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----- Active space ----- PHYSIOLOGY REVISION 9

Glomerular filtration rate (GFR) 00:00:12

• Normal GFR = 125 ml/min or 180 L/day.

• Ultrafiltration happens in kidneys.
• Proteins are not filtered because :
a. Charge [negatively charged protein repelled by heparan sulphate
(anion) in the basement membrane].
b. Size (fenestrations in capillaries restrict protein entry).
c. Slit diaphragm (formed by foot process of podocytes whose intergrity
maintained by nephrin).
i. Nephrin mutation : Steroid unresponsive congenital finnish type
nephrotic syndrome.
ii. Podocin mutation causes steroid resistant nephrotic syndrome.
iii. Alpha actinin mutation : FSGS.

Determinants of GFR :
Net filtration pressure = Capillary hydrostatic pressure (~60 mmHg) -
Bowmans capsule hydrostatic pressure (~18 mmHg) - Colloidal oncotic pressure
(~32 mmHg).

Clearance :
Gold standard GFR estimation Inulin clearance
Most commonly used Creatinine
New marker- GFR Cystatin C

• Cs : Clearance.
• Us : Urine concentration of substrate.
• V : Urine flow rate.
• Ps : Plasma concentration of substrate.

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Factors affecting GFR : ----- Active space -----

Factor RBF GFR

Constriction of :
Afferent arteriole ↓ ↓
(Example : Nor epinephrine)
Efferent arteriole ↓ Biphasic response :
(Example : Angiotensin-II) Initially GFR ↑, Later ↓
Dilatation of :
Afferent arteriole ↑ ↑
(By Prostaglandins- PGE2)
Efferent arteriole ↑ ↓
(Example : ACEI)
Mesangial cells (surround glomerular capillaries)

Contraction Relaxation

Compress glomerular Expansion of glomerular

capillaries capillaries

Decrease in GFR Increase in GFR

Example : Example :
Endothelin, angiotensin II Nitric oxide, ANP

Renal circulation 00:15:29

• Renal blood flow : 1250 ml/min (23% of cardiac output).

• Renal plasma flow = 55% of RBF = 625 ml/min.
• Filtration fraction = GFR/renal plasma flow=20%
• For GFR estimation : Inulin.
• For RPF estimation : Para-aminohippuric acid
(PAH).

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Nephron 00:00:00

Parts of nephron :
Proximal convoluted tubule Distal convoluted tubule
Glomerular capillaries
Collecting ducts

Ascending loop of Henle Descending

loop of Henle

Events in PCT :
• PCT has maximum reabsorption capacity.
• Brush border cells on the apical side : Increases surface area for resorption.
• Have large number of mitochondria to support active transport processes.
• Obligatory water reabsorption (no hormones involved).
• PCT reabsorbs :
a. 2/3rd (70%) of filtered NaCl, water, k+,
urea, Ca2+.
b. 80 % of filtered phosphate & bicarbonate.
c. 100% of filtered glucose & amino acids.

• Glucose resorption in PCT is by : SGLT-2

(example of secondary active transporter,
shows saturation kinetics).
• Transport maximum glucose = 375 mg/min
→ Corresponds to plasma glucose value of
180 mg/dL (renal threshold).

Events in LOH :
• Countercurrent mechanism seen in LOH.
• Fluid entering LOH is isotonic.
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• Vasa recta : Counter current exchanger.

• Na+ K+ 2Cl- cotransporter blocked by furosemide.

Events in DCT :
• NaCl cotransport blocker : Thiazide
diuretic.
• Nacl cotransporter mutation :
Gitelman syndrome.
• Ca2+ reabsorbed by TRPV5 channel
(stimulated by PTH & vitamin D).

Juxta glomerular apparatus : 00:33:58

Cells Function
1. Juxta glomerular cells aka granular cells : Produce renin (↑Na+ and H2O
(in afferent arteriole) reabsorption).
2. Macula densa GFR sensors, senses ↑in GFR → release adenosine
(in thick LOH) → constrict AA & ↓ GFR (tubulo glomerular
feedback)
3. Extra glomerular Supportive cells aka Lacis cells/polkissen cells.
mesangial cells
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JGA
Collecting duct :
• Two parts : Cortical & medullary collecting duct.
• Two cells : Principal cells & intercalated cells
• Two hormones : Aldosterone & anti-diuretic hormone (Vasopressin).
• Facultative water resorption (hormone dependent) occurs in collecting duct.

Collecting duct
Vasopressin receptors :
• V1 receptor : Vasoconstriction.
• V2 receptor : Water resorption using aquaporin-2.
V2 blocker : Conivaptan for treatment of SIADH.
• V3 receptors : Releases ACTH from anterior pituitary.

Bladder innervation & control 00:41:32

• Parasympathetic system : Facilitates micturition by causing contraction of

detrusor muscle & relaxation of internal urethral sphincter.
• Sympathetic system : Least role in micturition (carry pain signals from
bladder).
• Somatic supply : From pudendal nerve → External urethral sphincter.
• Higher centres :
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a. Facilitatory centers in pons & posterior hypothalamus. ----- Active space -----
b. Inhibitory centre : In midbrain.
c. Cortical level control : Paracentral lobule (supplied by ACA).

Cystometrogram :
• 1a : As bladder starts to fill, volume and
pressure in the bladder increase.
• 1b : Volume increases but the pressure
remains constant (Laplace’s law).
• 11 : Tremendous rise in pressure which leads to
micturition.
• First urge to void : 150 ml.
• Marked sensation to void : 400 ml.

Acid base balance 00:46:31

• Normal pH : 7.35 – 7.45.

• pH values above 7.8 0r below 6.9 are not compatible with life.
• Enzymatic activity and protein structure are very sensitive to pH.
• pH changes can denature proteins.
• Low pH (acidosis) : CNS becomes less excitable.
• High pH (alkalosis) : There is hyperexcitability leading to muscle twitches.
• Regulation of H+ ion concentration :
1. First line : Buffer systems (fast).
2. Second line : Respiratory mechanism.
3. Third line : Solute excretion via kidneys (slow).

Buffers :
• Most important extracellular buffer : Bicarbonate.
• Important intracellular buffer & buffer in tubular fluid (Kidney) : Phosphate.
• Most plentiful intracellular buffers : Protein.

Respiratory regulation :
• Increase in ventilation : Causes CO2 washout and reduce H+ concentration.
• Decreased ventilation : Co2 accumilation and increases H+ concentration.

Role of kidneys in acid base balance :

• Reabsorption of bicarbonate in PCT.
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----- Active space -----

• Generation of new bicarbonate : Uses phosphate and ammonia buffer in
place of bicarbonate to neutralise acid.
• Intercalated cells in collecting duct : Type A is acid excreting during acidosis
& type B (Base excreting during alkalosis).
Hensin
A B
Conversion between A & B type cell during acidosis & alkalosis done by Hensin
protein.

Anion gap
• Refers to unmeasured anions.
• Mainly due to plasma protein anions, sulfate, phosphate.
• Anion gap = [Na+] - [HCO3- + Cl–] = [140 mEq/L] - [25 mEq/L + 105 mEq/L]
• Anion gap = 10 mEq/L.

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