Urinary Flashcards
What are the hormones synthesised in the kidneys?
Epo
Renin
Prostaglandins
Functions of the urinary system
Regulation of concentrations of key substances in ecf By virtue of above effecting icf Excretion of waste products Endocrine Metabolism
What is the metabolic activity of the kidney?
Activation of vit D
Catabolism of insulin
What proportion and amount of body mass is fluid?
60%
42L
What proportion and amount of body fluid is ECF
1/3rd
14L
What proportion and amount of ECF is plasma?
20%
3L
What is the difference between osmolarity and osmolality?
Osmolarity - number of osmoles of solute per litre solvent
Osmolality - number of osmoles of solute per kilogram solvent
How much ultrafiltrate is produced by the kidneys each day? Hw much is reabsorbed?
180 L produced
178.5 L reabsorbed
What are the vertebral levels of the kidneys?
Left T11-L2
Right T12-L3
What are the layers surrounding the kidney from inside out?
Capsul Perinephric fat Renal facia (anterior and posterior) Paranephric fat (posteriorly) Parietal peritoneum (anteriorly)
How does the kidney attach to the diaphragm? What is the consequence for the kidney position?
Via the renal fascia to the diaphragmatic fascia
Moves with respiration
How can the renal medulla be subdivided?
Renal pyramids containing nephrons
Renal columns carrying blood flow from hilum to cortex
How many major and minor calices are in each kidney
2 or 3 major calices each with 2 or 3 minor calices
Which vessel, artery or vein, is anterior as it enters the kidney?
Vein
What is the medical consequence of the segmental arteries not anastamosing in the kidney?
Each segment is surgically resectable
What are the autonomic nerves to the kidney?
The splanchnic nerves
Where do the ureters origionate? What is their abdominal course?
Uretopelvic junction posterior to artery and vein.
Pass down just anterior to the tips of the transverse processes of the spine
Where do the ureters enter the pelvis?
By the bifurcation of the common iliac artery (by the sacroiliac joint)
What is the course of the ureters in the pelvis?
Turn anteriomedially at the level of the ischial spines
How is backflow prevented from bladder to ureters?
They enter obliquely. Increased bladder pressure and constriction of the muscle on voiding close the lumen
What is the only thing that passes between the peritoneum and the ureter in males?
The vas defrans
Is the ureter anterior or posterior to the uterine artery in females?
Posterior
What is the arterial supply of the ureter?
Branches of the renal, gonadal, aorta, common iliac arteries snd internal iliac arteries
Many anastamoses
What nerves innervate the ureters?
Where do pain fibres travel?
Adjacent autonomic plexuses
Pain follows sympathetics back to T11 to L1
What is the space between the pubic bone and the bladder?
He potential reteropubic space
What supports the neck of the bladder?
Puboprostatic ligament (males) and pubovesicular ligament (females)
What is the triangle between the ureters and urethra termed?
Trigone
What is the arterial supply to the bladder?
Superior and inferior vesicular arteries
What are the three stages of urinary development?
Pronephros
Mesonephros
Metanephros
When and where does the pronephros form?
What does it do?
In the cervical region creating a duct to the cloaca
Beginning of week 4, regresses after several days
Where does the mesonephros develop? What is formed?
Caudal to the pronephros in the intermediate mesoderm.
Excretory tubules appear associated with capillary tufts. As they develop the urogenital ridge is formed
What happens to urine produced by the mesonephros?
Drains to the cloaca (not ruptured until week 7) so passes up the alantois into the umbilical cord
How does the mesonephros degenerate
Starting cranially even as the caudal end is still developing
How does the metanephros form?
Formation of the uteric bud by the mesonephros
Drives development of the metanephric blastema from the surrounding intermediate mesoderm
When the uteric bud contacts the metanephric blastema it branches forming the collecting system up to the collecting ducts of the nephrons
How does the metanephros reach its adult position?
What is the consequence?
Ascends from the pelvis
Partely due to cranial movement, partly done by remaining still as the trunk elongates.
Sequential ascending blood supply, usually degenerates but can create accessory vessels either into the hilum or into poles
What is renal agenesis?
Uteric bud fails to stimulate metanephric blastema
If bilateral not compatible with life?
What is duplication defect of the kidney?
The uteric bud splits forming two collection systems, these can open atopically eg. into the vagina causing incontinance
What are the two cyctic kidney diseases? What is different about them?
Multicystic kidney disease is a developmental disease where there is failed recanalisation of the ureter
Polycystic kidney disease is a genetic diaorder that causes renal failure, it has a poor prognosis
What is the consequence of failure of the kidneys in utero called? What is it?
Potters sequence:
Oligourea
Oligohydraminos
Hypoplastic lung disease
What is the urachus in healthy adult life?
Median umbilical ligament
How is the urogenital sinus formed?
Decent of the urorectal septum forms the rectum anteriorly and the urogenital sinus posteriorly
What are the three parts of the urogenital sinus? What do they form?
Upper part - future bladder
Pelvic and phallic part - future urethra
Where does the uteric bud open? How does this change during development?
Into the mesonephric duct
As the bladder expands it absorbs this junction and the uteric bud then opens directly into the bladder
What is the fate of the mesonephric duct in men?
As the bladder expands its opening is pushed further caudally into the developing prostate
What is the renal corpuscle?
The glomerulus within bowmans capsule
How does bowmans capsule form?
Blind ended tube of the metanephric blastema contacts and envelopes the glomerulus creating a double layered space with a visceral and parietal layer.
Viceral layer develops into podocytes wrapping around the glomerular capillaries.
What does the plasma have to cross to become ultra filtrate in the kidneys?
Fenestrated capillary endothelium
Basement membrane
Filtration slits between podocytes
Where is the PCT found? How does it appear in section?
Mainly in the cortex, though does dip into the medulla
Simple ciliated cuboidal
What are the four parts of the loop of henle?
Pars recta
Thin descending
Thin ascending
Thick ascending
How does the thin limbs of the loop of henle appear histologically?
Simple squamous, no blood cells (distinguish from capillaries), no brush border
How does the thick ascending limb of the loop of henle appear?
Simple cuboidal with no brush border
How does the dct appear histologically? Where is it found?
In the cortex
A squashed simple cuboidal epithelial tube. No cilia
How does the collecting duct appear histologically?
Non ciliated simple cuboidal epithelium. Appears very similar to thick loop of henle but slightly larger and more irregular
What are the components of the juxtaglomerular apparatus?
Dct - macular densa cells
Afferent arteriole - juxtaglomerular cells
Between - lacis cells
Hw many layers of muscle does the ureter have?
2/3rds bilayered
1/3rd trilayered
Where is transitional epithelium found?
Ureters, bladder, proximal urethra
What is then structure and function of transitional epithelium?
Stratified cells that are distensible. Covered in umbrella cells that are impermiable even at full stretch.
Function to protect from urine but also prevent tissue fluid entering the hypertonic urine
What is the charge on the basement membrane of the renal corpuscle?
Negative
Which are filtered more at the renal corpuscle anions or cations?
Cations are filtered more redily ( more end up in ultrafiltrate)
What effects filtration rate?
Capillary hydrostatic pressure vs ultrafiltrate hydrostatic pressure and osmotic gradient (outwards due to oncotic pressure)
What two methods of autoregulation exist to ensure constant filtration?
Myogenic response (contraction of smooth muscle on stretch) Tubular glomerular feedback
How does tubular glomerular feedback work?
High gfr causes high na+ and cl- at dct
This is detected by macula densa cells causing release of adenosine resulting in afferent arteriole vasoconstriction
Low gfr causes reverse with macula densa releasing prostaglandins dilating afferent arteriole.
How is glucose reabsorbed in the pct?
Right the way into the blood please!
Na/k atpase sets up gradient of na+
Glucose and na+ reabsorbed using SGLT2 channels
This moves it against conc gradient into cell
It then moves down conc gradient into ecf then into blood
What substances are secreted into the tubule? Why?
Only 20% of plasma filtered therefore secretion necessary if more is needed to be removed K+ H+ Anions and cations Drugs (adrenaline, morphine, penicillin)
What is normal gfr for males and females?
Males 115-125ml/min
Females 90-100ml/min
What is renal plasma flow?
1.1 L/min of blood, 55% plasma thus 605ml/min plasma
What is the filtration fraction? How is it calculated?
20%
GFR/renal plasma flow x 100
What is clearance in the kidney?
The volume of plasma from which a substance is completely removed by the kidneys/minute
Clearance = ([substance in urine] x urine flow)/[substance in plasma]
What properties does a substance need in order to apply its clearance to calculate gfr?
Not secreted or reabsorbed
Filtered freely
Not metabolised in the urine
What does egfr account for when measuring serum creatinine?
Age sex mass
What is the ideal substance for calculating gfr?
Inulin
What is filtered load of a substance?
Plasma concentration x gfr
amount of substance filtered per minute
What is the transport maximum?
The amount of substance the tubule can reabsorb
What is the renal threshold?
The plasma concentration of a substance that will exceed the filtered load that would exceed the renal threshold!
Why must the kidneys be able to vary sodium excretion?
To deal with varied dietary absorption
To allow BP control
What drives na reabsorption in the kidneys?
What ion comes with it? What is the exception to this rule?
Na/k atpase on basal membrane
Cl but in early pct hco3
What is the effect of the early pct reabsorbing hco3- alongside na rather than chlorine?
Increases cholorine tubular concentration allowing paracellular reabsorption
Where is most sodium and water reabsorbed? How much?
PCT
65% water
67% sodium
What are the sodium channels in the PCT
Which one is under regulation of hormone? Which hormone?
Na/glucose, Na/aa, Na/phosphate, Na/H exchanger
Na/Phosphate under PTH control
How do ion channels differ along the PCT?
All present in the first segment
Latter two segments only have Na/H exchanger
Why is the reabsorptionin the PCT described as isoosmotic?
Fully permeable to water so no change in osmolarity
What is the degree of reabsorption of na and water in the loop of henle?
Decending - 10-15% water
Ascending - 25% na
How is na reabsorbed in the ascending loop of henle?
In thin limb passive paracellular due to high osmolarity in tubule
In thick limb Na/k atpase driving NKCC2
In the thick ascending limb where do the cl- and k+ ions go after reabsorption?
Cl into ecf
K through romk back into tubule
What is the character of the fluid found at the top of the ascending limb?
Hypoosmotic
What cell type is found in the early DCT?what does it absorb and how?
Tubular cells
Na/KATPase drives Na/Cl synporter with the Cl being extruded basally
Where is calcium reabsorption controllable? How?
Tubular cells of Early DCT
NCX on basal membrane allows apical reabsorption from tubule under PTH influence
Where is most calcium reabsorbed? Where else?
PCT
Ascending loop by lumen positive potential
Explain the principle of glomerulotubular balance
By reabsorbing by percentage rather than amount any increase of decrease in gfr is compensated for
How much water and na is reabsorbed in the early dct? What happens to the osmolarity of the filtrate?
5-8% sodium
No water
Becomes more hyposmotic
How much sodium and water is reabsorbed in the late dct and cd?
3% sodium
5-25% water depending on adh
What are the two cell types in the late dct / cd
Principal cells
Intercalated cells
What is the function of principal cells? What are they sensitive too? What is the effect on the lumen?
Na/K atpase sets up na gradient Enac uniporter for sodium reabsorption Romk uniporter for K secretion Sensitive to aldosterone More na absorption than k secretion so lumen becomes -ve driving the k secretion and Cl reabsorption
What are the general functions of the intercalated cells of the dct?
Acid base balance
Active cl reabsorption
What systems influence long term blood pressure control?
RAAS
SNS
ADH
ANP
What stimulates renin release?
SNS
Low perfusion of afferent arteriole detected by baroreceptors
Low Na/Cl in DCT thus low GFR detected by macula densa
Actions of angiotensin II
Stimulates aldosterone release
Vasoconstriction
Increased Na/H in PCT
Effect of SNS on BP
Stimulates renin release
Decreases renal bloodflow decreasing GFR
Activates Na/H and Na/KATPase in PCT
How does ADH influence blood pressure?
Increased osmolarity or hypovolemia stimulate ADH release resulting in water retention
Also stimulates NKCC2
Role of ANP in blood pressure regulation?
Released by atria in response to excessive stretch
Causes vasodilation of afferent arteriole increasing GFR and inhibits Na reabsorption in nephron
Why do NSAIDs cause renal failure?
If GFR decreases tubuloglomerular feedback results in prostaglandin release from juxtaglomerular apparatus to dilate afferent arteriole. NSAIDs block the prostaglandin synthesis
What are the physiological consequences of HTN?
Increased afterload:
LVH
Myocardial ischemia due to increased demand
Arterial damage (athereosclerosis and weakened vessels): Aneurysm Thrombus (Cerebrovascular disease) Retinopathy Kidney damage
How are changes in osmolarity detected?
How does this occur?
Swelling or shrinkage of hypothalmic osmoreceptors
Surrounding capillaries have fenstrated epithelium exposing the receptor to the plasma osmolarity directly
What occurs if plasma osmolarity increases?
Stimulation of osmoreceptors stimulates ADH release and increases thirst.
What is the thirst pathway?
Large increased osmolarity or decreased plasma volume increases thirst
Induces drinking behaviour
Immediately pathway is sated - anticipation of water being absorbed once drunk
Where is ADH released from?
Posterior pituitary
What is the structure of ADH?
Small peptide hormone
What are the actions of ADH on the kidney generally?
Vasoconstriction of glomerulus reducing GFR
Increased NKCC2
Activates Gs GPCR on late DCT and CD with increased PKA causing insertion of aquaporin 2 into the apical membrane
How does water travel through the basal membrane of the late DT and CD?
Through aquaporin 3 and 4
If there is no ADH what happens to urine? Condition?
Large volumes of dilute urine
Diabetes insipitus
What takes priority in a case of low blood volume (low BP) and low osmolarity?
The low volume - ADH will be secreted in spite of low osmolarity
What is the corticopapillary osmotic gradient? How is it formed?
The gradient of increasing interstitial osmolarity in the interstitium from the top of the cortex (low osmolarity) to the renal papilla (high osmolarity)
- countercurrent multiplying and exchange from the loop of henle and the vasa recta respectively
- recycling of urea
How does urea cycling effect the corticopapillary osmotic gradient?
Urea is at high concentration in the collecting duct
It is reabsorbed through aquaporin 2 thus reabsorption increases when ADH is high
It is then reabsorbed into the ascending limb
How is a corticopapillary osmotic gradient set up using Na/Cl and water?
The loop of Henle acts as a countercurrent multiplier - the ascending limb reabsorbs Na into interstitium decreasing filtrate osmolarity and increasing interstitial osmolarity by up to 200momol/l
Water leaves descending limb and is reabsorbed by vasa recta due to high oncotic pressure and counter current exchanger giving it high osmolarity. This concentrates the descending limb fluid
Water from the descending limb moves into the ascending limb, as it is now a higher osmolarity it can have more na reabsorbed concentrating the interstitium further still and so on!
What are the actions of PTH?
Increases osteoblasts decreases osteoclasts
Increases DCT reabsorption of calcium
Decreases PCT Pi reabsorption
Activates vitamin d
What is the half life of PTH? What causes its release?
4 minutes so can respond quickly to changes in calcium
Released as low calcium increases mRNA transcription and stability
Where is PTH produced and degraded?
Chief cells of the parathyroid gland
What are the two precursors to vit D? How do they differ?
Cholecalciferol (from light)
Ergocalciferol (from diet)
What are the steps of activation of vit d? Where?
Cholecalciferol
LIVER - 25hydroxycholecalciferol
KIDNEY - 1.25dihydroxycholecalciferol (calcitriol)
Which step of vit. D synthesis is controlled by pth?
25hydroxyvitd to 1.25dihydroxyvitd
What is another name for 1.25dihydroxycholecalciferol?
Calictriole
When sufficient calcitriol has been produced where is excess 25.hydroxycholecalciferol diverted too?
24.25dihydroxycholecalcifeole
What increases risk of vit d deficiency?
Non-caucasian Lack of sunlight (indoors, clothes, sunscreen, climate) Lack of fish oil (ergocalciferol) Elderly/obese Cyp450 inducers
Actions of calcitriol
Increased gi calcium absorption Cell differentiation and proliferation Decreased cell growth Increase insulin Decreases renin
What is primary hyperparathyroidism?
Biochemical presentation
Adenoma of parathyroid gland
High PTH driving high Ca
What is secondary hyperparathyroidism?
Biochemical presentation
Low calcium driving raised PTH to return to normal
Low (uncompensated) or normal (compensated) calcium
High PTH
What is malignant hyperparathyroidism?
Release of PTHrP causing high calcium
Calcium very high, PTH low as supressed
What is tertiary hyperparathyroidism?
Biochemical presentation?
Long term secondary hyperparathyroidism causing autonomous pth release and thus hypercalcaemia
High pth and high calcium
What type of hyperparathyroidism is more likely to be present in raised calcium on investigation of renal calculi. Which one is unlikely?
Primary hyperparathyroidism is likely
Malignant hyperparathyroidism is unlikely
What type of hyperparathyroidism is characterised by a rapid onset?
Malignant
What are signs and symptoms of hypercalcaemia?
Stones Moans (constipation) Grones (depression) Short QT HTN Drowsiness Polyurea / polydipsia
What is the treatment of hypercalceamia?
Underlying condition Hydration to increase excretion Loop diuretics Bisphosphonates Calcitonin
What diuretics can worsten hypercalcemia? Why?
Thiazides
Block na/cl = decreased na reabsorption = low sodium in cells = increased basal NCX = low calcium in cells = increased calcium absorption
What are the four most common types of renal calculi?
Calcium (70%)
Magnesium ammonium phosphate
Urate
Cystine
What sort of renal calculi is radiolucent
Urate
If you have had one renal stone what is your chance of having another?
50%
Which gender is more likely to get renal stones?
2:1 males:females
What increases risk of renal stones?
Male, dehydrated, previous stone, infection, hypercalcemia/hypercalciurea
Drugs
Loop diuretics - calcium stones
Thiazides - urate stones
How do renal calculi present?
Asymptomatic
Haematuria
Pain
General treatment options of renal calculi
Surgery
Lithotripsy
Fluid
What is used in uric acid stones
Allopurinol
What tests in renal calculi?
Blood screen
Urine screen
Radiography
What are the effects of alkalaemia?
Increases calciums affinity for albumin lowering serum free calcium. Low free calcium increases NCX, increasing intracellular sodium causing depolarisation - tetany
What are the systemic effects of academia
H excreted in exchange for K reabsorption in the kidneys - similar in cells - h taken in extruding k all causing hyperkalaemia.
Damage to enzymes causing decreased muscle contractility, glycolysis and hepatic function
What do the kidneys do to compensate or correct pH disturbance. Which type of does the kidney do each for?
Changes HCO3- excretion and creation
Compensates for respiratory
Corrects metabolic
What is the general response of the kidney to acidosis?
Recover all filtered HCO3-, secretes H+ and create new HCO3-
How does the kidney reabsorb HCO3-?
Secretes H+ through Na/H antiporter H+HCO3- to CO2 and water Reabsorb CO2 Recombine with water in cell excrete H again NOTE there is no net H+ excretion by this method
What is it that triggers bicarbonate reabsorption in the kidneys?
Not just acidosis - what about it and what else!
High CO2 in PCT cells increases H for secretion
Volume depletion increases reabsorption of Na+ thus excretion of H and also increases RAAS and Ang 2 increases NHE
Where and how does the kidney make hco3- in acidosis?
Alpha intercalated cells
H2O and CO2 to H and HCO3-
H actively secreted into lumen in exchange for K (uses ATP)
HCO3- enters ECF
Also secretes NH3 from aa breakdown to buffer H+ in urine to NH4+
What buffers H+ in urine, why is this necessary?
Phosphate and ammonia
Prevents damage and maintains concentration gradient
How do the kidneys increase H+ secretion? Where from?
H/K exchange in alpha intercalated cells as HCO3- is produced
What is the anion gap?
The difference between principle cations (Na+ and K+) and principle anions (HCO3- and Cl-). A high gap means a large number of unusual anions suggesting high acid production (e.g. lactate ions) rather than increased loss of HCO3- (e.g. renal tubular acidosis)
How do the kidneys aim to correct or compensate for alkalosis? What may stop this occurring?
Increase HCO3- excretion
But if volumed depleted unable to do this as Na reabsorption also stimulates HCO3- reabsorption
Thus fix by rehydration
Why do small changes in the. Balance of K have huge effects on the body?
98% k is in icf thus little change in balance will dramatically shift extracellular concentration
How does the body respond to rapid fluctuations in k? Why?
Intracellular buffering
Kidneys cant respond fast enough
What is internal k balance
Stabilising ecf K by moving in and out of icf
What is external k balance?
Matching excretion to intake
What increases K uptake into cells?
Increased ecf K
Hormones (insulin, aldosterone, catacholamines)
Alkalosis (shunt K in for H out)
What increases K release from cells?
Low ecf k
Exercise (repolarisation and muscle damage)
Cell lysis (rhabdomyolysis, haemolysis)
Increased ECF osmolarity (relative decreases as water moves out)
Acidosis (K out to allow H in)
Where and how in the kidney is K reabsorbed?
PCT - paracellular diffusion
Thick ascending limb - NKCC2
Alpha intercalated cells - K/H antiporter
Where and how in the kidney is K secreted?
Principal cells
Apical ROMK
How is K reabsorption and secretion controlled in the kidney?
By altering secretion amounts from 15-120%
Responsive to aldosterone
What factors cause K secretion in principal cells?
High intracellular K
High intracellular Na (through ENaC) creating electrical gradient with negative luminal and positive cellular potential
What increases secretion of k from principal cells?
Increased ecf k activating na/k atpase Increased na reaching them in lumen Increased flow in lumen removing secreted k increasing gradient Increased aldosterone Alkalosis (stimulates na/k atpase)
How does acidosis result in hyperkalaemia?
Increased H/K atpase in alpha intercalated cells
Decreased na/k atpase in principal cells lowering k secretion
What can cause hyperkalaemia?
Increased intake (needs renal dysfunction OR IV dose) Decreased excretion (kidney disease, adrenal disease) Internal shift (acidosis, cell lysis, exercise)
How should hyperK be treated?
Calcium gluconate
Glucose and insulin
Salbutamol
Dialysis
Causes of hypokalaemia
Increased loss (diarrhoea, vomiting, diuresis, high aldosterone) Internal shift (alkalosis, aldosterone, adrenaline)
Treatment of hypok
K replacement
Block aldosterone
What diseases result in high aldosterone secretion?
Conns syndrome (aldosterone secreting adenoma)
What is the lifetime risk of uti in women?
When are they most likely?
50%
Children, sexually active (honeymoon), pregnancy, elderly
Risk factors for uti
Short urethra (women) Obstruction (calculi, prostate, tumour, pregnancy) Neuro problems (unable to empty bladder fully) Ureteric reflux (especially children)
What adaptations to bacteria aid them in surviving to cause uti
Fimbriae for attachment
Polysaccharide capsule to avoid immune system
Urease production to increase ph
How does a lower uti present?
Cystitis
Increased urinary frequency
Mild fever
Dysuria
How does an upper uti present
Loin pain
High fiver
Who is more at risk of asymptomatic uti?
Elderly
Catheters
Define complex uti?
Treatment resistant Male Pregnancy Children Elderly Pyleonephritis
What urine dip sign is very sensitive for uti? What is very specific?
Leucocyte esterase very sensitive
Nitrites very specific
What. Is the negative predictive value of turbidity in urine for uti?
97%
When would you culture a uti? What specific test is applied to it?
Complicated uti
Fermenting lactose to dx ecoli
What proportion of females with uti symptoms have significant bacteriuria? What may cause this?
50%
Sti urethritis, vaginal infection, mechanical cause, on abx, tb, fastidious organism (complex requirements so hard to grow)
When is microscopy of urine indicated?
Kidney disease
Endocarditis
Children under 6
What could squames visible on microscopy of urine indicate?
Contaminationn
Tx for simple, complex and pylonephritis uti
Simple 3 days
Complex 7 days
Nitrofurantoin or trimethoprim
Pylo 14 days
Ciprofloxacin or ceftrioxone or gentamicin
What can be done for frequently reoccurring utis?
More than three a year, prophylactic nitrofuritoin or trimethoprim
Which uti patients need imaging?
Children
Suspicion of problem with posterior urethral valve (men)
Suspicion of vesicouteric reflux (women)
What is the somatic, sympathetic and parasympathetic innervation to the bladder?
Som - pudendal
Symp - hypogastric nerve
Para - pelvic nerve
What does parasympathetic stimulation to the bladder do on a cellular level?
Stimulates M3 Ach receptors causing activation of GalphaQ to IP3 and DAG causing detrusor muscle contraction
What does sympathetic stimulation to the bladder do on a cellular level?
Detrusor muscle
Stimulates Beta3 receptors triggering GalphaS resulting in K efflux and hyperpolarisation thus muscle relaxation
Internal sphincter
Stimulates Alpha1 receptors triggering GalphaQ resulting in IP3 and DAG thus contraction and sphincter closure
What are the two phases of the bladder?
Storage
Voiding
What is the reflex involved in storing urine?
Low levels of stretch stimulate pelvic afferents
These activate the spinal continence centre
1) causing pudendal to close sphincter
2) causing hypogastric to stimulate detrusor relaxation and internal sphincter contraction
How can higher centers influence urinary storage?
Cerebral storage centre activates pontine storage centre which bilaterally activates the spine continence centre to activate the pudendal nerve closing the external sphincter.
What is the effect of detrusor relaxation during bladder filling?
Very little change in pressure
How does the micturition reflex occur?
Stretch of bladder detected by pelvic afferents, triggers stimulation of parasympathetic pelvic nerve and inhibition of the pudendal and sympathetic hypogastric nerve. This promotes voiding.
How do higher centres influence micturition?
Also recieve afferents informing them of stretch.
Cerebral micturition centre stimulates pontine micturition centre which in turn causes the increased parasympathetic and decreases symp and somatic. If urination not desirable can consciously activate storage centres promoting contraction of the external sphincter.
What would happen to the bladder in a spine injury above S2?
Lack of conscious control
On filling sacral spine reflex will cause detrusor contraction but lack of stimulation from pontine micturition centre will mean:
1) incomplete voiding
2) dyssynergia - external sphincter will not relax in time with contraction causing retention
What would happen to the voiding of the bladder in a sacral or peripheral nerve damage?
Flaccid bladder - overfilling with overflow incontinence
4 types of incontinance
Stress (SUI) - leakage on effort, sneezing, cough, exertion
Urge (UUI) - leakage preceded by urgency
Mixed (MUI) - SUI and UUI
Overflow (OUI) - dribbling of urine secondary to LMNL
What is overactive bladder syndrome?
Polyuria, nocturia and urge +/- UUI
What are non modifiable risk factors for incontinance?
Family hx
Anatomical abnomalities
Neurological abnormalities
Age
Modifiable risk factors for incontience
Drugs, uti, chronic cough, obesity, preggo, childbirth, pelvic surgery, dementia
Examinations in incontinent patients?
Bmi Abdo DRE Vaginal Urine dipstick Frequency volume chart/diary
Advanced investigations for incontinace
Invasive urodynamics
Pad test
Cystoscopy
SUI management
Stop smoking (decrease cough) Pelvic floor training Duloxetine (NA/5HT reuptake inhibitor) Vaginal tape Fascial sling Intermurial bulking
UUI Management
Decrease caffine Scheduled voiding with gradual increase in duration over months Anticholinergics e.g. Oxybutynin Beta 3 agonists Botulinum toxin Sacral nerve neuromodualtion Urinary diversion into a bag
Management of overflow incontinance
Treat compression
Avoid constipation
Ways of mitigating incontinance?
Catheters
Sheaths
Incopads
What is AKI?
Clinical syndrome causing acute decline in GFR over days to weeks
Diagnostic criteria of AKI
Raise in serum creatining greater than 26.5mmol/l in 48 hrs or 1.5x baseline in 7 days
Maybe low urine volume (<0.5ml/kg/hr) for 6 hours
What can AKI cause?
Changes to ecf volume
Electrolyte abnormalities
Ph abnormalities
What is the in hospital incidence of. AKI
5%
Cause of prerenal AKI
Decreased renal perfusion
- volume depletion, chf, systemic vasodilation, preglomerular vasoconstriction (NSAID), postglomerular vasodilation (ACEi/ARB)
What is the effect of pre renal aki on sodium excretion?
Active reabsorption of na and h2o thus fractional na excretion less than 1%
Treatment of pre renal aki
Fluids
Underlying cause
Stop offending meds
What different pathologies can cause renal aki?
ATN
Glomulonephritis
Interstitial disease
Intrarenal obstruction
Causes of ATN
Sepsis
Nephrotoxins
Ischemia
Continum from pre renal AKI
What effect does ATN have?
Damage to tubular cells impaired salt and water reuptake with expulsion of excess water.
Examples of endogenous nephrotoxins
Bilirubin
Myoglobin
Urate
Examples of exogenous nephrotoxins
Xray contrast Nsaids Animoglycosides Lithium Antifreeze Weedkiller
What can cause a low fractional excretion of sodium that isn’t pre renal AKI.
Glomerulonephritis Early rhabdomyolitis Hypercalcemia Vasoconstrictive drugs (e.g. NA) Hepatorenal syndrome Contrast nephropathy
Signs that an AKI is. Prerenal?
Postural hypotension Low JVP Sepsis/CHF Rapid weak pulse Low CVP
Why does ATN cause decreased GFR and thus fluid overload if aggressively resuscitated
Increased sodium - tubularglomerular feedback - afferent constriction
Back leak of filtrate in pct
Obstruction of tubule by debris from dying tubular cells
What can cause tubulointersitial nephritis?
Pyleonephritis
Toxins
What causes post renal AKI?
Obstruction if bilateral or effecting a sole functioning kidney
Examples of. Obstruction causing post renal aki
Luminal - calculi, blood clots,
Wall - neuromuscular dysfunction, neurogenic bladder, stricture
External - tumour, prostate, AAA, ligation
BLOCKED CATHETER
Tests in AKI?
Dipstick Culture Microscopy Biochemistry (U+E, FENa+) Imaging in post renal or non refractory prerenal/renal CVP and CXR if risk of fluid overload Histology in renal if not clear ATN
When would dialysis be considered in AKI?
HyperK not responsive to medical tx Non refractory metabolic acidosis Fluid overload not refractory to diuretics Dialysable nephrotoxin (eg aspirin OD) Uremia
Signs of uremia
Pericarditis
Lowered GCS
N+V
What different dysfunctions can renal disease present with?
Excretion - hyperK, fluid overload, acidosis
Glomerular - proteinuria, haematuria
Tubular - nocturia, polyuria, glycosuria
Hormonal - osteomalacia, anaemia, htn
Causes of microscopic haematuria
Uti Polycystic kidneys Renal stones Tumours AV malformations Glomerular disease
At what age should all haematuria cases receive a cystoscopy?
> 45
Differentiate haematuria from glomerular disease and lower urinary tract
Glomerular - smoky brown +- protein, painless
LUT - red, clots, pain, no protein
Non blood causes of red/brown urine
Myoglobinuria
Beetroot
At what point in GFR do CKD symptoms present?
<30ml/min
Presentation of proteinuria
Frothy urine
Oedema due to low oncotic pressure
Infection due to low plasma immunoglobulin
Thrombus risk due to imbalanced coagulation factors
Types of protienuria
Glomerular - increased permiability
Tubular - decreased reabsorption of filtered small proteins
Overflow - filtration of small proteins above transport maximum
Cause of overflow proteinuria
Multiple myeloma
What is nephrotic syndrome. How does it feed back on itself? What random thing does it cause?
Proteinuria with oedema 2ndry to hypoalbuminia
Decreases circulating volume increases RAAS increases sodium retention, increases oedema
High cholesterol
What is nephritic syndrome?
Rapid onset oligouria, low GFR, HTN, oedema, haematuria, normal albumin.
How can the renal capsule result inpathology?
Blockage
Leakage
What 4 points of the glomerulus are vulnerable to damage?
Subepithelial
Basement membrane
Subendothelial
Mesangial
Glomerular causes of nephrotic syndrome
Minimal change glomerulonephritis
Membranous glomerulonephtitis
Diabetes mellitus
Age distribution of minimal change glomerulonephritis?
Treatment?
Consequence of this
Most common nephrotic syndrome in children
Very good response to steroids
Treat and if responds no need to biopsy
Changes of minimal change glomerulonephritis on biopsy?
None to light microscopy
On electron loss of podocyte foot processes
Prognosis of minimal change glomerulonephritis?
Responds well to steroids. May progress to renal focal segmental glomerulosclerosis and renal failure. If so often returns post transplantation.
What is the commonest adult glomerular nephrotic syndrome?
What causes it?
Membranous glomerulonephritis
Immune complexes forming and damaging subepithelial layer - autoimmune or secondary to SLE or plasmodium malariae
How does membranous glomerulonephritis appear histologically?
What is the treatment?
Masses of immunoglobulin deposition
Immunosuppressants
How does diabetes cause glomerular disease?
Microvascular glomeruli disease causing progressive proteinuria
Basement membrane thickens
Podocytes detach
Scarring and nodules form
Primary causes of nephritic syndrome
IgA nephropathy
Thin glomerular basement membrane disease
Alports syndrome
Goodpastures syndrome
When does IgA nephropathy tend to occur?
What does it cause?
Post mucosal infection
Immune complex deposition in mesangium
Haematuria
What is the prognosis of IgA nephropathy?
Progression to renal failure with transplant as the only option
What is the prognosis of thin glomerular basement membrane disease?
Benign
What is alports syndrome?
X linked inherited disease causing split basement membrane
Progresses to renal failure
What is goodpastures syndrome?
Rapidly progressing nephritic syndrome with autoantibodies against basment membrane
Treatable with immunosupression and plasmaphoresis if caught early
What is. Goodpastures syndrome associated with?
Pulmonary haemorrhage in smokes
What is a secondary cause of nephritic syndrome? What marker will be raised?
Vasculitis e.g. Wegners
Antineurtophil cytoplasmic antibody ANCA
What is the epidemiology of prostate cancer?
Most common male cancer
Second most common cause of male cancer death
What is the prognosis of prostate cancer?
Most people diagnosed are unlikely to die of the cancer
What increases the risk of prostate cancer?
Age
Family history
Black ethnicity
Why is the fact that prostate cancer incidence increases with age problematic?
Urinary symptoms and benign enlargement also increase with age so harder to detect
What can cause a raised prostate specific antigen? What does this mean for screening?
Malignant cancer
Prostatic hypertrophy
Benign cancer
Prostatic inflammation
Massive overdiagnosis
What are the risks involved with prostate cancer treatment?
1/3 risk LUT symptoms
1/3 risk erectile dysfunction
5% risk incontinence
What is the prevalence of prostate cancer in 80 year old males
80%!
What are symptoms of prostate cancer?
Asymptomatic Bladder overactivity Metastatic bone pain Urinary tract obstruction Uncommonly weight loss and haematuria
What investigations are warranted in diagnosing prostate cancer (two routes)
DRE and PSA - transrectal ultrasound guided biopsy
LUT symptoms - TURP
How is prostate cancer graded?
Gleason grade - two numbers
First - grade of the most common area of the biopsy
Second - grade of the least differentiated area that is not the first
What treatments are available for prostate cancer?
Surveillance
Radical prostatectomy
Radiotherapy (external or brachytherapy)
What hormone treatment is used in metastatic prostate cancer?what complication does this have?
Surgical or chemical castration to reduce testosterone (as cancer is testosterone sensitive)
Flare - initial surge in testosterone
What non hormonal treatments are available for metastistied prostate cancer?
Targeted radio and chemo therapy for the bone mets
Bisphosphonates
What is the normal type of bladder cancer?
Transitional cell carcinoma
What are risk factors for bladder cancer?
Smoking
Occupational exposure to rubber, plastic, oil
Schistosomiasis causing metaplasia
How are bladder tumours staged?
Superficial (most)
In situ
Invading muscle
How are superficial bladder tumours treated?
Transureathral resection of bladder tumour
Hw are bladder tumours that have invaded muscle treated?
Radical cystectomy
Palliative
Risks for renal cell carcinoma
Smoking
Obesity
Dialysis
How can renal tumours spread?
Perinephric
Lymph nodes
Into IVC to right atrium
How can upper tract transitional cell carcinomas spread?
Pelvis to bladder NOT reverse usually due to urine. Flow
How are renal cell carcinomas treated
Radical or partial nephrectomy
How are upper tract transitional cell carcinomas treated
Nephrouterectomy (kidney, fat, ureter, cuff of bladder)
What is ckd
Irreversible and sometimes progresive loss of renal function over months to years
Cuases of ckd
Glomerulonephritis Pyelonephritis Obstruction Htn Vascular disease Dm
How is ckd. Detected?
Opportunistic testing of at risk groups
How id ckd graded?
g1-G5 based on GFR
A1-A3 based on protein:creatinin ratio in urine
What. Grade of ckd is kidney failure?
G5
What. Is the main cause of death in CKD
Cvd
What does proteinuria mead diagnostically in ckd?
Increased risk of need of dialysis
When should a biopsy be performed in ckd?
Normal sized kidney with no obvious diagnosis
Complications of CKD
Acidosis Anaemia Bone disorders. Non bone calcification Cvd
What are the bone disorders of ckd?
Osteomalacia due to low active vit d thus low calcium absorption
Ostitis fibrosa cystica due to high PTH resulting in areas of reabsorbed bone replaced with fibrous cysts
Benefits and costs of haemodialysis
Benefits - others to talk to, low responsibility, days off
Costs - disruption to life, see others get ill, time consuming, high diet restrictions, high fluid restrictions, large number of meds
Contraindications and side effects of haemodialysis
Contraindications - failed vascular access, heart failure (relative - can it cope with extra 300ml)
Complications - infection of central line, thrombus at fistual, steal syndrome, cvs instability, bleeding
Benefits and costs of peritoneal dialysis
Benefits - convinience, independence, low diet and fluid reatrictions, initially better renal preservation
Costs - high responsibility, frequent bag changes or on every night
Contraindications and complications of peritoneal dialysis
Contraindications - adhesions, hernias, extensive abdo surgery, unable to do at home by pt or carer
Complications - peritonitis, infection, leaks into scrotum, hernia, failure of ultrafiltration due to scarring
When is the largest risk post kidney transplant?
3 months
What are the risks post kidney transplant?
Infection
Cancer
HTN
What type of donor provides best chance?
What is ave. life expectancy
Related live
12 years
What meds are used to prevent kidney donor rejection?
Mycophenolate
Tacrolimus
