Urinary Flashcards
State the four sites of potential glomerular injury
Supepithelial - affecting podocytes
Within basement membrane
Subendothelial - inside basement membrane
Mesangial - supporting capillary loop
What affect will a blocked glomerular basement membrane have?
Renal failure
Decrease GFR
What affect will a leaky glomerular basement membrane have?
Proteinuria
Haematuria
Define proteinuria
Presence of excess serum proteins in urine
What is the cause of proteinuria?
Due to podocyte or subepithelial damage
Widened fenestration slits allow protein to leak through
Define nephrotic syndrome
Over 3.5g of protein in urine in 24hrs
What is a systemic symptom of nephrotic syndrome? Why?
Generalised oedema
Protein is lost in urine
Reduced oncotic pressure
State three causes of primary nephrotic syndrome
Minimal change glomerulonephritis
Focal segmental glomerulonephritis (FSGS)
Membranous glomerulonephritis
State secondary causes of nephrotic syndrome
Diabetes mellitus
Amyloidosis
Describe the pathogenesis of minimal change glomerulonephritis
Podocytes damaged
Widened fenestration slits
Describe the epidemiology of minimal change glomerulonephritis
Presents in childhood/adolescence
As age increases incidence reduces
Describe the treatment of minimal change glomerulonephritis
Steroids
No progression to renal failure
Describe the pathogenesis of FSGS
Circulating factor damages the podocytes, which become scarred
What is the most common form of nephrotic syndrome in adults?
Membranous glomerulonephritis
Describe the pathogenesis of membranous glomerulonephritis
Immune complex deposits in subepithelial space - IgG
Autoimmune
Describe the consequences for patients of membranous glomerulonephritis
1/3rd get better
1/3rd have proteinuria but are fine
1/3rd progress to renal failure
Define nephritic syndrome
Haematuria
Hypertension
AKI
What is IgA Nephropathy?
Deposition of circulating IgA in the glomerulus
Mesangial proliferation and scarring occurs
Haematuria
State two hereditary nephropathies
Thin GBM Nephropathy
Alport syndrome
Describe Thin GBM Nephropathy
Isolated haematuria
No renal failure
Describe Alport Syndrome
X linked Abnormal collagen IV deafness Abnormal GBM Progresses to renal failure
What happens in Goodpasture syndrome?
Acute onset glomerulonephritis
Association with Pulmonary haemmorhage
IgG to collagen IV
Treated by immunosuppression and plasmapheresis
How does vasculitis affect the kidney?
Inflammation of blood vessels
Nephritic
What are the symptoms and signs of prostate cancer?
Nocturia Frequency Hesitancy Haematuria ED
Prostate hardness
Where are the most common sites for a prostate cancer metastasis?
Bone
Lymph nodes
Where are most prostate cancers found?
Adenocarcinoma in the peripheral zone
What are the risk factors for prostate cancer?
Old age
Family history
BRCA2 gene
Black or white ethnicity
What are the symptoms and signs of bladder cancer?
Painless Haematuria
Dysuria
Frequency
What type of cancer are most bladder cancers?
Transitional cell carcinomas
What are the risk factors for bladder cancer?
Age
Smoking - polycyclic aromatic hydrocarbons
Occupational exposure to aromatic amines - paint, dye, metals
What is a radical cystectomy?
Removal of the urinary bladder
What are the symptoms and signs of renal cancer?
Haematuria Loin pain UTI Mass in flank Varicocoele Ankle oedema Paraneoplastic syndromes
Where do renal cancers spread?
MOST COMMON = lungs Adrenal glands Liver spleen Colon Pancreas Renal vein then IVC
What is the most common kind of renal cancer?
Renal cell carcinoma
What are the risk factors for renal cancer?
Smoking
Obesity
Hypertension
Dialysis
Describe the signs and symptoms of testicular cancer
Change in shape or texture of testis - usually painless
Painful
Hydrocoele
Gynacomastea from beta-hCG
Back pain from para-aortic lymph node metastasis
What kind of cells do most testicular cancers arise from?
Germ cells
Two types:
Seminoma
Non-Seminoma
When is testicular cancer most common?
Between 15 and 40
What are the risk factors for testicular cancer?
Cryptorchidism - absence of testes from the scrotum Klinefelter's syndrome - XXY Male infertility Low birth weight Young parental age Infantile hernia Tall TGCT1 gene on X chromosome
What are the tumour markers for testicular cancer?
Alpha-fetoprotein - not produced by Seminomas, but by yolk sac tumours
Beta-hCG - elevated in teratomas and Seminomas
Define clearance
the volume of plasma that is completely cleared of a substance per unit of time
how can clearance be calculated?
concentration in plasma
How can renal clearance rate be calculated?
concentration in plasma
How is the filtration fraction calculated?
renal plasma flow
When does renal clearance = GFR?
If the substance is
freely filtered
non reabsorbed
non secreted
What can GFR be used to assess?
kidney function
the filtration process
Describe tubular glomerular feedback
change in flow rate -> change in GFR ->change in amount of NaCl reaching distal tubule
macula densa cells take up NaCl via NaK2Cl cotransporter which is concentration dependant
if NaCl increases, adenosine is released
vasoconstriction of afferent arteriole
if NaCl decreases, prostaglandins are released
vasodilation of afferent arteriole
Which transporter do loop diuretics act on?
Which segment of the nephron is this in?
NaKCC2
thick ascending limb
Which transporter do thiazide diuretics act on?
Which segment of the nephron is this in?
NCC
DCT
Which transporter do potassium sparing diuretics act on?
Which segment of the nephron is this in?
ENaC
Collecting duct
How is chronic kidney disease seen histologically?
glomerulosclerosis
tubular interstitial fibrosis
In CKD, what is functioning renal tissue replaced by?
What does this cause?
extra-cellular matrix
progressive loss of excretory and hormone functions of the kidney
Why does CKD result in anaemia?
decreased erythropoietin
decreased RBC survival
Why does CKD result in renal bone disease?
Decreased GFR
less Phosphate is excreted, increasing its serum concentration.
Phosphate forms complexes with free Calcium, reducing calcium’s effective serum concentration.
Parathyroid gland stimulated to produce PTH, causing over activity of Osteoclasts, leading to Osteitis Fibrosa Cystica.
Why does CKD result in osteomalacia?
Damage to the kidneys means less Vitamin D undergoes its 2nd Hydroxylation to its active form
Describe the conservative management of CKD
To prevent oR delay progression o Stop smoking o decrease obesity o Exercise o Treat Diabetes (If present) o Treat Blood Pressure (If high) o ACE Inhibitors / Angiotensin Receptor Blockers in proteinuria o Lipid Lowering (Diet / Statins)
When is renal replacement therapy initiated?
When native renal function declines to a level that is no longer adequate to support health, usually when GFR is
What are the options for renal replacement therapy?
transplant
haemodialysis
peritoneal dialysis
What GFR indicates Stage 1 CKD?
What are the signs and symptoms?
GFR >90+
Normal kidney function but urine findings or structural abnormalities or genetic trait point to kidney disease
What GFR indicates Stage 2 CKD?
What are the signs and symptoms?
GFR 60-89
Mildly reduced kidney function, and urine findings or structural abnormalities or genetic trait point to kidney disease
What GFR indicates Stage 3a CKD?
What are the signs and symptoms?
45-59
Moderately reduced kidney function
What GFR indicates Stage 3b CKD?
What are the signs and symptoms?
30-44
Moderately reduced kidney function
What GFR indicates Stage 4 CKD?
What are the signs and symptoms?
15-29
Severely reduced kidney function
What GFR indicates Stage 5 CKD?
What are the signs and symptoms?
What are the treatment option for the stages of CKD?
Stages 1, 2 and 3: Observation, control of blood pressure and risk factors
Stage 4: plan for endstage renal care
Stage 5: renal replacement therapy
Describe haemodialysis
creation of a Ateriovenous (AV) Fistula
The difference in pressure means that blood moves from the artery to the vein, causing it to dilate and develop a muscular wall.
Using this vascular access, the patient is connected up to a dialysis machine, which contains highly purified water across a semi-permeable membrane. This allows for ‘filtering’ of the patient’s blood.
Anti-coagulation is also needed to prevent the patient’s blood from clotting in the machine.
What are the advantages of haemodialysis?
Effective (Survivors > 25 years)
4/7 days free from treatment
Dialysis dose easily prescribed
What are the disadvantages of haemodialysis?
Fluid/Diet restrictions Limits holidays Access problems CVS instability High cost
Describe peritoneal dialysis
Peritoneal Dialysis Fluid is put into the peritoneal cavity, and the dialysis occurs across the peritoneal membrane (semi-permeable membrane). The fluid is then drained away and disposed of.
What are the advantages of peritoneal dialysis?
Low Technology Home technique Easily learned Allows mobility CVS stability
What are the disadvantages of peritoneal dialysis?
Frequent exchanges (~4/day) Frequent treatment failures Peritonitis Limited dialysis dose range High revenue costs
Where is a transplanted kidney located?
iliac fossa - connected to iliac vessels
What are the advantages of kidney transplantation?
Restores near normal renal function Allows mobility and “rehabilitation” Improved survival Good long term results Cheaper than dialysis
What are the disadvantages of kidney transplantation?
Not all are suitable Limited donor supply Operative morbidity and mortality Lifelong immunosuppression Still left with progressive CKD
Define acidaemia
blood pH
What are the effects of acidaemia?
increased [K+] reduced enzyme function Reduced cardiac and skeletal muscle contractility Reduced glycolysis Reduced hepatic function
Define alkalaemia
blood pH >7.45
What are the effects of alkalaemia?
reduces the solubility of calcium salts, causing them to come out of solution,
decreased concentration of free calcium ions
This increases neuronal excitability
paraesthesia
tetany
What causes respiratory acidaemia?
Hypoventilation leads to hypercapnia (rise in pCO2)
leads to a fall in pH
What causes respiratory alkalaemia?
Hyperventilation leads to hypocapnia (fall in pCO2),
so pH increases.
How is respiratory acidaemia compensated for by the kidneys?
[HCO3-] rises proportionately to restore pH
How is respiratory alkalaemia compensated for by the kidneys?
[HCO3-] falls proportionately to restore pH
Why does metabolic acidosis occur?
Metabolically produced H+ ions react with HCO3- to produce CO2 in venous blood.
This CO2 is then breathed out through the lungs.
there is a reduction in [HCO3-]
as the pCO2 is unchanged, there is a fall in pH.
What do the central chemoceptors detect?
pCO2
What do the peripheral chemoceptors detect?
pCO2
plasma pH
Why does metabolic alkalosis occur?
plasma [HCO3-] rises, for example after persistent vomiting, (due to H+ ions being lost in vomit, hence increasing the [HCO3-]
the [HCO3-] : pCO2 ratio will be increased,
causing a pH increase.
How is metabolic acidosis compensated for by the respiratory system?
peripheral chemoreceptors detect changes in plasma pH increase ventilation rate to decrease pCO2,
which will correct the pH
How is metabolic alkalosis compensated for by the respiratory system?
By decreasing ventilation rate,
increasing pCO2,
this can be PARTIALLY compensated for.
Where in the kidney can HCO3- be made?
proximal cells
alpha-intercalated cells in distal tubule
How is HCO3- made in proximal tubule cells?
Glutamine is converted to α-ketoglutarate and NH4+
α-ketoglutarate splits to give 2HCO3-
The HCO3- enters the ECF by a sodium cotransporter in the basolateral cell surface membrane
NH4+ enters the lumen of the PCT.
How is HCO3- made in alpha-intercalated cells in the distal tubule?
CO2 produced by metabolism
CO2 reacts with water to form HCO3- and H+.
The HCO3- enters the plasma by Cl- antiporter
H+ enters the lumen of the DCT via H+ ATPase
How is HCO3- reabsorbed in the PCT?
H+ enters lumen via NHE
HCO3- in lumen reacts with H+ to produce CO2 and H2O which diffuse into cell
carbonic anhydrase in tubular cell converts back
HCO3- enters ECF by Na cotransporter
How is H+ excreted in the DCT?
If the ECF [HCO3-] is low, more HCO3- moves out of the cells to the ECF, so there will be more H+ in the cells.
low pH inside cells detected
increased activity of H+ ATPase on luminal membrane
How is H+ excreted in the PCT?
If the ECF [HCO3-] is low, more HCO3- moves out of the cells to the ECF, so there will be more H+ in the cells.
low pH inside cells detected
increased activity of the Na+/H+ exchanger on luminal membrane
Why does Metabolic acidosis lead to hyperkalaemia?
H+ uptake by cells to increase pH
K+ out of cells
Why does Metabolic alkalosis lead to hypokalaemia?
H+ moves out of cells to decrease pH
K+ into cells
Why can vomiting lead to hypokalaemia?
[HCO3-] increases after persistent vomiting, so the body stops actively secreting H+, as it would make metabolic alkalosis worse.
As H+ secretion has stopped, so has K+ reabsorption
How is the anion gap calculated?
([Na+] + [K+]) – ([Cl- ] + [HCO3-])
How does insulin lead to a fall in serum [K+]?
Insulin increases the amount of Na-K-ATPase, as it provides the drive for the Na-Glucose transporter.
The increase in Na-K-ATPase results in uptake of K+ by the muscle cells and liver.
How do catecholamines lead to a fall in serum [K+]?
Beta 2 adrenoceptors stimulate Na-K-ATPase.
How does aldosterone lead to a fall in serum [K+]?
increases the transcription of Na-K-ATPase in the basolateral membrane
increases transcription of ENaC / K+ channels in the apical membrane.
increased K+ excretion.
Which components of the blood cannot be filtered by the glomerular basement membrane?
RBCs
plasma proteins
Mr 5200
What are the layers of the filtration barrier in the glomerulus?
capillary endothelium
basement membrane
podocyte layer
How are proteins prevented from moving through the basement membrane?
-ve ly charged glycoproteins repel protein movement
What determines the size of molecule that can fit through the filtration barrier?
filtration slits between the podocyte pseudopodia
How much of the blood in the glomerulus is filtered?
20%
Describe the sympathetic innervation f the bladder
T10-L2
Hypo gastric nerve
Innervates detrusor and internal sphincter
Describe the parasympathetic innervation of the bladder
S2-S4
Innervates detrusor
What provides the sensory innervation of the bladder?
Pelvic nerve
S2-S4
Describe the neural mechanism for storage of urine in the bladder
Stretch receptors in bladder - APs along Pelvic nerve
Inhibition pre synaptic parasympathetic neurones - no stimulation M3 receptors in detrusor by pelvic nerve. No contraction
Stimulation hypogastric nerve
Internal sphincter contracts, Detrusor relaxed
Conscious contraction of external sphincter - pudendal nerve to Nicotinic receptor
Describe the neural mechanism of voiding of the bladder
Voluntary relaxation external sphincter - micturition centre in pons to inhibit pudendal nerve
Increased stretch in bladder wall
Stimulation parasympathetic pelvic nerve M3 - detrusor contracts
Inhibition sympathetic hypogastric - internal sphincter relaxed
