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Urogenital, Reproductive, Genetics, Endocrine > Renal system > Flashcards

Renal system Flashcards

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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
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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
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3
Q

Name 3 stages of converting plasma to urine

A
  • Glomerular filtration
  • Tubular reabsorption & secretion
  • Water conservation
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4
Q

Increased aldosterone causes:

A

Increased Na+ reabsorption
Increased K+ secretion

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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
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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

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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

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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

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9
Q

Male vs female urethra

A

male - 18-20cm long, involves prostate

female - 3-5cm long

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10
Q

Symptoms of prostatic enlargement

A
  • Hesitancy
  • Terminal dribble
  • Urinary retention
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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
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12
Q

2 phases of micturition reflex

A

1 - Storage phase

2 - voiding phase

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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
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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

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15
Q

Risk factors for incontinence

A
  • older age
  • pregnancy childbirth
  • UTI
  • BMI
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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
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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)

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18
Q

Drugs and hormones affecting renin release

A

↑ - Loop diuretics, Diuretics in general, epinephrine/norepinephrine, ACE inhibitors

↓ - NSAIDs, β blockers,

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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

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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
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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
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22
Q

Upper urinary tract infection signs include:

A
  • Vomiting
  • Fever
  • Loin pain and tenderness
  • Night sweats
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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

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24
Q

What are the 3 layers (in→ out) of the glomerular filtration system?

A
  • Fenestrated endothelial cells
  • Glomerular basement membrane
  • Podocytes
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25
Q

What are the most common subtypes of Renal Cell Carcinomas?

(RCC)

A

Clear Cell Renal Cell Carcinoma (ccRCC)

Papillary RCC (PRCC)

Chromophobe RCC (ChRCC)

26
Q

2 most common ways of finding Clear Cell RCC

A

Incidental imaging - 60-80%

Painless Haematuria

27
Q

Common genes involved in RCC (renal cell carcinoma)

A
  • 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
Q

What are the 5 types of diuretics

A
  • Osmotic
  • Proximal Tubule
  • Loop
  • Distal Tubule
  • Potassium sparing & Spironolactone
29
Q

Describe Osmotic Diuretics

A

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
Q

Describe proximal tubule diuretics

A

Carbonic anhydrase inhibitors
- Increase HCO3-, Na+, H+, H2O excretion

Indications: Glaucoma - reduce aqueous humour formation

31
Q

Describe loop diuretics

A

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<u>+</u> , Ca2+ & Mg2

Indications: Hypertension, Heart failure, Acute pulmo oedema, hypertension, hypercalcaemia

Side effects: ↓ Na+, ↓ K+, ↓ Ca2+ ↓ Mg2+
Hyperuricaemia (gout), Dizziness, orthostatic hypotension

32
Q

Describe distal tubule diuretics

A

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
Q

Describe potassium sparing diuretics

A

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
Q

Describe aldosterone antagonists

A

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
Q

Risk factors for renal calculi

A
  • Male (3:1)
  • Most common 30-50y
  • Recurrence rate ~50%
  • FHx ~55%
36
Q

Types of renal stones

A
  • Calcium Oxalate 80%
  • Uric acid 7-10%
  • Struvite / infection / (Na, Mg, NH4) phosphate 10%
  • Cysteine stones 1%
  • Calcium phosphate
  • Rare - drug/xanthine related
37
Q

How do urinary stones form

A
  • Supersaturation of urinary chemicals
  • Precipitation and aggregation of solutes to form crystalline structures
  • Calcium oxalate (CaPO4) forms initially as Randall’s plaques
38
Q

Major factor for uric acid stones

A

Acidic urine

UA is 100x more soluble in pH>6 vs pH<5.5

39
Q

Struvite stone major risk factor

A

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
Q

Cystine renal stone causes

A

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
Q

Renal calculi presentation

A
  • Asymptomatic
  • Pain- most common - Acute renal colic
  • Assoc Nausea and vomiting
  • Haematuria- micro or gross (90-95%)
  • UTI or Urosepsis
  • LUTS- irritative
42
Q

3 factors affecting GFR

A

hydrostatic pressure - out of capillaries

colloid - into capillaries

Fluid - into capillaries

43
Q
A
44
Q

Referred levels of pain of renal and ureteric calculi

A

“Loin to groin”

T11-L2

Loin → Lumbar

Groin → Inguinal

45
Q

Renal calculi can become impacted most commonly at which 3 locations?

A
  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
Q

4 most common types of renal stones

A

Calcium oxalate - Hypercalcuria + hyperoxaluria
Uric Acid - Hyperconcentration of urine
Struvite - NH4+ producing bacteria
Cystiene - Congenital

47
Q

The major nitrogenous waste product found in urine is?

A

Urea

Urine also contains uric acid, creatinine and ammonium ions, but in smaller amounts than urea

48
Q
  • 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)
A
  • Escherichia coli
  • Candida albicans (yeast, does not respond to antibiotic therapy)
49
Q

What is the best practical clinical indicator of “Glomerular Filtration Rate” and why?

A

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
Q

The main site for renal Na+ reabsorption is?

A

PCT (prox conv tubules)

→ 65 - 70%

51
Q

Explain how osmotic diuretics work, and give some examples

A
  • Mannitol (IV), Isosorbide (oral)
  • Increase osmolality (solute concentration) within renal tubules, and cause water to be retained within the tubule due to osmosis
52
Q

Explain how loop diuretics work, and give some examples

A
  • 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
Q

Explain how thiazide diuretics work, and give some examples

A
  • Hydrochlorothiazide, Chlorothiazide
  • Work on the DCT (distal convoluted tubule)
  • Inhibit NaCl reabsorption transporter in the distal convoluted tubule
54
Q

Explain how potassium sparing diuretics work, and give some examples

A
  • 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
Q

Describe how carbonic anhydrase inhibitors work and give some examples

A
  • Work at PCT (prox conv tub)
  • Generally “weakest” diuretic
  • Prevent reabsorption of NaHCO3

Acetazolamide

56
Q

What stimulates renin secretion?

A

Low BP sensed at juxtaglomerular cells → afferent renal arteriole

57
Q

What stimulates Aldosterone secretion

What does aldosterone do?

A

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
Q

Describe the RAAS system -

what is released from where, and final pathway effects

A
59
Q

Describe the juxtaglomerular apparatus

A
60
Q

Abnormal things in urine and fancy names:

A

Glycosuria - glucose

Proteinuria - protein

Ketonuria - ketone bodies

Pyuria - leukocytes

Bilirubinuria - bile pigments

61
Q

What do you test for on a Urine bedside “dipstick” test?

A
  • 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

Urogenital, Reproductive, Genetics, Endocrine (3 decks)

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