147 - Pathophysiology of Acute & Chronic Renal Failure

Question 1

Definition of acute renal failure

Answer 1

Urine flow less than 500 ml/day

Question 2

Common time-course for chronic renal failure to develop

Answer 2

6 months or more

Question 3

Normal GFR

Answer 3

125mL/min, 180L/day

Question 4

GFR of significant chronic renal failure

Answer 4

Under 50mL/minute, under 72L/day

Question 5

Reversibility of acute and chronic renal failure

Answer 5

Acute is often reversible.

Chronic is irreversible

Question 6

Hallmark of chronic renal failure

Answer 6

Creatinine excretion and a decrease in CFR from a loss of functional nephrons

Question 7

Broad types of nephron pathology

Answer 7

Glomerular and tubular. Often a mixed pathology.

Question 8

Examples of renal endocrine impairment
1
2
3

Answer 8

1) Ras (renin-angiotensin system) (excessive activation)
2) Vitamin D activation
3) Epo

Question 9

Ras endocrine pathologies

Answer 9

Excessive activation (but rarely): vasoconstriction can impair RBF; possibility of “malignant hypertension”

Question 10

Most important endocrine dysfunction in CRF

Answer 10

Vitamin D activation.

Leads to a unique pattern of bone disease.

Question 11

Effects of vitamin D activation in CRF

Answer 11

Osteo-dystrophy, renal rickets; exacerbated by hypocalcaemia

Question 12

Effects of epo dysregulation with CRF

Answer 12

CRF seems to be invariably associated with anaemia

Question 13

Effectiveness of urea in assessing GFR

Answer 13

Poor

Question 14

Proportion of urea that is reabsorbed

Answer 14

~50%

Question 15

What can alter urea in urine without affecting kidneys

Answer 15

Diet. Urea is produced from protein

Question 16

States where urea can be elevated

Answer 16

CRF, catabolic states, steroid use, cachexia in cancer

Question 17

What suppresses urea excretion?

Answer 17

Malnutrition, liver disease

Question 18

Features of creatinine in GFR assessment 
1
2
3
4
5

Answer 18

1 Creatinine production is constant
2 Filtered, but 15% bound to plasma proteins (underestimates GFR)
3 Not reabsorbed
4 Small amount of secretion (overestimates GFR)
5 (2) and (4) tend to cancel out

Question 19

Normal serum creatinine level

Answer 19

50-120 μM/L

Question 20

What is daily production of creatinine proportional to?

Answer 20

Muscle mass

Question 21

What is equal to creatinine filtration?

Answer 21

Creatinine excretion

Question 22

What is equal to creatinine clearance?

Answer 22

GFR

Question 23

Aspects of creatinine that can skew calculation of GFR from creatinine excretion
1
2

Answer 23

15% of creatinine is bound to plasma proteins.
Therefore can underestimate GFR>

Some secretion of creatinine occurs. This can overestimate GFR.

These two roughly cancel out.

Question 24

Equation for creatinine clearance

Answer 24

UV/P

U = urinary concentration of creatinine 
V = Urine volume/day
P = Plasma concentration of creatinine 

Because UV is often constant, can say that creatinine clearance is inversely proportional to creatinine plasma concentration

Question 25

What must you do for plasma creatinine concentrations to be meaningful?

Answer 25

Take more than one. People can have normally high creatinine. As creatinine levels should be constant, look for increases in concentration.

Question 26

Net filtration pressure

Answer 26

10mmHg from glomerulus into Bowman's capsule

Question 27

``` Features of acute renal failure 1 2 3 4 ```

Answer 27

* Oliguria * Anuria (rarely) * GFR falls acutely (hours to days) * Easily missed (depending on cause) because of itself may be asymptomatic

Question 28

Types of acute renal failure

Answer 28

Pre-renal Renal Post-renal

Question 29

Most common cause of acute renal failure

Answer 29

Pre-renal. | EG: shock, dehydration.

Question 30

Pre-renal acute renal failure

Answer 30

Anything that drops blood pressure to the point where no filtration occurs across glomerulus and Bowman's capsule

Question 31

Systemic perfusion pressure at which ARF occurs

Answer 31

Under 70mmHg

Question 32

Glomerular hydrostatic pressure at which ARF occurs

Answer 32

Under 45mmHg

Question 33

``` Examples of causes of pre-renal ARF 1 2 3 4 5 ```

Answer 33

``` – Shock – Sepsis – Haemolysis – Rhabdomyolysis – Nephrotoxic drugs (actually cause tubulo-interstitial nephritis, a renal cause) ```

Question 34

``` Examples of things that can cause intrinsic renal ARF 1 2 3 4 ```

Answer 34

•Glomerular disease •Interstitial nephritis (Tubulo-interstitial) –Inflammatory reaction, often drug-related •Tubular damage –ischemia •Acute tubular necrosis, vascular obstruction •toxins -antibiotics, X-ray contrast media, myoglobin

Question 35

ATN

Answer 35

Acute tubular necrosis. | So common as to be almost synonymous with ARF.

Question 36

Most common renal cause of ARF

Answer 36

Acute tubular necrosis

Question 37

Things that can cause acute tubular necrosis

Answer 37

Ischaemia, toxins

Question 38

``` Effects of acute tubular necrosis 1 2 3 4 ```

Answer 38

•oliguria (

Question 39

Main concern with CRF

Answer 39

Accumulation of toxic metabolites, EG creatinine. | Loss of hormonal function of kidneys (EG: vitamin D, epo, renin)

Question 40

Main concern with ARF

Answer 40

Accumulation of H+ and K+ ions. Leads to acidosis and hyperkalaemia.

Question 41

Treatment of ARF

Answer 41

Rehydration.

Question 42

Post-renal ARF

Answer 42

•Outlet Obstruction –Ureteric, cystic or urethral –stones, clots, fibrosis, tumors

Question 43

Treatment of post-renal ARF

Answer 43

Not just rehydration. Also need to remove the obstruction.

Question 44

``` Features of chronic renal failure 1 2 3 4 5 ```

Answer 44

* Irreversible loss of renal function * Reduction in functional renal mass * Develops over months to years (highly variable rates of decline) * Aka “uraemia” * Leads to End-Stage Renal Disease (ESRD)

Question 45

Effect of CRF on glomeruli 1 2 a, b, c

Answer 45

``` •Remaining nephrons hypertrophy •Glomerular hyperfiltration –loss of functional reserve –glomerular hypertension –further damage and glomerulosclerosis ```

Question 46

Uremia 1 2 3 a, b, c

Answer 46

``` •Accumulation of “uremic” toxins •Mostly urea, but not exclusively •Symptomatic with under 30% of renal function –Fatigue –Loss of appetite –Skin pigmentation (lemon) ```

Question 47

``` Main causes of CRF 1 2 3 4 ```

Answer 47

1) Diabetes 2) Hypertension 3) Chronic glomerulonephritis 4) Polycystic kidney disease

Question 48

Salt and water imbalances in CRF 1 2

Answer 48

``` •Predominantly glomerular disease –Sodium retention and hypertension •Predominantly tubular disease –Sodium wasting and low BP –Impaired concentrating ability & polyuria ```

Question 49

Potassium in CRF

Answer 49

–Tends to rise, especially late-stage –Higher in diabetes –If rapidly rises, can lead to arrhythmia

Question 50

``` pH in CRF 1 2 3 4 5 ```

Answer 50

–Falls i.e. H+ accumulates; failure to excrete non-volatile acids •Produced at high rate in normal metabolism •Excretion requires high GFR •Reduced ammonia production •Low [HCO3-]

Question 51

Calcium and phosphate in CRF 1 2 3

Answer 51

* Reduced phosphate excretion * Still reabsorbs same amount of phosphate, while secretion is decreased * Leads to rise in [PO4] (should be 1 - 1.3 milimols) * Reciprocal reduction in [Ca]

Question 52

Part of nephron that transports phosphate

Answer 52

Epithelial pump in proximal tubule. | Clears ~1 milimol/day

Question 53

Effect of elevated phosphate in CRF

Answer 53

Calcium phosphate can begin precipitating (EG on bones)

Question 54

Effect of CRF on vitamin D3

Answer 54

–Reduced renal mass and Vit D activation –Hyperphosphatemia –Renal “rickets”: osteomalacia with fractures and subperiosteal resorption

Question 55

Hormonal effect of high phosphate

Answer 55

High parathyroid hormone release. | Leads to excessive osteoclastic activity.

Question 56

Osteomalacia

Answer 56

Similar to osteoporosis. | If there is low serum Ca2+, then body starts taking Ca2+ from bones.

Question 57

Renal osteodystrophy

Answer 57

Combination of low serum Ca2+, leading to body taking Ca2+ from bones. Also increased PTH leads to excessive osteoclast activity