Kidneys: location
Located in the superior lumbar region
Situated against the posterior abdominal wall
Are retro-peritoneal organs
◦ located behind the peritoneal membranes
Protected by
◦ fibrous connective tissue capsule
◦ layer of perirenal fat
Kidneys supplied with blood through renal arteries
◦ derived from branches of the abdominal aorta
◦ blood drains through veins into inferior vena cava
Functions of the kidneys
Regulation of fluid and electrolyte balance.
◦ Including solute content and therefore osmolarity of extra cellular fluid.
Excretion of metabolic wastes and foreign substances
◦ Nitrogenous wastes e.g. urea and creatinine plus foreign wastes such as drugs
Regulation of pH (acid-base balance)
◦ By conserving or eliminating hydrogen (H+) and bicarbonate(HCO3 - ) ions Maintenance of blood pressure
◦ Through control of blood volume and production of renin
Regulation of erythropoiesis.
◦ Produces the hormone erythropoietin for stimulation of red blood cell production
Metabolic functions:
◦ Activating vitamin D
◦ Production of new glucose through gluconeogenesis when fasting/starving
Kidneys: Gross anatomy
Three regions
◦ Renal cortex
◦ Renal medulla
◦ Renal pelvis
Renal cortex
◦ Outer region containing cortical nephrons
Renal medulla
◦ Cone shaped tissue called renal pyramids
Renal pelvis
◦ Funnel shape continuous with ureter
◦ Drains papillae into minor calyces, then into major calyces
The nephron: functional unit of the kidney
Nephron consists of:
1. The renal corpuscle
◦ composed of a tight collection of capillaries called glomerulus
◦ plus a surrounding glomerular (Bowman’s) capsule
Specialised for filtration
- The renal tubule
◦ Proximal tubule PT (Proximal convoluted tubule)
◦ Nephron loop (loop of Henle)
◦ Distal tubule DT (Distal convoluted tubule)
Reabsorption and secretion occur here. - Nephron drains into collecting duct CD
◦ Not part of the nephron unit
Nephron: classes
Nephrons:
- Urine forming units of the kidneys
- Around 1 million per kidney
- Divided into two type
1. Cortical nephrons
◦ Found in renal cortex
◦ 85% of all nephrons
2. Juxtamedullary nephrons
◦ Nephron loop descend deep into renal medulla
◦ 15% of all nephrons
◦ Important for forming concentrated urine
Renal blood supply
Kidneys process around 1200mls/min. This is 20-25% of cardiac output
At the kidney blood:
◦ enters by the renal artery
◦ exits by the renal vein
At the nephron blood:
◦ enters the glomerulus by the afferent arteriole
◦ exits the glomerulus by the efferent arteriole
◦ efferent arteriole then feeds into the peritubular capillaries
Nephron blood supply (capillary networks of the nephron)
- Glomerular capillaries
◦ Within renal corpuscle
◦ Specialised for filtration
◦ Filtration driven by blood pressure (high pressure within glomerulus) - Peritubular capillaries
◦ Close to renal tubules
◦ Low pressure, highly porous capillaries
◦ Readily absorb solutes and water from tubule cells - Vasa recta
◦ Long straight vessels extending deep into the medulla to service the nephron loops of juxtamedullary nephrons
◦ Important for forming concentrated urine
These blood vessels also provide oxygen and nutrients to surrounding cells
Urine production.
Three major processes
1. Glomerular filtration
◦ Passive process
◦ Filtrate= plasma- proteins, RBCs
2. Tubular reabsorption
◦ Passive or active transport
◦ What is needed is reabsorbed
3. Tubular secretion
◦ Active transport
◦ Adds to filtrate
Urine production = filtration + secretion - reabsorption
Glomerular Filtration Membrane
Filtration of solutes from blood is determined by size and charge
◦ Small molecules are filtered freely
◦ Larger molecules are blocked (remain in blood). Includes RBCs and large proteins.
◦ Negatively charged particles are repelled by negative charge of the basement membrane (remain in blood). Includes most proteins.
This filter allows free passage of water and most solutes, including ions, glucose, amino acids, small proteins, vitamins and nitrogenous wastes from the blood into the glomerular capsule.
Urine production: Glomerular filtration
Glomerular filtration:
A non-selective process in which hydrostatic (blood pressure) forces fluids through the glomerular filtration membrane into the glomerular capsule
A result of positive net filtration pressure
Glomerular hydrostatic pressure drives filtration
Does not consume metabolic energy
Forces determining filtration pressure
1. Glomerular hydrostatic pressure
◦ Blood pressure in glomerular capillaries
◦ Much higher than other capillaries
◦ Greatest force
◦ Drives filtration
2. Glomerular Colloid Osmotic Pressure
◦ Osmotic pressure exerted by plasma proteins in glomerular capillaries.
◦ Small force opposing filtration
3. Capsular hydrostatic pressure
◦ Fluid pressure exerted by filtrate in capsular space
◦ Smallest force opposing filtration
NFP = GHP - (GCOP + CHP)
Net filtration pressure = 10 mm Hg
Glomerular filtration rate (GFR)
Total volume of filtrate formed each minute
◦ Combined activity of all glomeruli
◦ Two healthy kidneys means around 2 million glomeruli
◦ GFR in a healthy person usually 120–125mL/min approx. 180L/day
Factors determining GFR
Net filtration pressure (NFP)
◦ This is closely regulated
Total surface area (SA) available for filtration
◦ Decreased numbers of functioning nephrons seen with age and disease
Filtration membrane permeability (PERM)
◦ Permeability altered by some drugs
◦ Filtration membrane damaged in disease & infectious conditions
GFR = NFP x SA x PERM
Urine production: tubular reabsorption
Tubular reabsorption:
- A selective process that reclaims most of the filtrate formed during glomerular filtration
- Commences as soon as filtrate enters proximal tubule
- Entire renal tubule involved in reabsorption to varying degrees
- Solutes move through cells of tubular epithelium and capillary endothelium back into the blood of peritubular capillaries
- Substances reclaimed include water, glucose, amino acids and electrolytes.
Glomerular filtration rate (GFR)
- Glomerular filtration rate (GFR) – Total volume of filtrate formed by entire collection of renal nephrons.
- GFR closely regulated in order to
◦ Remove nitrogenous wastes from the blood
◦ Remove any excess solutes and water from the blood
◦ Ensure the body tissues have a constant blood volume and pressure - GFR needs to be relatively constant
◦ Maintains production of filtrate and therefore adequate reabsorption and secretion
◦ Maintains extracellular fluid homeostasis
- Small changes in GFR greatly affect the volume of filtrate to be processed
- GFR regulated by Intrinsic and Extrinsic mechanisms
Intrinsic regulation of GFR
- Intrinsic mechanism involves responses within renal structures that modify the hydrostatic pressure of glomerular capillaries. Termed renal autoregulation.
- Maintains almost constant GFR despite fluctuations of blood pressure during daily activities e.g. blood pressure increased during exercise and decreased during sleep.
- Renal autoregulation
◦ Protects glomerulus from damage at high blood pressures.
◦ Ensures kidneys still receive sufficient blood flow to allow necessary filtration and removal of wastes
◦ Operates as long as mean arterial pressure is maintained at 80-180mmHg
If mean arterial pressure low, for example in haemorrhage, extrinsic mechanisms activate.
MYOGENIC MECHANISM
- Relies on inherent properties of arteriole walls.
- Composed of vascular smooth muscle
◦ Contracts when stretched
◦ Relaxes when not stretched - Increased blood pressure g stretches vascular smooth muscle g afferent arteriole constricts in response g GHP i g GFR i
- Declining blood pressure allows dilation of afferent arterioles g GHP h g GFR h
- Both responses serve to maintain normal NFP and GFR
TUBULOGLOMERULAR FEEDBACK MECHANISM
- Relies on interactions between the nephron tubule and glomerulus.
- Response to changes in solute concentrations in filtrate within tubule
- Flow dependent
- If GFR increases less time for reabsorption g concentration of NaCl in filtrate remains high g macula densa cells respond to cause constriction of afferent arteriole g GHP i g GFR i g slows down flow of filtrate g more time for processing meaning g more reabsorption of NaCl
Neural control
- When extracellular fluid volume is extremely low it is necessary to maintain blood flow to vital organs.
- Neural controls may override autoregulation.
- When blood pressure falls g noradrenaline is released from sympathetic nerve fibres g constricting afferent arterioles g GFR i
Renin-Angiotensin-Aldosterone-System
- Primary purpose is to maintain blood pressure
- Preserves GFR as a secondary effect
- Low blood pressure causes granular cells of juxtoglomerular complex to release renin
- Three ways to stimulate granular cells
◦ Sympathetic nervous system
◦ Low glomerular hydrostatic pressure
◦ Activated macula densa cells
Pathway of urine
Ureters
- Continuation of renal pelvis
- Transports urine to bladder
- Capable of peristalsis
- Stretch to allow volume changes
Urinary bladdder
- Openings for ureters and urethra (Trigone)
- Stores around 500ml of urine
- Smooth muscle permits expansion
Urethra
- Muscular tube
- Sphincters Internal urethral sphincter
◦ Involuntary control (smooth muscle)
- External urethral sphincter
◦ Voluntary control (skeletal muscle)
Micturition reflex
- Urination or voiding
- Controlled by nerve impulses that can be inhibited when needed
- For micturition to happen three things must occur simultaneously
1. Detrusor muscle must contract
2. Internal urethral sphincter must open
3. External sphincter must open
Regulation of blood pressure
- Mean arterial pressure (MAP): pressure that propels blood to tissues. Blood pressure.
- Must be maintained to ensure all cells have adequate supply of oxygen, nutrients and removal of wastes
- Short-term neural and hormonal controls
◦ Counteract fluctuations in blood pressure by altering peripheral resistance and CO - Long-term renal regulation
◦ Counteracts fluctuations in blood pressure by altering blood volume - Renal mechanisms that alter blood volume provide long term regulation of blood pressure
Long-term renal regulation of BP
- Long-term mechanisms control BP by altering blood volume via the kidneys
- Kidneys regulate BP via
1. Direct renal mechanism
2. Indirect renal mechanism (renin-angiotensin-aldosterone system)
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