The Renal & Urological System - Abnormal Urine Flashcards
1
Q
What features of blood are regulated by the kidneys
A
pH
Volume
Pressure
Osmolality
2
Q
Where are the kidneys located
A
Between T12 and L3 (retroperitoneal)
R sits slightly lower than L due to liver
3
Q
What does the renal hilum act as entry and exit for
A
Ureter
Renal arteries
Renal veins
Lymphatics
Nerves
4
Q
Layers of kidney
A
Renal facsia
Adipose capsule
Renal capsule
5
Q
What % of cardiac output is received by kidneys and why
A
25% as kidneys filters ~150L of blood/ day
Flows into R and L renla arteries
6
Q
What are nephrons divided into
A
Renal corpuscles and renal tubule
7
Q
Whats found in the renal corpuscle
A
Glomerulus and bowman’s capsule
8
Q
Once fluid is passed through the renal corpuscle, what is it referred to
A
Filtrate (urine precursor)
9
Q
What do filtration slits allow the passage of
A
Water
Glucose
Ionic salts
10
Q
What is the renal tubule surrounded with
A
Peritubular capillaries
11
Q
What does the renal tubule consists of
A
Proximal convoluted tubule
DCT
Collection duct
12
Q
What is the role of the juxtaglomerular complex
A
Help regulate BP and GFR
13
Q
Where is the juxtaglomerular complex found
A
Between afferent arteriole and DCT
14
Q
What is the juxtaglomerular complex composed of
A
Macula dense cells - sense low [Na] & [Cl]
Juxtaglomerular cells - helps w/ signalling
Extraglomerular mesangial cells - senses low bP –> secretes renin –> increased Na absorption
15
Q
Metabolic function of kidney
A
Gluconeogeneisis, esp in conditions of prolonged fasting
Vit D activation - controls Ca and phosphorus metabolism
16
Q
Main function of renal tubules
A
Recovering solutes filtered at glomerulus - occurs mainly in PCT
17
Q
Main function of Loop of Henle
A
Forming concentrate or dilute urine
18
Q
Role of distal tubule and collecting duct system
A
Fine control of slat and water excretion
(Most hormones exert their main effects on electrolyte and water secretion here e.gh. aldosterone)
19
Q
What do the sympathetic fibres to the kidney regulate
A
Blood flow
Glomerular filtration
Tubule reabsorption
20
Q
What is renal blood flow proportional to
A
Pressure gradient
(Pressure in renal artery - pressure in renal vein)/ reisstance in renla arterioles
21
Q
How does increased renal blood flow, affect GFR
A
increases it
22
Q
Which hormones affect renal arteriole reistsnace
A
Adrenaline and AngII
23
Q
How does adrenaline affect arteriole resistance
A
Released when SNS is activated
Binds to alpha-1 adrenergic receptors on aff and eff arterioles –> constriction
Increased resistance
24
Q
When is angiotensin released and how
A
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
25
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
26
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
27
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
28
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
29
Autoregulation of kidneys
Mechanism within kidney to keep renal blood flow & GFR constant, despite systemic BP
Kidney adjusts own arteriole resistance
30
Two mechanisms involved in kidney autoregulation
Myogenic mechanism
Tubuloglomerular mechanism
31
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
32
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
33
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
34
Where does glomerular filtration membrane sit
Between blood and Bowman's capsule
35
What does GFR represents
Total amount of filtrate produced bu all glomeruli in BOTH kidneys/ minute
36
How does oncotic pressure change in both arterioles
Low in aff and increase through glomerulus
Maximum at eff
37
What is the. et filtration pressure at eff arteriole
0
Has reached filtration equilibrium, so blood is no longer filtered
38
How does capillary hydrostatic pressure affect GFR
As it increases, as does GFR
39
How does capillary oncotic pressure affect GFR
As it increases, GFR decreases
40
How does hydrostatic pressure in Bowman's space affect GFR
As it increases, GFR decreases
41
What may cause increased hydrostatic pressure in Bowman's space
Stone in ureter
42
Physiological buffers
Bicarb
Phosphate
Plasma proteins
Hb
43
Equation of bicarb buffer system
CO2 + H2O <---> H2CO3 <----> H+ + HCO3-
44
Lines of defence against pH reduction
Lungs can blow off excess CO2
Kidneys reabsorb excess bicarb
45
What kind of acidosis is caused by disturbances of CO2
Primarily resp
46
What kind of acidosis is caused by disturbances of HCO3
Primarily metabolic
47
What must be equal to maintain pH and acid-base balance
Net endogenous acid production (NEAP) and renal net acid excretion (RNAE)
48
Acidaemia
Arterial pH below normal range (<7.35)
49
Alkalaemia
Arterial pH above normal range (>7.45)
50
Acidosis
Process that tends to lower extracellular fluid pH
51
Alkalosis
Process that tends to raise extracellular fluid pH
52
How do we produce H+
Tissue metabolism
Diet
53
Reclamation
Reabsoprtion of filtered bicarb
54
What is required to neutralise NEAP
Reclamation and generation of new bicarb
55
Where does majority of bicarb occur in nephron
PCT
56
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
57
Bicarb reabsorption in DCT and CD
Same process as PCT but ATP pump in alpha0-intercalated cells pushes H+ into urinary space
58
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
59
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
60
Urinary buffers - Pi
Phosphate ions enter tubules from plasma
Phophate ions poorly reabsorbed so builds up
Pi combines w/ H+ and lost through urine
61
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
62
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
63
Calculating urine anion gap
[Urine sodium + urine potassium] - urine chloride
64
What does a negative UAG indicate
Another cation (as opposed to Na+ and K+) is being excited e.g. ammonium
65
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
66
Focal in terms of GN
Only affecting some glomeruli
67
Diffuse in terms of GN
Affecting all glomeruli
68
Segmental in terms of GN
Affecting only part of glomerulus
69
Global in terms of GN
Affecting whole glomerulus
70
Proliferation vs expansion in GN
Proliferation is increase in no. cells but expansion is increase in intercellular matrix
71
Types of mechanisms underlying glomerulonephritides
Immune
Vascular
72
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?
73
Complications of renal bc
Pain
Bleeding - macroscopic haematuria +/- clot retention
74
Contraindications for renal bx
Abnormal clotting/ thrombocytopenia
Uncontrolled HTN
Single kidney - relative
Hydronephrosis
UTI (pyelonephritis)
75
Hydronephrosis
Kidneys swell as a result of obstruction to urine output
76
Interpretation of renal bx
Light microscopy
Immunostaining
Electron microscopy
77
How may renal disease px
Haematuria
Proteinuria
Nephrotic syndrome
Nephritic syndrome
A/c renal
C/c renal failure
78
What sx are involved in nephrotic syndrome
Proteinuria
Hypoalbuminamia
Oedema
Hypercholesterolaemia
79
What sx are involved in nephritic syndrome
Haematuria
HTN
Renal impairment e.g. reduced urine output
80
Commonest cause of nephrotic syn in children
Minimal change disease
81
Bx findings for minimal change disease
Normal light microscopy
Fusion of podocytes on electron microscopy
82
Causes of minimal change disease
Usually idiopathic
May be caused by NSAIDs or lymphoma
Associated w/ URTI
83
Mx of minimal change
Usually steroid responsive
May relapse, requiring heavy immunosuppression
1% go on to end stage renal failure
84
Px of focal segmental glomerulosclerosis
Nephrotic syn +/- renal impairment
85
Associations w/ FSGS
Berger's disease, sickle cell, HIV
More common in afro-caribbean population
86
Bx findings for FSGS
Focal scarring
Segmental sclerotic lesion
C3 and IgM deposition
87
Mx for FSGS
Steroids or cyclophosphamide/ ciclosporin
40% progress to end-stage renal dialler, may recur following transplant
88
Types of FSGS
Primary or secondary - obesity, IVDU, HIV, pamidronate
89
Commonest cause of nephrotic syn in Aleuts
Membranous nephropathy
90
Associations seen in membranous nephropathy
Malignancy - lung, colon, breast
Infections - Hep B, malaria
AI teases - SLE, thyroid issue
Drugs - pencillamine, gold, captopril
91
Bx for membranous nephropathy
Spikes on basement membrane - IgG deposition
Subepithelial immune complex deposits
92
Rule of 1/3rd in membranous neohropathy
1/3 gets better speonatnouesy
1/3 stays the same
1/3 gets worse
93
Px of mesnagiocapillaru (membranoprolofertaive glomerulonephritis )
Nephritic or nephrotic syn
94
Bx findings for mesangiocapillary GN
Thckened capillary walls
'Double contouring' of basement membrane
+ve immunoflurosece (C3)
Serum complement levels may be low
95
Associations w/ mesnagiocapillary GN
Infection - hep B/C, endocarditis, malaria
Cryoglobulinaemia
Malignancy
96
Clinical features of diabetic nephropathy
Low level proteinuria - earliest sign
Pts usually have other micro vascular complications (retinopathy, peopgeral neuropathy, diabetic neohropathy)
97
Histology for diabetic nephropathy
Kimmelsteil-Wilson lesions
98
How may amyloidosis present
Heavy proteinuria +/- nephrotic syndrome & renal failure
99
What does amyloidosis stain with
Congo red
Apple green birefrigence under polarised light
100
Commonest form of glomerulonephritis WW
IgA nephropathy (Berger's disease)
101
Px of IgA nephropathy
Ranges drom microscopic haematuria to paroxysmal macroscopic haematuria (e.g. exercise, resp tract infection) and progressive c/c renal failure
102
Bx findings for IgA nephropathy
IgA deposition in mesangial area
103
Associations w/ IgA nephropathy
C/c li9ver disease
Henoch Schonlein Purpura
104
When does post-stop GN px
2/3 weeks after Gp A strep infection (throat. skin)
Usually px as neohritic illness
105
Investigative findings for post-stop GN
Low C3
Normal C4
+ve ASO titre (anti-streptolysin O)
106
IgA nephropathy vs post-strep GN
IgA occurs 3-4 days after and post-strep is 2/3 weeks
107
Mx for post-strep GN
Supportive
108
How does renal involvement of systemic vascilutis (GPA and MPA) px
Nephritic illness
109
Goodpasture's disease pathophys
AKA anti-glomerular basement disease
Antibodies to tupe IV collagen (found in glomerular and alveolar basement membrane)
110
Px of Goodpasture's disease
A/c renal failure (often absolute anuria) and/ or pulm haemorrhage (in smokers)
111
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
112
Causes of rapidly progressive GN
Can be due to many causes incl systemic vasculitis and Goodpasture's
113
Ix for pts w/ glomerular disease - urine
Dipstick
Microscopy and culture
Electrophoresis (light chains - Bence Jones proteins)
Protein quantification
114
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)
115
Imaging for pts w/ glomerular disease
CXR
Renal ultrasound
Other (CT, MRI, angiography)
116
Normal urine protein
<150mg/ day (usually 40-80mg/day)
117
Urine proteins
Albumin - highest %
Low molecular weight proteins - beta2 microglobulins, polypeptides
Secreted proteins e.g. immunomodulatory
118
Calculating excretion in neohron
Filtration - rebaosrption + secretion
119
How does proteinuria present
Asymptomatic and incidental detection on urine dipstick
Heavy proteinuria --> peripheral oedema, frothy urine
120
Advantages of urine dipstick
Simple bedside tetst
Rapid dx
Inexpensive
121
Disadvantages of urine dipstick
Operator dependent
Semi-quantitive
Insensitive to low level proteinuria
Doesn't detect non-albumin proteinuria
122
Ways of detecting proteinuria
Urine protein: creatinine ratio and albumin: creatine ratio - spot urine sample
24hr urine protein collection
123
Which types of dysfunction mechanisms cause proteinuria
Glomerular
Tubular
Overflow
Post-renal
124
Glomerular mechanism for proteinuria
Disruption in glomerular filtration barrier (loss of structural/ functional integrity)
125
Tubular mechanism for proteinuria
Defects in reabsorption and secretion (infl condns can cause this)
126
Overflow mechanism for proteinuria
Production of excess amounts of protein - overwhelms filtration and tubular reabsorption (associated w/ myeloma and massive hameolysis)
127
Post-renal mechanism for proteinuria
Characterised by infl in urinary tract AFTER level of nephron
128
Types of benign proteinuria
Orthostatic proteinuria
Transient proetinuria
129
Orthostatic proteinuria
Children and adolescent
Usually <3.5g/day erect but not supine
130
What may transient proteinuria be due to
Fever
Heavy exercise
Vasopressor
IV albumin
131
Primary glomerulonephritides
Minimal change disease
1' FSGS
Idiopathic membranous nephropathy
IgA nephropathy
Idiopathic mesangiocapillary GN
132
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
133
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
134
Causes of tubular proteinuria
Tubulo-intertstitial nephritis caused by infl reaction
135
Causes of tubulo-interstitial nephritis
Drugs - e.g. abx, NSAIDs, PPis
AI disease - Crohn's, sarcoidosis, Sjorgen's disease
Infections - TB, CMV infection, Leptospirosis
136
Overflow proteinuria
Excess production of LMWP exceeds reabsorptive capacity of tubules
137
Condns causing overflow proteinuria
MM (free light chains)
Rhabdo (myyoglobin)
Haemolysis (Hb)
138
What may post-renal proteinuria be caused by
Infl of lower urinary tract - infection, stones
139
Clinical significance of proteinuria
Proteinuria is a risk factor for CDV disease and progressive CKD
140
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
141
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)
142
Complication of nephrotic syn
Infection
Thrombosis
Renal failure
143
Infection as a complication of nephrotic syn
Loss of albumin accompanied w/ loss of immunomodulatory proteins (Ig)
144
Thrombosis as a complication of nephrotic syn
Loss of anticoagulant proteins (protein C, protein S, antithrombin III) creates pro-thrombotic state
145
Renal failure as a complication of nephrotic syn
Proteinuria causes reduction in GFR --> CKD
146
Renal pathophys of nephrotic syn
Disruption of glomerular filtration barrier w/ podocyte effacement
147
Rarer clinical features of nephrotic syn
Pulm oedema and pleural effusion
Hyperlipidaemia
Thromboses
148
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)
149
Causes of nephritic syn
SLE
Henoch-Schonlein Purpura
Anti GBM
Rapidly progressive GN
Post-strep GN
Alport syn
IgA nephropathy
Membranoproliferative GN
150
Alport syndrome
Genetic disease that affects renal blood vessels leading to GN and defness
May also cause catracts and bulging of the lens
151
Pathophys of Alport syn
X-inked disease causing mutation of type 4 collagen
Abnormal collagen of basement membrane of kidneys, ears and eyes
152
Management of nephrotic syndrome
Low Na diet and fluid restriction due to 2' hyperaldosteronism
Diuretics
BP control
Statin
Anticoagulant
153
How does angiotensin increase GFR
Constricting the eff arteriole increases pressure in glomerulus
154
How does angiotensin decrease proteinuria
By dropping pressure in glomerular capillariess
155
What antibody be tested for in primary membranous nephropathy
Anti-PLA2R
156
How is diabetic nephropathy managed
Glycaemic control
BP control
RAAS inhibition
157
AL amyloidosis
Raised by light chain deposition (closely related to MM)
158
AA amyloidosis
2' amyloidosis caused by protein serum amyloid A released in c/c infl (infection, CTD)
159
Which cells release renin
Juxtaglomerular cells release renin (via exocytosis)
160
How is pro-renin converted to renin
By proteolytic enzymes
161
Factors that will increase renin release
Decrease in arterial BP
Decreased BP in glomerular vessels
Increased loss of Na and water
Increased sympathetic activity
162
Factors that decrease renin release
Na and water retention
Increased BP
Activation of AngI receptors (short loop -ve feedback)
163
Which pathways control renein secretion
Macula densa
Intrarenal barorecptor
Beta-receptor
164
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
165
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
166
What modulates the macula densa pathway for rent please
ATP
Adenosine
PGI2
167
Intrarenal baroreceptor pathway for renin release
Increase in BP or renal perfusion pressure in preglomeruluar vessels inhibit renin release and vice versa
168
What may modify the intrarenal baroreceptor pathway for renin release
Stretch receptors in arterial walls and.or by PG synthesis
169
Beta receptor pathway for control of renin related
Via beta-1 receptors on JG cells
170
-ve feedback for renin release
Increased renin secretion enhances formation of AngII which is responsible for short loop -ve feedback
171
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
172
Physiological factors affecting renin release
Systemic blood pressure
Dietary salt intake
Pharmacological agents
173
Pharmacological agents modifying renin release
NSAIDS
Loop diuretics
ACEi, ARBs, renin inhibitors
Centrally acting sympatholytic agent and beta blockers
174
How do NSAIDs affect renin release
NSAIDS inhibit PG synthesis --> decreased renin release
175
How do loop diuretics affect renin release
Loop diuretics decreased BP and increase NaCl reabsorption
Causing increased renin release
176
How doe centrally acting sympatholytic agents and BBs affect renin release
Decreased renin secretion by reducing beta-receptor activation
177
Role of ACE
Convert AngI to AngII
Also inactivates vasodilators (identical to kinin 2)
178
Where is angiotensinogen made
Liver
179
Where is the major site of conversion of AngI to AngII
Lungs
180
What is the local (tissue) renin-angiotensin system important for
Its role in hypertrophy, infl and remodelling and apoptosis
181
Which tissue can local RAAS occur in
Brain
Pituitary blood vessels
Heart
kidney
Adrenal glands
182
Extrinsic vs intrinsic local RAAS
Extrinsic - vascular endothelium of the tissues
Intrinsic - tissues having mRNA expression
183
Local (tissue) RAAS
Binding of renin or pro-renin receptors located on cell surface
184
Enzymes that act as alternative conversion of angiotensinogen to AngI or AngII
Cathepsin
Tonon
Cathepsin G
Heart chemise
185
Angiotensin receptors
Most effects of AngII are mediated by AT1
