Endocrine impacts on renal function

What are the functional units of the kidney?

• nephrons

What is the principle role of the kidney?

• filter out and excrete water-soluble waste metabolites whilst preventing loss of ALL other water-soluble important metabolites.

what are the three components of kidney function?

1. filtration

2. selective resorption

3. secretion

what does kidney function fundamentally depend on

• number of available nephrons

Where does ultrafiltration occur?

• between capillaries of glomerularis and Bowman’s capsule

What causes the filtration?

• Pressure

• caused by having narrower efferent arterioles

What does filtration depend on?

• molecule size and charge

  • only molecules small enough will get through → consider this clinically in terms of renal failure and what we may detect if the kidneys aren’t functioning properly.

What does GFR stand for, what does it mean and what does it depend on?

1. glomerular filtration rate

2. how much plasma gets filtered

3. renal blood flow/pressure and no. available nephrons

Where does most reabsorption occur in the nephron?

• proximal convoluted tubule: PCT

What adaptations does the PCT have to assist with reabsorption?

• microvilli at the luminal surface

• folds at capillary surface

• many mitochondria

What are 5 example metabolites that the body preserves in the PCT (aka reabsorbs)

• water

• electrolytes

• glucose

• amino acids

• urea (partially)

What are 4 examples of metabolites the body removes via ultrafiltration?

Nitrogenous waste:

1. urea (partially)

2. creatinine

Also:

1. phosphorus

2. potassium

How is water preserved from the filtrate and urine concentrated?

Medullary concentration gradient

• depends on permeability to water OR electrolytes along the nephron

• facilitated by associated vascular network (vasa recta)

• facilitated by urea in the interstitium

• takes place in loop of Henle and collecting ducts

In the loop of Henle

1. what takes place in the ascending limb

2. descending limb

1. active transport of ions, impermeable to water →

2. osmosis and concentrated tubule fluid

What has a large impact on water reabsorption in the collecting ducts?

Hormones:

1. ADH - water channels and urea (for medullary conc gradient)

2. aldosterone (RAAS) - preservees water by absorbing Na+ in exchange for K+ and H+

What results in glucosuria?

• high blood glucose, which exceeds the transport maximum → can’t all be reabsorbed → glucose in urine

What is the normal blood glucose concentration of a dog?

3.5 to 5.5 mmol/L - species and size variation

What does a blood glucose concentration of >14mmol/L usually indicate, but what are two other possible causes

• diabetes mellitus

  • IV glucose fluids or stress

When does glycosuria tend to start occurring?

• approx double normal blood glucose concentration

• 10-12mmol/L

what is the transport maximum (in terms of glucose)

• point at which all glucose transporters in PCT are saturated therefore all remainder glucose stays in tubule/urine

What problems are glycosuria associated with?

• osmotic diuresis → glucose is osmotically active, attracting water, therefore draws water into the tubule → greater urine production

Caused by:

• diabetes mellitus

• fanconi syndrome

• could be due to salts rather than glucose - CKD

• therapeutic osmotic diuresis - (e.g. by a drug called mannitol)

What is azotaemia? Potential causes?

• increased blood levels of urea/creatinine

Causes:

1. pre-renal azotaemia (not enough blood filtered)

2. renal disease (not enough nephrons to do the job)

What is urine specific gravity

• a measure of how many osmotic particles are in urine

• in the range of 1.008-1.012 (species variation)

• dehydration → poor renal flow → high USG

How do the end proximal tubulese and end loop of Henle affect urine concentration?

• they diulte tubular fluid

what effect do the end distal/collecting tubule and ADH have on urine concentration

• help water retention therefore causing concentrated urine formation

what is defective renal function? What will its result in regardless of hydration status?

• inability to concentrate or dilute urine

• isothenuric urine (fixed USG of 1.008-1.012)

• this helps confirm renal disease - due to tubular dysfunction in an animal.

How do we measure USG?

• refractometer

what is ‘adequately concentrated urine’. What is something to bare in mind however?

1. USG >1.030 in dog, >1.040 in cat and >1.025 in large animals indicates kidneys CAN concentrate urine

• renal disease is unlikely, but some animals can have glomerular disease without tubular dysfunction

What is meant by ‘inadequately’ concentrated urine?

• USG is low 1.008-1.012 - in a dehydrated animal suggests kidney can’t concentrate urine

• renal disease is therefore affecting proximal tubules and loop of Henle

What comes first with polydipsia and polyuria?

Polyuria before polydipsia (kidneys first, thirst responds)

what is polyuria?

Excessive urination:

• insufficient nephrons to handle all filtered salts so osmotic diuresis occurs

What will we see with polyuria followed by polydipsia?

• azotaemia with inappropriately dilute USG

what kind of azotaemia is it when we have azotaemia with concentrated urine?

pre-renal

What do these three hormones affect in the kidney:

1. ADH

2. aldosterone

3. parathyroid

1. regulates water resorption, affecting membrane H2O permeability

2. regulates sodium resorption, by affecting sodium pump activity

3. affects calcium/phosphate

How is low serum Ca corrected?

• Low serum Ca → increased PTH → increased Ca uptake from bone → increased renal uptake → 1,25 cholecalciferol.

• This leads to → GI Ca uptake and increased renal Ca uptake

NOTE these hormones are also involved in K regulation.

How does hypoadrenocorticism affect the kidneys?

• lack of aldosterone → Na not resorbed and K not excreted in its place

why is hyperphophataemia?

• too high phosphorous retention

what disease can cause hyperphosphataemia?

• Chronic Kidney Disease → retention of P → parathyroid gland responds → secondary hyperparathyroidism

What can primary hyperparathyroidism lead to?

• excessive PTH production

• renal calcium retention and phosphate loss

what does hyperthyroidism lead to

• increased GFR

What is primary nephrogenic DI?

• inherited resistance to effects of ADH

What are some example conditions that can lead to secondary nephrogenic DI

• hypercalcaemia

• hypercortisolism

• hypoadrenocorticism

• hyperthyroidism

• pyelonephritis

• pyometra

• liver disease

What is osmotic diuresis?

• inability to resorb water despite adequate ADH induced permeability.

How may a condition that causes low blood urea limit an animals ability to concentrate urine and cause polyuria

• little urea → less able to be resorbed into the renal medullary concentration gradient → less ability to concentrate urine + resorb water

How might an animal with dramatic polyuria end up with low blood urea concentration

• High GFR

• less time for urea to be filtered back as it passes through the nephron

What are the 8 endocrine conditions associated with polyuria

1. diabetes insipidus

2. diabetes mellitus

3. hyperadrenocorticism

4. hypercalcaemia

5. hyperthyroidism

6. hypoadrenocorticism

7. hypovolaemia

8. CKD

What are each of the mechanisms of these conditions that cause polyuria?

1. diabetes insipidus

2. diabetes mellitus

3. hyperadrenocorticism

4. hypercalcaemia

5. hyperthyroidism

6. hypoadrenocorticism

7. hypovolaemia

8. CKD

1. ADH production, ADH action, medullary concentration

2. osmotic diuresis

3. ADH block, secondary DI

4. ADH block, secondary DI (often due to hyperparathyroidism)

5. GFR (increased CO)

6. aldosterone not promoting Na and water resorption in response to hypovolaemia

7. GFR and osmotic diuresis

A blood test has been performed in an unwell dog and the creatinine result has come back high. How could you tell if that is because there is insufficient blood supply to the kidneys (hypovolaemia such as dehydration) or if it because the kidneys themselves are damaged? 

• check USG

• dehydration → high USG

• damage → inappropriately dilute USG

• don’t forget DI can also produce very dilute urine, so low USG

How does hypoadrenocorticism result in a dangerously high blood potassium level? 

• aldosterone regulates Na+ resorption and K+ excretion as an exchange.

• no aldosterone → no mechanism for removing excess potassium → dangerously high concentrations.