Renal system Flashcards
1
Q
What are the functions of the kidney?
A
- Maintenance of extracellular environment
- Water, solutes
- Acid base balance
- Excretion of metabolic waste products
- Produces vascular mediators
- systemic & renal hydrodynamics
- BP regulation
- Hormone secretion - EPO
- Participates in bone metabolism - Ca, P
- Catabolism of peptide hormones - insulin
- Gluconeogenesis in fasting
2
Q
Causes of decreased renal perfusion
A
- Total body lack of fluid - dehydration, trauma, third space loss
- Total body excess, but in wrong compartment - cirrhosis, nephrotic syndrome
- Cardiac Failure - reduced CO/ pump failure
- Sepsis
- Renal vasoconstriction - acute hypercalcemia, hepatorenal syndrome, drugs (NSAIDs, noradrenaline)
- Renal Artery stenosis
3
Q
Name 3 stages of converting plasma to urine
A
- Glomerular filtration
- Tubular reabsorption & secretion
- Water conservation
4
Q
Increased aldosterone causes:
A
Increased Na+ reabsorption
Increased K+ secretion
5
Q
Ethyl alcohol inhibits ADH secretion. What effect will this have on urine?
A
- Lack of ADH → distal tubules become relatively impermeable to H2O
- Water cannot be removed from distal tubule to capillary via osmosis
- Increase in dilute urine output
6
Q
Describe primary and secondary VesicoUriteric Reflux (VUR)
A
VesicoUriteric reflux is backflow of urine from bladder into ureters or kidney
Primary:
Congenital birth defect - ureters having lower, or more perpendicular entry pathway into bladder - hence less overlapping epithelium and worse “valve” to prevent backflow
Secondary:
Blockage in urinary tract causes urine backflow - common in enlarged prostate
7
Q
What is special about ureteric epithelium?
A
It is TRANSITIONAL
When empty - is columnar
When full - can stretch to be cuboidal as lumen increases
Continuous with bladder and urethral epithelium
8
Q
What are the regions of the urinary bladder?
A
Dome - Majority of bladder, Highly compliant
- Expands at low pressure, but contracts with bladder opening
Trigone - Triangular region bound by ureteral openings and uretheral sphincter
- Situated towards the bottom
- highly innervated, thought to play a role in bladder sensation
Bladder Neck - Muscular internal urethral sphincter
- Smooth muscle → under involuntary control → ANS
Urethra - Joins bladder to the external
- Continuous transitional epitheliumm with ureters and bladder
- Muscular tube between internal and external urethral sphincter
External urethral sphincter - AKA Rhabdosphincter
- Voluntary control - SKM
9
Q
Male vs female urethra
A
male - 18-20cm long, involves prostate
female - 3-5cm long
10
Q
Symptoms of prostatic enlargement
A
- Hesitancy
- Terminal dribble
- Urinary retention
11
Q
Bladder nerve supply
A
- Hypogastric sympathetic nerve - to body/dome of bladder, trigone, internal urethra
- Pelvic splanchnic nerve - parasympathetic - body of bladder, internal urethra
- Pudendal somatic motor nerve - voluntary - external urethral sphincter
12
Q
2 phases of micturition reflex
A
1 - Storage phase
2 - voiding phase
13
Q
3 causes of urinary incontinence
A
- sphincter muscles lose tone - post pregnancy
- cns control of micturition - sci, alhzeimers
- obstruction and urinary retention - prostate enlargement
14
Q
types of urinary incontinence
A
~⅓ stress - involuntary leakage due to stress/force - running, lifting etc -mostly women post childbirth
~⅓ urge - sudden urge to void “driving car, must go behind a bush” - often inc frequency of voiding in day and at night
~⅓ mixed -
note - urinary incontinence is very common esp in elderly, but ~50% won’t/don’t speak to GP about it
15
Q
Risk factors for incontinence
A
- older age
- pregnancy childbirth
- UTI
- BMI
16
Q
Pharma for OAB -overactive bladder
A
- Muscarinic receptor antagonists - dry mouth, constipation, blurred vision side effect
- Afferent nerve targets - block sensory nerves - botox, resiniferotoxin - may need to self catherise to urinate
- B3 adrinergic mimetic drugs - no affect of B1, B2 - only else wise present in adipose tissue
17
Q
Describe the RAAS (renin-angiotensin-aldosterone system) and overall effects on BP
A
Angiotensin II:
Think VAT
- Vasoconstriction - widespread
- Aldosterone release - adrenal cortex → stimulates Na+ retention thus more water in distal tubules
- Thirst - hypothalamus stimulation → increase fluid input
Also - Increase Na+ reabsorption in proximal tubules (Na+/H+ exchange)
18
Q
Drugs and hormones affecting renin release
A
↑ - Loop diuretics, Diuretics in general, epinephrine/norepinephrine, ACE inhibitors
↓ - NSAIDs, β blockers,
19
Q
What are the names of infections in various sites of the urinary tract?
A
Urinary bladder → cystitis
Renal pelvis → pyelitis
Renal cortex, nephrons (acute) → pyelonephritis
Kidney (chronic) → nephropathy
20
Q
5 Factors that usually prevent against a UTI include:
A
- Immune factors in bladder wall - white cells, complement
- High urine osmolarity and extreme urine pH
- Commensal organisms - lactobacilli, corynebacteria, streptococci and bacteroides
- Urine flow & normal micturition - Urine stasis (delays between or incomplete voiding) increase risk recurrent cystitis
- Urothelium covered with uroplakins and a mucus proteoglycan layer.
This creates permeability barrier preventing urine absorption across urothelium, and limits bacterial access to urothelial cell surface
21
Q
Lower urinary tract signs and symptoms include:
A
- Frequent desire to void urine - even if only small amount passed
- Nocturia
- Painful voiding
- Suprapubic pain
- Haematuria
- Smelly/cloudy urine - pyuria, bacteriuria
22
Q
Upper urinary tract infection signs include:
A
- Vomiting
- Fever
- Loin pain and tenderness
- Night sweats
23
Q
Name some impacts of VUR (Vesico-Urinary Reflux) in children
A
Can lead to:
Chronic kidney damage
Hypertension later in life
End stage renal failure
24
Q
What are the 3 layers (in→ out) of the glomerular filtration system?
A
- Fenestrated endothelial cells
- Glomerular basement membrane
- Podocytes
25
What are the most common subtypes of Renal Cell Carcinomas?
| (RCC)
Clear Cell Renal Cell Carcinoma (ccRCC)
Papillary RCC (PRCC)
Chromophobe RCC (ChRCC)
26
2 most common ways of finding Clear Cell RCC
Incidental imaging - 60-80%
Painless Haematuria
27
Common genes involved in RCC (renal cell carcinoma)
* VHL Gene (Von Hippel Lindau) - ccRCC - Hypermethylation
* MET (MesenchymalEpithelial Transition factor) - 80% of PRCCs
* Multiple losses of whole chromosomes, most often 1, 2, 6, 10, 13, 17, 21 or Y
* Also TP53 & P10 -(ChRCC)
28
What are the 5 types of diuretics
* Osmotic
* Proximal Tubule
* Loop
* Distal Tubule
* Potassium sparing & Spironolactone
29
Describe Osmotic Diuretics
Pharmacologically inert- filtered in the glomerulus but not reabsorbed by the nephron
Stay in nephron, draw more water in via:
- Proximal tubule
- Descending limb of the loop
- In the presence of ADH in the collecting tubules
• Indications: treatment of raised intracranial or intraocular pressure
30
Describe proximal tubule diuretics
Carbonic anhydrase inhibitors
- Increase HCO3-, Na+, H+, H2O excretion
Indications: Glaucoma - reduce aqueous humour formation
31
Describe loop diuretics
Most powerful
* Inhibit reabsorption of Na+ and Cl- by inhibiting the Na+/K+/2Cl- co-transporter found on the ascending loop of Henle
* Increased loss of _K_+ , Ca2+ & Mg2
Indications: Hypertension, Heart failure, Acute pulmo oedema, hypertension, hypercalcaemia
Side effects: ↓ Na+, ↓ K+, ↓ Ca2+ ↓ Mg2+
Hyperuricaemia (gout), Dizziness, orthostatic hypotension
32
Describe distal tubule diuretics
Thiazide, hydrochlorothiazide, chlorthiladone
* Less powerful than loop diuretics
* Inhibit the reabsorption of sodium and chloride by acting on the Na+/Cl- co-transporter in distal convoluted tubule
Indications: Hypertension, mild heart failure, severe resistent oedema (w loops), prevent recurrent renal stones in idiopathic hypercalciuria, nephrogenic diabetes incipidus (Look up mechanism)
Side effects: ↓ Na+ loss, ↓K+, dizziness, ↓Mg2+ ,muscle cramps, ↑ uric acid
33
Describe *potassium sparing diuretics*
Weak diuretics
Amiloride, Triamterine
* Block Na+ reabsorption at the distal & collecting duct
* Interfere with Na +/K+ exchange → less K+ loss
Indications: Prevention of diuretic-induced K+ loss, Oedema due to heart failure, nephrotic syndrome
34
Describe aldosterone antagonists
Weak diuretics - eg spironolactone
Inhibit sodium absorption → acting as aldosterone antagonists (compete with aldosterone for its receptor)
Indications: – heart failure (with loop diuretic & ACE inhibitor)
– Primary hyperaldosteronism (hormone disorder ↑BP)
– Secondary hyperaldosteronism caused by liver cirrhosis complicated by ascites
– Resistant hypertension
35
Risk factors for renal calculi
* Male (3:1)
* Most common 30-50y
* Recurrence rate ~50%
* FHx ~55%
36
Types of renal stones
* Calcium Oxalate 80%
* Uric acid 7-10%
* Struvite / infection / (Na, Mg, NH4) phosphate 10%
* Cysteine stones 1%
* Calcium phosphate
* Rare - drug/xanthine related
37
How do urinary stones form
* Supersaturation of urinary chemicals
* Precipitation and aggregation of solutes to form crystalline structures
* Calcium oxalate (CaPO4) forms initially as Randall's plaques
38
Major factor for uric acid stones
Acidic urine
UA is 100x more soluble in pH\>6 vs pH\<5.5
39
Struvite stone major risk factor
UTI's - from **urease producing organisms** such as:
proteus mirabilis, klebsiella, xanthomonas, pseudomonas, staphylococcus
Struvite forms in more alkali conditions where constituents - magnesium ammonium phosphate - are present -NH4MgPO4·6H2O
40
Cystine renal stone causes
Very rare
Patients with homozygous recessive gene for cystine transport → excessive cystine levels
Normal excretion \<100mg/day, with gene \>600mg/day
V hard to treat, only dissolve \>pH 9.5
41
Renal calculi presentation
* Asymptomatic
* Pain- most common - Acute renal colic
* Assoc Nausea and vomiting
* Haematuria- micro or gross (90-95%)
* UTI or Urosepsis
* LUTS- irritative
42
3 factors affecting GFR
hydrostatic pressure - out of capillaries
colloid - into capillaries
Fluid - into capillaries
43
44
Referred levels of pain of renal and ureteric calculi
“Loin to groin”
T11-L2
Loin → Lumbar
Groin → Inguinal
45
Renal calculi can become impacted most commonly at which 3 locations?
1. Ureteropelvic junction (as pelvis narrows to meet the ureter)
2. Near the pelvic brim, where ureter takes a posterior turn
3. Ureterovesical junction → narrowest portion of the ureter
46
4 most common types of renal stones
Calcium oxalate - Hypercalcuria + hyperoxaluria
Uric Acid - Hyperconcentration of urine
Struvite - NH4+ producing bacteria
Cystiene - Congenital
47
The major nitrogenous waste product found in urine is?
Urea
Urine also contains uric acid, creatinine and ammonium ions, but in smaller amounts than urea
48
* Most likely causative organism of a UTI (urinary tract infection) is?
* Most likely causative organism for UTI that does not respond to ampicillin (high urinary pyuria, -ve nitrates)
* Escherichia coli
* Candida albicans (yeast, does not respond to antibiotic therapy)
49
What is the best practical clinical indicator of “Glomerular Filtration Rate” and why?
Creatinine clearance
* Freely filtered by glomerulus, not secreted or reabsorbed to a significant extent
Note → In removal of a kidney (ie - donation), creatinine excretion remains the same, as although GFR is halved, plasma creatinine concentration increases such that excretion remains equal (excretion=GFR x plasma creatinine conc)
50
The main site for renal Na+ reabsorption is?
PCT (prox conv tubules)
→ 65 - 70%
51
Explain how *osmotic diuretics* work, and give some examples
* Mannitol (IV), Isosorbide (oral)
* Increase osmolality (solute concentration) within renal tubules, and cause water to be retained within the tubule due to osmosis
52
Explain how *loop diuretics* work, and give some examples
* Furosemide, Bumetanide (oral)
* Inhibit the *"Na+, K+, 2Cl- symporter"* in the thick, ascending loop of Henle.
* Does this by competing for the Cl- binding site
* By preventing the reabsorption of these ions, especially sodium, it reduces the reabsorption of water
* Long term also affects Ca2+ and Mg2+ reabsorption
53
Explain how *thiazide* diuretics work, and give some examples
* Hydrochlorothiazide, Chlorothiazide
* Work on the DCT (distal convoluted tubule)
* Inhibit NaCl reabsorption transporter in the distal convoluted tubule
54
Explain how *potassium sparing diuretics* work, and give some examples
* Work in the distal convoluted tubule as well as the collecting duct
* 2 classes:
* _Amiloride, Triameterine_
* These inhibit Na+ reabsorption in the DCT
* Cells in DCT *secrete* K+ in exchange for Na+ reabsorption
* Thus, by inhibiting Na+ reabsorption, we spare K+ secretion
* Aldosterone inhibitors → _Spironolactone_
* Aldosterone is a steroid
* It triggers intracellular receptors in collecting ducts to produce Na+→K+ anti-transporters
* Thus, inhibiting this reduces Na+ reabsorption and K+ secretion
55
Describe how *carbonic anhydrase inhibitors* work and give some examples
* Work at PCT (prox conv tub)
* Generally “weakest” diuretic
* Prevent reabsorption of NaHCO3
Acetazolamide
56
What stimulates renin secretion?
Low BP sensed at juxtaglomerular cells → afferent renal arteriole
57
What stimulates Aldosterone secretion
What does aldosterone do?
Aldosterone release is stimulated by Angiotensin II
It is released from the zona glomerulosa cells of the adrenal gland
Aldosterone is a mineralocorticoid steroid hormone that:
* ⇡Na+ reabsorption in the distal tubules
* ⇡K+ *secretion* in distal tubules
* ⇡H+ secretion in collecting ducts
58
Describe the RAAS system -
what is released from where, and final pathway effects
59
Describe the juxtaglomerular apparatus
60
Abnormal things in urine and fancy names:
Glycosuria - glucose
Proteinuria - protein
Ketonuria - ketone bodies
Pyuria - leukocytes
Bilirubinuria - bile pigments
61
What do you test for on a Urine bedside "dipstick" test?
- Specific Gravity (Concentration/hydration)
- pH
- Proteinuria - Protein
- Pyuria - Leucocytes
- Nitrites - Nitrates are converted to Nitrites in the presence of Gram-negative bacteria such as E.coli and Klebsiella (Thus, it's a surrogate marker for bacteruria)
- Haematuria - Blood - (trauma, infection, inflammation, infaction, calculi, neoplasia)
- Ketonuria - Ketones - (ketone diet, starvation, diabetes, alcoholism, hyperthyroidism, overdose insulin, isoniazid (TB Rx))
- Bilirubinuria - Bilirubin - not present in healthy individuals - (hepatocellular disease, cirrhosis, viral or drug induced hepatitis, Choledocholithiasis (gallstone in common bile duct))
- Urobillinogen (normally present in low concentrations - increased in cirrhosis, infective hepatitis, haemolytic anaemia, malaria)
- Glycosuria - Glucose - not present in healthy individuals
