Tag (The renal system)

Question 1

Kidneys

Answer 1

Main part of the renal system.
Bean shaped organs.
Lie at the back of the abdominal wall (behind the peritoneum).
Filter blood and remove waste.
Blood enters kidneys via renal art and leaves via the renal vein.

Question 2

Functions of the kidneys

Answer 2

• Fluid and ion (electrolyte) levels balance in plasma
• Removal of waste products (drugs, toxic substances)
• Regulates blood pH by regulating loss of H+ and CO3 (bicarbonate)
• Endocrine function- releases hormones (erythropoietin, renin)
• Control blood pressure and retain valuable compounds such as glucose, amino acids
• Gluconeogenesis (glucose generation pathway)
• Regulates blood volume- gets rid of excess water to keep blood volume constant, renin restricts water volume in urine
• Regulates RBC production when blood O2 is low by releasing erythropoietin that stimulates the hemocytoblasts reproduction

Question 3

Structure of the kidney

Answer 3

Renal artery- brings blood to the kidney
Renal vein- takes blood away from kidney
Medulla- innermost part of kidney, split into renal pyramids
Ureter- connects kidneys to bladder to transport urine
Capsule- thin membranous sheath that covers the outer surface the kidney
Cortex- outside layer of the kidney, surrounds the inside of the organ
Renal pelvis- funnels urine to the ureter
Papillae- areas where the openings go the collecting ducts enter the kidney
Pyramids- tissues shaped like cones, make up the medulla

Question 4

The nephron

Answer 4

Functional unit of the kidney.
About 1 million in total.
2 types
- Juxtamedullary nephrons
- Corticol nephrons (shorter loop of Henle, lack the vasa recta)
No regeneration.

Question 5

Nephron structure

Answer 5

• Renal corpuscle (filter)
  
  • Bowman’s capsule
  • Glomerulus
• Loop of Henle
• Vasa recta (blood vessels that run parallel to Loop of Henle)
• Proximal Convoluted Tubule (PCT)
• Distal Convoluted Tubule (DCT)
• Collecting duct
• Afferent arteriole (takes blood into glomerulus)
• Efferent arteriole (takes blood away to capillaries)

Question 6

The renal corpuscle

Answer 6

Bowman’s capsule
Afferent arteriole
Efferent arteriole
Glomerulus
Glomerular filtration barrier
Capillary endothelial cells
Basement membranes
Podocytes

Question 7

The tubules

Answer 7

Narrow, single celled layer
8 segments
- Proximal convoluted
- Proximal straight
- Descending Loop of Henle (thin)
- Ascending L of H (thin)
- Ascending L of H (thick)
- Distal convoluted
- Corticol collecting duct
- Medullary collecting duct

Question 8

Renal formation of urine

Answer 8

Three processes account for renal excretion
1. Glomerular FILTRATION- movement of fluid and solutes from the Glomerular capillaries into Bowman’s space
2. Passive tubular REABSORPTION from tubule- movement of materials from the filtrate in the tubules into the peri-tubular capillaries
3. Active tubular SECRETION- secretion of solutes from the peri-tubular capillaries into the tubules

Question 9

Glomerular filtration

Answer 9

Produced filtrate is similar to plasma in salts concentration and content of organic molecules but it is protein free.
The filtrate passes through
- Pores between endothelial cells of the glomerular capillary
- Basement membrane
- Podocytes
Glomerular filtration of a molecule depends on its size and charge

Neutral solutes
- Solutes smaller than 180nm in radius are freely filtered
- Solutes between 180 and 360nm are filtered to various degrees
- Solutes greater than 360nm are not freely filtered
- About 10-20% of the blood which enters the glomerular is filtered
Blood cells cannot pass so if blood or protein is detected in urine it indicates kidney damage

Question 10

Glomerular filtration rate

Answer 10

Net Filtration Pressure (NFP) start = 16mmHg
Total surface area available for filtration and membrane permeability (filtration coefficient = Kf)
Glomerular filtration rate (GFR) = Kf * NFP

GFR is directly proportional to the NFP. Changes in GFR result from changes in glomerular capillary blood pressure.

Question 11

Glomerular filtration: pressures

Answer 11

The pressures involved in glomerular filtration are plotted against position in the glomerular capillary.
Types of pressure
- The glomerular capillary hydrostatic pressure (Pgc)
- The back pressure built up in the Bowman’s capsule (Pbc)
- The colloid osmotic pressure of the glomerular capillary plasma (πgc)

Net filtration pressure is greatest at the start of the glomerular capillary.

Question 12

Auto-regulation of GFR

Answer 12

Auto-regulation- the effects of changing arterial blood pressure on total renal blood flow and glomerular filtration rate in the absence of any extrinsic influences on the kidney.
Tubule-glomerular feedback mechanism consists of:
- a flow rate sensing mechanism of increased NaCL, GFR and RBF
- which triggers the release of vasoactive signals
- which constricts afferent arteriole
- leading to a decreased GFR and RBF

Question 13

Extrinsic regulation of GFR

Answer 13

When the sympathetic nervous system is at rest the renal blood vessels are dilated.
Under stress:
- the sympathetic nervous system releases noradrenaline
- the adrenal medulla releases adrenaline leading to constriction of afferent arteriole and inhibition of glomerular filtration

Question 14

Tubular secretion

Answer 14

Substances are secreted from tubule cells into filtrate via diffusion, osmosis, active and facilitated transport.
Substances move from tubule cell into filtrate to
- dispose waste, excess potassium
- eliminate certain compounds in the filtrate such as urea and uric acid
- control blood pH
80% of renal blood passes to capillaries in proximal tubules
Only 10-20% renal blood is filtered
The PCT reabsorbed 60-70% of the filtrate produced.
(Creatine is used as a major kidney function test because 100% should be excreted)

Question 15

Reabsorption any the PCT and DCT

Answer 15

The PCT reabsorbs:
- 60-70% of the filtrate produces
- Sodium, all nutrients, cations, anions, and water
- Urea and lipid soluble solutes
- Small proteins

The DCT reabsorbs:
- Na+ and Cl-
- Water (regulated by ADH)
- Na+, K+ regulated by aldosterone

Question 16

Reabsorption and mediated transport

Answer 16

Need to cross 2 membranes
- Diffusion
- Facilitated transport
- Active transport

Co-transported with sodium
- Glucose
- Inorganic ions
- Amino acids

Some substances are not reabsorbed if
- They lack carriers
- They are not lipid soluble
- They are too large to pass through membrane pores

Urea and uric acid are the most important examples of non-reabsorbed substances. Creatinine is the only one that is completely not reabsorbed.

Question 17

Renal clearance

Answer 17

Renal clearance is the volume of plasma that is cleared of a specific substance in a time unit. The test is used to:
- Detect glomerular damage
- Follow the progress of diagnosed renal disease
- Determine the GFR (GFR = conc in urine * volume of urine per time *plasma conc)

RC = CU*V/CP
where
RC. = renal clearance rate
CU = concentration of the substance in urine
V = flow rate of urine formation
CP = concentration of the same substance in plasma

Insulin is used in methods that involve constant infusions to maintain a steady state in the blood.

Question 18

Creatinine clearance

Answer 18

A test used to assess the excretory function of the kidneys. It is important for
- grading of chronic renal insufficiency
- to estimate the kidney function for drug dosing and determination of the dosage of drugs excreted in urine

Glomerular filtration rate can be calculated by measuring any chemical that has a steady level in the blood, and is filtered (but not absorbed).
The amount of creatinine in urine divided by the concentration in blood plasma over time gives the creatinine clearance..

Question 19

Regulation of urine

Answer 19

Body fluids are measured in miliosmoles (mosm).
Kidneys keep the solute concentration of body fluids constant at about 300 mosm through the counter current mechanism.
Urine volume and osmotic concentration are regulated by controlling water reabsorption.
Micturition (urination)- urine flows from the kidneys down the ureters to the bladder derived by contraction of smooth muscles. Contraction of the bladders smooth muscles empties it during micturition.
Bladder can hold 250-400ml
Spinal reflex leads to:
- parasympathetic stimulation (bladder contraction)
- internal sphincter to open
- external sphincter to relax due to inhibition

Question 20

Mechanisms of solute movement across plasma membranes

Answer 20

Primary active transport- uses energy (ATP-ADP) to transport molecules across a membrane against a concentration gradient.
Secondary active transport- transport of molecules without using ATP-ADP energy but other forms of energy that results from electrochemical gradients created by pumping ions out of the cell membrane.

Question 21

Sodium and water reabsorption

Answer 21

1. Sodium and potassium are reabsorbed by active transport
2. Negatively charged ions are attracted to positively charged ions
3. As the concentration of ions increases in plasma, osmotic pressure increases
4. Water moved from renal tubule to capillary by osmosis

Question 22

Countercurrent multiplier system

Answer 22

A mechanism that consumes energy to create a concentration gradient.
Happens in the Loop of Henle.
The Loop of Henle is responsible for the recovery of water and sodium chloride from the urine.
- Filtrate (from the collecting duct) enters the medullary interstitial fluid and diffuses into the Loop of Henle. As it passes up the ascending limp the filtrate will be more concentrated due to reabsorption of other ions occurring.
- Water leaves the tubule via osmosis
- Towards the thin ascending limb, salt enters the tubule passively due to the hypertonicity of the medulla and a gradient is created.
This causes:
- Na+ concentration gradient via active transport in ascending limb of the Loop of Henle
- Na+ concentration gradient against tendency to diffuse to recover water

Question 23

Reabsorption of salt and water

Answer 23

About 65% of salt and water is reabsorbed in the PCT.
Sodium is actively transported and chloride passively follows the sodium by electrical attraction without hormonal regulation.
Water follows the salt out of the PCT by osmosis.
Most of the remaining water is reabsorbed as a result of the countercurrent multiplier system.
As the ascending limb is water-impermeable, the remaining filtrate becomes hypotonic and through the tissue fluid of the medulla becomes hypertonic (positive feedback mechanism)

Question 24

Alteration in extracellular fluid (ECF) osmolarity

Answer 24

Osmolarity = osmolar concentration of plasma.
Cell membranes are permeable to water. This makes the osmolarity of the ECF almost equal to the intracellular fluid (ICF) osmolarity.
Increasing plasma osmolarity stimulates the secretion of ADH (antidiuretic hormone) which causes water reabsorption. Results in more concentrated urine, less concentrated plasma.
Low plasma osmolarity will suppress the release of ADH, resulting in decreased water reabsorption (more concentrated plasma, less concentrated urine).

Question 25

Mechanisms of detecting alterations in ECF osmolarity

Answer 25

No sodium sensing receptor.
Alteration in total body sodium appear as changes in ECF osmolarity and volume (BP).
Osmoreceptors sense 1% change in osmotic pressure.
Volume receptors sense 5-15% change in osmotic pressure (very sensitive).
When blood osmolarity changes, water diffusion into and out of the osmoreceptor cells change, This causes a neural signal to be sent to the hypothalamus, which increases or decreases ADH secretion from the posterior pituitary to return blood osmolarity to normal.

Excess H2O ingested –> decrease in body-fluid osmolarity (increase in H2O conc) –> decrease in firing by hypothalamic osmoreceptors –> posterior pituitary decreases vasopressin (ADH) secretion –> decrease in plasma vasopressin –> decrease in tubular permeability to H2O in collecting ducts –> less H2O reabsorption –> increase in H2O excretion.

Question 26

Renin angiotensin system

Answer 26

When blood volume or sodium levels in the body are low the juxtaglomerular cells in the kidney will be stimulated via b1-adrenergic receptor which triggers the release of the enzyme renin from the kidney.
Renin acts on angiotensin to release angiotensin I which is converted to angiotensin II. Angiotensin II stimulates adrenal cortex to release aldosterone which stimulates Na+ and H2O reabsorption. This leads to an increase in both systematic and glomerular hydrostatic pressure.

Question 27

Potassium reabsorption

Answer 27

% reabsorbed in :
- Proximal tubule = 67%
- Loop of Henle = 20%
- Distal tubule = 3%
- Collecting duct = 9%
- Excreted = 1%

Question 28

Potassium regulation

Answer 28

Increased potassium intake –> increase in plasma potassium –> increase in secretion of aldosterone from adrenal cortex –> increase in plasma aldosterone –> increase in potassium secretion in collecting duct –> increase in potassium excretion

Question 29

Potassium depletion- hypokalaemia

Answer 29

When potassium loss is greater than intake.
Signs- constipation, heart palpitations, fatigue, muscle weakness, numbness and tingling, high blood pressure and polyuria (increased urination frequency).
Causes- diuretics, diarrhoea, laxatives, vomiting.
Treatment- daily potassium supplements, diet rich in fruit and vegetables

Question 30

Acid-base balance - hydrogen ion regulation

Answer 30

Metabolic reactions are sensitive to H+ ion concentration.
pH = -log[H+]
- Acidosis = low pH
- Alkalosis = high pH
Increase in H+ concentration
- generation of CO2 from oxidative phosphorylation
- metabolism

Major intracellular buffers are proteins/phosphates.
Major extracellular buffer is CO2/HCO3.

Question 31

Acid base dysfunction

Answer 31

Four categories
- Respiratory acidosis
- Respiratory alkalosis
- Metabolic acidosis
- Metabolic alkalosis

Blood gas analysis of pH, pO2, pCO2, and HCO3 to detect the problem and the compensation

Question 32

Altitude sickness

Answer 32

High altitude means low levels of pO2.
Low pO2 levels induce hyperventilation.
Hyperventilation decreases pCO2, decreases respiratory drive (negative feedback loop).
Over period of days increased Na and HCO3 secretion which restored plasma pH allowing respiratory rate to increase, thus increasing oxygenation.
Other mechanisms:
- increase Hb concentration
- left shift of pCO2 ventilatory response

Question 33

Diuretic therapy

Answer 33

Main use of diuretics is treatment of
- Oedema (secondary to cardiac failure)
- Hypertension
- Renal failure

Groups of therapies
- Loop diuretics
- Thiazide
- Potassium sparing
- Osmotic diuretics

Question 34

Loop diuretics

Answer 34

Act at the ascending loop of Henle.
Treat hypertension and oedema.
Effective in impaired kidney function patients.
Act on the Na+, K+, Cl- symporter in the thick ascending limb.
Inhibit sodium, chloride and potassium reabsorption by competing for the Cl- binding site.
Decrease renal blood flow.
Cause less water to be reabsorbed into the blood (decrease blood volume).

Question 35

Thiazide diuretics

Answer 35

Used to treat hypertension.
Reduce the risk of stroke, heart attack, due to hypertension.
The first approved drug of this class is chlorothiazide.
Thiazides are the cheapest antihypertensive drugs.
Inhibit reabsorption of Na+ and Cl- from the DCT by blocking the thiazide sensitive Na+/Cl- symporter.

Question 36

Potassium sparing diuretics

Answer 36

Prevent the secretion of potassium into the urine.
Treatment of hypertension and congestive heart failure.
Competitive antagonists; compete with aldosterone for intracellular cytoplasmic receptor sites or directly block epithelial sodium channels by amiloride.
Prevent the production of mediator proteins that are synthesised in reaction to aldosterone.
Prevent sodium reabsorption.
Prevent potassium and hydrogen ion secretion.

Question 37

Osmotic diuretics

Answer 37

Also called Mannitol diuretic.
Inhibit reabsorption of water and Na.
Increases the blood osmolarity and renal filtrate.
Act at the water permeable portions of the nephron.
Increase the blood flow to the kidney and ECF while reduces ICF but increases plasma volume
Mainly acts on the Loop of Henle.
Holds in water molecules in the tubule, leading to a back leak of Na+ into the tubule and K+ and Cl- to be excreted through urine.