Chemical Pathology Of Renal Disease

Question 1

ADD CLINICAL CASES TO TEST

Answer 1

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Question 3

What are the homeostasis functions of the kidneys?

Answer 3

Waste products of metabolism
Fluid/electrolyte balance
Acid-base balance
Removal of drugs and toxins

Question 4

What are the endocrine functions of kidney?

Answer 4

RAAS
Erythropoietin production
Hydroxylation of vitamin D

Question 5

Which functions of the kidneys are effected by AKI and CKD?

Answer 5

AKI= excretion and homeostasis in early AKI

CKD= endocrine and then excretion later in CKD

Question 6

How are the different stages of AKI defined? Which stages is associated with increased in-hospital mortality?

Answer 6

Stage 1:
Serum creatinine: >=26.5 micro mol/L in 48 hrs or 1.5-1.9 x baseline
Urine output: <0.5ml/kg/h for 6-12 hours

Stage 2:
Serum creatinine: 2.0-2.9 x baseline
Urine output: <0.5ml/kg/h for >12 hrs

Stage 3:
Serum creatinine: >=3 x baseline or rise in >=353.g micromols/L or need for renal replacement therapy regardless of creatinine levels
Urine output: <0.3ml/kg/h for >24hrs

Stage 2

Question 7

What are the causes of AKI?

Answer 7

Renal underperfusion

Intrinsic renal damage

Obstruction

Question 8

What is the most common cause of AKI in hospitalised patients and why is this?

Answer 8

Renal underperfusion

Due to causes being associated with hosptial setting:

Hypovolaemia (trauma/GI bleed)

Sepsis (afferent arteriole vasodilation)

Renal artery stenosis/atherosclerosis

Pump failure (HF)

Question 9

Why does intrinsic renal damage occur?

Answer 9

Ischaemia

Nephrotoxins

Infection (pyelonephritis

Trauma

Early stage inflammation causes of CKD (glomerulonephritis)

Question 10

When is post-obstructive diuresis occur and what are the potential problems?

Answer 10

When catheter inserted to relieve retained urine in renal obstruction

Can then cause pre-renal injury due to fluid depletion associated with the diuresis= need to ensure fluids being replaced

Question 11

What are the stages involved in AKI development?

Answer 11

Pre-renal cause (hypovolaemia/sepsis/renal artery stenosis) leads to renal underoperfusion

Pre-renal renal failure leads to prolonged renal underperfusion which can cause acute tubular necrosis

Acute tubular necrosis can lead to intrinsic renal failure

Question 12

What are the precipitating factors of glomerular damage leading to intrinsic renal failure?

Answer 12

Trauma

Toxins

Infection

Infarction

Inflammation

Question 13

What are the most common causes of AKI in patients?

Answer 13

Hypovolaemia and sepsis

Question 14

How can you differentiate between a pre-renal renal failure and intrinsic renal AKI?

Answer 14

Pre-renal 
Low urine vol
Urine:plasma osmolality= high i.e. trying to preserve water (concentrated urine) 
Urine sodium conc= low 
Plasma sodium= high 
Serum elevation of urea >> creatinine 

Intrinsic
Initially high= due to kidney being unable to reabsorbed water and electrolytes
Urine:plasma osmolality= low or similar
Urine sodium conc= high
Plasma sodium= low
Serum elevation urea=creatinine

Question 15

What is the most specific test for differentiating between pre-renal and intrinsic renal AKI? What would the results be and why?

Answer 15

Urine sodium concentration

Pre-renal= LOW
Aldosterone being released to retain sodium

Intrinsic damage= HIGH
Kidney unable to reabsorb sodium

Question 16

How does the treatment of pre-renal AKI differ from intrinsic renal damage? Why is this?

Answer 16

Pre-renal= fluid cures
Due to low fluid volume being the reason for underperfusion

Intrinsic= fluid kills
Kidney unable to clear the fluid which lead to fluid overload

Question 17

What are the biochemical features of intrinsic AKI?

Answer 17

Retain acidic waste products= acidosis

Retain Potassium

Retain nitrogenous waste products
I.e. leads to uraemic symptoms= nausea, malaise, confusion

Retain salt and water = decreased GFR

Question 18

What serum concentration of potassium is life-threatening?

Answer 18

> 8mmol/L

Question 19

How would someone with intrinsic AKI present?

Answer 19

Hyperkalaemia metabolic acidosis

Malaise + nausea

Hyponatraemia due to fluid retention

Fluid overload

Question 20

How is AKI managed?

Answer 20

Determine whether pre-renal, intrinsic or post-renal causes

Identify underlying cause

Stop ACEi/ARBs/NSAIDs

Correct life-threading fluid and electrolytes and acid base abnormalities

Restore renal perfusion if pre-renal

Haemofiltration or dialysis to support renal function in life threatening AKI

Question 21

When is restoration of renal perfusion in pre-renal AKI contraindicated and why?

Answer 21

Heart failure

Leads to fluid overload

Question 22

What is CDK and what are the main causes?

Answer 22

Gradual irreversible change in kidney function

DM 
Hypertension 
Polycystic kidney disease 
Recurrent pyelonephritis 
Glomerulonephritis 
Interstitial nephritis 
Multisystem disease
Drugs

Question 23

How is CDK monitored?

Answer 23

24 hr urine collection for protein to determine GFR

Estimated GFR

Creatine (in end stage)

Albumin/creatine ratio

Question 24

Why is GFR used in early stages of CDK and creatine used in late stages?

Answer 24

Can loose 50% of kidney function before creatinine changes

EGFR changes less in later stages whereas creatinine changes a lot

Question 25

How is eGFR used to stage CKD?

Answer 25

>90= stage 1 
60-90= stage 2 
45-60= stage 3a 
30-44= stage 3b 
15-30= stage 4 
<15= stage 5 

NOTE= the 1st number of the range values is half of the upper value in previous stage range after stage 1 i.e. 90/2= 45

Question 26

At what stage of CKD does a patient present with clinical consequences? Which clinical signs are associated with the stages?

Answer 26

``` 3a= hypertension and increase CVD risk 3b= low calcium and secondary increase PTH (due to problems with vitamin D hydroxylation) 4= anaemia(due to erythropoietin prod)/anorexia/high phosphate 5= salt and water retention/acidosis/high potassium ```

Question 27

What are the biochemical changes associated with CKD stage 3-4?

Answer 27

Elevate creatine Reduced eGFR Elevated ACR Reduced 1-alpha hydroxylation of vitamin D = decreased amount of active vitamin D present Reduced erythropoietin production (renal anaemia) Elevated lipids and triglyceride (increased CVD risk) Impaired immune function

Question 28

Why are hypocalcaemia and secondary hyperparathyroidism associated with stage 3-4 CKD?

Answer 28

Decreased 1-alpha hydroxylation of vitamin D leads to impaired calcium absorption in GIT= hypocalcaemia Hypocalcaemia detected by parathyroid gland which stimulates increased production of PTH to promote increase osteoclast function to increase bone resorption to release calcium

Question 29

What are the biochemical changes associated with stage 4-5 CKD?

Answer 29

Elevate creatinine and urea= leads to uraemic symptoms High phosphate Acidosis Hyperkalaemia= only presents in later stages due to increased gut-losses offsetting it until that point

Question 30

How does the site of kidney damage influence the water balance in CKD?

Answer 30

Glomerular damage: Little glomerular filtrate= little urine produce (oliguria) i.e. fluid overload Healthy nephron in disease kidney Tubules unable to reabsorb electrolytes or water i.e. osmotic diuresis + polyuria Tubular damage Ineffective water reabsoprtion i.e. polyuria

Question 31

Is a CKD patient more likely to present with polyuria or oliguria?

Answer 31

Polyuria Oliguria only present in later stages of CKD

Question 32

What are the 2 possible mechanism contributing to renal bone disease?

Answer 32

1. Decreased 1-alpha hydroxylation= decreased plasma calcium and increased PTH 2. Decreased GFR - increased plasma phosphate= increase calcium/phosphate products - metabolic acidosis= dissolves bone buffers

Question 33

What bone diseases are associated with CKD and why?

Answer 33

Osteomalacia = decreased plasma calcium Osteitis fibrosa = increased bone resorption Metastatic calcification= increase calcium/phosphate products Osteoporosis= bone decay due to dissolved bone buffers

Question 34

How is CKD stage 2-3a managed?

Answer 34

Monitor patients via eGFR + ACR/ BP + lipids/ bone profile + PTH in stage 3a Treat causes (diabetes, hypertension, recurrent UTI) Avoid precipitates of AKI Block slow progression by blocking RAAS if ACR via ACEi/ARB

Question 35

How is stage 3b-5 CKD managed?

Answer 35

Endocrine abnormalities: Alfacalcidol= corrects calcium and prevens tertiary hyperparathyroidism Erythropoietin Phosphate binders= decreases risk of metastatic calcification Modified diet to decreased potassium Fluids Bicarbonate to correct acid-base disturbances Renal replacement therapy i.e. haemodialysis or peritoneal dialysis

Question 36

What is tertiary hyperparathyroidism?

Answer 36

Excessive production of PTH due to long-standing secondary hyperparathyroidism

Question 37

What are the different causes of renal tubular disorders?

Answer 37

Specific transport defects i.e. glucose/amino acids/phosphates Global tubular defect i.e. fanconi syndrome Renal tubular acidosis i.e. causes acid/base and electrolytes disturbances