Functions of Kidney ??
EXCRETION OF METABOLITES OR INGESTED SUBSTANCES
– Urea from protein catabolism
– Uric acid from nucleic acid breakdown
– Creatinine from muscle creatine
– End products of haemoglobin breakdown
– Foreign chemicals eg. drugs, pesticides
CONTROL OF BODY FLUID COMPOSITION - plasma fluid conc.
– Volume Regulation i.e. linked to sodium concentration
– Osmoregulation i.e. water balance
– pH regulation
What are some hormones that act on the kidney??
e.g. anti-diuretic hormone(ADH) (causes water to be reabsorbed back in to the body from the urine), aldosterone (causes Na+ reabsorbtion), natriuretic peptides(cause excretion of Na+ in to the urine) and parathyroid hormone (allows the kidney to excrete phosphate).
What are some hormones produced by the kidney ??
e.g. renin (important in controlling Na+ concentration in plasma), vitamin D, erythropoietin (it enters the blood and acts at the level of bone marrow to increase the production of red blood cells) and prostaglandins (important in maintaining vascular tone).
what are the two regions of the kidney ?
what is the basic unit of the kidney ??
What does the nephron consist of?
1. Renal copuscle
how many nephrons are there in the kidney
>1 million nephrons/kidney
Glomerulus or Glomerular Capillaries
focus on filtration interface
Ascending thin limb of Henle's loop
Thick ascending limb of Henle's loop
Descending thin limb of Henle's loop
Proximal straight tubule
Proximal convoluted tubule
Distal convoluted tubule
Cortical collecting duct from another tubule
Cortical collecting duct
Medullary collecting duct
Medullary collecting ducts from other nephrons
What are the types of nephrons?
A. CORTICAL (85%)
outer 2/3 of cortex.
- short Loop of Henle
inner 1/3 cortex
– long Loop of Henle
– producing concentrated urine
What does the juxtaglomerular apparatus consist of?
juxtaglomerular cells and macula densa cells
where are juxtaglomerular cells found?
in the walls of the afferent arteriole
where are macula densa cells found?
in the walls of the distal tubule - just as it arises out of the loop of henle
blood supply in the nephron??
2 sets of arterioles (afferent and efferent)
2 sets of capillary beds (glomeruli and peritubular) in series.
Basic Renal Processes ??
1) Glomerular Filtration
2) Tubular Reabsorption
3) Tubular Secretion
Glomerular filtration ??
The movement of fluid and solutes from the glomerular capillaries into Bowman’s space.
20 percent of the plasma that enters the glomerulus is filtered.
Tubular secretion ??
The secretion of solutes from the peritubular capillaries into the tubules
Tubular reabsorption ??
The movement of materials from the filtrate in the tubules into the peritubular capillaries.
amount secreted in the urine = ??
what happens to substance x??
Substance X is filtered and secreted but not reabsorbed. e.g. para-aminohippuric acid (PAH).
what happens to substance y??
Substance Y is filtered and some of it is reabsorbed. e.g. water and most electrolytes.
what happens to substance z??
Substance Z is filtered and completely reabsorbed. e.g. glucose
What gets through the glomerular filtration barrier?
Normally all plasma constituents MINUS proteins.
NB: Molecules that bind to proteins are also excluded.
However infection, damage to glomerulus, very high blood-pressure can result in:
-protein in urine (proteinuria)
-haemoglobin in urine (haemoglobinuria)
-red cells in urine (haematuria)
what is the Glomerular fltration rate (GFR) ?
what does it depend on?
what is it regulated by??
volume of fluid filtered from the glomeruli per minute (ml/min).
GFR depends on a combination of:
1) Starling forces
2) Hydraulic permeability
3) Surface area
And is regulated by both neural and hormonal input.
what are the forces involved in filtration ?
Starling forces (opposing)
Net glomerular filtration pressure = (60-15)-(29-0) = 16 mmHg
*Note: protein concentration in Bowman’s space filtrate is so low that the oncotic pressure is considered to be zero.
how does blood flow and vasoconstriction/dilation affect glomerular fltration rate (GFR) ?
Glomerular Filtration Rate ?
125 ml/min of filtrate formed 180 litres / day (180 litres/day)
Urine output typically 1.5 litres/day
because reabsorption occurs
CLEARANCE DEFINITION ??
The volume of plasma that is cleared of a substance in a given time
Equation for clearance??
Plasma Inulin Concentation PIN = 0.25 mg/ml
Urine Inulin Concentration UIN = 35 mg/ml
Urine Volume (per min) = 0.9 ml/min
What is the clearance??
Units for U and P cancel so answer is in units for V
Note: Rate of excretion is 35 x 0.9 = 31.5 mg/min
Inulin = plant polysaccharide
Clearance of inulin estimates GFR. Why?
It is freely filtered, but not reabsorbed or secreted.
Not metabolised and easily measured.
Inulin is used experimentally.
Creatinine is used in the clinic routinely.
(NB: creatinine is slightly secreted)
e.g. 1: most solutes 2: inulin 3: PAH
(Some substances that show net reabsorption may also be secreted (e.g. K))
(e.g. para-aminohippuric acid; PAH).
is filtered and completely secreted, but not reabsorbed.
All the plasma that enters the kidney per unit time is cleared of PAH.
So the rate of excretion of PAH must have been provided by a volume of plasma that contained that amount.
Therefore the clearance of X is a measure of renal plasma flow.
i.e. PAH Clearance = Renal Plasma Flow
Effective renal plasma flow ~600 ml/min.
Renal Plasma Flow is ~600ml/min
Whole blood is 45% cells (Packed cell volume)
Plasma occupies 55% of blood volume.
Therefore Renal Blood Flow is ????
The formula in general is ??
~600/0.55 = 1100 ml/min.
i.e. over 20% of the cardiac output
Blood Flow = (Plasma Flow)/(1 - haematocrit)
If haematocrit is given as a percentage (e.g. 45%) Then
Blood Flow = (100 x Plasma Flow)/(100 – haematocrit)
but also ??
2) Keeps or saves (reabsorbs).
Luminal membrane of tubule cells faces filtrate.
Basolateral membrane faces peritubular capillary.
How are the walls of the proximal tubule??
Walls are a single layer of columnar cells
what happens to glucose in the kidney??
Filtered glucose normally reabsorbed.
1.SGLT-Na+-dependent glucose co-transporter.
2.GLUT facilitated transporter.
3. Na+-K+-ATPase pump.
Renal handling of plasma glucose ??
Filtered load is linearly proportional to plasma concentration
and matches reabsorption below 200 mg% = 11 mM.
“Reabsorbed” line shows variation with plasma [glucose].
Excreted = Filtered – reabsorbed, and shows renal threshold at 200 mg%.
Amino acids in the kidney??
Reabsorbed proximal tubule.
At least 8 amino acid transporters.
Overlapping amino acid specificity
Summary of PCT reabsorption
Na+ coupled transporters for
– glucose, amino acids, phosphate, calcium, sulphate, chloride
– urea, chloride, potassium
Hydrogen Carbonate (bicarbonate)
...related to H+ secretion, important in acid- base balance.
Secretion in proximal tubule ??
ORGANIC ACIDS (Anions)
e.g. bile salts, fatty acids, prostaglandins.
e.g. furosemide, penicillin and acetazolamide
e.g. para-aminohippuric acid (PAH).
ORGANIC BASES (Cations)
e.g. choline, creatinine, dopamine, guanidine, histamine, serotonin.
e.g. atropine, cimetidine and morphine
Organic Anion Secretion in Proximal Tubule ??
1. Organic anion (OA-) enters cell in exchange for dicarboxylate (DC-) (A: organic anion transporters (OAT1 or OAT3))..
2. DC- accumulate in cells by metabolism and Na+-coupled cotransport (B).
3. OA- enters tubule lumen via ATP- dependent transporters (D).
Organic Cation Secretion in PCT ??
1. Enter cell via facilitated organic cation transporters (OCT2).
2. Enter tubule lumen via multidrug and toxin extrusion proteins (MATEs) antiporter in exchange for H+.