Renal structure and function Flashcards
How is the ultrafiltrate produced by the glomerulus?
- Efferent arteriole thinner than afferent = pressure gradient
- Ultrafiltrate from capillaries between afferent and efferent
- Podocytes around capillaries prevent passage of proteins
- Fenestrated lining of capillaries
- Negative change of basement membrane
Why is the basement membrane of the glomerulus negatively charged?
- Made up of acellular glycocalyx
- Thick (physical barrier)
- Negative charge (repels anions)
What components of blood can pass thorugh the glomerular barriers easily?
- Micromolecules i.e.:
- Urea
- Amino acids
- Glucose
- Toxins
- Salts
- Small hormones
What components are not contained within the normal ultrafiltrate?
- Macromolecules i.e.:
- Proteins
- Cells
How do podocytes aid the production of the ultrafiltrate?
- Make up inner epithelial layer of Bowman’s capsule
- Have pedicels with gaps
- Final barrier
What components are reabsorbed from teh ultrafiltrate in the tubule?
- Plasma proteins if present
- Glucose
- Amino acids
- Hormones
- Vitamins
- Salts/electrolytes
- Water
- Urea (partially)
What is filtration dependent on?
- Molecular weight
- Small molecules less than MW 700 Daltons filtered witout restriction
- Medium: MW 17000 Daltons filtered less
- Large: MW 70000 Daltons restricted completely
What is meant by glomerular filtration rate?
- Volume of fluid filtered per unit time
- Measure of kidney function
- Is scaled to bodyweight (thus affected by lean mass)
Where does the majority of the reabsorption of the ultrafiltrate occur and why?
- Proximal tubule
- Is structurally and functionally organised for bulk reabsorption
- Outer cortex
- Cortex receives most blood flow
- Involves cortical glomeruli
What proprtion of glucose and amino acids is reabsorbed from teh ultrafiltrate?
100%
Describe the process of ultrafiltrate reabsorption
- Coupled to movement of Na+ ions
- Generally iso-osmotic
- Filtered proteins reabsorbed
- Waste products retained in tubule to be excreted
- Primary and secondary active transport
How are proteins reabsorbed from the ultrafiltrate?
Endocytosis via recetpros megalin and cubulin)
Decribe primary active transport in ultrafiltrate reabsorption
- Directly uses ATP
- ATP to transport Na across basolateral membrane
- Creates concetration difference and difference in electrical charge due to K leak
- Na passively across apical membrane
- More Na into peritubular capillaries
- Ca-ATPase, H-ATPase and H/K-ATPase also use this
Why is ATP used to transport Na across the basolateral membrane in primary active transport for ultrafiltrate reabsorption?
Na/K+ ATPase not present in apical membrane
Describe secondary active transport in ultrafiltrate reabsorption
- Uses ATP indireclty as uses concentration gradient created by primary Na+ linked glucose transport
- Primary creates concentration difference
- Drives apical Na uptake, couples with other substances to reabsorb them
- Some molecules exchanged for Na
Explain the effects of hyperglycaemia on urine production
- Infection risk (sugary water attracting bacteria)
- Osmotic effects, draws water into tubules and so increased urine production
- Glucose symporters reach saturation, no more water reabsorbed
What is nephrotic syndrome?
Protein appearing in urine
What are the signs of nephrotic syndrome
- Weight loss
- Oedema
- Ascites
- Hypoalbuminaemia
How does oedema occur in nephrotic syndrome?
- Altered colloid osmotic pressure
- Abdominal leakage
How does weight loss occur in nephrotic syndrome?
- Loss of protein
- Liver accomodates
- Lose weight
Describe teh process of nephrotic syndrome
- Amyloid blocks glomerular basement membrane leads to loss of normal barrier function thus proteinuria, loss os plasma protein leading to oedema
- Chronic protein loss triggers renal inflammation leading to renal failure
- Chronic proteinuria leads to hypovolaemia acivating RAAS can lead to hypertension
What are the effects of hypertension on filtration?
Expansion of capillaries and so increased passage of large molecules
What is angiotensin II?
- Peptide hormone
- Causes vasoconstriction => increased blood pressure
- Results in enzyme binding (not protein production)
What are the primary functions of ADH?
- Retain water in body
- Constrict blood vessels
Give the biochemical class, site of production, site of action and if water or fat soluble for ADH
- Short peptide
- Hypothalamus
- Kidneys (aquaporins)
- Water
Give the biochemical class, site of production, site of action and if water or fat soluble for aldosterone
- Steroid
- Adrenal cortex
- Kidneys
- Fat
Give the biochemical class, site of production, site of action and if water or fat soluble for angiotensin II
- Peptide
- ACE acting on AT1 in the blood
- Blood
- Water
Give the biochemical class, site of production, site of action and if water or fat soluble for erythropoeitin
- Glycoprotein
- Kidney
- Bone marrow
- Water
Give the biochemical class, site of production, site of action and if water or fat soluble for renin
- Protein
- Juxtaglomerular apparatus
- Angiotensinogen in blood
- Water
What is the effect of hypernatraemia on renal function
- High ECF Na induces natriuresis to cause net loss of Na ions
- Hyper inhibits aldosterone
- Hyponatraemia induces Na retention to recover Na ions
Where is sodium mostly found?
In the ECF
Where is potassium mostly found?
In the ICF
What is the main method of Na control?
- Basolateral pump
- Control total body sodium not concentration
What are the key hormones in controlling ECF Na
- Aldosterone
- ADH
- Natriuretic peptides e.g. ANP
- RAAS
Describe the role of aldosterone
- RAAS stimulates aldosterone release
- Upregulates sodium receptors in order to reabsorb sodium
- Acts to reabsorbed Na and thus increase secretion of K
- Increase ECF volume and blood pressure
How does aldosterone carry out its function?
- Increases expression of sodium receptors
- ENaC on collecting duct
- Basolateral Na/K ATPase on distal tubule
What is the effect of K concentration on aldosterone
- Increased K concentration stimulates aldosterone
- Retention of Na/secretion of K is reciprocal
- High potassium intake leads to aldosterone activation
- Secretion of K and reabsorption of Na
What is the function of ADH?
- Acts to conserve water
- Increase water retention (prevent diuresis)
- In high concentrations has vasopressor effect to raise BP
How does ADH carry out its function?
- Mainly effect on distal tubule
- Increase expression of receptos in cortical and distal collecting duct
What is RAAS?
Renin Angiotensin Aldosterone System
What is the function of RAAS?
- Stimulates production of aldosterone
How does RAAS carry out its function?
- Decreased blood pressure
- Decreased perfusion to kidney (sensed in efferent arteriole)
- More renin secretion
- Conversion of angiotensinogen to angiotensin II
- Stimulates adrenal gland to produce aldosterone
What is the effect of angiotensin II on sodium channels?
- Insertion of Na+ channels
- Inproximal tubule: apical Na/H exchanger, basolateral Na+(HCO3-)3 and Na/KATPase
- In thick ascending limb: apical Na/H exchanger and Na+K+2Cl-
- In collecting duct: ENaC
What does ENaC stand for?
Epithelial Na+ Channel
What transport mechanisms for Na+, Cl-, K+ are used in the proximal tubule?
- basolateral Na/K-ATPase
- Na/H exchange transporter
- Due to carbonic anhydrase in lumen, net effect is HCO3- reabsorption
What transport mechanisms for Na+, Cl-, K+ are used in the loop of Henle?
- High Na and Cl in thinAL, some leave by passive diffusion
- Na+/K+/2Cl- in thick AL (1Na, 1K and 2Cl into interstitium, into epithelial cell, K+ acively into tubule by ROMK channel, net reabsorption of Na and 2Cl)
What transport mechanisms for Na+, Cl-, K+ are used in the distal tubule?
- 1na, 2Cl transporter (NCC)
What transport mechanisms for Na+, Cl-, K+ are used in the collecting ducts?
- Net positive charge in tubular lumen aids paracellular uptake of remaining positively charged ions in tubule (e.g. Na, K, Ca, Mg)
- Principle cells: ENaC, K/Cl cotransport secretor, NaKATPase, K+ leak (basolateral), Cl- leak (basolateral)
- Alpha-intercalated: K/H antiport, HCO3-/Cl- antiport (Cl- reabsorption, basolateral), Cl- leak (baso), K+ leak (baso)
- Beta-intercalated: HCO3-/Cl- antiport (HCO3- secretion), K/H antiport, Cl- and K+ leak (baso)
How does the H+ ATPase transport mechanism work in the collecting duct?
- type B intercalated cells
- Establishes H+ gradient
- Drives secretion of HCO3- coupled to reabsorption of Cl-
Explain what occurs when Na needs to be excreted
- If need to get rid of Na for example (Na+ load, ECF volume or BP high)
- Renin secretion inhibited
- Aldosterone deendent Na+ reabsortpion does not occur
- Excess Na+ excreted in urine
What are some causes of hypokalaemia?
- Renal loss increased (CKD), diuretic therapy
- Gastric loss (diarrhoea, vomiting)
- Shift in biodistribution (ICF to ECF, e.g. insulin treatment, hyperthyroidism)
- iatrogenic (nephrotoxic drugs, laxatives, bicarbonate therapy alkalosis)
What are the 3 main methods of K control?
- ECF/ICF shifts (short term buffer)
- Renal excretion
- GI excretion
What may cause chronic hyprekalaemia?
- Oliguric or anuric renal failure
- Urinary tract trauma or obstruction
- ACE inhibitors
- Potassium-sparing diuretics
- Hypoaldosteronism
- Hypoadrenocorticism
Where is potassium reabsorbed?
- Mainly proximal tubule (active reabsorption)
- Some in Loop of Henle
- Fine tuning in collecting duct
Where is potassium secreted in the nephron?
- The distal tubule
Describe the mechanism behind potassium secretion
- Principle cell main route
- Aldosterone
- Increased Na/K ATPase in basolateral of principle cells (drivign force for K secretion)
- K secretion through ROMK small (SK) or big conductance channels (BK)
- High potassium increases aldosterone, drives Na uptake and K loss
- Sodium entry via ENaC stimulates K secretion via apical leak channels
- Functional cotransport of potassium chloride affects potassium secretion
What are the mechanisms of potassium reabsorption?
- Alpha-intercalated cell, active K reabsorption driven by apical membrane proton potassium pump
- pH sensitive, acivaded by acidosis potassium restriction and aldosterone
What may cause hyperkalaemia?
- Imparied internal redistribution (insulin resistance, beta blockers)
- Increased potassium leak (cell destruction, acidaemia)- Structure abnormalities in the kidney (decreased GFR, decreased filtration, reduced abilty to compensate for rapid changes in K load)
- Function abnormalities in kidney (decreased luminal flow, metabolic acidosis, hypoaldosteronism)
Where is ANP stored and what stimulates its release?
- Right atrium of heart
- Stimulated by increased stretch due to increased blood volume
What is the function of ANP?
To increase sodium excretion
What happens when ANP is secreted?
- Renal vasodilation
- Increased GFR
- Decreased renin (opposes RAAS)
- Decreased aldosterone
- Decreased reabsorption of Na
- Decreased ADH secretion
Relate the physical properties of water to its physiological function
- Water is polar due to polarity of H-O bonds
- Properties of water are due to hydrogen bonding between molecules (loose association with each other)
- Leads to unique properties
What are the 2 “compartments” total body water can be divided into?
- Extracellular fluid (ECF) (20%)
- Intracellular fluid (ICF) (40%)
What are the components ECF can be split into?
- Plasma volume (5%)
- Interstitial fluid (15%)
- Transvellular fluid (<1%)
What are the main solutes found in ECF?
- Sodium
- Chloride
- Bicarbonate
What are the main solutes found in ICF?
- Potassium
- Magnesium
- Protein
Define concentration
- A measure of how much of a given solute is dissolved in a given volume of solvent (usually moles per litre (dm^3))
What is oncotic pressure?
- Colloid osmotic pressure
- Proportion of total osmotic pressure in plasma exerted by colloids
- Produced from endogenous plasma proteins or synthetic colloids
What are colloids?
Large molecular weight particles present in solution
How do colloids generate pressure?
- do not cross from arterial vessels into interstitial fluids
- Create oncotic pressure
What is tonicity?
- The effective osmolality of a solution/osmotic pressure of a fluid when compared with plasma
- Equal to sum of concentration of solutes which have capacity to exert an osmotic force across the membrane
- State of a solution in respect of osmotic pressure
What is a hypotonic solution?
Surrounding environment has less solutes
What is a hypertonic solution?
Surrounding environment has more solutes
What is an isotonic solution?
Surrounding environment has same concentration of solutes
What is an osmole?
The number of ions or particles into which a solute dissociates in solution
- e.g. 1 mole of NaCl = 2 osmoles
How is osmosis affected by osmolality?
- Osmolality is the number of osmoles of a solute per kg solvent
- Osmosis is dependent on the number of particles
- Osmolarity is the number of osmoles per litre of solution
Define osmolality
The number of osmoles of a solute per kg solvent
Deinfe osmolarity
The number of osmoles per litre of solution
Define molarity
The number of moles per litre (M)
- 5M solution = 5 moles per lite
Define molality
the number of moles per kg of solvent (m)
- 5m solution - concentration of 5 moles/kg
- Is always constant
What is meant by “equivalents”?
- The mount of material that will combine with 1 mole of OH-, H+ or electrons
- E.g. in HCL, 1 mol hydrogen combines with 1 mol chlorine, so amount of chlorine needed is 1 equivalent
- Can be given as mEq/L
How can equivalents be determined?
- By their mass
- mass of one equivalent can be found by dividing atomic mass by its valence
- .e.g calcium: 50/2 = 20g/Eq
Give the mmols for 1 equivalent of monovalent, divalent and trivalent ions
- Mono: 1mmol
- Di: 0.5mmol
- Tri: 0.333mmol
Define osmosis
- The process by which molecules of a solvent tend to pass through a semipermeable membrane from a more to a more concentrated to a less concentrated one
- In order to balance energy levels
Explain the effects of adding a solute on osmosis
- Water moves to balance energy levels
- Solutes decreased entropy (water molecules organise around them)
- Side with greater entropy (thus more energy) will lose water molecules to side with lower energy
What is water potential
- The tendency of water molecules to move out a solution
- Always from high to low
- Pure water, potential = 0
- Is equal to osmotic potential plus any additional pressure on the system
What is osmotic pressure?
The pressure exerted by the oslite particles in the solution which prevents movement of water across a membrane
What are ineffective osmoles?
Ones that do not exert any osmotic pressure e.g. urea
What are effective osmoles?
Ones that are able to dictate the direction and extent of diffusion e.g. Na+ or glucose
- Tonicity is a measure of only effective osmoles
Describe the process of exchange of water between the plasma and interstitial spaces
- Formation of ISF from plasma
- Water taken on by animal
- Enters circulatory system
- When enters arterial region, pressure and pores allow filtration of fluids and salts into interstitial fluid
- Excess dealt with lymphatics system
- Some absorbed by venous portion of system driven by osmosis
- Net filtration is sum of these processes
- Large particles cannot move from plasma to ISF
What is hypotonic fluid loss?
Loss of water but no loss of salts e.g. water deprivation
What is the effect of hypotonic fluid loss on ECF tonicity and ECF volume
- Hypertonic ECF (water out of cells)
- Increases ECF volume to preserve circulating fluid volume
What is isotonic fluid loss?
Loss of fuids and salts e.g. trauma leading to blood loss
What are the effects of isotonic fluid loss on ECF tonicity and ECF volume?
No effect on tonicity, loss of ECF volume
What is hypertonic fluid loss?
Loss of salt more than water, worst kind of fluid loss. E.g. salt depletion
What are the effects of hypertonic fluid loss on ECF tonicity and ECF volume?
- Hypotonic ECF (water moving into cells)
- ECF volume decreases, compounding fluid loss
What is the effect of isotonic crystalline fluids (IV) on plasma volume, ISF and ICV?
- PV: expanded proprtionally to its volume of ECF
- ISF: expanded
- ICV: unchanged
What is the effect of hypertonic crystalline fluid on plasma volume, ISF and ICV?
- Transient expansion in relation to ISF, draws water out from ISF initially as moves around to arterial system, water and salts pushed and filtered into ISF
- ISF expanded
- ICV decreased (pulling water out of cells)
What is the effect of colloid fluid on plasma volume, ISF and ICV
- PV: sustained expansion (water from ISF to plasma volume as colloids cannot move into cells)
- ISF: unchanged in healthy tissue
- ICV: unchanged
What is the effect of rapid vs fast changes in ECF tonicity?
- Rapid alter cell volume (may cause neurological complication)
- Slow (and moderate) have no effect on ICF volume
What is the effect of extracellular hypertonicity in gene expression?
- Increases expression of genes encoding proteins that increases intracellular osmoles
- Membrane transporters
- Enzymes that synthesise solute
