What does a nephron comprise of?
1 glomerulus and 1 tubule
What types of nephrons are there?
Cortical - 80%
Juxtaglomerulus - 20% - loop of Henle extends down to medulla giving the kidneys ability to concentrate
Are there new nephrons formed after birth?
No
What is the juxtaglomerular apparatus and what is its function?
Made up of
- Macula densa (epithelia cells near renal corpuscle)
- Juxtaglomerular cells (smooth muscle fibres in walls of afferent arterioles)
Secretes renin and angiotensin when
- arteriole pressure in afferent arteriole falls
- osmotic concentration of tubular fluid reduces (occurs when the rate of glomerular filtration reduces and tubular fluid spends more time in ascending limb of loop of Henle and conc of Na / Cl becomes abnormally low
What does filtration of a molecule depend on?
Molecular size
- <4nm passes freely
Molecular charge
- all layers are negative charged: repel anions
** Albumin is barely filtered because it is too big and negatively charged **
What is the glomerulus made up of?
Fenestrated endotherpium, basement membrane (homogenous glycoprotein) and podocytes
Mesangial cells are located between endothelium and BM to allow striation support. Also contractile and helps regular GBF and filtration
What is ultrafiltration dependent on?
Renal flood flow, hydrostatic pressure and plasma oncotic pressure
How do you measure GFR?
GFR x plasma [Cr] = urine flow rate x urine [Cr]
- slightly overestimates GFR due to small amount o tubular secretion
- inc Cr correlates with reduced GFR in steady state
- 50% nephrons lost, reduces GFR down to 80%
- 80% nephrons lost, reduces GFR down to 50%
True measurement of GFR
- excretion of inulin
- filtered, not secreted nor reabsorbed
What are tubular components?
Bowman’s capsule
- collects glomerular filtrate
Proximal tubule
- uncontrolled secretion of H+ and organic acids
- resorption of NaCl, K, HCO3, PO4, Ca, urine acid, glucose, AA, water (passively), urea
Loop of Henle
- establishes osmotic gradient
Distal tubule
- Controlled secretion of H, K, NH3, drugs
- Reabsorbs NaCl, water, HCO3
Collecting tubules
- variable water reabsorption
What occurs in the proximal tubule?
67% ultrafiltrate is reabsorbed
Active reabsorption of Na+ (Na/K ATPase)
- followed by water (osmosis)
- Also important in reabsorption of glucose, amino acids, chloride and urea
H+ excreted into urine in exchange for Na+
PO4 and HCO3 also absorbed
Osmolality doesn’t change as both solute and water reabsorbed at same rate
What occurs at Loop of Henle?
20-25% water and sodium reabsorbed
Descending - permeable to water, NOT solutes Ascending - permeable to solutes, NOT WATER - Fluid leaving always hypo osmotic
Urea contributes to establishment of osmotic gradient –> high protein diet facilitates ability to concentrate urine
What happens in the distal tubule?
NaCl reabsorption and K excretion
Urine acidification
Aldosterone controls active reabsorption of Na, in exchange for K. Also acidifies urine by HCO3 reabsorption and H+ secretion.
What happens at the collecting ducts?
Concentrate urine under control of ADH
What’s the function of renin?
Activates conversion of angiotensinogen (liver) to angiotensin I.
What is angiotensin II?
Angiotensin I is converted to angiotensin II in the lungs.
- Causes thirst
- potent vasoconstrictor of efferent arterioles to increase GFR (whereas vasodilation of afferent arterioles is caused by prostaglandin 2)
- Increases aldosterone from zona glomerulosa in adrenal cortex
What are the actions of aldosterone?
Acts on Na/K ATPase in the distal tubule & collecting duct
- Promotes resorption of Na and water and in exchange, excreting K / H
- Stimulated by increased K+ and RAS
What is the ANP?
Atrial natriuretic peptide is released from atrial tissue when when it stretched (fluid overloaded)
- causes increased GFR (afferent dilation, efferent constriction) –> Increasing Na / H2O excretion
- reduces tubular re-absorption of Na
- reduces renin
At birth, what does Cr reflects?
Maternal level.
Cr reduces to neonatal levels at 5 days of age
What happens to GFR at birth?
Rapidly increases in first 72 hours and reaches adult levels in 1st two years
What’s the significance of casts in urine?
Hyaline
- transparent, don’t indicate disease on their own
Granular
- precipitated protein on surface seen in glomerular and tubular disease
White cell cast
- acute pyelo and interstitial nephritis
Red cell casts
- always pathological due to GN
How do you calculate FeNa?
FeNa = 100 x (urinary Na x serum Cr) / (serum Na x urinary Cr)
Pre-renal
- Below 1
- the physiologic response to a decrease in renal perfusion is an increase in sodium reabsorption to control hyponatremia
Acute tubular necrosis
- 2-3%
- Either excess sodium is lost due to tubular damage, or the damaged glomeruli result in hypovolemia resulting in the normal response of sodium wasting