102 Renal/Excretory Physiology

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Renal Functions

  • Regulates:-
    • Blood osmolarity - measure of solute concentration in blood
    • Blood ionic composition - e.g. Na/K/Cl, controls quantities lost in urine
    • Blood pH - controls loss of hydrogen & bicarbonate ions in urine
    • Blood volume & pressure - adjusts volume of water lost in urine, releasing erythropoietin, releasing Renin
    • Blood glucose levels (gluconeogenesis) - during prolonged fasting, the kidneys synthesise glucose from amino acids & release into the blood
  • Produces hormones & enzymes
    • Erythropoeitin (hormone) - controls red blood cell production, synthesised in peritubular capillaries which run alongside the nephron and are associated with reabsorption/secretion
    • Renin (enzyme) - controls formation of angiotensin & influences blood pressure & Na balance - affects water reabsorption
    • 1, 25-dihydroxyvitamin D (acts as hormone) - influences calcium balance
  • Excretes wastes and foreign substances
    • nitrogenous wastes e.g. urea & uric acid
  • Assists liver in detoxifying poisins
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Basic Renal Processes

Filtration

  • Glomerular filtration (ultrafiltration)

Reabsorption

  • Tubular reabsorption
  • Retained by body

Secretion

  • Tubular secretion
  • Removed from body

AMOUNT OF ANY SUBSTANCE EXCRETED IN URINE:

= amount filtered + amount secreted - amount reabsorbed

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Locations

Glomerular filtration

  • The movement of fluid and solutes from the glomerular capillaries into the Bowman's space.

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
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The Nephron

  • Approx 1 million nephron per kidney
  • Number is constant from birth
    • decreases with age (60 yrs 50% decrease)
  • Cannot be repaired if the nephron is damaged, the remaining nephron must compensate

2 types of Nephron

  • Cortical (80-85%)
    • Renal corpuscle is located in the outer cortex
  • Juxtamedullary (15-20%)
    • Renal corpuscle lies close to cortical-medullary junction
    • Loop of Henle plunges deep into medulla
    • Responsible for generating osmotic gradient for H20 reabsorption
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Nephron Components

Renal Corpuscle - combination of glomerulus & Bowman's capsule

  • Initial filtering component where blood plasma is filtered
  • Forms filtrate from blood (free of cells & proteins)
  • Located in renal cortex

Renal Tubule - PCT, loop of Henle, DCT & dollecting duct

  • Extends from renal corpuscle into which the fluid passes once filtered
  • Substances are added & removed
  • Ultimately remaining fluid enters collecting duct & exits kidney as urine
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Glomerular Filtration

  • Same constituents as plasma in same concentrations
    • Except NO cells or proteins
  • Bulk flow process
  • Body has no control over what is filtered - non-selective
  • Any molecules small enough will pass through - passive
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Glomerular Filtration Rate (GFR)

volume of filtrate produced by both kidneys per minute

Regulated by...

  • sympathetic nerves - decreased blood pressure stimulates kidney to release Renin which stimulates vasoconstriction causing blood pressure to increase
  • 'renal autoregulation' - renal system requires a constant blood pressure and therefore flow rate; it is able to mitigate changes in systemic blood pressure.

125ml per minute in men, 115ml per minute in women

  • equals approx 180L per day
  • Total blood volume is only 5.5L
    • Filtered every 40 minutes
  • IF reabsorption didn't occur afterwards - urinate to death in minutes
  • We produce approx 2L urine a day
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Tubular Reabsorption

  • Concerned with conservation of solutes & water
  • Can be passive diffusion or active transport
  • Surface area of tubules is increased by microvilli (brush border)
  • Substance: H20 (l) - 180l filtered/day, 1.8l excreted/day - 99% reabsorbed
  • Substance: Na+ (g) - 630g filtered/day, 3.2g excreted/day - 99.5% reabsorbed
  • Substance: Glucose (g) - 180g filtered/day, 0g excreted/day - 100% reabsorbed
  • Substance: Urea (g) - 54g filtered/day, 30g excreted/day - 44% reabsorbed
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Proximal Convoluted Tubules

Retained tubular reabsorption

  • Both urea and water are passively absorbed
  • Bicarbonate, chloride, phosphate & sulphate
    • Exchanged for H+ ions
    • Process by which the pH of the filtrate/blood is maintained
  • Substances such as glucose, amino acids, Na+ and K+ are actively reabsorbed 
    • requires energy (ATP & carriers)
  • 65% filtrate is reabsorbed by the PCT
  • Independent of the body's needs
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Loop of Henle

Descending limb

  • Highly permeable to water (passively reabsorbed)
  • Low ion permeability - draws in Na+ and Cl- (active process)
  • Water is also reabsorbed as it follows salt concentration

Ascending limb

  • Impermeable to water
  • Permeable to ions
    • Cl- actively reabsorbed
    • Na+ passively reabsorbed
    • via concentration and electrical gradient 
    • Bicarbonate reabsorbed
  • 85% of water & 90% of salts have been reabsorbed 
  • Majority of reabsorption is not influenced by the body's needs
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DCT/Collecting Duct

  • Variable reabsorption of ions and water
  • Under hormonal control
  • Where 'fine tuning' occurs depending on the body's needs.
  • Sodium actively reabsorbed
    • Dependent on the presence of aldosterone
  • Potassium actively reabsorbed
  • Chloride actively reabsorbed

The distal part of the nephron is impermeable to water without antidiuretic hormone (ADH)

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Tubular Secretion

  • Transfer of substances from peritubular capillaries to tubular lumen of nephron.
  • Occurs via diffusion or transcellular mediated transport
    • active process requires presence of specific transmembrane proteins which form pores in the membrane
  • Most important secreted substances:
    • H+ excess - decreases pH
    • K+ excess (hyperkalemia) - cardiac arrythmia
  • Other anions:
    • Choline, creatinine, drug metabolites
    • Usually coupled with reabsorption of Na+
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Elimination of Urine

  • Urine flows from the kidney via ureter to the bladder
  • Urine is stored in the bladder and intermittenly ejected by urination (micturition)
  • Urethra carries urine from the bladder to exterior
    • External urethral sphincter ==> made of skeletal muscles and under voluntary control
  • Urination is a spinal cord reflex over which voluntary control may be exerted
  • The bladder can hold as much as 800ml of urine however the reflex is initiated before the maximum capacity is reached as approx 200-400ml
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Muscles of the Bladder

Detrusor (smooth muscle)

  • Parasympathetic (causes contraction)
  • Inhibited during filling
  • Stimulated during urination

Internal urethral sphincter (smooth muscle)

  • Sympathetic (causes contraction)
  • Stimulated during filling
  • Inhibited during urination

External urethral sphincter (skeletal muscle)

  • Somatic motor (causes contraction)
  • Stimulated during filling
  • Inhibited during urination
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Chronic Kidney Failure

  • Long-lasting irreversible condition
  • Caused by damage to the kidneys
  • Very serious as kidneys are responsible for:
    • filtering waste from the blood
    • regulating blood flow
  • Thought to affect between 1-4 people in every 1000
  • Risk increases with age (average age of 77)
  • Most common in South Asian, African and Afro-Carribbean communities
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Causes of Kidney Failure

Hypertension:

  • Causes damage by putting strain on the small blood vessels in the kidneys
  • Prevents the filtering process from working properly

Diabetes:

  • If not well controlled, too much glucose can build up in the blood
  • Damages the nephrons & affects the ability of the kidneys to filter out waste
  • Type 1 diabetes is more likely to lead to damage

Other causes:

  • glomerulonephritis
  • blockage (kidney stones
  • drug toxicity
  • physical injury
  • maldevelopment
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GFR & Stages of Kidney Disease

A healthy GFR should be more than 90 ml/min

  • Stage 1: normal GFR rate, other evidence of kidney disease
  • Stage 2: GFR rate <90
  • Stage 3: GFR rate <60
  • Stage 4: GFR rate <30
  • Stage 5: GFR rate <15 = established renal failure

In most cases, kidney disease never progresses beyond stage 2 and it is unlikely to cause serious problems.

However the symptoms do not normally begin until stage 4, at this point it is too late to undo the damage to the kidneys

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Established Renal Failure (ERF)

If the kidneys fail, an excess of waste products can build up in your blood, leading to these symptoms:

  • vomiting
  • itchy skin
  • fatigue
  • swelling of feet, hands and ankles

Without treatment, kidney failure will inevitably prove fatal

Patients will require haemodialysis or kidney transplant to stay alive

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Hormonal Regulation

3 main hormones regulating Na+ and Cl- reabsorption:

  • Angiotensin II
  • Aldosterone
  • Atrial Natriuretic Peptide (ANP)

Main hormone regulating water loss

  • Antidiuretic hormone (ADH aka vasopressin)
    • Secreted from neurosecretory cells
    • Released due to increased osmorlarity of body fluids, also a large decrease in blood volume, dehydration
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Antidiuretic Hormone (ADH)

  • Released from the pituitary gland in the brain
    • controls water reabsorption - negative feedback
  • Decrease in fluid in the blood signals the hypothalamus to stimulate the pituitary to release ADH into the blood
    • ADH increases water absorption in the kidneys i.e puts more water back in the blood and increases the concentration of urine
  • When too much fluid is present in the blood, sensors in the heart signal the hypothalamus to decrease the amount of ADH in the blood
    • Therefore decreases the amount of water absorbed, producing large quantities of more dilute urine.
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Aldosterone & Renin-Angiotensin System

Angiotensin II

  • Part of the Renin-Angiotensin system
  • Acts directly on the adrenal cortex to stimulate the secretion of aldosterone

Aldosterone

  • Produced by the adrenal cortex
  • Stimulates Na+ reabsorption by DCT
  • Water is also reabsorbed as it fallows salt via osmosis
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Maintaining Water Balance

Thirst centre in hypothalamus

  • Stimulates desire to drink fluids

Angiotensin II

  • Stimulates secretion of aldosterone

Aldosterone

  • Promotes reabsorption of Na+ and Cl-, increases water reabsorption via osmosis

ANP (atrial natriuetic peptide)

  • Promotes natriuresis, elevated urinary excretion of Na+ and Cl- accompanied by water

ADH (anti-diuretic hormone)

  • Promotes water channel proteins in collecting ducts. Therefore water permeability increases and more is absorbed
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