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Functions of kidney

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jiayan lim

on 9 March 2014

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Transcript of Functions of kidney

Functions of the kidney
1. Homeostasis - regulation of water and electrolytes -> blood volume and pressure
2. Excretory - metabolic waste, bioactive substances eg drugs
4. Acid base balance
5. Hormone production
6. Metabolic - gluconeogenesis
Water homeostasis
6 major functions
Excretory functions
1. Creatinine
- Freely filtered by renal tubule, not reabsorbed
- Small amount secreted by tubules
3. Uric acid
- Unbound urate filtered (~95%)
- Most reabsorbed in early PCT, then 50% secreted back in S2 segment of PCT

4. Drugs
- Amt excreted = amt filtered - amt reabsorbed + amt secreted
- Secreted as organic anions/ cations in PCT
Acid base balance
- Main extracellular buffer system
- For every excretion of H+, there is an addition of HCO3 to the blood and vice versa.
- pH = pKa + log [HCO3- / CO2] = 6.1 + log [24/1.2] = 7.4
- Combines with H+ secreted by tubules forming CO2 and H20 (under influence of carbonic anhydrase)
Renal handling of HCO3
Renal handling of H+
CO2- HCO3 buffer
Hormone production
1. Renin
- secreted by granular cells of Juxtaglomerular apparatus
- released when there is reduced renal perfusion pressure, hyponatremia
- key stimulus for aldosterone
- negative feedback from angiotensin II

2. Erythropoietin
- secreted in response to low blood oxygen content
- stimulates RBC production

3. Calcitriol
- production of 1,25 dihydroxyvitamin D3
Gluconeogenesis
During prolonged periods of fasting, kidneys aid in gluconeogenesis from non-carbohydrate sources.
Water reabsorbed via osmosis

- 65% reabsorbed in PCT, 10% in thin descending limb of LOH

- Main control in modulation of water re-absorption is in the collecting ducts by action of ADH (triggered by baroreceptors and osmoreceptors)

- Loop of Henle creates high medullary interstitial osmolality

- Reabsoption of urea from medullary collecting ducts contributes to interstitial osmolality
- Bicarbonate freely filtered by renal corpuscle
- Reabsorption occurs:
85% in PCT, 10% in thick ascending limb of LOH, remaining reabsorbed by DCT and cortical collecting duct
Nephron - functional unit of the kidney
Anatomy of kidney
Three major regions:
1. Cortex - mainly reabsorption of filtered substances, receives the most blood flow
2. Medulla - highly metabolic area, serves to concentrate urine
3. Renal pelvis - collect urine for excretion

Blood supply:
1. Renal arteries - 20% of cardiac output to the kidneys
2. Renal veins - drain peritubular capillaries into IVC

Autonomic supply:
1. Sympathetics (T8- L1) - causes vasoconstriction of renal vessels
2. Parasympathetics (vagal nerve CN X) - causes vasodilatation
- Within each kidney, there are approximately one million nephrons

- Each nephron consists of:
Renal corpuscle
- glomerulus and Bowman's capsule
Proximal convoluted tubule
Loop of Henle
- thin descending and ascending then thick ascending limb
Juxtaglomerular apparatus
(macula densa of thick ascending limb)
Distal convoluted tubule

Collecting duct
(cortical and medullary)

- Made up of single epithelial cell layer, separated from peritubular capillaries from basement membrane

- Regional differences of nephrons
Cortical nephrons
- short LOH, efferent arterioles continue as peritubular capillaries
Juxatamedullary nephrons
- long LOH, efferent arterioles extend to form vasa recta
Overview of functions of the nephron
Renal corpuscle
- Glomerular filtratation occurs, GFR ~125mls/ min
- Filtration barrier comprise of: capillary endothelium, basement membrane, podocytes of Bowman's capsule
- Molecules filtered are affected by:

Molecular weight
- <7000Da freely filtered

Electrical charges
- glomerular filtration barrier is negatively charged, hence negatively charged molecules are less able to filter
Proximal convoluted tubule
- Collects large volume of glomerular filtrate and reabsorbs 60-65% back
Loop of Henle
- Hairpin loops that allow for concentrating and dilution of urine via counter-current multiplier (reaches 1200 mOsm/L)
Distal convoluted tubule
Early distal tubule
Sodium reabsorption (5%) via co transport with chloride

Impermeable to water
Collecting duct
Late distal tubule and cortical collecting duct

1. Principal cells (main cells)
- Na channels present for reabsorption
- secrete potassium
2. Type A intercalated cells

- H/K ATPase (reabsorbs K, secrete H+)
3. Type B intercalated cells
- Cl reabsorption via counter transport with HCO3 (dependent on H-ATPase)
Factors affecting glomerular filtration:
1. Filtration coefficient (Kf)
- Surface area
- Permeability

2.Net filtration pressure

- Glomerular hydrostatic pressure
- Bowman's capsule hydrostatic pressure
- Glomerular oncotic pressure
Reabsorption of substances
1. Sodium (65%)
- co transported with glucose/amino acids
- counter transport with H+/ NH4+
2. Water (65%) via osmosis
3. Urea (50-60%), potassium (55%) by passive diffusion
4. Chloride (65%)
5. Bicarbonate (85%)
Secretion of substances
1. Hydrogen ions
2. Organic anions eg urate, bile salts, aspirin
3. Organic cations eg creatinine, acetylcholine, pethidine, morphine
Thin descending limb
- Only permeable to water
- Reabsorbs 10% of water via osmosis

Thick ascending limb
- Impermeable to water
- Sodium reabsorption (25%) via:
(A) co transport with K, 2Cl
(B) counter transport with H+
(C) paracellular diffusion
- HCO3 reabsorption (10%)

Vasa recta
- Serves as counter current exchangers preventing washout of solutes from interstitium
Medullary collecting duct
- Water and urea reabsorption via action of ADH
- Potassium reabsorption via Type A intercalated cells
Regulation of electrolytes
Autonomic control
- In situations of low blood volume, sympathetics activated
- Effects:
(A) Constriction of renal arterioles leading fall in GFR
(B) Increased tubular reabsorption of salt and water
(C) Stimulate release of renin -> angiotensin II -> aldosterone
Potassium
Potassium excretion = K filtered - K reabsorbed + K secreted
Other electrolytes
Calcium
- Only 50% of calcium filtered (remaining bound to plasma proteins/ anions
- 99% reabsorbed in tubules (65% in PCT, 25-30% in LOH, 4-9% in DCT/collecting duct)
- Affected by PTH: stimulates reabsorption at thick ascending LOH and distal tubules

Phosphate

- Freely filtered, reabsorbed at proximal tubules
- Transport maximum present for phosphate reabsorption, any excess above will be excreted
- Affected by PTH:
(A) Increases phosphate ions in extracelluar fluid from bone salts
(B) Decreases the transport maximum

Magnesium

- 10-15% filtered (rest bound to plasma proteins)
- Reabsorbed in: PCT 25%, LOH 65%, distal tubules and collecting ducts <5%
Sodium
Reabsorption:
- mainly driven by Na-K ATPase on basolateral membrane of tubules
- 65% in PCT, 25% in thick ascending limb, 5% in distal tubule
Intra-renal control of Na excretion
- Excretion of Na = glomerular filtration - tubular reabsorption
- Na reabsorption is closely matched to GFR
(A) Autoregulation of renal blood flow
- Myogenic mechanism
- Tubuloglomerular feedback via macula densa
(B) Presence of glomerulo-tubular feedback -> increased GFR leads to increased Na reabsorption from tubules
Pressure natriuresis

- Rise in BP
- Increase peritubular capillary hydrostatic pressure -> enhances back leak of sodium into tubular lumen
- Reduce angiotensin II production
Sodium - contd
Hormonal control
1. Angiotensin II
- constricts efferent arteriole preferentially in low Na/ volume depleted conditions
(A) Prevents decrease in glomerular hydrostatic pressure, hence GFR
(B) Decrease flow through peritubular capillaries -> allow more reabsorption of Na (and water)
- Stimulates reabsorption of Na via Na-K ATPase
- Stmulates aldosterone release

2. Aldosterone
- Stimulates Na-K ATPase and increase Na permeability in cortical collecting duct

3. Atrial natriuretic peptide
- Secreted when specific atrial cells distended
- Inhibit reabsorption of Na and water from tubules, esp collecting ducts
Reabsorption occurs:
1. PCT (55%) via passive diffusion
2. Ascending LOH (30%)
3. Collecting ducts via Type A intercalated cells

Secretion occurs:
Late DCT and early collecting duct via principal cells
Factors affecting K secretion:
1. Raised plasma K stimulates Na-K ATPase
2. Flow of luminal fluid
- Potassium moves out via diffusion gradient, hence dependent on luminal [K]
3. Aldosterone - Increase production of Na-K ATPase and luminal K channels
4. Acidosis - inhibits Na-K ATPase
Titrating excess H+
(Mechanism for generation of new HCO3
Secretion occurs by:
1. Secondary active transport in PCT, thick ascending LOH, early DCT

2. Primary active transport in late distal tubules and collecting system via intercalated cells
HCO3 is titrated against H+ in tubules
- H+ secretion 4400 mEq/day
- HCO3 filtration 4320 mEq/ day
- Combine to form CO2 + H20, hence titrating each other

- Excess of 80 mEq/day of H+ (due to production of non-volatile acids)
- Combined with urinary buffers
1. Phosphate buffer
- Important filtered urinary buffer
- Base form (HPO4 2-) combines with H+ to acidify urine
- Amount of H+ combined with phosphate/ organic buffers known as titratable acid
2. Ammonium buffer
- Glutamine metabolised to 2HCO3 and 2 NH4+ in PCT, thick ascending LOH, distal tubules
- In collecting ducts, H+ combine with NH3 forming NH4+
There is little control over filtration and reabsorption, hence K excreted is dependent on secretion
2. Urea
- Freely filtered
- Tubular reabsorption (40-60%)
Thank you!
1. Adjust the volume of water lost from the body
- hence regulating blood volume and pressure

2. Regulate plasma ion concentration

3. Stabilise blood pH by adjusting HCO3- and H+ ions secretion

4. Excretory function
- removal of waste products and drugs

5. Hormonal and metabolic functions
In summary..
Full transcript