Regulation of kidneys work role of kidneys in homeostasis maintenance
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Regulation of kidneys work. Role of kidneys in homeostasis maintenance. Balancing role of the kidney. Water balance Sodium / potassium / chloride intake and excretion balanced Average daily requirements: Water : 25 - 35 ml/kg/day Sodium : 1 - 1.4 mmol/kg/day

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Regulation of kidneys work role of kidneys in homeostasis maintenance
Regulation of kidneys work.Role of kidneys in homeostasis maintenance.


Balancing role of the kidney
Balancing role of the kidney

  • Water balance

  • Sodium / potassium / chloride intake and excretion balanced

  • Average daily requirements:

    • Water : 25 - 35 ml/kg/day

    • Sodium : 1 - 1.4 mmol/kg/day

    • Potassium: 0.7 - 0.9 mmol/kg/day

    • Chloride : 1.3 - 1.9 mmol/kg/day


Urine formation results from glomerular filtration tubular reabsorption and tubular secretion
Urine formation results from Glomerular filtration, Tubular reabsorption, and Tubular secretion

  • Urinary excretion rate = Filtration rate – Reabsorption rate + Secretion rate

Filtration only

Filtration, reabsorption

Filtration, secretion

GFR = C in

C sub. ˂C in.

C sub. ˃C in.

Urine

Urine

Urine


Glomerular filtration rate determinants
Glomerular Filtration Rate - Determinants reabsorption, and Tubular secretion

  • This is simplification of Starlings principle for movement across capillaries

  • Net Filtration = Kf NFP

  • Kf is Filtration co-efficient

    • Incorporates surface area  membrane permeability

  • NFP= Net filtration pressure in mmHg:

  • NFP = Glomerular capillary hydrostatic pressure – Bowman’s capsule hydrostatic pressure – Glomerular capillary oncotic pressure


Glomerular filtration rate gfr
Glomerular filtration rate (GFR) reabsorption, and Tubular secretion

  • Kf affected by:

    • Mesangial cell contraction  ↓ area

    • Causes - angiotensin II

      - ADH

      - bradykinin

    • Membrane permeability relatively constant

  • Think about the effects of each of the determinants of net filtration pressure –

    • GCHP e.g: if afferent arteriole constriction, efferent arteriole dilatation, GCHP falls. This leads to a fall in GFR

    • BCHP e.g: ureteric obstruction causes ↑BCHP and ↓GFR

    • GCOP e.g: fluid overload with low oncotic pressure - ↑GFR


Net filtration pressure along glomerulus
Net Filtration Pressure along glomerulus reabsorption, and Tubular secretion

  • Drop along capillary due to

    • Decreased glomerular capillary hydrostatic pressure

    • Increased glomerular capillary oncotic pressure

  • Glomerular capillary NFP:

    • NFP = GCHP – BCHP – GCOP

    • Numbers:

    • Afferent end:

    • 24 = 60 - 15 – 21

    • Efferent end:

    • 10 = 58 – 15 - 33


Factors affecting gfr summary
Factors affecting GFR - summary reabsorption, and Tubular secretion

  • 1. Mean Hydrostatic driving force

  • (pressure in GC-BC)

  • 2. Kf (filtration coefficient)

  • 3. Oncotic pressure gradient


Measuring gfr
Measuring GFR reabsorption, and Tubular secretion

  • Ideal is CLEARANCE of a substance that is freely filtered by the glomerulus but not secreted or reabsorbed. Also not stored, metabolised in kidney, not toxic, does not alter GFR and easy to measure.

  • INULIN is gold standard

    • Would need constant infusion to maintain a constant plasma concentration

    • Creatinine – not ideal – formed by muscle, released at reasonably constant rate, BUT – overestimates GFR by approx 10% due to SECRETION in tubules


Plasma clearance
Plasma Clearance reabsorption, and Tubular secretion

  • Plasma clearance is defined as the amountof plasma that is cleared or“cleansed” of a particular substanceinone minute. The kidneys will carry out this clearance process through the use of filtration, reabsorption and secretion


  • Filtration will reabsorption, and Tubular secretiondirectly affect clearance. As filtration increases, more material will be removed from the blood plasma. Reabsorption will indirectly affect clearance. As reabsorption increases, less material will be removed from the blood plasma. Secretion will directly affect clearance. As secretion increases, more material will be removed from blood plasma.


Plasma clearance1
Plasma Clearance reabsorption, and Tubular secretion

  • The formula used to calculate plasma clearance is:

  • C = V x U/P

  • C = plasma clearance rate in ml/min

  • V = urine production rate in ml/min

  • U = the concentration of a substance in the urine in mg/ml

  • P = the concentration of a substance in the plasma in mg/ml

  • As you track the units in the equation, you will notice that mg/ml cancel out, leaving ml/min.


  • Let us practice calculating plasma clearance using the clearance equation. In all your calculations, assume that the urine production rate (V) is 2 ml/min. Let’s start with the substance inulin (not insulin!). If after a dose of inulin, your urine has 30 mg/ml and your plasma has 0.5 mg/ml of this substance, what is the inulin clearance rate? If you got 120ml/min, you are correct!

  • 120 ml/min = 2 ml/min x 30 mg/ml/ 0.5 mg/ml


Renal blood flow rbf
Renal Blood Flow (RBF) clearance equation. In all your calculations, assume that the urine production rate (V) is 2 ml/min. Let’s start with the substance inulin (not insulin!). If after a dose of inulin, your urine has 30 mg/ml and your plasma has 0.5 mg/ml of this substance, what is the inulin clearance rate? If you got 120ml/min, you are correct!

  • Very high – 20% cardiac output at rest, (1200ml blood/min or 600ml of plasma/min). Kidneys <1% body wt

  • Tightly autoregulated (similar to heart, brain)

  • Why the high blood flow:

    • High O2 consumption –

      • 6ml/100g/min (C/W heart 8-10, Brain 3.5)

      • Second highest behind heart (per gram tissue)

  • Most blood flow and O2 consumption goes to cortex

  • Oxygen extraction quite low – 1.5vol% c/w 5vol% for body as whole

  • Related mainly to active Na+ reabsorption and H+ ATPase pumps. Linked to GFR. (↑ GFR ↑02 consumption.)


Regulation of rbf
Regulation of RBF clearance equation. In all your calculations, assume that the urine production rate (V) is 2 ml/min. Let’s start with the substance inulin (not insulin!). If after a dose of inulin, your urine has 30 mg/ml and your plasma has 0.5 mg/ml of this substance, what is the inulin clearance rate? If you got 120ml/min, you are correct!

  • SYSTEMIC and LOCAL (=autoregulation)

  • SYSTEMIC effects blood flow to more than just kidneys

    • Neural – sympathetic/noradrenergic

      • Vasoconstriction – ↓ RBF. Small ↓ GFR (partially offset by increased oncotic pressure in glomerular capillaries)

      • Increased renin secretion (direct effect on 1 receptors). Causes angiotensin II release Afferent and efferent V/C and also action on mesangial cells  ↓ GFR (but ↓ RBF more so filtration fraction increases)

      • Increased sensitivity of juxtaglomerular cells


  • Humoral clearance equation. In all your calculations, assume that the urine production rate (V) is 2 ml/min. Let’s start with the substance inulin (not insulin!). If after a dose of inulin, your urine has 30 mg/ml and your plasma has 0.5 mg/ml of this substance, what is the inulin clearance rate? If you got 120ml/min, you are correct!

    • Noradrenaline – V/C

    • Prostaglandins – PGI2, PGE2. Cause renal arteriole V/D

    • Renin (as per prev page)

    • Other – e.g. exercise, diet


Renin angiotensin system
Renin – Angiotensin system clearance equation. In all your calculations, assume that the urine production rate (V) is 2 ml/min. Let’s start with the substance inulin (not insulin!). If after a dose of inulin, your urine has 30 mg/ml and your plasma has 0.5 mg/ml of this substance, what is the inulin clearance rate? If you got 120ml/min, you are correct!


Autoregulation of rbf
Autoregulation of RBF clearance equation. In all your calculations, assume that the urine production rate (V) is 2 ml/min. Let’s start with the substance inulin (not insulin!). If after a dose of inulin, your urine has 30 mg/ml and your plasma has 0.5 mg/ml of this substance, what is the inulin clearance rate? If you got 120ml/min, you are correct!

  • MYOGENIC and METABOLIC components

  • Metabolic component here is tubuloglomerular feedback, that also regulates GFR

  • RBF relatively constant between approx MBP 75 and 170 mmHG


Reabsorption of sodium
Reabsorption of sodium clearance equation. In all your calculations, assume that the urine production rate (V) is 2 ml/min. Let’s start with the substance inulin (not insulin!). If after a dose of inulin, your urine has 30 mg/ml and your plasma has 0.5 mg/ml of this substance, what is the inulin clearance rate? If you got 120ml/min, you are correct!


Mechanisms of reabsorption
Mechanisms of reabsorption clearance equation. In all your calculations, assume that the urine production rate (V) is 2 ml/min. Let’s start with the substance inulin (not insulin!). If after a dose of inulin, your urine has 30 mg/ml and your plasma has 0.5 mg/ml of this substance, what is the inulin clearance rate? If you got 120ml/min, you are correct!


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