Chronic Kodney Disease

Question 1

Diabetic nephropathy

Answer 1

Albuminuria (less than 3.4) and decline gfr
See hypertension,Oedema,retinopathy,neuropathy,foot ulcers,haematuria,shortness of breath,nausea

Question 2

Pathophysiology

Answer 2

By hyperglycemia and increased glomerular pressure which promotes glomerular mesangial expansion and fibrosis of the GBM mediated by TGF beta and advanced glycation. Activation of renin angiotensin causes excess angiotensin II inducing efferent arteriole constriction
Initial glomerular hyperfiltration causes sheer stress to glomeruli causing podocyte injury thus increasing membrane permeability and causing albuminuria

Question 3

Treatment for albuminurea

Answer 3

Reduce proteinuria using ARB or ACEi
Smoking cessation
SGLT2 inhibitor
Renal transplant
Dialysis optimized diabetes control and treatment of hypertension

Question 4

How to reduce risk of kidney disease

Answer 4

Maintain blood glucose
Minimize blood pressure
Stop smoking

Question 5

Diagnosis

Answer 5

Urine test ACR checks for albumin to creatinine ratio . In kidney disease there is an elevated amount of albumin excreted

GFR uses creatinine level and standardizes it

Question 6

Treatment

Answer 6

Initial therapy is dual combo ACEi or ARB and CCB or with diuretic
Triply combo ACEi or ARB and CCB and diuretic
Triple combo and spironolactone

Give. ETA blockers if there is indication of heart failure or if it’s a young woman

Antihyoertensives such as ace inhibitors NSAIDS and angiotensin receptor blockers

Question 7

Renin angiotensin systemic

Answer 7

Angiotensinogen secreted by the liver and cleaved by renin making angiotensin I.. ACE converts this into angiotensin II which is a vasoconstrictor. This promotes thirst,ADH secretion,aldosterone synthesis and increased sodium reabsorption
Aldosterone stimulates potassium secretion and sodium reabsorption and causes water retention

Question 8

What affects RAS

Answer 8

Reduction in renal perfusion pressure or a decrease in sodium load is detected by macula densa which communicates with juxtaglomerular cells lining renal afferent arteriole.
In response to low renal perfusion pressure renin is released by JG cells

Question 9

Angiotensin II on kidney

Answer 9

Renal afferent arteriole-causes vasoconstriction by voltage gated calcium channels opening and allowing influx.
Efferent arteriole causes vasoconstriction by activating AT-1 within endothelium
Mesangial cells constrict leading to decreased filtration by activating Gq receptors and opening voltage gated calcium channels
PCT increases sodium reabsorption via increased sodium hydrogen ion antiportet activity (starling forces in oeritbukar capillaries)

Question 10

Aldosterone

Answer 10

Steroid hormone synthesized within Zona glomerulase in response to aldosteronensynthaseb
It’s a response to a drop in blood pressure
Causes increased sodium reabsorption and increased potassium secretion
In excess it can cause hypokalaemic alkalosis

Question 11

Aldosterone in the cortical collecting duct

Answer 11

Increased transcription and synthesis of ENaC the sodium potasssium ATPase pump

Question 12

ACE inhibitors

Answer 12

Reduce angiotensin II by inhibiting conversion of angiotensin I to angiotensin II
Net effect is lowers blood pressure
Eg ramipri,,lisinopril,enalapril

Vascular effects causes vasodilation to reduce bp
Diuretic effects reduces sodium uptake in PCT
Reduced aldosterone reduces sodium reabsorption and reduces osmotic different between tubular fluid and jnterstitium

Question 13

ACE inhibitor side effects

Answer 13

Dry cough
Hyperkalaemia
Headache
Dizziness
Fatigue
Renal impairment
Angiodema
Contraindicated in bilateral renal artery stenosis. Angiotensin II maintains GFR when renal perfusion is low thus inhibiting ang II with ACEi and ARBs cause acute kidney injury

Question 14

General treatment plan

Answer 14

Ramipril – First line treatment, capacity to reduce CKD proteinuria, reduces glomerular pressure and glomerular
injury.
Insulin – Target’s hyperglycaemia
Atorvastatin- Target’s dyslipidaemia (High blood cholesterol causes sclerotic glomeruli)

Question 15

Heparin sulphate proteoglycans

Answer 15

Act to restrict movement of negatively charged molecule acrosss basement membrane

Question 16

Podocytes

Answer 16

Specialized epithelial cells which form foot like processes and form filtration slits
Filtration slots Erie bridges formed by slit diaphragm,negatively charged glycoproteins cover podocytesrestrcting filtration of large anions

Question 17

Proteinuria

Answer 17

Presence of additional proteins in urine accompanied by elevated serum creatinine

Question 18

Overflow

Answer 18

Rhabdomyolosis
Low molecular widget proteins pass through the filtration barrier into the filtrate
Myoglobinuria is the presence of myoglobin in urine which interacts with Tamm horsfall protein to form solid aggregates
Associated with rapid degradation of skeletal muscle(trauma,exercise,toxins)causing a release of muscle constituents into circulation

Question 19

Glomerular damage

Answer 19

Due to damage to the glomerulus (diabetic nephropathy) albumin moves freely into filtrate
Excess amount of albumin overwhelms reabsorption capacities

Question 20

Acute tubulointerstitial nephritis

Answer 20

Immune mediated infiltration of the kidney interstitium causing tubular dysfunction

Question 21

Haemoglobinuria

Answer 21

Haemoglobin is found in high concentrations in urine as a result of overflow

Question 22

Albuminuria

Answer 22

Excess protein loss into filtrate
Important to consider when identifying a patient at risk
Micro=30-300mg/dy
Macro->300mg/day

Question 23

Nephrotoxic drugs

Answer 23

NSAIDS
ACE inhibitors
Amnioglyocsides
Contract agents eg contrats CT

Question 24

Pathophysiology of CKD

Answer 24

Damaged nephron reduces filtration
capacity
2) Functional nephrons undergo
adaptive hyperfiltration, renal blood
flow prioritises functional units
through nephron adaptability.
3) Excessive pressure and demand on
glomerular capillaries →
Glomerulosclerosis.
4) Glomerulosclerosis subsequently
leads to ischaemic injury leading to
loss of function and nephron
depletion.
5) Beyond 50% dysfunctionality- CKD progresses

Question 25

Diangostic tests of Ckd

Answer 25

ACR-estimates proteinuria,used in diabetes as it has greater sensitivity Urine dipstick-specific detection to albumin in urine but can’t detect proteinuria due to poor myoglobin sensitivity (false negatives) 24h urine test-total protein collection in urine over 24 hours total protein should be <150 majority of which is uromodulin (impractical method) Random albumin conc-detects albumin amount-unreliable

Question 26

GFR

Answer 26

GFR=Puf times Kf Elevation of serum creatinine is an indicator of poor filtration

Question 27

Creatinine

Answer 27

Waste product arising from Creatine phosphate in muscle stable function confers for stable creatinine Freely filtered and not reabsorbed

Question 28

Gold standard test

Answer 28

Isotopic method where UV injection of radioactive tracer used to measure clearance

Question 29

MDRD formula

Answer 29

Takes into account age ethnicity and sex Creatinine may also depend on dietary protein consumption Make young and Afro caribbeans have higher muscle masses

Question 30

Why is MDRD unreliable

Answer 30

Pregnancy-plasma creatinine can lag behind End stage renal failure prior to dialysis- creatinine calculations are overestimated,gfr decreases and proportion of swcret3 creatinine to filtered increases Acute kidney injury-rate of increase doesn’t parallel the fall in gfr Factors-trauma(muscle atrophy),trimethoprim(inhibits tubular secretion ,malnutrition or sepsis

Question 31

Decreased excretion

Answer 31

Water and salt-hypertension,volume overload and pulmonary failure Potassium-weakness and fatigue,arrhythmia Acid-metabolic acidosis Urea-nausea and vomiting ,weakness and fatigue,itch,pericarditis,encephalopathy,bleeding,seizures,coma Uris acid-gout Phosphate-hyperparathyroidism,renal bone disease

Question 32

Decreased biosynthesis

Answer 32

Vitamin D-hyperparathyroidism,osteomalacia,renal bone disease Erythropoietin-anaemia

Question 33

Altered metabolism

Answer 33

Lipids-accelerated atherogenesis,cardio disease Sex hormones-abnormalities in reproductive function

Question 34

Renal dysfunction

Answer 34

Disrupted filtration mechanism caused haematuria and proteinuria Hypertension (water retention)low serum calcium and calcitriol reduce negative feedback effect,PTH hormone secretion from chief cells accommodate hypocalcaemia

Question 35

Parathyroidism

Answer 35

Renal dysfunction is attributed to an impairment in the activity of renal 1-alpha-hydroxylase activity, therefore the second hydroxylation of 25-cholecalciferol to active Vitamin-D is reduced. • Hypocalcaemic conditions arise. • Low serum calcium concentrations are detected by calcium-sensing G coupled chief cells in the parathyroid glands – stimulates PTH synthesis and release. PTH stimulates osteoclastogenesis, binding to PTH receptors potentiating the release of OAF & RANKL, and the activation of osteoclasts to resorb bone (releasing calcium ions from calcium hydroxyapatite). PTH causes phosphate excretion from the distal convoluted tubule. In CKD, phosphate excretion is impaired, resulting in an elevation in serum phosphate. In CKD: • FGF-23 concentrations are elevated and is secreted by osteocytes. • Decreases expression of NPT2 and suppresses calcitriol production

Question 36

Treating complications

Answer 36

Volume overload-sodium and Intravascular volume are maintabjebd by homeostasis until GFR <10-15ml. Treat with sodium restriction and diuretics Hyperkalaemia develops in oliguric patients(less urine reaches distal tubule),those with high potassium diet,increased tissue break down or hypoaldosteronism. Treat with low potassium diet and avoid using drugs raising serum potassium Metabolic acidosis-increasing tendency to retain hydrogen ions. Treat with bicarbonate supplementation (can promote water retention)

Question 37

Treating complication s2

Answer 37

Mineral and bone disorders-renal osteodystrophy which is universal. Osteitis fibrosa reuksting from secondary hyperparathyroidism. Treat with dietary phosphate restriction,administer calcitriol(suppres PTH,vit D replacement Hypertension-combined therapy or diuretic and ACEi/AR. To reduce progression of CKD,loop diuretic for Oedema and hypertension,thiazide diuretic become less effective Anemia-normochromic and normocytic due to reduced EPO,monitor every 3-12 months. Use recombinant EPO Dylipodaemia-statins to correct LDL