Structure And Function Of The Kidney Flashcards

1
Q

What is the gross anatomy of the kidney?

A

In the retroperitoneal space
Between 11th thoracic and 3rd lumbar vertebra
Either side of vertebral column
Right situated slightly lower than left - to make room for the liver
~12cm long (x6x4cm)
~150g male, ~135g female

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is the renal blood supply?

A

25% cardiac output - mainly toward the glomerelulus, form a single abdominal aorta and out via the vena cava
90% of which supplies the renal cortex
Required to maintain highly active tubular cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is the microstructure of the kidney?

A

2 main parts, the outer part is the renal cortex and the inner part called the renal medulla.

Medulla is made up of pyramid structures where the functional parts of the kidneys are - the nephrons, they extend down the renal cortex into the medulla and out again.

There are long and short nephrons - same function just different reach into the medulla.

The nephrons feed into the bulb-like glomerulus where the blood is filtered.

The nephron acts to reabsorb anything we need back into the blood and secrete any waste.

Any waste goes into the vena cava that then feeds into the ureta and then the bladder to be excreted through the urethra.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are the features of the urinary tract?

A

Filtered toxins and water leave each kidney through the ureter.
Each ureter drains into the urinary bladder.
Urine is then excreted through the urethra

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are the major functions of the kidney?

A

Maintains water and electrolyte homeostasis:
- Maintenance of extracellular fluid (ECF) volume and composition

Removes water soluble waste products and toxins
- Nitrogenous compounds, eg urea and creatinine
- Maintains acid-base balance - body produces a net of acid, kidney
excretes H ions, to maintain blood ph (approx 7.5)

Produces/Responds to chemical messengers (hormones)
- Role in vitamin D metabolism (1-alpha hydroxylase converts vit D to the
active form which controls calcium absorption)
- Role in haemoglobin synthesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are the features of the nephrons?

A

0.4-1.2 million per kidney

Each nephron consists of five main functional units:

  • Glomerulus
  • Proximal convoluted Tubule
  • Loop of Henle
  • Distal Tubule
  • Collecting Duct

Each are structurally distinct

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is the nature and functions of the glomerulus?

A

Formed from specialised capillary network enclosed within the Bowman’s capsule ( outer bulb like structure)

Function: To form an ‘ultra-filtrate’ of plasma
- Blood is filtered to maintain important constituents like blood
cells in the blood but remove excess fluid, waste products and regulate
H+, Na+, K+ (filtered out across filtration barrier into renal lumen)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is the Glomerular Filtration Barrier?

A

Endothelium (barrier to RBCs and WBCs)

Basement membrane (filters based on size and charge, excluding large molecular weight species (68 KDa, eg albumin), anything positively charged will be more easily filtered out)

Podocytes (also regulate on size)

Waste is glomereluar filtrate that is then passed through the nephron.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is the glomerular filtrate?

A

An ‘ultra-filtrate’ of the blood enters the lumen of the glomerulus.

Composition similar to plasma except blood cells and molecules of protein >50kDa are absent.

Molecules around the size of albumin (68kDa) and larger are prevented from entering the lumen.

Proteins prevented according to charge as well as size (more negatively charged proteins retained in blood).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are the functions of the Proximal Convoluted Tubule?

A

Function: Bulk reabsorption of electrolytes from the glomerular filtrate back into circulation.

  • Active reabsorption:
    • Na+ (~75%) and therefore chloride (through sodium potassium
      ATPase pump)
  • Passive reabsorption:
    • Glucose
    • Amino acids
    • HCO3-
    • K+
    • HPO4
Secretion:
- H+ (from circulation into proximal convoluted tubule, amount depends 
   on the acid-base balance of blood)
- Organic anions
- Organic cations
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is the nature and functions of the Loop Of Henle?

A

Consists of a descending and ascending limb.
Extends from the cortex down into the medulla and back up again.

Function: Responsible for creating a hyperosmolar medulla - necessary for the production of a concentrated urine.
- Counter-current Multiplication System:
- Allows formation of a dilute urine after a H2O load
OR
- Allows formation of a concentrated urine after H2O restriction via the
action of ADH (anti-diuretic hormone) on the collecting duct (final
part of nephron)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is counter-current multiplication?

A
  1. Descending limb is highly permeable to water, so water can easily move out into the medulla. This water is drawn out of the filtrate down a concentration gradient due to the surrounding medulla tissue being hypoosmotic. So as you go down the filtrate becomes more concentrated.
  2. Ascending limb is impermeable to water, but allows the blood supply to reabsorb solutes from the tubular filtrate (~25% of sodium/chloride), by pumping out Na/Cl into the vasa recta. This makes the tubular filtrate more dilate (lower osmolality). The blood supply then carries solutes into the medulla in order to retain the hypoosmolality that causes water to freely move in the descending limb (1).
  3. Owing to NaCl reabsorption by the thick ascending limb, tubular filtrate reaching the collecting duct is hyposmotic
  4. Vasa recta capillary quickly removes water that is reabsorbed into the medulla from the descending limb to maintain a high medullary osmolality. This blood supply runs in the opposite direction to the tubular filtrate. So after reabsorbing solutes from the tubular filtrate in the ascending limb the blood ascends parallel to the descending limb (2), which is water permeable, so water passes into the concentrated ascending vasa recta, reducing the osmotic tension in the blood to normal (1). This interplay between the loop of henle and the vasa recta is the counter current multiplier.
  5. The result of the counter-current multiplier is a hypertonic medullary fluid compared to filtrate going into the distal convoluted tubule.
    - Dilute fluid enters the DCT and CD where water can be reabsorbed by passive diffusion down the concentration by the medullary hyperosmolality that has been created.
    - ADH makes collecting duct permeable to water making the water move into the hyperosmotic medulla where it is drawn up by the vasa recta and returned to the body.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is are the functions of the distal convoluted tubule?

A

Function: To carry out the ‘fine-tuning’ of electrolyte reabsorption or secretion.

Specifically Na+, K+, H+

Amount that occurs depends on concentration of electrolytes in plasma

Under hormonal control (e.g. Aldosterone - acts to increase sodium reabsorotion, in exchange for K and H ions)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is are the functions of the collecting duct?

A

Function: To carry out the reabsorption of water

Naturally impermeable to water

If there is a need to conserve water: ADH is stimulated
- Causes aquaporins ‘water transporters’ to move into the impermeable
membrane to allow water to pass through.
- Movement of water is via passive diffusion - under the control of
osmolar difference between tubular cells and the lumen (created by the
counter-current multiplication system of the Loop of Henle)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What does the kidney need in order to function?

A

The kidney needs….
- Adequate perfusion (rich blood supply)
- Positive partial pressure at the glomerulus (across filtration barrier is
passive dependent on hydrostatic pressure maintained between
glomerulus and lumen)
- Viable, semi-permeable glomular membrane
- Intact functioning tubular endothelium
- Channels, transporter, gradients
- Clear passage for filtrate to travel
- Appropriate hormonal activity/ability to respond

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What would an ideal marker of glomerular filtration be?

A

Endogenously produced

Appears in the plasma at a constant rate

Freely filtered at the glomerulus

Not reabsorbed or secreted by the renal tubules

Not eliminated extra-renally (i.e. Through the skin)

17
Q

How is urea a marker of glomerular filtration?

A

Urea is derived in the liver from amino acids and therefore protein (diet or tissues)

It is removed by kidneys

However, if rate of production exceeds the rate of clearance plasma concentrations can rise.

Rate of production increased:

  • High protein diet
  • GI bleeds

Increased catabolism due to:

  • starvation
  • sepsis
  • tissue damage

Conversely, plasma urea concentration can be low:

  • Low protein diet
  • Pregnancy (dilutions effect may makes kidney failure)

Therefore this is not a very good marker

18
Q

How is creatinine a marker of glomerular filtration?

A

Creatinine is a more accurate than urea

Produced at a constant rate from muscle creatine breakdown.

Not metabolised or excreted from the body other than by the kidney.

Very small amount secreted by renal tubules (doesn’t affect overall interpretation)

Can measure its clearance from plasma or excretion in urine.

Some methods are affected by:
Analytical interference: bilirubin - high gives falsely low creatinine, ketones and drugs cause falsely higher

However, the disadvantages of serum/blood creatinine measurements are:

  • Not sensitive
    Serum creatinine only starts to increase above normal when kidney function drops by half.
-Affected by:
Muscle mass
Diet
Age
Sex
So compare against a persons base line, not the reference range
19
Q

How is GFR a marker of glomerular filtration?

A

GFR is an an expression of the quantity of glomerular filtrate formed each minute in all the nephrons of both kidneys, calculated by measuring the clearance of specific substances.

3 ways to calculate, all of which are more sensitive than plasma creatinine:

  1. Creatinine clearance - plasma sample and 24 hour urine sample, remove effects of diet and muscle mass, but more room for error due to calculations and not convenient for patients.
    Creat clearance (ml/min) = ur creat (mmol/l) x ur volume (ml)
    ———————————————
    serum creat (mmol/l) x time (min)
  2. Estimated GFR (eGFR) - most commonly used. More convenient for patient - just blood sample, where calculation is made using plasma creatinine conc. certain calcs aren’t valid in certain populations.
    Formulas:
    - Cockcroft Gault
    - MDRD (Modification of Diet in Renal Disease)
    - CKD-EPI
    - Schwartz (Paediatric equation)
  3. Exogenous markers:
    - Inulin clearance (gold standard) - infusion of inulin then measure
    excretion in urine to measure clearance
    - 51Cr-EDTA (standard clinical measure of GFR) - measure clearance in
    plasma by repeated blood tests
20
Q

What are the advantages and disadvantages of using creatinine clearance as a measure of glomerular filtration?

A

Advantages:
- More sensitive than plasma creatinine at picking up small
changes in renal function.
- Removes effect of diet and muscle mass

Disadvantages:

  • Inconvenient
  • 24hr urine collection plus serum required.
  • Lots of measurements and calculation – lots of room for error!!!
21
Q

What are the advantages and disadvantages of using eGFR as a measure of glomerular filtration?

A

Advantages:

  • More sensitive than plasma creatinine
  • Uses only one serum sample and a calculation – more convenient
  • can assess AKI AND CKD

Disadvantages:
- Not to be used in certain situations such as in the acutely ill, patients
with limb amputations, pregnant woman, the very elderly, the obese and
malnourished.
- Uses serum creatinine in formula and is therefore still affected by
variations in muscle mass despite correcting for certain variables.

22
Q

When are exogenous markers most useful for measuring glomerular filtration?

A

In some situations, a very accurate GFR may be needed e.g. live kidney donors, or in pharmacy for accurate blood dosing
GFR is measured by measuring the disappearance from the blood of a test substance that is completely filtered by the glomeruli and neither secreted nor absorbed by the tubules following a single injection

23
Q

What is proteinuria?

A

The presence of abnormal quantities of protein in the urine which may indicate damage to the kidneys.

Normal urinary protein excretion is ~150mg/24hr with the majority consisting of secreted proteins such as Tamm-Horsfall protein.

Proteinuria defined as urine protein excretion >300mg/24hr

Generally pathological, however can occur due to fever, exercise, posture (upright - gives higher than lying down)

Rarely exceeds >1000mg/24hr if benign.

Pattern of urinary protein excretion is used to identify cause and to classify proteinuria as glomerular, tubular or overflow

24
Q

What does glomerular proteinuria signify?

A

Damage to glomerular integrity (increase in glomerular permeability or increased vascular permeability).

Most common and serious type of proteinuria.

Albumin predominant - only just excludes albumin usually, so damage leads to albumin in urine.

25
Q

What does Tubular proteinuria signify?

A

Characterised by the appearance of low molecular weight proteins (e.g. retinol binding protein, alpha-1-microglobulin, beta-2-microglobulin) normally filtered out in glomerulus but seen here in the urine as a result of decreased reabsorption by the (proximal) tubule.

Tubular proteinuria often exists with glomerular proteinuria

26
Q

What does Overflow proteinuria signify?

A

Not really a marker of kidney function

Occurs when proteins of low molecular weight are filtered normally by the glomerulus and reabsorbed at the proximal tubule, but produced in greater amounts so reabsorptive capacity of the kidney is exceeded (becomes saturated).

Eg glucose, high plasma level, will be excreted as normal, but reabsorption protein shakes are saturdated so you find glucose in urine

27
Q

How can proteinuria be measured and diagnosed?

A

Urine Dipsticks
- Blood – haematuria, Protein – Proteinuria

Protein:creatinine ratio (PCR)

Albumin:creatinine ratio (ACR) (more sensitive)
- Normalised to albumin
- Albumin is the predominant plasma protein responsible for many
physiological functions
- Normally NOT filtered by the glomerulus due to:
- Size (~66kDa)
- Charge (net negative charge)
- More sensitive than PCR (just excluded by glomerulus)
- Now part of CKD staging (NICE 2014)

24hr urine total protein

Low MW urine proteins - query tubular damage