The Renal & Urological System - Abnormal Urine Flashcards
What features of blood are regulated by the kidneys
pH
Volume
Pressure
Osmolality
Where are the kidneys located
Between T12 and L3 (retroperitoneal)
R sits slightly lower than L due to liver
What does the renal hilum act as entry and exit for
Ureter
Renal arteries
Renal veins
Lymphatics
Nerves
Layers of kidney
Renal facsia
Adipose capsule
Renal capsule
What % of cardiac output is received by kidneys and why
25% as kidneys filters ~150L of blood/ day
Flows into R and L renla arteries
What are nephrons divided into
Renal corpuscles and renal tubule
Whats found in the renal corpuscle
Glomerulus and bowman’s capsule
Once fluid is passed through the renal corpuscle, what is it referred to
Filtrate (urine precursor)
What do filtration slits allow the passage of
Water
Glucose
Ionic salts
What is the renal tubule surrounded with
Peritubular capillaries
What does the renal tubule consists of
Proximal convoluted tubule
DCT
Collection duct
What is the role of the juxtaglomerular complex
Help regulate BP and GFR
Where is the juxtaglomerular complex found
Between afferent arteriole and DCT
What is the juxtaglomerular complex composed of
Macula dense cells - sense low [Na] & [Cl]
Juxtaglomerular cells - helps w/ signalling
Extraglomerular mesangial cells - senses low bP –> secretes renin –> increased Na absorption
Metabolic function of kidney
Gluconeogeneisis, esp in conditions of prolonged fasting
Vit D activation - controls Ca and phosphorus metabolism
Main function of renal tubules
Recovering solutes filtered at glomerulus - occurs mainly in PCT
Main function of Loop of Henle
Forming concentrate or dilute urine
Role of distal tubule and collecting duct system
Fine control of slat and water excretion
(Most hormones exert their main effects on electrolyte and water secretion here e.gh. aldosterone)
What do the sympathetic fibres to the kidney regulate
Blood flow
Glomerular filtration
Tubule reabsorption
What is renal blood flow proportional to
Pressure gradient
(Pressure in renal artery - pressure in renal vein)/ reisstance in renla arterioles
How does increased renal blood flow, affect GFR
increases it
Which hormones affect renal arteriole reistsnace
Adrenaline and AngII
How does adrenaline affect arteriole resistance
Released when SNS is activated
Binds to alpha-1 adrenergic receptors on aff and eff arterioles –> constriction
Increased resistance
When is angiotensin released and how
In response to low BP
Renin released for JG cells –> cleaves angiotensinogen to AngI (works on endothelial cells in blood vessels) –> ACE made in lungs, converts AngI to AngII
AngII binds to receptors on aff and eff arterioels –> constriction
Increased resistance
How is GFR maintained, in terms of hormones affecting arteriole resistance
Eff arterioles more receptive to AngII, when low levels only eff contracts –> less blood leaving glomerulus, preserving GFR
High levels cause both to constrict
Role of ANP and BNP in regulating renal blood flow
Both release when there’s increased cardiac workload
Binds to receptors on smooth muscle and causes DILTATION of aff & CONSTRICTION of eff arterioles –> increasing renal blood flow
Role of PGI2 and PGE2 in regulating renal blood flow
Produced during SNS stimulation
Dilates both arterioles to ensure renal blood flow isn’t too low during SNS response
Role of dopamine in regulating renal blood flow
Dilates small vessels around heart and kidneys (but constricts in skin and muscle)
Even low levels increases renal blood flow
Autoregulation of kidneys
Mechanism within kidney to keep renal blood flow & GFR constant, despite systemic BP
Kidney adjusts own arteriole resistance
Two mechanisms involved in kidney autoregulation
Myogenic mechanism
Tubuloglomerular mechanism
Myogenic mechanism - autoregulation
Reflex of smooth muscle cells to contract when stretched (high BP, more contraction)
Leads to vasoconstriction of aff and eff arterioles
Increased resistance to decrease GFR
Tubuloglomerular mechanism - autoregulation
Macula densa cells can sense when GFR increases due to [Na] and [Cl]
Increased BP —> increased renal blood flow –> more filtrate produced , w/ more Na and Cl –> MD cells release adenosine, diffuses to afferent arteriole (constriction) –> increases arteriole resistance –> decreased GFR
Layers of glomerular filtration barrier
Endothelium - fenestration allow solutes and proteins
Basement membrane - pores percent plasma proteins (-ve charge) entering filtrate
Epithelium - filtration slits of podocytes
Where does glomerular filtration membrane sit
Between blood and Bowman’s capsule
What does GFR represents
Total amount of filtrate produced bu all glomeruli in BOTH kidneys/ minute
How does oncotic pressure change in both arterioles
Low in aff and increase through glomerulus
Maximum at eff
What is the. et filtration pressure at eff arteriole
0
Has reached filtration equilibrium, so blood is no longer filtered
How does capillary hydrostatic pressure affect GFR
As it increases, as does GFR
How does capillary oncotic pressure affect GFR
As it increases, GFR decreases
How does hydrostatic pressure in Bowman’s space affect GFR
As it increases, GFR decreases
What may cause increased hydrostatic pressure in Bowman’s space
Stone in ureter
Physiological buffers
Bicarb
Phosphate
Plasma proteins
Hb
Equation of bicarb buffer system
CO2 + H2O <—> H2CO3 <—-> H+ + HCO3-
Lines of defence against pH reduction
Lungs can blow off excess CO2
Kidneys reabsorb excess bicarb
What kind of acidosis is caused by disturbances of CO2
Primarily resp
What kind of acidosis is caused by disturbances of HCO3
Primarily metabolic
What must be equal to maintain pH and acid-base balance
Net endogenous acid production (NEAP) and renal net acid excretion (RNAE)
Acidaemia
Arterial pH below normal range (<7.35)
Alkalaemia
Arterial pH above normal range (>7.45)
Acidosis
Process that tends to lower extracellular fluid pH
Alkalosis
Process that tends to raise extracellular fluid pH
How do we produce H+
Tissue metabolism
Diet
Reclamation
Reabsoprtion of filtered bicarb
What is required to neutralise NEAP
Reclamation and generation of new bicarb
Where does majority of bicarb occur in nephron
PCT
Bicarb reabsorption in PCT
Na-K ATPase creates Na gradient
Na/H transporter protein brings Na into tubular cell and H+ secreted out
H+ + HCO3- –> H2CO3 (in urinary space)
Carbonic anhydrase causes dissociation into H2O and CO2, these move into tubular cells
H2CO3 reforms in tubular cells before dissociating into H+ and HCO3-
Na+/HCO3- con transporter brings both into peritubular capillary
HCO3-/Cl- exchanger brings Cl- from peritubualr capillary into tubular cells and HCO3- into capillary
Bicarb reabsorption in DCT and CD
Same process as PCT but ATP pump in alpha0-intercalated cells pushes H+ into urinary space
Generation of new bicarb - urinary buffers
Urinary phosphate buffers –> acidosis stimulates excretion of urinary Pi buffers as acid
Synthesis of NH4+ from NH3 –> acidosis stimulates renal ammoniagenesis from glutamine
These allow H+ excretion
Urinary buffers - ammoniageneisis
Most important buffer mechanisms
PCT cells brake down amino acids into ammonia
NH3 diffuses into tubule and combines w/ H+ –> NH4+
NH4+ combines w/ Cl- in urine to create a weak acid - maintaining pH
Urinary buffers - Pi
Phosphate ions enter tubules from plasma
Phophate ions poorly reabsorbed so builds up
Pi combines w/ H+ and lost through urine
Why do we need urinary buffers
pH of urine cannot be reduced below 4.5
H+ builds up in urinary space so needs to be excreted as to not lower pH
What would happen to urinary HCO3- excretion if a drug inhibiting carbonic anhydrase is administered
Metabolic acidosis
Lack of lumen reaction - increases H+ conc in tubular lumen
Calculating urine anion gap
[Urine sodium + urine potassium] - urine chloride
What does a negative UAG indicate
Another cation (as opposed to Na+ and K+) is being excited e.g. ammonium
What is the correct renal response to metabolic acidosis
Increased ammonium exertion
Implies tubular function is intact and cause of metabolic acidosis is extra-renal
Focal in terms of GN
Only affecting some glomeruli
Diffuse in terms of GN
Affecting all glomeruli
Segmental in terms of GN
Affecting only part of glomerulus
Global in terms of GN
Affecting whole glomerulus
Proliferation vs expansion in GN
Proliferation is increase in no. cells but expansion is increase in intercellular matrix
Types of mechanisms underlying glomerulonephritides
Immune
Vascular
Indications for renal bx
Nephrotic syndrome (adults)
Renal dysfunction of unknown cause (esp a/c)
Dysfunction of transplant kidney
Guide treatment or assess prognosis where dx known
Haematuria/ proteinuria?
Complications of renal bc
Pain
Bleeding - macroscopic haematuria +/- clot retention
Contraindications for renal bx
Abnormal clotting/ thrombocytopenia
Uncontrolled HTN
Single kidney - relative
Hydronephrosis
UTI (pyelonephritis)
Hydronephrosis
Kidneys swell as a result of obstruction to urine output
Interpretation of renal bx
Light microscopy
Immunostaining
Electron microscopy
How may renal disease px
Haematuria
Proteinuria
Nephrotic syndrome
Nephritic syndrome
A/c renal
C/c renal failure
What sx are involved in nephrotic syndrome
Proteinuria
Hypoalbuminamia
Oedema
Hypercholesterolaemia
What sx are involved in nephritic syndrome
Haematuria
HTN
Renal impairment e.g. reduced urine output
Commonest cause of nephrotic syn in children
Minimal change disease
Bx findings for minimal change disease
Normal light microscopy
Fusion of podocytes on electron microscopy
Causes of minimal change disease
Usually idiopathic
May be caused by NSAIDs or lymphoma
Associated w/ URTI
Mx of minimal change
Usually steroid responsive
May relapse, requiring heavy immunosuppression
1% go on to end stage renal failure
Px of focal segmental glomerulosclerosis
Nephrotic syn +/- renal impairment
Associations w/ FSGS
Berger’s disease, sickle cell, HIV
More common in afro-caribbean population
Bx findings for FSGS
Focal scarring
Segmental sclerotic lesion
C3 and IgM deposition
Mx for FSGS
Steroids or cyclophosphamide/ ciclosporin
40% progress to end-stage renal dialler, may recur following transplant
Types of FSGS
Primary or secondary - obesity, IVDU, HIV, pamidronate
Commonest cause of nephrotic syn in Aleuts
Membranous nephropathy
Associations seen in membranous nephropathy
Malignancy - lung, colon, breast
Infections - Hep B, malaria
AI teases - SLE, thyroid issue
Drugs - pencillamine, gold, captopril
Bx for membranous nephropathy
Spikes on basement membrane - IgG deposition
Subepithelial immune complex deposits
Rule of 1/3rd in membranous neohropathy
1/3 gets better speonatnouesy
1/3 stays the same
1/3 gets worse
Px of mesnagiocapillaru (membranoprolofertaive glomerulonephritis )
Nephritic or nephrotic syn
Bx findings for mesangiocapillary GN
Thckened capillary walls
‘Double contouring’ of basement membrane
+ve immunoflurosece (C3)
Serum complement levels may be low
Associations w/ mesnagiocapillary GN
Infection - hep B/C, endocarditis, malaria
Cryoglobulinaemia
Malignancy
Clinical features of diabetic nephropathy
Low level proteinuria - earliest sign
Pts usually have other micro vascular complications (retinopathy, peopgeral neuropathy, diabetic neohropathy)
Histology for diabetic nephropathy
Kimmelsteil-Wilson lesions
How may amyloidosis present
Heavy proteinuria +/- nephrotic syndrome & renal failure
What does amyloidosis stain with
Congo red
Apple green birefrigence under polarised light
Commonest form of glomerulonephritis WW
IgA nephropathy (Berger’s disease)
Px of IgA nephropathy
Ranges drom microscopic haematuria to paroxysmal macroscopic haematuria (e.g. exercise, resp tract infection) and progressive c/c renal failure
Bx findings for IgA nephropathy
IgA deposition in mesangial area
Associations w/ IgA nephropathy
C/c li9ver disease
Henoch Schonlein Purpura
When does post-stop GN px
2/3 weeks after Gp A strep infection (throat. skin)
Usually px as neohritic illness
Investigative findings for post-stop GN
Low C3
Normal C4
+ve ASO titre (anti-streptolysin O)
IgA nephropathy vs post-strep GN
IgA occurs 3-4 days after and post-strep is 2/3 weeks
Mx for post-strep GN
Supportive
How does renal involvement of systemic vascilutis (GPA and MPA) px
Nephritic illness
Goodpasture’s disease pathophys
AKA anti-glomerular basement disease
Antibodies to tupe IV collagen (found in glomerular and alveolar basement membrane)
Px of Goodpasture’s disease
A/c renal failure (often absolute anuria) and/ or pulm haemorrhage (in smokers)
Rapidly progressive GN
Clinical syn of nephritis w/ rapid decline in renal function
Often associated w/ presents on bx - cellular proliferation in Bowman’s space
Causes of rapidly progressive GN
Can be due to many causes incl systemic vasculitis and Goodpasture’s
Ix for pts w/ glomerular disease - urine
Dipstick
Microscopy and culture
Electrophoresis (light chains - Bence Jones proteins)
Protein quantification
Ix for pts w/ glomerular disease - bloods
Haem - FBC, ESR, coagulation, blood film
Biochem - U&Es, LFTs, Ca, PO4-, CRP
Immunology
Microbio - blood cultures, serology (Hep B/C, HIV, ASO titre)
Imaging for pts w/ glomerular disease
CXR
Renal ultrasound
Other (CT, MRI, angiography)
Normal urine protein
<150mg/ day (usually 40-80mg/day)
Urine proteins
Albumin - highest %
Low molecular weight proteins - beta2 microglobulins, polypeptides
Secreted proteins e.g. immunomodulatory
Calculating excretion in neohron
Filtration - rebaosrption + secretion
How does proteinuria present
Asymptomatic and incidental detection on urine dipstick
Heavy proteinuria –> peripheral oedema, frothy urine
Advantages of urine dipstick
Simple bedside tetst
Rapid dx
Inexpensive
Disadvantages of urine dipstick
Operator dependent
Semi-quantitive
Insensitive to low level proteinuria
Doesn’t detect non-albumin proteinuria
Ways of detecting proteinuria
Urine protein: creatinine ratio and albumin: creatine ratio - spot urine sample
24hr urine protein collection
Which types of dysfunction mechanisms cause proteinuria
Glomerular
Tubular
Overflow
Post-renal
Glomerular mechanism for proteinuria
Disruption in glomerular filtration barrier (loss of structural/ functional integrity)
Tubular mechanism for proteinuria
Defects in reabsorption and secretion (infl condns can cause this)
Overflow mechanism for proteinuria
Production of excess amounts of protein - overwhelms filtration and tubular reabsorption (associated w/ myeloma and massive hameolysis)
Post-renal mechanism for proteinuria
Characterised by infl in urinary tract AFTER level of nephron
Types of benign proteinuria
Orthostatic proteinuria
Transient proetinuria
Orthostatic proteinuria
Children and adolescent
Usually <3.5g/day erect but not supine
What may transient proteinuria be due to
Fever
Heavy exercise
Vasopressor
IV albumin
Primary glomerulonephritides
Minimal change disease
1’ FSGS
Idiopathic membranous nephropathy
IgA nephropathy
Idiopathic mesangiocapillary GN
Secondary glomerulonephritiides
DM
Systemic amyloidosis
2’ FSGS e..g obesity, HTN, HIV infection
AI disease e.g. SLE
2’ membranous nephropathy e.g. cancer, drugs
Mesangiocapillary GN - Hep B/C
Tubular proteinuria
Usually 1-2 g/ day
Low molecular weight proteins are filtered at glomerulus an reabsorbed by proximal tubules so proximal tubular function can be tested by looking ta levels of LMWP
Causes of tubular proteinuria
Tubulo-intertstitial nephritis caused by infl reaction
Causes of tubulo-interstitial nephritis
Drugs - e.g. abx, NSAIDs, PPis
AI disease - Crohn’s, sarcoidosis, Sjorgen’s disease
Infections - TB, CMV infection, Leptospirosis
Overflow proteinuria
Excess production of LMWP exceeds reabsorptive capacity of tubules
Condns causing overflow proteinuria
MM (free light chains)
Rhabdo (myyoglobin)
Haemolysis (Hb)
What may post-renal proteinuria be caused by
Infl of lower urinary tract - infection, stones
Clinical significance of proteinuria
Proteinuria is a risk factor for CDV disease and progressive CKD
Assessment of a pt w/ proteinuria
Hx
Physical exam
Urine dipstick and quantification
Assessment of renal function - creatinine and GFR
Renal imaging - USS
Relevant bloods
Renbal bx - definitieve test
Reevant bloods for proteinuria
ANA
ANCA
Anti GBM
Serum protein electrophoresis and free light chain ratio
Hep B/C serology
Complement
Anti-PLA2 (membranous nephropathy)
Complication of nephrotic syn
Infection
Thrombosis
Renal failure
Infection as a complication of nephrotic syn
Loss of albumin accompanied w/ loss of immunomodulatory proteins (Ig)
Thrombosis as a complication of nephrotic syn
Loss of anticoagulant proteins (protein C, protein S, antithrombin III) creates pro-thrombotic state
Renal failure as a complication of nephrotic syn
Proteinuria causes reduction in GFR –> CKD
Renal pathophys of nephrotic syn
Disruption of glomerular filtration barrier w/ podocyte effacement
Rarer clinical features of nephrotic syn
Pulm oedema and pleural effusion
Hyperlipidaemia
Thromboses
Why is hyperlipidaemia seen in nephrotic syn
Possible 2’ to increased hepatic lipoprotein synthesis - up-regulation of synthetic function of liver (goal is increased albumin)
Causes of nephritic syn
SLE
Henoch-Schonlein Purpura
Anti GBM
Rapidly progressive GN
Post-strep GN
Alport syn
IgA nephropathy
Membranoproliferative GN
Alport syndrome
Genetic disease that affects renal blood vessels leading to GN and defness
May also cause catracts and bulging of the lens
Pathophys of Alport syn
X-inked disease causing mutation of type 4 collagen
Abnormal collagen of basement membrane of kidneys, ears and eyes
Management of nephrotic syndrome
Low Na diet and fluid restriction due to 2’ hyperaldosteronism
Diuretics
BP control
Statin
Anticoagulant
How does angiotensin increase GFR
Constricting the eff arteriole increases pressure in glomerulus
How does angiotensin decrease proteinuria
By dropping pressure in glomerular capillariess
What antibody be tested for in primary membranous nephropathy
Anti-PLA2R
How is diabetic nephropathy managed
Glycaemic control
BP control
RAAS inhibition
AL amyloidosis
Raised by light chain deposition (closely related to MM)
AA amyloidosis
2’ amyloidosis caused by protein serum amyloid A released in c/c infl (infection, CTD)
Which cells release renin
Juxtaglomerular cells release renin (via exocytosis)
How is pro-renin converted to renin
By proteolytic enzymes
Factors that will increase renin release
Decrease in arterial BP
Decreased BP in glomerular vessels
Increased loss of Na and water
Increased sympathetic activity
Factors that decrease renin release
Na and water retention
Increased BP
Activation of AngI receptors (short loop -ve feedback)
Which pathways control renein secretion
Macula densa
Intrarenal barorecptor
Beta-receptor
Macula densa pathway of renin release
Reabsorption of Na Cl occurs via MD cells
Changes in Na reabsorption modifies release by JG cells
Increase in NaCl reabsorption inhibits renin release and vice versa
Which ion conc is mainly required for macula dense pathway of renin release
Cl- rather than Na
[CL-] required for saturation of symporter are high so changes in conc mainly effect MD mediated renin release
[Na+] in tubular lumen is higher than required for symporter
What modulates the macula densa pathway for rent please
ATP
Adenosine
PGI2
Intrarenal baroreceptor pathway for renin release
Increase in BP or renal perfusion pressure in preglomeruluar vessels inhibit renin release and vice versa
What may modify the intrarenal baroreceptor pathway for renin release
Stretch receptors in arterial walls and.or by PG synthesis
Beta receptor pathway for control of renin related
Via beta-1 receptors on JG cells
-ve feedback for renin release
Increased renin secretion enhances formation of AngII which is responsible for short loop -ve feedback
Other factors causing -ve feedback for renin release (NOT renin secretion)
Activating high pressure baroreceptors and thereby reducing renal sympathetic tone
Increasing pressure in pre-glomerular vessels
Reducing NaCl reabsorption from proximal tubule (pressure natriuresis) thereby reducing MD pathway
Physiological factors affecting renin release
Systemic blood pressure
Dietary salt intake
Pharmacological agents
Pharmacological agents modifying renin release
NSAIDS
Loop diuretics
ACEi, ARBs, renin inhibitors
Centrally acting sympatholytic agent and beta blockers
How do NSAIDs affect renin release
NSAIDS inhibit PG synthesis –> decreased renin release
How do loop diuretics affect renin release
Loop diuretics decreased BP and increase NaCl reabsorption
Causing increased renin release
How doe centrally acting sympatholytic agents and BBs affect renin release
Decreased renin secretion by reducing beta-receptor activation
Role of ACE
Convert AngI to AngII
Also inactivates vasodilators (identical to kinin 2)
Where is angiotensinogen made
Liver
Where is the major site of conversion of AngI to AngII
Lungs
What is the local (tissue) renin-angiotensin system important for
Its role in hypertrophy, infl and remodelling and apoptosis
Which tissue can local RAAS occur in
Brain
Pituitary blood vessels
Heart
kidney
Adrenal glands
Extrinsic vs intrinsic local RAAS
Extrinsic - vascular endothelium of the tissues
Intrinsic - tissues having mRNA expression
Local (tissue) RAAS
Binding of renin or pro-renin receptors located on cell surface
Enzymes that act as alternative conversion of angiotensinogen to AngI or AngII
Cathepsin
Tonon
Cathepsin G
Heart chemise
Angiotensin receptors
Most effects of AngII are mediated by AT1
