Renal Flashcards
(285 cards)
1
Q
How is glomerular filtration rate measured?
A
creatinine
* if elevated = kidney disease
2
Q
Significance of proteinuria?
A
> 150 mg/day = significant glomerular damage
3
Q
Normal kidney?
Microalbuminuria?
Clinical proteinuria?
Nephrotic?
A
Normal
- dipstick = negative
- PCR <15
- total protein <0.150g
- ACR <2.5 (M), <3.5 (F)
Microalbuminuria
* ACR = 2.5 - 30 (M), 3.5 - 30 (F)
Clinical proteinuria
- 1+ or 2+ on dipstick
- PCR = 45 - 449
- Total protein = 0.45 - 1.49
- ACR = >30
Nephrotic
- 3+ on dipstick
- PCR > 450
- total protein > 4.5 g
- ACR >30
4
Q
Microalmbuminaemia?
Significance?
A
excretion of almbumin in abnormal quantities but still below limit of protein detection by dipstick
* earliest expression of diabetic nephropathy!!
5
Q
Tubular function in oliguric patient?
A
Pre-renal failure i.e. tubules working
- urine Na = <20
- Urea = >10 (urine): 1 (serum)
- osmolality = >1.5 (urine): 1 (serum)
Renal damage (tubules not working)
- Na = >40
- Urea = 3 (urine): 1 (serum)
- osmolality = <1 (urine): 1 (serum)
6
Q
what hormones does kidney release? (3)
A
- Renin
- 1, 25 dihydroxycholecalciferol (gut)
- erythroprotein (bone marrow)
7
Q
Function of kidney? (3)
A
- maintain water and electrolyte balance
- excrete toxic metabolic waste (urea + creatinine)
- produces renin and erythroprotein
8
Q
lobe of kidney?
A
each medullary pyramid
9
Q
basic functional unit of kidney?
A
nephron
10
Q
what is kidney nephron made up of?
A
renal corpuscle and renal tubules
11
Q
function of renal corpuscle?
A
production and collection of glomerular filtrate
12
Q
Order of nephron structures?
A
- renal corpuscle: production and collection of glomerular filtrate
- proximal convoluted tubule: reabsorption of water, proteins, amino acids, carbohydrates + glucose
- loop of henle: creates hyperosmotic environment in medulla
- distal convoluted tubule: acid-base and water balance
13
Q
Bowman’s capsule?
A
simple squamous epithelium at blind end of nephron that capillaries invaginate into
14
Q
podocytes?
A
specialised epithelium which seperates blood from glomerular filtrate (sit on top of glomerular capillaries)
15
Q
mesangial cells?
A
produce connective tissue core called mesangium
16
Q
Blood supply and drainage to renal corpuscle?
How do they enter/leave?
A
supply = afferent arteriole drain = efferent arteriole
(enter and leave thru bowman’s capsule)
17
Q
Poles of renal corpuscle?
A
- Vascular pole (bowman’s capsule)
* Urinary pole (opposite end - proximal convoluted tubule)
18
Q
components of glomerular filter?
A
1) fenestrated endothelium of capillary wall
2) thick basement membrane (endothelium + podocyte)
3) filtration slits between pedicels
19
Q
Function proximal convoluted tubule?
A
reabsorption of water, proteins, amino acids, carbs + glucose
20
Q
significance of proximal tubule?
A
- 70% of sodium + water reabsorbed
21
Q
Function of loop of Henle?
A
creation of hyperosmotic environment in medulla
22
Q
Blood supply to medulla?
A
Vasa recta
23
Q
structure of loop of Henle?
A
1) thick descedning limb
2) thin descending limb which makes ahairpin turn and becomes thin ascending limb
3) transitions to thick ascending limb
24
Q
What are thick limbs of loop of Henle lined with?
Thin limbs?
A
Thick = simple cuboidal epithelium Thin = simple squamous
25
Vasa recta?
loops of thin walled blood vessels that dip down into the medulla and then climb back up to the cortex
26
function of distal convoluted tubule?
acid-base and water balance
27
What is reabsorption of Na+ in distal convoluted tubule controlled by?
Aldosterone (results in greater Na+ and water reabsorption therefore increases blood pressure)
28
Function of collecting tubules and collecting ducts?
Reabsorption of water under the control of ADH
29
what are medullary rays?
proximal + distal tubules + collecting ducts running in parallel bundles
30
What hormone is active in collecting ducts?
ADH (vassopresin)
| * results in concentrated urine as water is reabsorbed
31
what are conducting areas of the urinary tract lined with?
| What is special about the luminal (i.e. facing the lumen) cells?
transitional epithelium/urothelium (renal papilla, minor calyx, major calyx, bladder, urethra)
* luminal cells are called umbrella cells because they are domed = highly impermeable barrier
32
what exists below urothelium?
lamina propria + 2-3 layers of smooth muscle
33
Explain structure of urethra?
Females
* 3-5 cm
* lined by transitional epithelium then transitions to stratified squamous
Males
* 20 cm
* prostatic urethra
* membranous urethra (from prostate to bulb of penis) - it is at this point transitional epithelium changes to stratified columnar
* penile urethra = stratified columnar becomes stratified squamous
34
What is osmolarity?
Concentration of osmotically active particles present in a solution
35
Units for osmolarity?
osmol/l or mosmol/l
| mosmol/l for body fluids
36
How is osmolarity calculated?
1) molar concentration of solution
2) number of osmotically active particles present
e. g. 150 mM NaCl
* molar concentration = 150
* no. of osmotically active particles = 2 (Na+ and Cl-)
* osmolarity = 2(150) = 300 mosmol/l
37
Osmolarity of body fluids?
~300 mosmol/l
38
Tonicity?
Effect a solution has on cell volume
| e.g. hypo, hyper, iso
39
Isotonic?
doesn’t mean water isn’t moving across membrane – just means no net movement of water
40
Hypotonic?
| Hypertonic?
```
Hypo = increase in cell volume (more water, less salt)
Hyper = decrease in cell volume
```
41
Osmolarity of cell <300?
| >300?
```
<300 = hypotonic
>300 = hypertonic
```
42
Difference between 300 mM urea and 300 mM sucrose on red blood cells?
* Sucrose = isotonic (RBC impermeable)
| * Urea = hypotonic
43
TBW males and females?
* Male = ~60% of body weight
| * Female = ~50%
44
Total body water compartments?
| What is ECF composed of?
* ICF = 67%
* ECF = 33%
ECF
* plasma (20%)
* interstitial fluid (80%)
* Lymph + transcellular fluid (negligible)
45
How are body fluid compartments measured?
| Examples?
using "tracers"
* TBW = 3H20
* ECF = inulin
* plasma = labelled albumin
TWB = ECF + ICF (so can calculate ICF if we know TBW and ECF)
46
Greatest loss of water from body?
| Input and output?
Urine
Homeostasis
Input = output
i.e. 2500 = 2500
47
How is water balance increased?
Water balance is maintained by increased water ingestion. Decreased excretion of water by the kidneys alone is insufficient to maintain water balance
48
Ionic composition of ICF and ECF?
ICF = more K+, less Na, less Cl, less HCO3
ECF = less K+, more Na, more Cl, more HCO3 (think sea water!)
49
Main ions in ICF?
K+ and Mg2+
50
Osmotic concentrations of ICF and ECF?
Identical ~300 mosmol/l
51
Fluid shift?
Movement of water between the ICF and ECF in response to an osmotic gradient
52
What would happen to ECF and ICF volumes for the following situations:
1) if osmotic concentration of ECF increases
2) if osmotic concentration of ECF decreases
Increases
* Would become hypertonic compared to ICF
* Cell volume decreases
Decreases
* ECF were to gain additional water but not salt
* Would become hypotonic compared to ICF
* Cell volume increases
53
ECF NaCL gain?
| ECF NaCl loss?
* Gain = increase ECF volume, decrease ICF volume
| * Loss = decrease ECF, increase ICF
54
Effect of gain or loss of isotonic fluid on fluid osmolarity?
Example?
No change in fluid osmolarity
(change in ECF volume only!)
* e.g. 0.9% NaCL solution
55
What alters composition + volume of ECF?
Kidney
56
Why is it vital to regulate Na?
Major determinant of ECF volume
| for ICF it is potassium
57
What can increase/decrease of K+ lead to? (2)
1) muscle weakness (paralysis)
2) cardiac arrest
(because it plays a major role in establishing membrane potential)
58
What is the key role of K+?
Establishing membrane potential
59
Function of kidney nephrons?
* filtration
* reabsorption
* secretion
60
Blood supply to nephron?
* Afferent arteriole drains into glomerular capillary (called glomerulus)
* Then drains into efferent arteriole
* Efferent arteriole drains into peritubular capillaries which eventually drain into renal vein
61
What is the fluid that flows through nephron?
| End product?
Tubular fluid
| * end product is urine
62
difference between juxtamedullary and cortical nephrons? (3)
* Juxta = has much longer loop of henle
* Cortical = have peritubular capillaries (juxtamedullary have vasa recta, single capillary), follows loop of henle
* Juxta = able to produce much more concentrated urine
63
What are most nephrons?
```
80% = cortical
20% = juxtamedullary
```
64
Function of macula densa?
salt sensitive cells, monitor level of salt in tubular fluid
65
Function of granular cells?
Production + secretion of renin
66
What percentage of plasma that enters glomerulus is filtered?
20%
67
Relationship between filtration, secretion, reabsorption and excretion?
* Filtration + secretion = reabsorption + excretion
| * Rate of excretion = rate of filtration + rate of secretion - rate of reabsorption
68
Rate of filtration =?
Rate of filtration = [X] in plasma x GFR
69
What is normally the value of GFR?
~125 ml/min
(plug in to equations)
so would be 0.125 l/min
70
Rate of excretion =?
Rate of excretion = [X] in urine x Vu
Vu = rate of urine production
71
Rate of reabsorption =?
rate of reabsorption = rate of filtration - rate of excretion
72
What if rate of filtration > rate of excretion?
Net reabsorption of that substance has occured
| * rate of reabsorption = rate of filtration - rate of excretion
73
Rate of secretion =?
Rate of secretion of = rate of excretion – rate of filtration
74
What if rate of filtration < rate of excretion?
Net secretion of the substance has occured
75
Filtration barriers in glomerular filtration?
(1) Glomerular Capillary Endothelium (barrier to RBC)
(2) Basement Membrane (basal lamina) = plasma protein barrier)
(3) Slit processes of podocytes (plasma protein barrier)
76
Podocytes?
Make up inner membrane of bowman's capsule
77
Which arteriole has larger diameter?
Afferent arteriole larger than efferent
78
what must fluid filtered from glomerulus into bowman's capsule pass through?
three layers that make up glomerular membrane
79
why does basement membrane have a net negative charge?
| fluid passes from capillary through endothelial cell -> basement membrane -> podocyte -> bowman's capsule
Net negative charge – plasma proteins should be contained within the capillary (none should enter lumen of bowman’s capsule)
80
Forces that increase net filtration pressure? forces that compromise net filtration pressure?
so what is total net filtration pressure?
Increase
* glomerular capillary blood pressure
* bowman's capsule oncotic pressure
Decrease
* bowman's capsule hydrostatic pressure
* Capillary oncotic pressure
Net filtration pressure = 10 mm Hg
81
Starling forces?
balance of hydrostatic pressure and osmotic forces
82
does glomerular filtration require energy?
| Biggest driver of process
No, passive
| * glomerular capillary blood pressure
83
glomerular filtration rate (GFR)?
| Biggest determinant of GFR?
rate at which protein-free plasma is filtered from the glomeruli into the Bowman’s capsule
* glomerular capillary blood pressure
84
Equation GFR?
GFR = Kf x net filtration pressure
kf = filtration coefficient
85
Normal GFR?
125 ml/min
86
Regulation of GFR and renal blood flow?
Extrinsic
* baroreceptor reflex
Intrinsic
* myogenic
* tubuloglomerular feedback mechanism
87
Effect of increased arterial blood pressure on GFR?
GFR increases
| if BP falls, then decrease
88
Vasoconstriction of afferent arteriole?
| Vasodilation?
```
Vasoconstriction = decreases blood flow to glomerulus (decrease GFR)
Vasodilation = increases (thus increase in GFR)
```
89
Baroreceptor reflex GFR?
* fall in blood volume e.g. haemorrhage
* decrease BP
* baroreceptors increase sympathetic activity
* cause vasoconstriction (incl. afferent arterioles)
* decreased BPgc
* decreased GFR
* decreased urine production
90
Do slight changes in arterial BP cause changes in GFR?
No, renal blood blow and GFR protected over a wide range of MABP
91
Autoregulation (intrinsic) of GFR? (2)
Myogenic
* vascular smooth muscle constricts in response to stretching (i.e. increased BP)
Tubuloglomerular feedback
* if GFR rises, more NaCl flows into tubule causing constriction of afferent arteriole
92
what can cause increase in bowman's capsule pressure?
| What does this result in?
kidney stone
| * decreased GFR
93
what can cause increase in capillary oncotic pressure?
| What does this result in?
Diarrhoea
| * decreased GFR
94
What causes decreased capillary oncotic pressure?
| Resulting in?
Severe burns
| * increased GFR
95
Plasma clearance?
A measure of how effectively the kidneys can ‘clean’ the blood of a substance (each substance will have a different plasma clearance value)
96
Plasma clearance equation?
| Units?
clearance of X = rate of excretion of X/plasma concentration of X
otherwise written as
clearance = [X]urine x V(urine)/[X] plasma
Units = ml/min
97
Example of substance that clearance = GFR?
| Why is this?
Inulin (creatinine can also be used)
| * inulin is filtered but is NOT secreted or reabsorbed!
98
Example of substance for which clearance = 0?
| Why?
Glucose
| * it is filtered, COMPLETELY reabsorbed, and NOT secreted
99
Example of substance for which clearance < GFR?
| Why?
Urea
* filtered, PARTLY reabsorbed, and NOT secreted
(
100
Example of substance for which clearance> GFR?
| Why?
H+
| * filtered, secreted but NOT reabsorbed
101
If clearance < GFR?
If clearance = GFR?
If clearance > GFR?
* clearance < GFR = reabsorbed
* clearance = GFR = substance is neither reabsorbed nor secreted
* clearance > GFR = secreted
102
What is para-amino hippuric acid (PAH)?
| Why?
Used to measure renal plasma flow
| * it is fully secreted (not reabsorbed)
103
Normal value of renal plasma flow?
650 ml/min
104
Requirements of a GFR marker?
| A RPF marker?
* GFR marker = should be filtered but NOT secreted nor reabsorbed!!
* RPF marker = should be filtered AND completely secreted!
105
Filtration fraction?
Value?
Remaining %?
fraction of plasma flowing that is filtered into the tubules
* value = 20% filtered
* remaining 80% enters efferent arteriole then peritubular capillaries
106
Renal blood flow value?
| What % of CO do kidneys receive?
~1200 ml.min
| * kidneys receive ~24% of CO
107
GFR?
125 ml/min
| * 180 litres/day
108
How much fluid is reabsorbed in the proximal tubule?
| So how much, therefore, flows into loop of Henle?
80 ml/min of filtered fluid
* so 125 ml/min (GFR) - 80 ml/min = 45 ml/min
* 45 ml/min flows into loop of Henle
109
Substances reabsorbed in proximal tubule? (5)
| Secreted in proximal tubule? (7)
Reabsorbed
* sugars, amino acids, phosphate, sulphate, lactate
Secreted
* H+, hippurates, neurotransmitters, bile pigments, uric acid, drugs, toxins
110
Types of reabsorption? (2)
* Transcellular (tubular)
| * paracellular
111
How is glucose transported into cells? (2)
Either by
* Facilitated diffusion
* secondary active transport with Na+
112
What is essential for Na+ reabsorption?
NaKATPase carrier
| active transport
113
How is Na reabsorbed in proximal tubule?
Due to:
* osmotic gradient
* oncotic pressure gradient
114
Glucose reabsorption in proximal tubule?
100% of glucose reabsorbed in proximal tubule
115
What do substances have to pass thru in reabsorption?
Tubular epithelial cell, interstitial fluid and peritubular capillary endothelium
116
Transport maximum for glucose?
2 mmol/min
117
What percentage of salt and water is reabsorbed in PT?
~67%
118
What is Na reabsorption in proximal tubule driven by?
basolateral Na+-K+-ATPase
119
What does Na reabsorption in proximal tubule drive?
Reabsorption of Cl through paracellular pathway
120
What is tubular fluid described as once it leaves proximal tubule?
Iso-osmotic (i.e. 300 mosmol/l)
121
Function of loop of Henle?
genereates cortico-medullary concentration gradient
| * enables formation of hypertonic urine
122
what is the opposing flow in the descending limb and ascending limb of loop of Henle called?
Countercurrent flow
123
What term is used to describe function of loop of henle?
Countercurrent multiplier
124
Compare ascending limb of loop of Henle to descending limb?
What is this important for?
THICK part of Ascending limb
* Na and Cl are reabsorbed
* impermeable to water
Descending limb
* does not reabsorb NaCl
* highly permeable to water
Selective permeabilities of the ascending and descending limbs of the Loop of Henle enable an osmotic gradient to be established in the medulla
125
Where do loop diuretics act?
Loop diuretics block the NaKCL (triple) co-transporter in the thick ascending limb
126
Explain processes in the loop of Henle
1. Water leaves the descending limb by osmosis
2. Fluid in the descending limb is concentrated
3. Solute removed from lumen of ascending limb (water cannot follow)
4. Tubular fluid is diluted and osmolality of interstitial fluid is raised
127
How does the osmolaity differ at the start and the end of the loop of Henle?
* Iso osmotic fluid leaves the proximal tubule
| * Hypo osmotic fluid enters the distal tubule
128
What is the purpose of countercurrent multiplication?
To concentrate the medullary interstitial fluid
| * allows kidney to produce urine of different volume and concentration depending on ADH
129
Normal Vu?
~1 ml/min
| can be 0.3 - 25 ml/min
130
What does vasa recta act as?
A countercurrent exchanger
131
How does vasa recta prevent the loss of NaCl and urea?
* Vasa recta capillaries follow hairpin loops
* Vasa recta capillaries freely permeable to NaCl and water
* Blood flow to vasa recta is low (few juxtamedullary nephrons)
132
Chronic kidney disease classification?
| End stage renal disease?
Chronic = CDK3 - 4
| End stage = CDK5
133
Renal replacement therapies? (3)
* Haemodialysis (GFR = 7)
* Peritoneal dialysis (GFR = 7)
* transplant (GFR = 50)
134
Contraindications to renal transplant? (8)
* malignancy
* active HCV/HIV infection
* untreated TB
* severe IHD
* severe airway disease
* Active vasculitis
* Severe PVD
* hostile bladder
135
Which tissue types should e matched to avoid an immune reaction?
HLA type:
* A
* B
* DR
136
Sensitising events that can lead to pre-formed antibodies prior to transplant?
* blood transfusion
* pregnancy or miscarriage
* previous transplant
137
Explain process of kidney transplant?
* Native kidneys stay in place
* Transplant inserted in iliac fossa
* Kidney grafted into iliac vein and artery
* Ureter and bladder also grafted onto transplant
138
What kind of procedure is kidney transplant?
Extra-peritoneal procedure
139
Surgical complications of renal transplant?
* Bleeding
* Arterial stenosis
* Venous stenosis / kinking
* Ureteric stricture & hydronephrosis
* Wound infection
* Lymphocele
140
Transplant function? (3)
Immediate graft function
* good urine output
* falling urea and creatinine
Delayed graft function
* need haemodialysis
* usually works within 10-30 days
Primary non-function
* transplant never works
141
Types of transplant rejection? (3)
Hyperacute rejection
* Due to preformed antibodies
* Unsalvageable
* Transplant nephrectomy required
Acute Rejection
* Cellular or Antibody mediated
* Can be treated with increased immunosupression
Chronic Rejection
* Antibody mediated slowly progressive decline in renal function
* Poorly responsive to treatment
142
Immunosuppressive therapy for renal transplant?
Induction treatment
* basiliximab/dacluzimab
Prednisolone IV during operation
Maintenance tx
* prednisolone, tacrolimus, MMF
* prednisolone, ciclosporin, azathioprine
143
Anti-rejection therapies? (5)
* pulsed IV methylprednisolone
* anti-thymocyte globulin
* IV immunoglobulin
* Plasma exchange
* rituximab, eculizimab
144
What should prophylaxis be given for following immunosuppression?
Pneumocystis jiroveci pneumonia (PJP)
145
What is a common cause of morbidity in immunosuppressed patients in first 3 months of transplant?
Complications?
Tx?
Cytomegalovirus
* renal and hepatic disease
* oesophagitis, colitis
* increased risk of rejection
Prophylaxis
* PO valganciclovir
Treatment
* IV ganciclovir
146
What is the cause of BK virus nephropathy?
| Tx?
Over-immunosuppression
Tx
* there is no effective antiviral
* tx is to reduce immunotherapy
147
POST TRANSPLANT LYMPHOPROLIFERTIVE DISEASE (PTLD)?
* Occurs in all forms of transplantation
* Usually related to EBV infection
(leads to lymphoma)
148
Tx for PTLD?
* reduce immunosuppresion
* chemotherapy
there is no role for antiviral therapy!!
149
Examples of monoclonal antibodies?
Mechanism?
Why are they only used for prophylaxis?
Basiliximab or Dacluzimab
* Block IL-2 receptor on CD4 T-cells
* Not useful if rejection has already started
150
Glucocorticoid mechanism?
Inhibit lymphocyte proliferation + suppress cytokines
151
Examples of calcineurin inhibitors?
Mechanism?
Side effects? (4)
Tacrolimus & Ciclosporin
* inhibiting activation of T-cells
Side effects
* Renal dysfunction
* Hypertension
* Diabetes
* Tremor
152
Anti-metabolites examples?
Mechanism?
Side effects? (3)
Azathioprine & Mycophenolate Mofetil (MMF)
* Block purine synthesis -> suppression of proliferation of lymphocytes
Side effects
* leucopenia
* GI upset
* anaemia
153
Glomerular disease classed as?
Type of parenchymal disease
154
Types of glomerular disease? (4)
Diabetic Nephropathy
Glomerulonephritis (GN)
Amyloid/ Light Chain Nephropathy
Transplant Glomerulopathy
155
Glomerulonephritis?
Immune-mediated disease of the kidneys affecting the glomeruli
(secondary tubulointerstitial damage)
156
Pathogenesis of GN?
* Humoral (antibody-mediated)
* Cell-mediated (T-cells)
* Inflammatory cells, mediators and complements
157
Pathophysiology GN?
Disruption of glomerular capillary wall leads to haematuria/proteinuria
158
Damage to endothelial/mesenagial cells?
| Damage to podocytes?
* Endothelial/mesangial = leads to proliferative lesion and RBCs in urine
* Podocytes = non-proliferative lesion and protein in urine
159
Why does damage to podocytes result in proteinuria?
| What is different about this response compared to endothelial/mesangial damage?
Atrophies.
Loss of size/charge specific barrier so proteins leak out
* it is NON-INFLAMMATORY
160
Result of damage to mesangial cells?
Proliferate and release angiotensin 2, chemokines + attract inflammatory cells
161
Result of damage to endothelial cells?
Vasculitis (e.g. acute GN)
162
24 year old man incidentally found to have ++ blood and + protein on dip, BP 148/92.
Protein quantified at 0.7g/day. Creat 72.
What glomerular cells are most likely to be injured?
Mesangial cells. High BP, protein and blood in urine.
163
Dx of GN? (6)
* Urinalysis - haematuria, proteinuria
* Urine microsopy - RBC (dysmorphic), RBC & granular casts, lipiduria
* Urine Protein: Creatinine Ratio/24 hour urine - quantify proteinuria
* Kidney biopsy
* Blood tests
164
Clinical presentation glomerulonephritis? (5)
* Haematuria (either asymptomatic microscopic haematuria or painless macroscopic)
* Proteinuria
* impaired renal function
* hypertension
* NephROTIC syndrome (if affects podocytes!)
* NephRITIC syndrome (if affects endothelial cells)
165
How is proteinuria classified?
* Microalbuminuria (30-300mg albuminuria/day)
* Asymptomatic proteinuria ( 1 g/day)
* Heavy proteinuria (1-3 g/day)
* Nephrotic syndrome (> 3 g/day)
166
What is microabluminuria a sign of?
| Tx??
Diabetic nephropathy - give an ACEI asap!!
167
Urine microscopy of RBCs?
Microscopy can give a clue where red cells have come from
| Red cells squeezed out of shape going through glomerulus so will be dysmorphic
168
Red cell casts?
pathognomonic of glomerular bleeding
169
NephrITIC syndrome indicative of?
| S/s? (5)
Indicative of a proliferative process affecting endothelial cells
* acute renal failure
* oliguria (not peeing)
* oedema/fluid retention
* hypertension
* haematuria!
170
NephrOTIC syndrome indicative of?
| S/s? (5)
Indicative of a non proliferative process affecting Podocytes
* Proteinuria 3 g/day (mostly albumin, also globulins)
* Hypoalbuminaemia (<30)
* Oedema
* Hypercholesterolaemia
* Usually normal renal function (unlike nephritic syndrome)
171
Complications of nephrotic syndrome?
* Infections - loss of opsonising antibodies
* Renal vein thrombosis (this would cause sudden decline of renal function which isn't normal in nephrotic syndrome so watch out!)
* Pulmonary emboli
* Volume depletion (overaggressive use of diuretics) - may lead to acute renal failure (pre-renal)
172
How does the presentation of GN differ from a non glomerular disease like Interstitial Nephritis?
Get proteinuria in glomerular disease, don’t get it in tubular disease
173
Classification of GN?
1) Idiopathic - THE MAJORITY
| 2) caused by eg. infections, drugs, malignancies, ANCA, lupus, Goodpastures, HSP
174
What is the use of immunofluoresence in GN?
IgG staining can indicate glomerulonephritis
175
Histological classifications of GN?
* Proliferative or non-proliferative (usually refers to presence or absence of proliferation of mesangial cells)
* Focal/Diffuse (< or > 50% glomeruli affected)
* Global/Segmental (all or part glomerulus affected)
* Crescentic (presence of crescents - epithelial cell extracapillary proliferation eg. RPGN in vasculitis)
176
Tx glomerulonephritis?
Non-immunosuppressive
* anti-hypertensives (target BP <130/80, <120/75 if proteinuria)
* ACEI/ARBs
* Diuretics
* Statins
Immunosuppressive
* corticosteroids/azathioprine/ calcineurin inhibitors/ mycophenolate mofetil (MMF)
* plasmapheresis (therapeutic plasma exchange)
* antibodies
177
Tx nephrotic patients?
* Fluid restriction
* Salt restriction
* Diuretics
* ACE Inhibitors/ ARBs
* IV albumin (only if volume deplete)
* immunosuppression (to achieve sustained remission)
178
What is the goal of immunosuppression in GN?
To achieve sustained remission
* complete remission (proteinuria <300 mg/day)
* partial remission (proteinuria <3 g/day)
179
What are the risks of immunosuppressing a patient who is nephrotic?
High risk of infection (they are already losing immunoglobulins i.e. protein)
180
Main types of idiopathic GN?
* MINIMAL CHANGE
* FSGS (focal segmental glomerulosclerosis)
* MEMBRANOUS
* MEMBRANOPROLIFERATIVE
* IgA NEPHROPATHY
181
Minimal change disease?
Commonest GN in children
(EM pictures allow you to see where damage is)
DOES NOT CAUSE PROGRESSIVE RENAL FAILURE
182
Tx minimal change nephropathy?
* 1st line = oral steroids
| * 2nd line = cyclophosphamide
183
What does minimal change nephropathy appear like on EM?
podocytes are all fused together. Foot process fusion—fingers have retracted
184
Focal segmental glomerulosclerosis (FSGS)?
| Ax?
Commonest cause of nephrotic syndrome in adults
* Idiopathic
* type 2 = HIV, heroin use, obesity, reflux nephropathy
185
Dx FSGS?
Renal biopsy = light miscoscopy with minimal Ig/complement deposition
186
Tx FSGS?
* Remission with prolonged steroids in 60%
| * 50% progress to end stage renal failure after 10 years
187
Membranous nephropathy?
| Ax?
2ND commonest cause of nephrotic syndrome in adults
* Idiopathic
* infections (hepatitis B/ parasites)
* connective tissue diseases (lupus)
* malignancies (carcinomas/ lymphoma)
* drugs (gold/penicillamine)
188
Dx membranous nephropathy?
| Tx?
Renal biopsy: immune complex deposition in the basement membrane
* Steroids/ Alkylating agents/B cell monoclonal Ab
189
What is anti PLA2r antibody?
| What does it cause?
Anti-podocyte antobody! (plasminogen lipase antigen 2 receptor)
It causes menbranous nephropathy (nephrotic syndrome)
190
Histology membranous nephropathy?
Thickened basement membrane due to immune complex deposition
191
IgA nephropathy?
| S/s? (4)
Commonest GN in the world
* asymptomatic microhaematuria
* macroscopic haematuria after resp/GI infection
* AKI/CKD
* associated with henoch-schonlein purpura (arthritis/colitis/purpuric rash)
192
Dx IgA nephropathy?
| Tx?
Renal biopsy = mesangial cell proliferation + IgA deposits in mesangium (immunofluorescence)
Tx
* BP control = ACEI + ARBs
* Fish oil
(treatment is NOT immunosuppression)
193
Pathogenesis IgA nephropathy?
* IgA is abnormal
* Immune complexes form in circulation
* Immune complexes deposited in mesangium causing immune activation and injury
194
Rapidly progressive glomerulonephritis (RPGN)?
| S/s? (3)
A treatable cause of acute renal failure (affects endothelial cells)
* Rapid deterioration in renal function over days/weeks
* Active urinary sediment (RBC’s, RBC & Granular Casts)
* May be part of systemic disease
195
Dx rapidly progressive glomerulonephritis (RPGN)? (2)
* Urinary sediment (RBCs, RBC casts)
| * glomerular crescents on biopsy
196
Systemic diseases associated with RPGN?
ANCA positive (systemic vasculitis)
* GPA
* microscopic polyangitis
ANCA negative
* Goodpasture's (anti-GBM)
* Henoch scholein purpura
* SLE
197
Tx RPGN?
Strong immunosuppression with dialysis if needed!!
* Steroids (IV methylprednisoone/oral prednisolone)
* Cytotoxics (cyclophosphamide/azathioprine)
* plasmapheresis
198
74 year old woman. Hypoxic. Haemoptysis. creat 430. blood and protein on dip. Red cell casts on microscopy. Purpuric rash.
Cells affected?
Diagnosis?
Invetsigation?
* Cells affected = endothelial cells (remember RBC = endothelial cells)
* ANCA +ve vasculitis (RPGN)
* Endothelial injury in lungs causes haemoptysis and hypoxia
Investigation
* blood test for ANCA
199
Describe pathway and concentration of tubular fluid leaving the loop of Henle?
* tubular fluid entering disal tubule is hypo-osmotic to plasma (100 mosmol/l)
* surrounding interstitial fluid of renal cortext is 300 mosmol/l
* empties into collecting duct
* collecting duct bathes by increasing concentrtions of interstitial fluid (300 - 1200 mosmol/l)
200
what % of ions are reabsorbed before filtrate enters the distal tubule?
95% (but residual load 700-1000 mmol NaCl is very important for salt balance!)
201
How is ion and water balance regulated?
By hormones
* ADH = increases water reabsorption
* Aldosterone = increases Na reabsorption, and H+ and K+ secretion
* Atrial natriuretic hormone = decreases Na reabsorption
* Parathyroid hormone (PTH) = increases calcium reabsorption + increases phosphate secretion
202
Distal tubule permeability?
| Osmolality?
Low permeability to water and urea (therefore, urea is concentrated in tubular fluid)
* tubular fluid is hypo-osmotic (100 mosmol/l) to plasma
203
2 segments of the distal tubule?
Early and late
* Early: NaK2Cl transport (NaCl reabsorption)
* Late: Calcium reabsorption, H+ secretion, Na and K reabsorption (aldosterone causes K secretion)
204
2 segments of the collecting duct?
Early and late
* Early collecting duct is similar to late distal tubule
* Late collecting duct: low ion permeability, permeable to water and urea and influenced by ADH
205
ADH secretion from the posterior pituitary?
* Octapeptide (ADH) synthesised by the supraoptic and paraventricular nuclei in the hypothalamus
* Transported down nerves to terminals where it is stored in granules in the posterior pituitary
* Released into blood when action potentials down the nerves lead to Ca2+-dependent exocytosis
206
Effect of ADH on water permeability of the collecting duct?
* increase in intracellular cyclic AMP
* Cyclic AMP initiates insertion of water channels into apical membrane of tubular cell (water reabsorption)
* Aquaporins become internalised within intracellar vesicles once ADH level decreases
207
High ADH?
| Low ADH?
* High ADH = high water permeability (more reabsorption) + thus hypertonic urine (1400 mosmol/l)
* Low ADH = low water permeability thus hypotonic urine (<50 mosmol/l)
208
In presence of maximal ADH?
| Minimal ADH?
Tubular fluid equilibrates with interstitium via aquaporins (small volume of concentrated urine)
* Minimal = Collecting duct is impermeant to water, so no water reabsorption (large volume of dilute urine)
209
Diabetes insipidus classification?
* Central diabetes insipidus (unable to secrete ADH)
| * Nephrogenic diabetes insipidus (ADH production normal, problem with target cells)
210
S/s diabetes insipidus? (2)
| Tx?
Large volumes of dilute urine
Constant thirst
* Tx = ADH replacement
211
Most important stimulus for ADH release?
```
Hypothalmic osmoreceptors
(less important = left atrial stretch receptors i.e. decreased atrial pressure = increased ADH release)
```
212
Stimulation of stretch receptors in upper GI tract?
Feed-forward inhibition of ADH
213
Drugs and substances increase/inhibit ADH?
* Nicotine stimulates ADH release
| * Alcohol + ecstacy inhibits ADH release
214
Aldosterone?
| When is it secreted?
Steroid hormone secreted by the adrenal cortex
Secreted in response to
* rising K or falling Na in blood
* activation of renin-angiotensin system
215
Function of aldosterone?
Stimulates Na+ reabsorption and K+ secretion
| Na retention contributes ot increased blood volume + pressure
216
Effects of aldosterone on K+?
* 90% K+ is reabsorbed in proximal tubule
* When aldosterone absent the rest (10%) K+ reabsorbed in the distal tubule (therefore, no K+ is excreted in the urine)
* Aldosterone stimulates the SECRETION of K+
217
Direct and indirect secretion of aldosterone?
* An increase in [K+] directly stimulates adrenal cortex
| * decrease in plasma [Na+] = indirect secretion of aldosterone via juxtaglomerular apparatus
218
Which cells release renin?
Granular cells in the juxtaglomerular apparatus
219
What causes granular cells to release renin? (3)
* Reduced pressure in afferent arteriole
* If macula densa cells sense reduced NaCl in the distal tubule
* Increased sympathetic activity as a result of reduced arterial blood pressure
220
Effect on aldosterone on Na?
increases Na+ reabsorption in the distal and collecting tubule
221
Pathophysiology renin angiotensin system?
| Tx? (3)
Responsible of the fluid retention associated with congestive heart failure
Tx
* low salt diet
* diuretics
* ACE inhibitors (stop salt and fluid retention)
222
Atrial natriuretic peptide?
When is it released?
Effect?
Produced by the heart
* released when atrial muscle cells are stretched due to increased BP
Effect
* causes excretion of Na+ and diuresis lowering BP
223
Micturition?
| Controlled by?
Urination
* micturation reflex
* voluntary control
224
When is micturation reflex triggered?
| What kind of nerve reflex?
bladder can accommodate up to 250-400 ml of urine before stretch receptors in within its wall initiate the micturation reflex
* parasympathetic
225
How is voluntary control of urination exerted?
Micturation can be voluntarily PREVENTED by deliberate tightening of the external sphincter and surrounding pelvic diaphragm
226
PH equation?
pH = log 1/[H+]
227
Is venous or arterial blood more acidic?
Venous - due to CO2
| CO2 + H2O = carbonic acid
228
pH of arterial blood?
| Venous blood?
```
Arterial = 7.45
Venous = 7.35
```
229
How can fluctuations in [H+] affect the body? (4)
* Acidosis = depression of CNS
* Alkalosis = overexcitability of CNS
* Changes in [H+} affect enzyme activity
* changes in [H+] affect K+ levels
230
HA [H+] + A-
What happens if [H+] is added?
Equilibrium shifts to the left, [HA] rises, [A- falls]
231
Dissociation constant equation?
K = [H+][A-]/[HA]
pK = -log K
232
Henderson-Hasselbalch equation?
pH = pK + log [A-]/[HA]
233
Most important buffer system?
CO2-HCO3 buffer
234
Mechanism of [HCO3] reabsorption in proximal tubule?
HCO3- disappears from the tubular fluid and appears in the interstitial fluid
* Unorthodox reabsorption – the same HCO3- ion does not cross the epithelium
235
What happens when [HCO3] is low?
secreted H+ combines with the next most plentiful buffer in the filtrate…
phosphate
236
What 3 things does H+ secretion by tubule allow? (3)
* Reabsorption of HCO3
* Formation of acid phosphate
* Formation of ammonium ion
237
Total H+ secretion/day?
| Total H+ excretion?
```
Secretion = 4360 mmol/day
Excretion = 60 mmol/day
```
238
Acute urinary retention s/s?
| Ax?
* Inability to urinate
* Painful urination
Usually complication of benign prostatic hyperplasia
239
Tx acute urinary retention?
* Catheter
| * Alpha-blocker: alfuzosin, tamulosin
240
Acute loin pain Ax?
* Ureteric colic secondary to calculus
| * AAA
241
Tx ureteric colic?
* NSAID/opiate
* alpha blocker (for small stones that are expected to pass)
* Surgical intervention if too large to pass
242
Dx kidney stone?
* Definitive test = non-contrast CT scan
243
Surgical interventions for kidney stone? (3)
* Ureteric stent
* Stone fragmentation/removal
* percutaneous nephrostomy for infected hydronephrosis
244
Frank haematuria caused by?
```
Infection
Stones
Tumours
Benign prostatic hyperplasia (BPH)
Polycystic kidneys
Trauma
Coagulation/platelet deficiencies
```
245
Tx clot retention urinary system?
3-way irrigating haematuria catheter
246
Ix haematuria?
* CT urogram
| * Cytoscopy
247
S/s torsion of spermatic cord?
Examination?
Age group?
S/s
* acute onset pain
* nausea/vomiting
* referral of pain to lower abdomen
Examination
* testes high + transverse
* absence of cremasteric reflex
Most common at puberty
248
Ix torsion of spermatic cord?
| Tx?
Doppler USS
Tx
* If testis necrotic, remove
* MUST fix contralateral side (bell clapper deformity)
249
S/s torsion of testicular appendage?
* Can be identical to torsion of cord
* "blue spot" sign
* Cremasteric reflex is present!
250
Epididymitis difficult to distinguish from?
Testicular torsion
* dysuria/pyrexia more common
* Hx of UTI, urethritis, catheterisation
251
O/E epididymitis?
* absent cremasteric reflex
* pyuria
* doppler = swollen epididymis
252
Ax epididymitis?
Associated with chlamydia
253
Tx epididymitis?
* Analgesia
| * Ofloxacin 400mg/day for 14 days
254
Idiopathic scrotal oedema?
| S/s?
* self-limiting, unknown cause
S/s
* tender
* pruritis
* no fever (unlike epididymitis)
255
Paraphimosis?
| Ax?
Painful swelling of the foreskin distal to a phimotic ring
* Often happens after foreskin retracted for catheterization or cystoscopy and staff member forgets to replace it in its natural position
256
Tx paraphimosis?
* Iced glove
* granulated sugar for 1-2 hrs
* punctures in oedematous skin
* manual compression
* dorsal slit
257
Priapism?
| Ax?
Prolonged erection (> 4hrs), often painful and not associated with sexual arousal
Ax
* Papaverine injetion for ED
* Trauma
* Sickle cell
258
Classification priapism? (3)
* Ischaemic
* Vascular stasis (compartment syndrome)
* Corpora cavernosa (rigid and painful)
259
Dx priapism?
* Aspirate blood (in low flow, will have low O2 and high CO2)
* Colour duplex USS - low flow = absent flow in cavernosal arteries (normal flow in non-ischaemic priapism)
260
Tx priapism?
Ischaemic
* aspiration
* alpha-agonist e.g. phenylephrine
* surgical shunt
Non-ischaemic
* may resolve spontaneously
261
Fournier's gangrene?
| S/s? (4)
necrotizing fasciitis of the male genitalia
* starts as cellulitis - swollen, erythematous, tender, fever
* crepitus of scrotum
* dark purple areas
262
Tx fournier's gangrene?
Antibiotics + surgical debridement
263
Emphysematous pylonephritis?
| Risk factors?
Infective emergency!!
* acute necrotizing parenchymal and perirenal infection caused by gas-forming uropathogens, usually E coli
* risk factor = diabetes
264
S/s emphysematous pylonephritis?
Dx? (2)
Tx?
S/s
* fever
* vomiting
* flank pain
Dx
* gas on KUB
* CT
Tx = nephrectomy
265
Perinephric abscess?
| S/s? (5)
Usually results from rupture of an acute cortical abscess into the perinephric space
* flank mass
* not usually pyrexial
* high WCC
* high creatinine
* pyuria
266
Ix perinephric abscess?
| TX?
```
Ix = CT
Tx = antibiotics + percutaneous surgical drainage
```
267
Indications for imaging?
| Ix?
* Frank haematuria
Ix = CT contrast (unlike non-contrast CT for kidney stone)
268
Bladder injury associated with?
| S/s? (5)
Associated with pelvic fracture
* abdominal pain
* inability to void
* lower abdominal bruising
* guarding
* diminished bowel sounds
269
Ix bladder injury?
| Tx?
Ix = CT cystography
Tx
* large-bore catheter
* antibiotics
270
Urethral injury associated with?
| S/s? (5)
often associated with fracture of pubic rami
* blood at meatus
* inability to urinate
* full bladder (palpable)
* "high-riding" prostate
* BUTTERFLY perineal haematoma!
271
Ix urethral injury?
| Tx?
Retrograde urethrogram
Tx
* suprapubic catheter
272
Penile fracture?
| S/s?
Typically happens during intercourse – buckling injury when penis slips out of vagina and strikes pubis
* Cracking or popping sound followed by pain, rapid detumescence, discolouration and swelling
273
Tx penile fracture?
Circumcision incision with degloving of penis to expose all 3 compartments
274
Testicular injury Ix?
USS to assess integrity / vascularity
275
Infective inflammation of the kidney?
| Non-infective inflammation of the kidney?
* Infective = pyelonephritis
| * Non-infective = glomerulonephritis
276
What does bowman's space contain?
Urine
277
What is glomerulus held together by?
Mesangial cells
278
Which glomerulonephritis involves a direct attack of the glomerulus?
Good pasture's syndrome (lung + renal)
279
Types of vasculitis? (2)
* cANCA = GPA
| * pANCA = microscopic polyangiitis
280
Classification of glomerulonephritis? (2)
* Nephritic syndrome
| * Nephrotic syndrome
281
Difference between nephritic and nephrotic syndrome?
Nephritic
* haematuria, hypertension
Nephrotic
* proteinuria (protein loss = immunosuppression due to loss of antibodies)
* Oedema
* hyperlipidaemia
* renal vein thrombosis
282
Crescents histology?
| Granulomas?
* Crescents = RPGN (poor prognosis)
| * granulomas = GPA or sarcoid
283
Dx goodpasture's?
Immunofluorescence = linear IgG
284
Minimal change glomerulonephritis? (4)
* Kids
* nephrotic
* appearance = duh, not much to see
* prognosis = very good (usually resolves with steroids)
285
Focal segmental glomerulosclerosis?
* obesity, HIV, sickle cell, IV drug users (heroin)
* adults
* nephritic
* appearance - duh, segmented sclerosis (appears pink)
