Chem path 10 - renal part 2

Question 1

What are some key differences between AKI and CKD

Answer 1

AKI: abrupt decline in GFR, reversible, treatment targeted at precise cause of AKI
CKD: gradual decline in GFR, irreversible, treatment targeted to prevention of CKD complications

Question 2

What is the definition of AKI?

Answer 2

rapid reduction in kidney function, leading to inability to maintain electrolyte, acid-base and fluid homeostasis.

Question 3

What is the standardised definition of AKI (KDIGO)?

Answer 3

Stage 1 - increase in serum cr >26umol/l or 1.5-1.9x the reference serum Cr. UO <0.5ml/kg/hr 6-12hrs
Stage 2 - increase in reference serum cr 2-2.9x. UO <0.5ml/kg/hr >12hrs
Stage 3 - increase >354umol/L or reference serum cr >3x UO <0.3ml/kg/hr >24hr, anuric>12hr

Question 4

What is the hallmark of pre-renal AKI?

Answer 4

Reduced renal perfusion (no structural abnormality)

Question 5

Outline the normal response to reduced circulating volume

Answer 5

1) Activation of central baroreceptors –> 2) Activation of RAAS –> 3) Vasopressin release –> 4) SNS activation
SNS activation: a) vasoconstriction b) increased CO c) renal sodium retention

Question 6

Renal blood flow is able to stay constant over a huge range of pressures due to two main mechanisms

Answer 6

Myogenic stretch

Tubuloglomerular feedback

Question 7

What is the myogenic stretch mechanism?

Answer 7

If the afferent arteriole gets stretched due to high pressure it will then constrict to reduce the transmission of that high pressure in to Bowman’s capsule and to maintain GFR

Question 8

What is the tubuloglomerular feedback mechanism?

Answer 8

High chloride levels in the early distal tubule (Sign of high GFR) stimulates constriction of the afferent arteriole which lowers GFR and reduces chloride levels in the distal tubule

Question 9

What are the causes of pre-renal AKI?

Answer 9

True volume depletion (haemorrhage)
hypotension
oedematous state (heart failure, liver failure)
selective renal ischaemia e.g. RAS
Drugs affecting renal blood flow
- ACEi/ARB - reduce efferent constriction
- NSAIDs or calcineurin inhibitors - decrease afferent dilatation
- Diruetics - affect tubular function, reduce preload

Question 10

What drug class is strongly contraindicated in RAS?

Answer 10

ACEi

Question 11

Outline some differences between pre-renal AKI and ATN

Answer 11

Pre-renal AKI will be reversed by restoration of circulating volume, pre-renal AKI is not associated with structural damage, in ATN, epithelial casts or seen on urine microscopy. However, prolonged AKI can result in renal ischaemia (ATN)

Question 12

What is a common cause of post-renal AKI (appears as hydronephrosis on USS)q

Answer 12

Benign prostatic hypertrophy

Question 13

What is the hallmark of post-renal AKI?

Answer 13

Physical obstruction (At any level) to urine outflow

Question 14

What does prolonged obstruction lead to?

Answer 14

Glomerular ischaemia, tubular damage, long term interstitial scarring

Question 15

What is the most common cause of intrinsic/renal AKI?

Answer 15

ATN (direct tubular injury)

Question 16

What are some endogenous and exogenous toxins to the tubules?

Answer 16

Endogenous: myoglobin, immunoglobulins (myeloma)
Exogenous: contrast medium, amphtocerin, acyclovir, aminoglycosides

Question 17

What are the most common casues of AKI?

Answer 17

Pre-renal and ATN

Question 18

Which two measures do we use to define AKI?

Answer 18

Serum creatinine and urine output

Question 19

Why do some rneal AKIs resolve and others don’t?

Answer 19

Pathological responses are characterised by an imbalance between scarring and remodelling. Replacement of renal tissue by scar tissue –> chronic disease

Question 20

How many stages of CKD are there and what is it based on?

Answer 20

5, GFR

Question 21

Why do stages 1 and 2 have a lower prevalance than stage 3?

Answer 21

they often go undiagnosed

Question 22

What is a good marker of poor outcome in CKD?

Answer 22

Albumin creaitnine urine ratio

Question 23

What is the commonest cause for renal transplant in the UK?

Answer 23

Diabetes

Question 24

What are the two most common causes of CKD?

Answer 24

Diabetes and HTN

Question 25

What are some roles of the kidney?

Answer 25

Excretion of water-soluble waste e.g. urea ACid-base handling Water balance Electrolyte balance Endocrine functions (EPO, RAAS, vitamin D)

Question 26

What are some consequences of CKD/

Answer 26

Acidosis, hyperkalaemia Impared hormonal function --> anaemia, renal bone disease, cardiovascular disease (vascular calcification, uraemic cardiomyopathy), uraemia and death

Question 27

What is a major cause of hyperkalaemia in CKD?

Answer 27

Dietary intake, high potassium foods include chocoalte, dried fruits, milk and tomatoes

Question 28

Describe the consequences of renal acidosis in CKD

Answer 28

inability to excrete protons --> metabolic acidosis which results in muscle and protein degradation and osteopaenia due to mobilisation of bone calcium (protons can be stored in the bone) and cardiac dysfunction

Question 29

What is the treatment for renal acidosis?

Answer 29

Oral sodium bicarbonate

Question 30

What dose hyperkalaemia cause?

Answer 30

Membrane depolarisation which impacts on cardiac and muscle function

Question 31

What are some medications that can cause hyperkalaemia?

Answer 31

ACEi, NSAIDs, spironalactone (potassium sparing diuretic)

Question 32

What are the ECG changes seen in hyperkalaemia?

Answer 32

1) tall tented T waves 2) loss of P waves 3) broad QRS complexes

Question 33

What is the cause of anaemia in CKD?

Answer 33

Loss of EPO producing cells with loss of renal parenchyma

Question 34

What type of anaemia is caused in cKD?

Answer 34

Normochromic normocytic anaemia

Question 35

How do you treat CKD anaemia?

Answer 35

With artificial erythropoiesis-stimulating agents (ESAs)

Question 36

What is the cause of renal bone disease in CKD?

Answer 36

Lack of 1a hydroxylase production and phosphate retention. Phosphate retention stimulates FGF-23/klotho production --> lowers vitD --> 2nd hyperparathyroidism to get rid of phosphate PTH also increased to raise vitD levels Increased phsopahte in blood will couple with calcium --> hypocalcaemia --> deposition in kdiney --> renal osteodystrophy Bone will become resistant to PTH due to high levels

Question 37

What is osteitis fibrosa cystica caused by?

Answer 37

Osteoclastic resorption of calcified bone and replacement with fibrous tissue. This is a feature of hyperparathryodiism.

Question 38

What is the most important consequence of CKD?

Answer 38

CARDIOVASCULAR DISEASE, most likely thing to kill them

Question 39

What is the risk of a CVS event most directly related to?

Answer 39

GFR

Question 40

What is the difference between renal vascular lesions compared to the traditional lipid-rich atheromas?

Answer 40

They are heavily calcified plaques

Question 41

What are the three phases of uraemic cardiomyopathy?

Answer 41

1) LV hypertrophy 2) LV dilation 3) LV dysfunction

Question 42

What are the three main treatment options for CKD?

Answer 42

Transplantation, haemodialysis and peritoneal dialysis

Question 43

What is a contraindication to transplant?

Answer 43

Active sepsis

Question 44

What are not contraindications to transplantation?

Answer 44

HIV BMI>30 Malignancy Age >65y

Question 45

How often is haemodialysis performed?

Answer 45

3x/week for ~6 hrs

Question 46

What are the indications for dialysis?

Answer 46

``` Refractory hyperkalaemia Refractory fluid overload Metabolic acidosis Uraemic symptoms (encephalopathy, nausea, pruritis, malaise, pericarditis) CKD stage 5 (GFR <15l/min) ```