Chronic Kodney Disease Flashcards
Diabetic nephropathy
Albuminuria (less than 3.4) and decline gfr
See hypertension,Oedema,retinopathy,neuropathy,foot ulcers,haematuria,shortness of breath,nausea
Pathophysiology
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
Treatment for albuminurea
Reduce proteinuria using ARB or ACEi
Smoking cessation
SGLT2 inhibitor
Renal transplant
Dialysis optimized diabetes control and treatment of hypertension
How to reduce risk of kidney disease
Maintain blood glucose
Minimize blood pressure
Stop smoking
Diagnosis
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
Treatment
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
Renin angiotensin systemic
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
What affects RAS
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
Angiotensin II on kidney
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)
Aldosterone
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
Aldosterone in the cortical collecting duct
Increased transcription and synthesis of ENaC the sodium potasssium ATPase pump
ACE inhibitors
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
ACE inhibitor side effects
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
General treatment plan
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)
Heparin sulphate proteoglycans
Act to restrict movement of negatively charged molecule acrosss basement membrane
Podocytes
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
Proteinuria
Presence of additional proteins in urine accompanied by elevated serum creatinine
Overflow
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
Glomerular damage
Due to damage to the glomerulus (diabetic nephropathy) albumin moves freely into filtrate
Excess amount of albumin overwhelms reabsorption capacities
Acute tubulointerstitial nephritis
Immune mediated infiltration of the kidney interstitium causing tubular dysfunction
Haemoglobinuria
Haemoglobin is found in high concentrations in urine as a result of overflow
Albuminuria
Excess protein loss into filtrate
Important to consider when identifying a patient at risk
Micro=30-300mg/dy
Macro->300mg/day
Nephrotoxic drugs
NSAIDS
ACE inhibitors
Amnioglyocsides
Contract agents eg contrats CT
Pathophysiology of CKD
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
Diangostic tests of Ckd
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
GFR
GFR=Puf times Kf
Elevation of serum creatinine is an indicator of poor filtration
Creatinine
Waste product arising from Creatine phosphate in muscle stable function confers for stable creatinine
Freely filtered and not reabsorbed
Gold standard test
Isotopic method where UV injection of radioactive tracer used to measure clearance
MDRD formula
Takes into account age ethnicity and sex
Creatinine may also depend on dietary protein consumption
Make young and Afro caribbeans have higher muscle masses
Why is MDRD unreliable
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
Decreased excretion
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
Decreased biosynthesis
Vitamin D-hyperparathyroidism,osteomalacia,renal bone disease
Erythropoietin-anaemia
Altered metabolism
Lipids-accelerated atherogenesis,cardio disease
Sex hormones-abnormalities in reproductive function
Renal dysfunction
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
Parathyroidism
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
Treating complications
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)
Treating complication s2
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
