Block 10 Flashcards
Describe the fat and fascia that surrounds the kidney
It is surrounded by perinephric/ perirenal fat.
Covering this is the renal fascia.
Behind the kidneys is the paranephric fat.
Behind the paranephric fat is the transversalis fascia.
At the very front is the peritoneum.
What vertebral level do the kidneys lie?
T12 - L3
Describe the anatomy of the kidney
Outer renal cortex
Inner renal medulla
Extensions of renal Cortex are the renal columns
These split the medulla into renal pyramids
Bases of pyramids directed out
Apex is called the renal papilla and it points to the renal sinus
What are the functions of the kidney in terms of homeostasis?
Excretion of metabolic waste and foreign chemicals
Regulation of water and electrolyte balance
Regulation of body fluid osmolarity and electrolyte balance
Regulation of arterial pressure and acid base balance
Secretion, metabolism and excretion of hormones
Gluconeogenesis
What are the 2 capillary beds within the kidneys?
Glomerular - high hydrostatic pressure = rapid filtration
Peritubular - low hydrostatic pressure = fluid reabsorption
What are the components of a nephron?
Bowmans capsule Proximal tubule Loop of Henle Macula densa Distal tubule Cortical collecting tubule Collecting duct
What are the 2 types of nephrons?
Cortical
Justamedullary
What are the differences between cortical and juxta medullary nephrons?
Cortical
Glomeruli in outer cortex, short loops of Henle that just enter the medulla
Juxtamedullary (25%)
Lie deep in the renal cortex, close to the medulla. Long loops of Henle , long efferent arterioles from glomeruli form vasa recta
What determines GFR?
Balance of hydrostatic and colloid osmotic forces acting across capillary membrane
The capillary filtration coefficient Kf
What are the 3 layers of the glomerular capillary membrane?
Endothelium of capillary
Basement membrane
Epithelial cells, podocytes
How does the capillary membrane filter?
Size, Small fenestrae
Fixed negative charges that repel
What determines glomerular hydrostatic pressure?
Arterial pressure
Afferent arteriolar resistance
Efferent arteriolar resistance
How can glomerular filtration be controlled?
- Sympathetic nervous system increase increases GFR
- Constricting renal blood vessels - adrenaline, NA, endothelin - constricting efferent and efferent decreases GFR
- Constrict efferent arterioles - angiotensin 2 to increase GFR
- Decrease renal vascular resistance - nitrous oxide decreases vascular resistance and decreases GFR
- Vasodilation - caused by Prostaglandins and bradykinin. Increase GFR
What is the macula densa?
A group of specialised epithelial cells that comes in close contact with arterioles.
The cells sense changes in volume delivery to the distal tubule.
Detects decrease in NaCl
What happens when the volume of fluid being delivered to the kidneys is reduced?
Macula densa cells detect this by a drop in NaCl
This causes
Decreased resistance to blood flow in afferent arterioles
Increased renin release from juxta glomerular cells that leads to the construction of the efferent arterioles
What effect do ACE inhibitors have on a reduced Renal arterial pressure?
They prevent the formation of angiotensin 2 and causes greater reductions of GFR when renal arterial pressure falls
What is the first part of the nephron and what moves across the membrane (in and out)?
Proximal tubule
Out: Na, Cl, HCO3, K, H2O, glucose, amino acids
In: H, organic acids, bases
Na co transported with amino acids and glucose
Na/K ATPase
Na with Cl due to higher Cl in later proximal
What moves in and out in the thin descending loop of Henle?
Out: water 20% is reabsorbed
Highly permeable to water and occurs by simple diffusion
What moves in and out of the thick ascending loop of Henle?
Out: Na, Cl, K, Ca, HCO3, Mg
In: H
Na/K ATPase
Na crosses membrane by Na/2Cl/K
Loop diuretics act here
Impermeable to water
What moves in and out of the early distal tubule?
Out: Na, Cl, Ca, Mg
Na/Cl co transporter - thiazide diuretics act here
What moves in and out of the medullary collecting duct?
Out - Na, Cl, h2o, urea, HCO3
In - H
Actively reabsorbs Na and secrete H
Permeability to water is controlled by ADH
Regulates acid base balance
What moves in and out across the late distal tubule membrane?
Principal cells reabsorb Na and secrete K+
Potassium sparing diuretics act here,
Intercalated cells secrete H and reabsorb K and HCO3
Reabsorbs Na controlled by aldosterone
PH regulation
Active H ATPase
What is the function of intercalated cells?
Regulate pH
Secrete H+ and reabsorb HCO3
ALDOSTERONE
Effects
Site of action
MOA
Increase NaCl, increased water, increased potassium
Collecting tubule and duct (principal cells)
Stimulates Na/K ATPase on basolateral membrane to increase sodium permeability of luminal side. Prevents decreases of Na and increased K
ANGIOTENSIN 2
Effects
Site of action
MOA
Increased NaCl and Water reabsorption
Increased H secretion, retains sodium
Proximal tubule, distal tubule and collecting tubule
Stimulates aldosterone and constricts efferent arterioles. Stimulates NaK ATPase and NaH exchange
ANTIDIURETIC HORMONE, ADH
Effects
Site of action
MOA
Increased water reabsorption
Distal tubule, collecting tubule and duct
No ADH= increased dilute urine. Binds to V2 receptors, increased camp, stimulates aquaporin 2 to open water channels
What controls body water levels?
Fluid intake
Renal excretion of water
ATRIAL NATIURETIC PEPTIDE
Effects
Site of action
MOA
Decreased NaCl reabsorption
Distal tubule, collecting tubule and duct
inhibits reabsorption of Na and water. Increased urinary excretion to decrease blood volume
What is the function of ADH and where is it secreted?
Concentrates urine
Secreted from posterior pituitary when water levels are too high
Doesn’t alter solute excretion, reduces permeability of distal tubule to water
What are the 3 categories for acute renal failure and their causes?
Prerenal (decreased renal blood flow) intrarenal (blood vessels, glomeruli, tubules) post renal (obstruction of urinary collection)
What are some causes for acute prerenal renal failure?
Intravascular volume depletion - haemorrhage, diarrhoea, vomiting, burns
Cardiac failure - MI, vascular damage
Peripheral vasodilation - hypotension, anaphylactic shock, anaesthesia, sepsis
Primary renal haemodynamic abnormalities - renal artery stenosis, embolism or thrombosis
What are some causes for acute intrarenal renal failure?
Small vessel and/or glomerular injury - vasculitis, cholesterol emboli, malignant hypertension, acute glomerulonephritis
Tubular epithelial injury - acute tubular necrosis due to ischemia or due to toxins
Renal interstitial injury - acute pyelonephritis, acute allergic interstitial nephritis
What are some causes for acute postrenal renal failure?
Bilateral obstruction of ureters
Large stones or clots
Bladder obstruction
Obstruction of urethra
If only one is blocked the other will compensate
Describe glomerulonephritis
Usually caused by an abnormal immune reaction that damages the glomeruli.
Occurs 1-3 weeks after an infection with group A beta streptococci.
Antibodies develop against the antigen and forms an insoluble immune complex that gets trapped in glomeruli
Deposit in kidneys, attract WBCs and either block glomeruli or cause them to become overly permeable
Describe tubular necrosis
Ischaemia can impair the delivery of oxygen and nutrients causing the destruction of epithelial cells
Tubular cells slough off plugging nephrons
reducing urine output
certain toxins can damage basement membrane e.g. heavy metals of tetracyclines
What are the physiological effects of acute renal failure?
water, electrolyte and waste retention oedema and hypertension metabolic acidosis due to H+ retention Hyperkalcaemia Complete stop of urine formation Death within 8-14 days
Define chronic renal failure
Progressive and irreversible loss of functioning nephrons
Symptoms occur at 70% below normal
Causes of chronic renal failure
Metabolic disorders (diabetes, obesity, amyloidosis)
Hypertension
Renal vascular disorders (atherosclerosis, nephrosclerosis)
Congenital disorders (polycystic disease, renal hypoplasia)
Infections (pyelonephritis, tuberculosis)
Primary tubular disorders (nephrotoxins)
Urinary tract obstruction (renal calculi, hypertrophy of prostate, urethral constriction)
What is the vicious cycle of end stage renal disease
Primary kidney disease causes a reduction in nephron number
The reduction in nephron number caused hypertrophy and vasodilation of surviving nephrons and an increase in arterial pressure
Both of these lead to an increase in glomerular pressure and/or infiltration
Leading to glomeruloscelersis
Which causes a reduction in the number of nephrons! :(
Define azotemia
elevation of blood urea nitrogen and creatinine levels
usually reflects a decrease in GFR
What is nephritic syndrome
Haematuria (with dysmorphic RBC and casts in urine)
Oliguria and azotemia
hypertension
What are the top 3 causes of nephritic syndrome?
acute post-streptococcal glomerulonephritis
IgA nephropathy
Hereditary nephritis
What is nephrotic syndrome?
Proteinuria
Hypoalbuminaemia
Hyperlipidaemia
(oedema)
What are the top 3 causes of nephrotic syndrome in adults?
focal segmental glomerulosclerosis
membranous nephropathy
membranoproliferative glomerulonephritis
What are the top 3 causes of nephrotic syndrome in children?
Minimal change disease
focal segmental glomerulosclerosis
membranoproliferative glomerulonephritis
What is acute kidney injury?
Dominated by oliguria or anuria and recent onset azotemia
Glomerular injury, GN, interstitial injury, vascular injury, acute tubular injury
What is minimal change disease?
glomeruli have normal appearance by light microscopy but show diffuse effacement of podocyte foot processes
1-7 years
corticosteroid therapy
What is focal segmental glomerulosclerosis?
Sclerosis affecting SOME glomeruli (focal)
Involving segments of affecting glomerulus (segmental)
Injury to podocytes
What is membranous nephropathy?
presence of subepithelial immunoglobulin containing deposits along GBM
Caused by autoantibodies that cross react with antigens expressed by podocytes
Form of chronic immune complex glomerulinephritis
What is isasthenuria?
inability to concentrate or dilute urine
What are the effects of renal failure?
generalised oedema acidosis increased non protein nitrogen concentration uremia anaemia osteomalacia
What is BPH?
Benign prostatic hyperplasia
Hyperplasia of prostatic stromal and epithelial cells forming nodules in periurethral region of the prostate
It compresses and narrows the urethral canal
What is the incidence of BPH?
20% by 40
70% by 60
90% by 80
50% develop clinical symptoms
What is the main androgen in the prostate and how is it formed?
Dihydrotestosterone (DHT)
Testosterone + type 2 5 alpha reductase = DHT
Where is DHT found?
Only found in stromal cells and these are the cells responsible for androgen dependent prostatic growth
Pathogenesis of BPH
Impaired cell death resulting in accumulation of senescent cells
DHT binds to nuclear androgen receptor in epithelial and stromal cells
DHT+AR = activates transcription of androgen dependent genes that increase growth factors
FGF7 - fibroblast growth factor 7
Increased proliferation of stromal cells and decreased death of epithelial cells
In BPH where does the hyperplasia occur?
inner aspect or the transition zone
Clinical features of BPH?
Urethral obstruction Bladder hypertrophy and distension Urine retention Unable to empty bladder completely Increased infection due to residual urine Increased urine frequency Nocturia Difficulty starting and stopping Overflow dribbling Dysuria
Management of BPH
Mild - decreased fluid intake
Mediation - alpha 1 blockers reduce prostate muscle tone. 5 alpha reductase inhibitors decrease DHT
TURP - transuretral resection of prostate
Intensity focused ultrasound
laser therapy
needle ablation
Name some lower urinary tract symptoms
urinary frequency urgency dysuria nocturia poor stream hesitancy dribbling incomplete voiding overflow incontinence haematuria
Where do the ureters enter the pelvic cavity?
bifurcation of the common iliac artery
Describe the anatomy of the kidney
Outer cortex
Inner medulla - pyramids
Minor calyx - major calyx
Renal blood supply?
Renal arterys from the aorta at L1-L2
Renal artery Segmental (5) Lobar (2) Interlobar (2/3) Arcuate Interlobular Afferent arterioles
Histology of ureter
muscular tubes lined with transitional epithelium
2 layers of smooth muscle - longitudinal and circular
What are the 3 narrowings of the ureters?
junction of renal pelvis with abdominal part of ureter
pelvic brim, where ureter enters pelvis
pelviureteric junction, where ureter enters bladder wall
What are the 4 parts of the ureter and their blood supplies?
Renal pelvis - aorta and renal arteries
abdominal - aorta, renal, testicular/ovarian
pelvic - testicular/ovarian, internal iliac
intravesicular - internal iliac, inferior vesicular
What are the ligaments what anchor the neck of the bladder?
Female - pubovesical
Male - puboprostatic
What forms the trigone of the bladder?
internal meatus
2 uteric orifices
Describe the internal urethral sphincter
Circular smooth muscle fibres - trigone
Describe the external urethral sphincter
striated muscle (part of urogenital diaphragm)
Blood supply to the bladder?
internal iliac artery –> superior and inferior vesiscular branches
Innervation of the bladder?
interior hypogastic plexus L1-2
Splanchnic nerves S2-4
What are the 4 parts of the male urethra?
Preprostatic - 1cm
Prostatic - 4cm. Longitudinal fold of mucosa forms the urethral crest. The depression on either side of the crest = prostatic sinus
Midway down the urethral crest is elevated - seminal coliculus
Membranous - narrow, passes through the perineal pouch
Spongy - surrounded by erectile tissue
Describe urothelium
Stratified with 3-6 layers of cells
Basal cells are cuboidal or columnar
Surface cells are umbrella cells
Maintain impermeability even at full stretch
How May kidney disease present?
A symptomatic
Hypertension
Kidney pain
Bleeding from urothelium
Causes of polyuria
Early chronic kidney disease - due to loss of concentrating ability
Osmotic diuretic e.g. Glucose in diabetes
Post renal obstruction
What causes oliguria?
Acute kidney injury
What causes anuria?
Severe acute kidney injury
Long standing end stage renal failure
Complete post renal obstruction
Features of urine in disease to be aware of
Colour Volume Odour Cloudiness Thickness Frothiness - excess protein Gravel Debris I.e. Infection Air
What does the urine dipstick test for?
Leukocyte esterase Nitrites Urobilinogen Protein PH Blood Specific gravity Ketones Bilirubin Glucose
What does urobilinogen in urine suggest?
Haemolysis
What does protein in the urine suggest?
Glomerular injury
What does blood in the urine suggest?
Glomerular injury
Bleeding from uroepithelium
What are the functions of the kidney?
Excretion - urea, creatinine, Uric acid, phosphate
Water and sodium balance
Electrolyte control
Acid base control
Endocrine - erythropoietin, vitamin D and renin
What is the first line way of viewing the kidneys?
What are the benefits to this?
Ultrasound
Cheap, non invasive, no radiation, no risk, no contrast
Operator dependent
What methods can be used to view the kidneys?
Ultrasound CT - contrast is nephrotoxic MRI Angiography Nuclear medicine - static or dynamic
Disadvantages and advantages of screening?
Difficulty with employment or insurance
Ethical issues with passing on to next generation
Aware of possible problems
Monitoring and treating
Supervision during pregnancy
Advantages of dialysis
Immediately life saving
Mdt support
Bridge to transplantation
Relief from loneliness and isolation
Impacts of dialysis
Often have multiple medical problems Frequent hospital admissions Depressed and psychological illness common Heavy time burden Limitation if travel because of treatment Restrictions on fluid intake and diet Employment difficulties Cost to health care providers
What is glomerular filtration dependent on?
Surface area
Membrane permeability
Net filtration pressure
How do you calculate net filtration pressure?
Blood hydrostatic pressure - filtrate hydrostatic pressure in bowmans space + colloid oncotic pressure
What does auto regulation maintain?
Maintains renal blood flow over a range of systemic blood pressures
Maintains glomerular filtration rate over a range of systemic blood pressures
What are the 2 mechanisms of renal auto regulation?
Myogenic (fast) - protects against high pressure
Increased blood flow - increased pressure in afferent - increased smooth muscle stretch - vasoconstriction of afferent - decreased glomerular pressure
Tubuloglomerular - slow. Dependent on the macula densa (juxta glomerular apparatus)
Decreased blood flow and GFR - decreased Cl to macula densa - renin release - increased efferent arteriolar resistance
Where is angiotensinogen produced?
Liver
What are the effects of angiotensin 2?
Increased tubular sodium and chloride resorption Efferent arteriolar vasoconstriction Systemic arteriolar vasoconstriction Activates sympathetic nervous system Vasopressin /ADH release Aldosterone release
What is the normal GFR rate?
120ml per minute
What are the qualities required in a substance to measure GFR?
Freely filtered
Not secreted
Not resorbed
How do you calculate creatinine clearance?
Concentration in urine x urine flow rate
/plasma concentration
What are the problems for using serum creatinine to measure GFR?
It is actively secreted by the tubules - it over estimated GFR
Insensitive for early marker of kidney disease
Affected by muscle mass
Affected by certain drugs
What are the general causes of glomerular injury?
Abnormalities of the slit diaphragm between podocytes
e. g. defect in gene that codes for nephrin
e. g. defect in podocyin (change in cytoskeleton)
Immune complex trapping blocking the glomerulus
e.g. SLE
In situ antigen
e.g. Good pastures disease
Implanted antigen - infectious GN (post streptococcal)
Endothelial cell injury
What are the consequences of the loss of function of the GBM?
- Protein loss (asymptomatic or nephrotic syndrome)
2. Blood loss (non visible, visible, nephritic syndrome)
Why do people with nephrotic syndrome develop oedema?
- capillary hydrostatic pressure is forcing fluid into interstital space
- interstital hydrostatic pressure pushes it back
- Also have capillary oncotic pressure maintains pressure in capillary (due to albumin)
Capillary oncotic pressure is reduced due to hypoalbuminaemia
What are the causes of nephritic syndrome in children?
Haemolytic uraemic syndrome
Post streptococcal GN
What are the main causes of nephritic syndrome in adults?
Goodpastures syndrome
SLE
Primary or secondary mesangiocapillary GN
What are the causes of intrarenal acute kidney injury?
Glomerulonephritis Pyelonephritis Drug induced interstitial nephritis Hypertension Vasculitis Kidney failure in type 1 diabetes
How many stages of chronic kidney disease are there and how are they determined?
5
Determined based on eGFR
Symptoms develop at stage 4
What are the main causes of chronic kidney disease in adults?
Diabetes Glomerulonephritis Interstital nephritis Vascular nephropathy Polycystic kidney disease
What are the main causes of chronic kidney disease in children?
Renal dysplasia and reflux
Obstructive uropathy
Glomerular disease
Congenital nephrotic syndrome
What are the symptoms of uraemia?
Non specific metallic taste anorexia nausea and vomiting itching fatigue chest pain (percarditis) breathlessness cognitive impairment
What type of anaemia would you expect in kidney failure?
No production of EPO
normocytic normochromic anaemia
Where in the kidney to carinomas most frequently occur?
Renal cortex
What are the predisposing factors for kidney cancer?
Smoking Obesity High blood pressure Acquired cystic renal disease Transplantation Familial
What are the most common kidney cancers?
Clear cell renal cell
Papillary
What grading system is used to stage kidney tumours?
Fuhrman nuclear grade
1-4
What are the different types of bladder cancer and how common are they?
Urothelial (TCC) 90%
Adenocarcinoma 5%
Squamous 5%
What are the predisposing factors for transitional cell carcinomas?
Smoking
Chemicals
Age
Chronic infection/calculi/drugs
What is the typical presentation of someone with a transitional cell carcinoma?
Haematuria
Hydronephritis
Retention (urethral)
Can be silent
What is the typical presentation of someone with a transitional cell carcinoma?
Haematuria
Hydronephritis
Retention (urethral)
Can be silent
What is the smooth muscle of the bladder?
detrusor muscle
Describe the micturation reflex
- Bladder fills due to increased urine
- detected by sensory stretch receptors
- conducted to sacral plexus via pelvic nerves
- reflexively back via parasympathetic
The fuller the bladder gets the stronger the reflex and the harder it is to override.
Completely autonomic but can be inhibited or facilitated by areas in the brain
What is the management for bladder cancer?
cystoscopy
biopsy, TURBT
Surgery
Describe the control the brain has over urination
- Higher centres keep the reflex partially inhibited except when desired
- Can prevent micturation via continual tonic contraction of external sphincter until convienient
- Cortical centres can initiate the relflex
What are the 4 zones to the prostate?
Peripheral
Transitonal
Anterior fibromuscular
Central
Where do the most common prostate cancers occur?
Peripheral zone
What are the symptoms of a urinary tract infection?
frequency dysuria haematuria foul smelling and cloudy urine urgency urinary incontinence pyrexia confusion
What are the symptoms of a urinary tract infection?
frequency dysuria haematuria foul smelling and cloudy urine urgency urinary incontinence pyrexia confusion
What are the signs and symptoms of pyelonephritis?
fever nausea vomiting costovertebral pain haematuria anorexia
What is the incidence of UTIs?
females more common
increases with age
18-30 due to sexual contact
post menopausal
Presdisposing factors for UTIs?
Female sexually active post menopausal catheterisation pregnancy developmental abnormalities renal transplantation diabetes
What would expect to find on a urine dipstick with someone with a UTI?
Nitrites
Proteins
Hb
leukocyte esterase
What are the 2 types of testicular cancer?
Germ cell tumour 95%
non germ cell tumour
What antibiotic treatment would you use for a UTI?
trimethoprim
2nd line - cefalexine or co-amoxiclav
What can cause a UTI?
E. Coli Coagulase negative staphylococci Proteus Klebsiella Adenovirus
What are the 2 routes of UTI acquisition?
Ascending (most common)
Haematogenous
What are the 3 layers to the
Outer adventitial connective tissue layer
Middle smooth muscle (detrusor)
Inner - transitional epithelium
What area of the brain is responsible to bladder voiding?
pontine micturition centre
Describe the prostatic part of the urethra
Midline ridge - urethral crest
On either side of the ridge is a depression 0 prostatic sinus
Elevation midway down - colliculus seminalis
This contains - 2 ejaculatory ducts and the prostatic utricle
define acute urinary retention
painful inability to void, with relief of pain following bladder drainage by catheterisation
What are the effects of alpha blockers when used for BPH?
Improves symptoms and flow
Onset of symptom relief in 1-2 weeks
Delay symptoms progression
What are the effects of 5 alpha reductase inhibitors when used for BPH?
Improve symptoms
Delay symptom progression
Reduce prostate volume and maintain the reductions
Reduce longer term risk of surgery
Define incontinence
The complaint of an involuntary loss of urine
Can seriously influence the physical, psychological and social wellbeing of those effected.
What are the different types of incontinence?
- Stress - weakness of urinary outlet
- Urge - failure of the bladder to store urine
- Overflow - overfilling bladder
What are some of the causes of urinary incontinence in men?
overactive bladder
neuropathic bladder
prostatectomy
overflow incontinence
What is the prevalence of urinary incontinence?
15-44years = 5%
45-64 years = 8-15%
65+ years = 10-20%
Nursing homes = 40%
What do people with urinary incontinence worry about?
Coughing or sneezing Getting worse as they age Smelling of urine Embarrassed Sex Limiting clothing
What are the risk factors for urinary incontinence?
Pregnancy and childbirth Age/menopause Obesity Constipation Pelvic organ prolapse Chronic cough Smoking
What are some of the treatments available for women with stress incontinence?
Behaviour therapy Pelvic floor exercises Vaginal weights alpha adrenergic agonists oestrogens tricyclic antidepressants vaginal wall suspension suburethral retropubic slings suburethral obturator foramen procedures
How common are UTIs?
5% of women each year present to their GP each year with UTI symptoms
50% of women will in their life time
At what points in life are you more likely to get a UTI?
honeymoon cystitis - beginning sexual activity
Pregnancy
(small amount at pre-school/infancy)
increasing age
What are the 2 points in which males are more likely to present with a UTI than a woman?
Infancy - congential urinary tract infections are higher in males
Prostatism
What are the most common bacterial causes of nosocomial UTI?
E.Coli (40%) - less than community acquired
Gram negatives - Klebsiella, enterobacter, psudomonas
Proteus
