factors: 10% population are at risk of CKD
- Age
- Sex (particularly men)
- Ethnicity (maori)
- Low income
- Obesity
- Smoking: associated with progression of both non-diabetic and diabetic kidney disease
• Progression: lack of control of primary disease will lead to progression of CKD to end stage kidney disease (severe illness that usually requires dialysis). Secondary factors may also contribute, these include:
- Systemic hypertension: lowering BP alters speed of progression
- Intraglomerular hypertension
- Glomerular hypertrophy
- Calcium and phosphate: content increase in CRF and ESRF as result of renal impairment and reduction of function
- Dyslipidaemia: common
- Proteinuria: important prognostic factor as reduction in proteinuria improves outcome
- Tubule-interstitial fibrosis
- Toxicity of iron/ammonia/middle molecules
• Intervention: aimed to slow progression through targeting secondary factors or preventing primary disease
- Hypertension: exercise, weight loss, smoking cessation
- Proteinuria: weight loss, ACE-I inhibitor to decrease GFR, moderate protein restriction
- Calcium and phosphate: limiting phosphate in diet and take phosphate binders. Aim for a Ca/P product to be less than 4.5
• Water balance: CDK patient are prone to both dehydration and volume overload
- In addition to water balance, kidney also regulate salt balance which will be disrupted due to CKD.
• Acid-base regulation: long term regulatory mechanism of maintain the pH and with CKD, a metabolic acidosis develops due to lack of excretion of non-organic acids.
• Uraemia: a systemic intoxication condition that occurs due to renal dysfunction such as that with CKD 4 and 5. It is due to multiple factors/toxins that accumulate in body and contribute to the pathogenesis.
- Neurological: fatigue and lethargy with headaches, seizures encephalopathy, peripheral neuropathy and paralysis
- Haematological: anemia, bleeding tendency, infection and platelet dysfunction
- Cardiovascular: pericarditis, hypertension, heart failure, IHD etc
- Pulmonary: pleuritis, and uraemic lung
- GI tract: anorexia, nausea and bleeding
- Metabolic: glucose intolerance, hyperlipidemia, malnutrition, sexual dysfunction, infertility, osteodysplasia
- Skin: pigmentation (yellow), easy bruising, pruritis (itchness from inability to remove phosphate), uraemic frost
- Psychological: depression, anxiety, denial and psychosis
• Management of CRF:
- Treat primary disease
- Treat secondary factors
- Avoid nephrotoxins
- Correct abnormalities such as acid base balance, blood volume and calcium phosphate PTH
- Renal replacement therapy
• Treatment options of ESKD:
- Conservative
- Dialysis (peritoneal or haemodialysis)
- Renal transplant from dead or living donor

Infection of Genitourinary tract

• Routes of infection: urinary tract is usually sterile with only the anterior urethra colonized by bacteria of faecal origin
- Ascending infection: bacteria that usually colonize the urethra ascend to the bladder and then kidneys
- Haematogenous infection: infection of renal parenchyma by blood borne organism, straphyloccocus aureus is most common.
• Bacterial virulence factors:
- Adhesions: adherence to vaginal and uroepithelial cells using pili or fimbriae (filamentous) or protein of the outer membrane (non-filamentous).
- Flagella: ascend through the ureter against flow of urine
- Endotoxin of gram-negative bacilli: decrease ureteral peristalsis
- Haemolysin: tissue invasion
- Aerobactin: iron acquisition in iron poor environments
- Urease: enzyme that hydrolyze urea to ammonia and CO2 which increase the pH of urea. This consequently promotes precipitation of phosphate, carbonate and magnesium leading to formation of struvite calculi. The calculi are colonized by bacteria and lead to urinary stasis.
• Host factors:
- Normal urinary tract, except urethral mucosa is resistant to colonisation
- High osmolaility, urea and low pH of urine inhibit bacterial growth and flush them out
- Mucopolysaccharide covering bladder mucosa resistant bacterial adherence
- Host immune system
• Risk of abnormalities:
- Obstruction leads to urine stasis
- Formation of calculi
- Vesicoureteric reflux contributes to upper tract infection
- Incomplete emptying of bladder (mechanical or neurological causes)
- Indwelling urinary catheters (candida species)
• Microbiology: most UTI are caused by a single organism but multiple organism can be found in patients with structural abnormalities
- Caused by aerobic gram-negative and positive bacteria (anaerobes rarely cause UTI)
- Escherichia coli (“-“) are responsible for 80% of UTI
- Other species include staphylococcus (“+”), streptococcus (“+”), proteus
• Epidemiology: UTI more frequent in females with 10-20% have symptomatic UTI during lifetime.
- Risk factors: frequent intercourse, diaphragm/spermicide use, diabetes and previous UTI
- Older men have increased UTI risk with prostatic disease
• Clinical presentation:
- Urethritis: dysuria, urinary frequency, urethral discharge
- Cystitis: dysuria and urinary frequency/urgency, cloudy urine
- Pyelonephritis: same as cystitis plus fever, flank pain, nausea and vomiting
- Young children have non-specific symptoms with failure to thrive and vomiting
• Diagnosis:
- Presentations from above
- Urine sample: pyuria (>107 white blood cells), dipstick (presence of nitrite produced by bacteria), leucocyte esterase, presence of epithelial cells (contamination)
- Urine culture: often contaminated by quantification of bacteria can differentiate infection from contamination. Infection is usually associated with >108 colony per unit/L./ However younger women have UTI below that threshold due to early phase infection, genital herpes, urethritis and non-infectious cause
- Blood culture
• History:
- Children without obstruction or reflux have very good prognosis
- Those with obstruction/reflux cause renal scarring and lead to ESRF and hypotension
- Pyelonephritis associated with premature delivery
• Asymptomatic UTI: common in elder people
- > 108 colony forming units/L
- Do not treat except pregnancy, young children, renal transplant and before surgery
• Catheter associated UTI:
- Inevitable bacteriuria and pyuria
- Asymptomatic usually and treatment should be avoided unless significant
- Eradication not possible without removal of catheter
• Complications of UTI:
- Intrarenal abscess: follows haematogenous infection or complication of pyelonephritis (slow to respond to treatment)
- Perinephric abscess: uncommon and occurs secondary to obstruction
• Imaging: used for recurrent infection, infection of young men and infections slow to respond to antibiotics
- Plain x-ray detect calculi
- Ultrasound can assess obstruction and renal changes (abscess)
- CT most sensitive imaging modality but has radiation risk
• Treatment:
- Antibiotics such as gentamicin and beta-lactam and trimethoprim
- Duration: 3 days for cystitis, 7-14 days intravenous then oral dose for pyelonephritis
- Drain abscess
- Correction of obstruction and removal of calculi

Childbirth:

• Dystocia: abnormal or difficult childbirth. There are many causes including
- Abnormal fetal lie
- Disproportional cephalopelvic ratio
- Treatment: oxytocin is used to treat uncoordinated uterine contraction.
• Passage of childbirth:
- Pelvic inlet: wider transverse diameter
- Pelvic outlet: wider A-P dimension (vertical oval)
• Problems of passage:
- small stature
- straight sacrum
- narrow bispinous diameter
- narrow subpubic arch
• Passenger of birth:
- Sagittal suture connects the two parietal bone of the skull
- Anterior fontanelle: diamond shaped soft area bordered by 2 frontal and 2 parietal bones
- Posterior fontanelle: small area covered in tough membrane between the occipital and 2 parietal bones
- Vertex: area between the fontanelles, extending laterally to the parietal eminences.
- Suboccipito-bregmatic: the diameter of the head from the lowest point of the occipital bone to the center of the anterior fontanelle. This represents the smallest diameter of the head.
- Occiput: the posterior of the head (hard part) and reference point for defining position in labour when vertex presents.
• Position of passenger:
- Lie: the position of the infant’s spine in relation to the mother – transverse (rare), cephalic (common) or oblique
- Presentation: the position of the baby as it moves through the birth canal – crown (normal presentation with head first and face down).
- Position: position of fetal head to
• Malpresentation:
- Breech: baby arrives feet first
- Compound: more than one part of the baby arrives together usually head and arms. Sometimes is presenting with cord which is a emergency and may require caesarean, i.e. blood supply of cord maybe compressed
- Shoulder: shoulder arriving first
• Malposition:
- 50% LOL, 45% ROL, 5% OP
- Brow presentation: deflexion of heart and brow in contract with pelvic bone. Requires caesarean
- Face presentation: mento-anterior deliverable vaginally
• Predisposing factors to malpresentation and malposition:
- Passenger: high parity, anatomical abnormalities or muscular abnormality
- Passages: placenta praevia, pelvic abnormality, pelvic tumour and uterine abnormality
- Power: uncoordinated uterine activity
• Powers:
- Regular painful uterine contractions
- Retraction in true labour (irreversible expansion of the uterus)
- upper segment shortens and thickens while lower segment and cervix stretch and thin
- effacement (disappearance of the length of cervix) and then dilation of the cervix
• Obstetric examination:
- Distension at 3rd trimester gestation
- External signs – striae gravidarum (stretch marks due to pregnancy), pigmented linea nigra (pubis to umbilicus becomes pigmented), everted umbilicus and scars
- Symphisio-fundal height
- Fetal lie
- Presentation
- Engagement (how descended is head, i.e. bipatrietal down the pelvic brim)
- Position of fetal back (faces left due to right liver)
- Fetal heart (hear fetal heart)
- Fetal movement (felt)
- Amniotic fluid volume (increased or decreased)
• Mechanism of normal labour:
- first stage: onset to full cervical dilatation
- second stage: full dilation to delivery of the baby with active phase (pushing) and passive phase
- third stage: delivery of the baby o delivery of the placenta with normal uterine contraction
• Events of second stage:
- Engagement in transverse diameter
- Descent
- Flexion
- Internal rotation
- Delivery by extension
- External rotation
- And delivery of shoulder and body
• Events of third stage
- Active management: early clamping and ligation and controlled cord traction
- Physiological management: no clamping of cord until pulsation cease, expulsion of placenta by maternal effort and no traction
• Breech delivery:
- Vaginal versus caesarean
- Vaginal breech delivery: increased perinatal morbidity (low Apgar scores, umbilical artery acidaemia, duration of neonatal unit admission) and mortality
• Instrumental delivery:
- Low and mid cavity
- Forceps: possibly quicker. Causes more maternal birth canal injuries and more neonatal facial nerve palsies
- Ventouse: rotation possible but more neonatal cephalhaemotomas
• Caesarean section:
- Elective maternal: previous caesarean and placenta block
- Elective fetal: malposition/presentation and high parity
- Emergency maternal: failure to progress due to cephalo-pelvic disproportion etc and fulminating preeclampsia (hypertensive and oedema)
- Emergency fetal: fetal distress and failed instrumental delivery

Glomerulonephritis – Clinical and Pathology

• Proteinuria: kidney handles 60 – 80g/L of proteins per day. Normal human urine have less than 150mg of protein in a day.
- Body barriers: glomeruli filters protein and tubules reabsorbs and degrades most of the filtered proteins
- Glomeruli: major problem, leads to microalbuminuria and proteinuira
- Tubule: minor problem
- Content: Mainly albumin and other proteins in small amounts
- Measurements: 24 hour urine, albumin:creatinine ratio, protein:creatinine ratio
• Micro-albuminuria:
- >25mg/mmol is proteinuria
- Causes: diabetes, fever, exercise, heart failure and poor glycemic control
- MA in diabetes is very high. If not treated can lead to kidney failure, nephropathy and death.
• Nephrotic syndrome: related to protein and independent of kidney function
- Large amount of protein loss lead to hypoalbuminaemia and oedema (swollen ankle and eyes)
- Frothy urine (due to presence of protein)
- Hypercholesterolaemia
- Blood clots
• Haematuria: occurs in glomerular, collecting system and focal lesion
- Glomerular: microscopic changes with blood cells in urine. May have proteinuria, hypertension and abnormal renal function.
- Collecting system: usually macroscopic and no proteinuria. Symptoms include loin-groin pain, haematuria , vomiting /nausea and anuria
- Focal lesions: macro and microscopic and usually asymptomatic. Caused by tumours.
- Tumour malignancy can cause haematuria anywhere in the urinary tract
• Blocked filter:
- Decreased blood flow
- Glomerular obstruction
- Tubular obstruction
• Effect of diabetes on kidney:
- Diabetic glomerulosclerosis: basement membrane of glomerular capillary thickens and protein leaks in early stage. In nodular advanced stage, the capillary becomes compressed and lead to renal failure
- Arteriolar hyalinisation
- Acute pyelonephritis
• Membranous GN: the basement membrane on which the glomerular cells sits is thicken with no increase in cells.
- Staining with fluorescence shows diffuse granular uptake of IgG and C3 immune complex and accumulation causes damage
- Idiopathic and can progress to glomerulosclerosis and kidney failure
• Thin membrane disease: autosomal dominant condition in which GBM is very thin compared to before and foot process become relatively thicker. Complications include benign haematuria.
• Post-infectious GN: occurs after streptococcus infection that affects the skin. The endothelial and mesangial cells proliferates causing reduction of the Bowen’s capsule (appears as a crescent shape)
- Renal function is impaired. Deposits are big coarse granules
• Renal cell carcinoma:
- Aetiology: smoking and genetic VHL disease
- Macroscopy: well circumscribed red, yellow and brown mass (necrosis).
- Microscopic: appears as adenocarcinoma with clear cells. Grade depends on nuclear feature (longer and uglier)
- Can invade into renal vein and grow into the right atrium.
- Tumour usually don’t present renal failure as they just push aside the parenchyma which is well encapsulated
- Clinical: late symptoms such as haematuria, flank pain and palpable abdominal mass. Also lead to ectopic hormone production from the tumours such as polycythemia, hypertension and hypercalcaemia.
- Spread: local spread and mainly blood borne passing into lungs, bone,s liver and brain etc. Some through regional lymph nodes.

Acute Renal Failure – Clinical and Pathology

• Acute renal failure: acute deteriorations of renal function from baseline
- Associated with anuria (almost no urine) and oligouria (passing some urine)
- Sign of uraemia (not symptoms) such as peripheral and lung oedema (accumulation of fluid with no urination), vomiting, nausea, prutitis
- 99% of time, the kidney will recover
• Causes of acute renal failure:
- Pre-renal: due to reduction in renal perfusion such as hypovolemia reduced cardiac output, systemic vasodilation and renal vasoconstriction. The kidney is starved of blood and becomes septic and dehydrated.
- Renal: intrinsic damage to tubule, vessels or glomeruli
- Post-renal: due to obstruction downstream by stone or tumour leading to urine retention and reflux. This is damaging to kidney function. Best diagnostic modality is ultrasound
• Urine microscopy:
- Normal: no protein, rbc, wbc and casts
• Casts: aggregate of particulates within urine and usually formed in distal convoluted tubule or collected duct via precipitation of proteins.
- Conditions of formation: low urine flow, concentrated urine, and acidic environment (damage in tubule)
- Hyaline cast: solidified mucoprotein secreted by tubular epithelial cells
- Granular cast: aggregation of plasma protein such as albumin or cellular cast breakdown
- Red cell casts: presence of red blood cells within cast and indicative of glomerular damage (glomerulonephritis).
• Acute tubular necrosis:
- Causes: 90% pre-renal conditions such as sepsis, dehydration, heart failure and low BP. Lack of blood flow compromise viability of cells as renal cells is high ATP dependent.
- Mechanism: urine leaks back into the interstitum and pass to blood.
- Example: car accident causes haemorrhage and decrease in BP. Patients becomes very dehydrated and high creatinine. If resuscitation does not work, the kidney undergoes ATN.
- Drugs: NSAIDs, aminoglycosides and IV contrast all toxic to kidney
- Rhabdomyolysis: muscle injury causes necrosis of cells and release of cytokine which is toxic to kidneys.
• Clinical presentation of ATN:
- Unwell
- oliguric/anuric
- Fluid status variable
- Mid stream urine (no significant red cells or protein, casts present)
- BP variable
• Treatment and progression of ATN:
- Dialysis for up to 6 weeks
- Oliguric phase (damage with GFR loss) to polyuric phase (in recovery phase, GFR restores but tubules can’t absorb fluid)
• Rapidly progressive glomerulonephritis: irreversible kidney failure if left untreated (causes are idiopathic)
- Severe immune-mediated injury to kidney’s glomeruli, e.g. anti neutrophils C and anti-GNM antibodies
- Crescentic glomerulonephritis: due to distribution of immune-complex around the basement membrane, glomeruli give a characteristic crescent appearance.
- Crescent formation: capillary rupture from antibody damage leads leakage of plasma protein, with fibrin being the most importance. Fibrin forms clot and epithelial cells of the glomerulus proliferate along with infiltrating leukocytes. Compression of the glomerulus occurs and hence the crescentic scar.
• Clinical presentation of RPGN:
- Unwell
- Acute nephritic syndromes
- Red cell casts and haematuria (antibodies in the kidney damage blood vessels)
- Sign of multi-system disease: haemoptysis (anti-GBM antibodies attach to alveolar, causing damage and pulmonary haemorrhage), rash, arthritis and fever
• Diagnosis of acute renal failure:
- History and examination for pre-renal
- Ultrasound for post renal
- Urine microscopy for sighs of ATN or glomerular disease when others have being excluded
- Biopsy
• Summary:
- Blocked filter is divided into pre-renal, renal, post-renal
- Leaky filter is divided into tubule-interstitial or glomerular
- Both glomerular damage lead to haematuria and proteinuria
- Nephritic syndrome: collection of signs that indicate kidney damage (renal failure)
- Nephrotic syndrome: disorder where the kidney is damaged causing leakage of protein

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