Raymond (Physiology and pathology of the kidney)

Question 1

What are the kidneys?

Answer 1

Located in the abdomen. One on either side of the spine. Sit below the liver and behind the stomach.
Look like kidney beans.

Question 2

Role of the kidney

Answer 2

Act as the filtration system of the human body.
Remove toxins and excess fluid from the body and is responsible for urine production.
Regulates the electrolytes in the body.
Regulates the blood pressure in the body.
Releases some important hormones such as erythropoietin and renin.
Maintains homeostasis: pH, BP, osmolarity

Question 3

Clinical importance

Answer 3

If they kidneys don’t work as they should:
- Leads to a build up of toxins and harmful substances
- Swelling
- High blood pressure
-CKD can progress to end stage and become terminal
- Everyday over 20 people develop kidney failure

Question 4

Physiology of the kidney

Answer 4

Cortex
Medulla
Renal vein
Renal artery
Renal pelvis
Ureter

Question 5

Nephron

Answer 5

Functional unit of the kidney and is the target for some commonly used drugs in pharmacy.
Each kidney contains around 1 million nephrons.

Question 6

How do the kidneys process fluid?

Answer 6

4 main processes:
- Filtration
- Reabsorption
- Secretion
- Excretion

Question 7

Filtration

Answer 7

Happens in the Bowman’s Capsule.
The Bowman’s Capsule contains the glomerulus, a bundle of blood vessels.
The afferent arteriole brings blood in. It is thicker and wider than the efferent to maintain pressure.
The efferent arteriole is thinner and takes blood away.
The glomerulus and afferent and efferent arterioles make up the renal corpuscle.

The glomerulus contains podocytes. These contain filtration slits and act as filter paper. Larger molecules like RBCs and proteins cannot pass through this membrane.
Filtrate contains amino acids, glucose, NaCl and H2O.
This process is driven by pressure.

Question 8

Reabsorption

Answer 8

Mainly takes place in the PCT and LoH.

PCT:
- Where about 80% of H2O, glucose, amino acids, and NaCl is reabsorbed into the. mood by protein channels.
- The stage at which urea and creatinine enters the filtrate from the blood.

LoH:
- Separated into 2 limbs: ascending and descending
- In the ascending limb about 25% of Na, Ca, K, and Mg is reabsorbed into the blood by ion channels
- In the descending limb there are aquaporins and this is the part where water is reabsorbed into the capillaries.

Question 9

Secretion

Answer 9

Happens in the DCT.
A small amount of NaCl, Ca and Na is reabsorbed here via co-transporters.
Ions such as H+, K+, NH3+ and HCO3- are actively removed from the capillaries into the filtrate.

Question 10

Excretion

Answer 10

Process of eliminating the fluid from the body. the fluid goes from the collecting duct to the ureters into the bladder.

Question 11

Pathology of the kidney

Answer 11

CKD is very prevalent- about 7.2 million people have it the disease.
The kidney are responsible for the filtration and elimination of toxins.
If a patient has impaired kidney function this could lead to a build up of toxins from medication, and result in increased blood concentration of medicines potentially causing toxicity.
We have to consider dose reductions in those patients.

Question 12

Pharmacists role

Answer 12

We might need to calculate dose changes based on a patients kidney function.
Might spot a patient with impaired kidney function is on too high a dose of medication.
Need to understand how the medicine works (diuretics).
Need to understand and interpret a patients kidney function measurements (GFR and CrCL).

Question 13

Diseases

Answer 13

Some diseases either affect the kidney directly or indirectly but ultimately lead to reduces kidney function.
- AKI
- CKD
- End stage renal disease
- Diabetes
- Hypertension

Question 14

AKI

Answer 14

Acute kidney injury.
Defined as a sudden loss of kidney function. Happens over a course of hours or days.
Can lead to fluid and electrolyte balance.
Can lead to retention of metabolic waste such as urea and creatinine.
Can be separated into 3 stages: pre-renal, renal, and post-renal.

Question 15

Pre-renal AKI

Answer 15

When the problem has occurred in the parts of the kidney leading upon to the kidneys i.e. renal vein, renal artery.
Common causes include: hypovolaemia, haemorrhage, heart failure. These result in lower blood input into the kidneys.
This results in a lower GFR resulting is lower creatinine clearance and therefor creatinine levels increase.
If the GFR is lowered this also results in activation of the RAAS.
(RAAS- renin angiotensin aldosterone system)

Question 16

Renal AKI

Answer 16

Happens within the kidney- can affect the tubules or glomerulus.
Tubules- acute tubular necrosis or acute interstitial nephritis.
Glomerulus- acute glomerularnephritis.
Can be caused by inflammation (which is caused by toxins such as tobacco or drugs such as NSAIDs).
Can be direct damage.
Can be caused by debris obstructing tubules.

Question 17

Post-renal AKI

Answer 17

Happens in the collection part of the kidney.,
Caused by obstructions to urine flow- kidney stones, BPH, congenital abnormalities.

Question 18

CKD

Answer 18

Defined as GFR <90ml/min/1.73m^2 over the course of 3 months.
Long term kidney damage.
The end result of diabetes and hypertension.

As GFR decreases we get an increase in urea levels in the blood. This leads to azotemia.
Azotemia is the build up of urea and other metabolic and endocrine products leading to nausea and loss of appetite.
Build up of urea can cause encephalopathy which can cause asterixis (hand tremor), lead to Oma and death, can cause pericarditis and excess bleeding as presence of urea causes platelets to be less likely to stick.

Hyperkalaemia- build up of potassium in the body.
Can lead to cardiac arrhythmia and potentially cardiac arrest.
not enough K+ being filtered into urine.

Calcium and real osteodystrophy.
- The kidneys activate vitamin D which is responsible for calcium absorption in the diet. With lowered amount of vitamin D, the body takes calcium from the bones leading to hypocalcaemia.
- When hypocalcaemia occurs, the parathyroid hormone is activated, which takes Ca2+ from the bones leading to renal osteodystrophy.

Question 19

Hypertension

Answer 19

High blood pressure causes thickening of blood vessels resulting in less O2 and blood going into the kidneys. This can lead to ischaemic injury.
Immune cells in glomerulus then release macrophages which secretes growth factors causing the mesangial cells to release and extracellular matriculates. this leads to scarring and a lower GFR.
High blood pressure also activates the RAAS leading to higher blood pressure.
(RAAS- renin angiotensin aldosterone system).

Question 20

Diabetes

Answer 20

The extra glucose in a patients blood sticks to proteins in the efferent arteriole, causing obstructions and making the arteriole stiff and narrow.
This then increases the pressure of the glomerulus, leadings to glomerulosclerosis (scarring)

Question 21

Diuretics

Answer 21

Used to increase fluid loss from the body.
4 classes:
- Carbonic anhydrase inhibitors
- Loop
- Potassium sparing
- Thiazides

Question 22

Carbonic anhydrase inhibitors

Answer 22

Act on the PCT- stops the formation of HCO3- from H2O and CO2. Leads to more H2O being excreted and NaHCO3.
Only mils diuresis.
Examples
- Acetazolamide
- Dorzolamaide
- Brinzolamaide

Question 23

Loop diuretics

Answer 23

Work in the ascending limb of the LoH.
Inhibit the NaK2Cl co-transporter which transport ions into the blood.
Examples
- Furosemide
- Bumetanide
Side effects- hypokalaemia, acute hypovolaemia, ototoxicity.

Question 24

Thiazide diuretics

Answer 24

Act on the DCT and act within 1-2 hours. The duration of action is 12-24 hours.
Inhibit the NaCl co-transporter, leading to more H2O loss. Can cause vasodilation.
Example
- Indapamide

Question 25

Potassium sparing diuretics

Answer 25

Act on the collecting ducts.
Act on collecting tubule by inhibiting the sodium channel, which then leads to fewer K+ leaving due to the loss difference in ions.
Can lead to hyperkalaemia.
Also acts on aldosterone receptor- aldosterone increases reabsorption of Na+ and increases loss of K+. These inhibit the aldosterone receptor.
Examples
- Spironolactone
- Eplerenone