The document discusses renal and kidney function including: 1. The functions of the kidney including regulation of fluid balance, electrolytes, acid-base balance, and hormone production. 2. The structure of the nephron and how it filters blood to form urine through processes like glomerular filtration and reabsorption. 3. Factors that influence kidney function like the renin-angiotensin-aldosterone system and how different drugs can impact renal excretion and dosing considerations in renal failure.

1. Renal Revision
Renal Revision

2. Learning objectives
• Blood supply to the kidneys
• Function of the kidneys
• RAAS and hypertension
• Acidosis and alkalosis
• UTIs and treatment
• Renal failure and dialysis
• Mechanism of action of diuretics

3. Functions of the kidney
• Regulation of body fluid volume and osmolality
• Regulation of electrolyte balance
• Regulation of acid-base balance
• Excretion of waste products (urea, ammonia, drugs,
toxins)
• Production and secretion of hormones
• Regulation of blood pressure
 Maintaining balance

4. Blood supply

5. A. Renal Vein
B. Renal Artery
C. Ureter
D. Medulla
E. Renal Pelvis
F. Cortex
1. Ascending loop of
Henle
2. Descending loop of
Henle
3. Peritubular
capillaries
4. Proximal tubule
5. Glomerulus
6. Distal tubule
Structure of the kidney and nephron

6. The Nephron
• Functional unit of the kidney (1,000,000)
• Responsible for urine formation:

7. • Glomerulus
• Afferent and Efferent
arterioles
• Proximal Tubule
• Loop of Henle
• Distal Tubule
• Collecting Duct
Components of the nephron

8. Overview of nephron function

9. • Components of plasma cross the 3 layers of the
glomerular barrier
• Capillary endothelium
• Basement membrane (net negative charge)
Plasma is filtered through the
glomerular barrier
• Epithelium of Bowman’s Capsule (Podocytes –filtration slits
allow size <60kD)
• The ability of a molecule to cross the membrane depends on
size, charge, and shape
• Glomerular filtrate therefore contains all molecules not
contained by the glomerular barrier - it is NOT URINE YET!

10. Filtration barrier
Capillary
hydrostatic
pressure Podocytes
with foot
processes
Fenestrated
endothelium
Bowman’s space
Glomerular
capillary
Basement
membrane
Intracapsular
pressure
Colloid
osmotic
pressure of
plasma
Pb

11. K+ Secretion
• Final [K+] controlled
in collecting duct by
aldosterone
– When aldosterone is
absent, no K+ is
excreted in the urine
• High [K+] or low
[Na+] stimulates the
secretion of
aldosterone
• Only means by
which K+ is secreted
Insert fig. 17.24

12. Glomerular Filtration Rate (GFR)
• Measure of functional capacity of the kidney
• Volume of plasma from which a substance (e.g. creatinine) is
completely removed in 1 min by excretion in the urine
• Dependent on difference in pressures between capillaries
and Bowman’s space
• Normal = 120 ml/min =
7.2 L/h =
180 L/day!!
179 L of fluid filtered is reabsorbed!

13. Glomerular Filtration Rate (GFR)
GFR = U x V
P
• U = concentration of substance in urine
• V = urine volume per minute
• P = concentration of substance in plasma
• Estimated GFR ([Creatinine], age, sex (M↑F↓), ethnicity)

14. Clearance of Urea
• Urea is secreted into blood and filtered into
glomerular capsule
• Urea clearance is 75 ml/min, compared to
clearance of creatinine at 120 ml/min
– 40-60% of filtered urea is always reabsorbed
• Passive process because of the presence of
carriers for facilitative diffusion of urea

15. Reabsorption
• Active Transport (requires ATP)
– Na+, K+ ATP pumps
• Passive Transport
– Na+ symporters (glucose, amino acids, etc)
– Na+ antiporters (H+)
– Ion channels
– Osmosis

16. Factors influencing reabsorption
• Saturation: Transporters can get saturated by high
concentrations of a substance - failure to resorb all
of it results in its loss in the urine (eg, renal
threshold for glucose is about 180mg/dl)
• Rate of flow of the filtrate: affects the time available
for the transporters to reabsorb molecules

17. What is reabsorbed where?
• Proximal tubule - reabsorbs 65 % of filtered Na+ as well as
Cl-, Ca2+, PO4, HCO3
-. 75-90% of H20. Glucose, carbohydrates,
amino acids, and small proteins are also reabsorbed here
• Loop of Henle - reabsorbs 25% of filtered Na+
• Distal tubule - reabsorbs 8% of filtered Na+ and reabsorbs
HCO3-
• Collecting duct - reabsorbs the remaining 2% of Na+ only if
the hormone aldosterone is present. H20 depending on
hormone ADH

19. Secretion
• Proximal tubule – uric acid, bile
salts, metabolites, some drugs,
some creatinine
• Distal tubule – Most active
secretion takes place here including
organic acids, K+, H+ and drugs

20. Hormones produced by the kidney
• Renin:
– Released from juxtaglomerular apparatus when low blood flow or
low Na+. Renin leads to production of angiotensin II, which in turn
ultimately leads to retention of salt and water
• Erythropoietin:
– Stimulates red blood cell development in bone marrow.
Will increase when blood oxygen low and anemia (low hemoglobin)
• Vitamin D3:
– Enzyme converts Vit D to active form 1,25(OH)2VitD.
Involved in calcium homeostasis

21. Renin-Angiotensin-Aldosterone system:
Regulation of Salt/Water Balance

24. ACE

26. Acid-base regulation

27. DETERMINE STATUS OF pH:
pH > 7.45 = alkalaemic
pH < 7.35 = acidaemic
Step 1

28. DETERMINE RESPIRATORY COMPONENT:
Normal PaCO2 = 4.5-6.0 kPa
(below = respiratory alkalosis, above = respiratory acidosis)
Step 2

29. DETERMINE METABOLIC COMPONENT:
Normal HCO3 = 22-26mmol/L
(below = metabolic acidosis, above = metabolic alkalosis)
Normal base excess (BE) = -2 to 2
Step 3

30. COMBINE THE INFORMATION FROM STEPS 1-4
Interpret in clinical context
Which is main component and which is compensatory?
Is the compensation full or attempted?
Step 4

31. Typically E. Coli (also Proteus, Klebsiella, Staph e.g. epidermidis)
Risk Factors:
• Gender (ascending infection- shorter urethra in females)
• Stasis of urine (eg renal calculi, reflux, tumours)
• Medical plastic (catheters)
P/C:
Lower UTI (cystitis & urtheritis)- frequency, urgency, dysuria
Upper UTI (pyelonephritis)- as above plus fever, loin pain, rigors
Ix:
• Pre-treatment MSSU for microscopy & culture. Urine dipstick
• May need structural /functional imaging to rule of reflux & renal scarring if UTIs
recurrent
UTI

32. Common causes of UTI

33. Clinical features of UTI
Upper UTIs
- Fever, nausea, malaise, loin
pain, tenderness
Acute lower UTIs cause:
- Dysuria, urgency, frequency,
nocturia, haematuria,
suprapubic pain, smell

34. Types of UTI
• Uncomplicated - UTI by a usual pathogen in a
normal urinary tract in a person with normal
renal function
• Complicated - UTI where there is anatomical,
functional, pharmacological factors
predisposing to persistent infection

35. Complicated UTI
• Anatomical: stones, vesicoureteric reflux, neurogenic
bladder, catheter, urinary obstruction
• Virulent microorganism: S aureus
• Impaired host defence: diabetes mellitus,
immunosuppressed
• Impaired renal function or post renal
transplant

36. Laboratory diagnosis – urine collection
• Urine in bladder is normally
sterile
• Clean-MSU – before antibiotics
• Collected into sterile container
• Cultured within one hour or
held at 4C

37. Infection
Properly collected MSU contain >105
CFU/ml of
single bacterial spp
Vs
Contamination
104
CFU/ml – more than one spp

38. Dipstick
• Detects urinary nitrite
• Detects urinary leucocyte esterase
• Not suitable in pregnant women
+/+ =UTI very likely – treat empirically
-/- = UTI unlikely – no treatment
-/+ = Possible UTI – consider culture…..

39. Renal drugs

40. Identify the main site of action of:
- loop diuretics
- thiazide diuretics
- aldosterone antagonists

41. Site of Action of Diuretics

42. Mechanisim of Action of Diuretics

43. Diuretics: thiazide
Bendroflumethiazide
• MOA: inhibit Na reabsorption in DCT
• Indications: Hypertension, heart failure
• Cautions: can worsen gout, diabetes
• NOT IN PREGNANCY
• Side effects: postural hypotension, hypok+, hypona+,
hypomg+, hyperca2+,gout (hyperuricaemia)

44. Furosemide
• MOA: Na/K/2Cl co-transporter blocker
• Indications: oedema e.g. HF, resistant hypertension
• Cautions: can worsen gout, diabetes
• Contra-indications: hypok+, anuria
• Side effects: postural hypotension, hypok+, hypona+,
hypomg+
Diuretics: loop

45. Spironolactone
• MOA: aldosterone receptor antagonist
• Indications: oedema/ascites from liver cirrhosis, heart
failure, primary hyperaldosteronism
• Cautions: look out for hyperk+
• Contra-indications: hyperk+, Addison’s disease
• Side effects: gynacomastia, testicular atrophy,
menstrual disorders, alopecia, hirsutism
Diuretics: K+ sparing

46. Amiloride and Triamterene
• MOA: block luminal Na channels in collection
system (usually controlled indirectly by
aldosterone)
• Indications: oedema, K conservation (amiloride:
CCF, hepatic cirrhosis)
• Cautions: monitor electrolytes
• Contra-indications: hyperk+, Addison’s disease
Diuretics: K+ sparing

47. Renal Effects of Drugs

48. Glomerular filtration - gentamicin
digoxin
Proximal tubular secretion - methotrexate
salicylates
Renal excretion of drugs

49. Should be avoided in renal failure
e.g. NSAIDs, ACE-I, ARBs, aminoglycosides, large doses of
penicillins, ciclophosphamide, ciclosporine A, gold, penicillamine
What are the general principles of prescribing in renal failure?
• Reduced dose and/or increase the dosage interval according to
renal function, especially with drugs which have a small
therapeutic index
• Base changes on measures of renal function i.e. glomerular
filtration rate, serum creatinine
• Use plasma levels if possible – digoxin, gentamicin, ciclosporin.
• Avoid drugs which are nephrotoxic
Nephrotoxic drugs