RENAL: Chronic Kidney Disease Flashcards
Define chronic kidney disease
Abnormality of kidney structure or function that persists for >3 months- Includes all individuals with markers of kidney damage or those with an eGFR of less than 60ml/min/1.73m3 on at least 2 occassions 90 days apart (with or w/o markers of kidney damage)
Markers of kidney disease can include:
- Albuminuria (ACR >mmg/mmol)
- Haematuria (or presumed or confirmed renal origin)
- Electrolyte and other abnormalities due to tubular disorders
- Renal histological abnormalities, structural abnormalities detected by imaging (e.g. polycystic kidneys, reflux nephropathy)
- History kidney transplantation
What are the main functions of the kidneys and describe what happens to them as a result of kidney disease
- Excretory, endocrine and metabolic function decline together in most chronic kidney diseases
- Excretory function - GFR
- GFR declines = variety complications reflecting loss of endocrine or exocrine function of kidneys develop including anaemia, acidosis, malnutrition, bone + mineral disorders
How is CKD staged based on EGFR?
- Based on eGFR and Albumin:Creatinine ratio
CKD can be classed as A1, A2 or A3:
If eGFR b/w ≥ 90 or b/w 60-89 and ACR is <3, category A1
If eGFR is ≥ 90 or b/w 60-89 or 45-49, and ACR b/w 3-30, A2
See rest on notion
What are the consequences of worsening kidney function?
- Lack of waste substance excretion
- Acid/base imbalance
- Vitamin D inactivation (alpha 1 - hydroxylase, converts inactive Vitamin D to active, this is calcitrol, which will then allow calcium to be reabsorbed)
- BP not controlled
- RBCs not produced (need erythropoietin for this)
- Water balance not regulated
- Mineral content of ECF not regulated
Describe anaemia as a result of CKD
- Anaemia characteristic of advanced CKD (≥ stage 3)
- Anaemia of CKD is normochromic-normocytic (RBCs have same size and normal red colour)
- Usually caused by deficient erythropoietin production due to reduction of functional renal mass
- Other causes can include iron deficiency, folate and vitamin B12 deficiency
Describe the role of erythropoietin
- EPO stimulated RBC production by stimulating erythropoiesis in bone marrow
- EPO production can be triggered by low RBC numbers, reduced availability of O2, increased O2 demand by tissues
- Erythropoietin produced by peritubular cells of kidney - These are the cells that line the capillaries and surrounnd the cortical parts of the proximal and distal tubules
- EPO produced predominantly in renal tissue but small amounts produced spleen, liver, bone marrow, lung, brain
- In normal circumstances, EPO production driven by low pO2, low Hb lvls → this environment will induce an increase in hypoxia induceable factor which will induce EPO production
- In CKD, damage to kidneys causes limited EPO secretion by peritubular cells
Describe the role of CKD in Bone Mineral Disease
- Changes in bone + mineral metabolism and alterations in calcium and phosphate homeostasis occur early in course of CKD and progress as kidney function worsens
- Phosphate major problem in CKD, followed by inadequate active vitamin D
- Abnormalities of calcium, phosphate, parathyroid hormone (PTH) and vitamin D metabolism can occur, leads to Renal osteodystrophy
Phosphate is absorbed from the GI tract (we get our intake from food), and is excreted in the kidneys, where can then be reabsorbed by the PCT. In CKD, there’s decreased renal nephron mass, therefore phosphate cannot be excreted. Phosphate binds to Ca2+ to increase its stability. High phosphate = low calcium, meaning there’s less free calcium as it’s bound to phosphate molecules
Hypercalcaemia – Parathyorid gland has calcium sensing receptors, detect free calcium. Parathyroid hormone increases calcium levels, and this moves out of the bones into the blood. This is why patients with CKD have reduced bone density
- Decrease renal production of calcitriol (active Vit D hormone) contributes to hypocalcaemia
- Decreased renal excretion of phosphate results in hyperphosphataemia
- Secondary hyperparathyroidism is common and can develop in renal failure before abnormalities in calcium or phosphate concentrations occur
- Hence, monitoring PTH patients with moderate CKD even before hyperphosphatemia has been recommended
- Renal osteodystrophy (abnormal bone mineralisation resulting from hyperparathryoidism, calcitriol deficiency, elevated serum phosphate, or low or normal serum calcium) usually takes form of increased bone turnover due to hyperparathyroid bone disease (Osteitis fibrosa)
- Calcitriol deficiency may cause osteopenia or osteomalacia
Describe acid base dysregulation in CKD
- Failure of H+ excretion and compounded by bicarbonate loss and accumulation of organic acids
- Moderate metabolic acidosis (plasma bicarbonate content 15-20 mmol/L)
- Acidosis causes:
- Muscle wasting due to protein catabolism
- Bone loss due to calcium buffering of acid
- Accelerated progression of kidney disease
- Aggravates hyperkalaemia
How does the kidney failure cause hyperkalaemia?
Decrease in nephron so maximal capacity of K secretion limited
Outline the progression of CKD
- Progression of CKF predicted in most cases by degree of proteinuria
- Patients with nephrotic-range proteinuria )> 3g/24 hr or urine protein/creatinine ratio >3) usually have a poorer prognosis and progress to renal failure more rapidly
- Progression may occur even if the underlying disorder is not active
- In patients with urine protein <1.5g/24 hr, progression usually occurs more slowly if at all
- Hypertension, acidosis and hyperparathyroidism are associated with more rapid progression as well
Discuss the role of RAAS
Important role in:
- Regulating blood volume
- Systemic vascular resistance
3 main components are:
- Renin, stored and released by justaglomerular cells- stimulated by:
- Sympathetic nerve action of B1 adrenoceptors on JG cells
- Renal artery hypotension (caused by systemic hypotension e.g. bleeding patient) - Reduction in afferent arteriole pressure causes the release of renin
- Decrease sodium delivery to the distal tubules of the kidney - Macula densa in distal tubules lie adjacent to JG cells of afferent arteriole. Macula densa will sense Na concentration, responds accordingly. So increase in Na concentration will lead to inhibition of renin production and vice versa.
- When afferent arteriole is reduced, GFR is reduced, reducing Na in distal tubule
- Angiotensin
- Renin acts upon angiotensinogen (produced in liver) by converting it to Angiotensin 1. Angiotensin 1 converted into Angiotensin 2 by ACE
- Aldosterone
Describe blood flow through the nephron
Blood passes from afferent arteriole, into glomerulus, and then into efferent arteriole
Describe the juxtaglomerular apparatus
Specialised structure formed from DCT and glomerular afferent arteriole. Made up of specialised epithelial cells - part of DCT called macula densa, detects Na concentration of fluid in tubule, and juxtaglomerular cells - derived from smooth muscle cells of afferent arteriole, which are highly innervated, and secrete renin in response to drop in BP in arteriole
Describe the effects of angiotensin II
- CVS effect - Acts on AT1 receptors forund in endothelium of artrioles, causes vasoconstriction. This increases TPR
- Neural effects - Acts on hypothalamus to stimulate thirst and increase secretion of ADH from pituitary gland (increases BP and concentrated urine)
- Renal effects - Vasoconstriction of afferent «efferent arteriole and increase Na absortion in PCT
- Adrenal effects - Release of aldosterone (mineralocorticoid), aldosterone acts in ENaC channel and Na/K ATPase, so additonal sodium rebasorbed with excretion of potassium into urine
Describe the effects of ACEi and ARB on GFR
- Angiotensin 2- main effector of RAAS
- Exerts vasoconstrictor effect predominantly glomerular arteries
- This increases glomerular hydraulic presure
- Increased ultrafiltration of plasma proteins
- Increases Na and H2O retention
- Acts on aldosterone that increases Na and H2O retention
- Stimulates release of vasopressin (ADH) from posterior pituitary → Increase water retention
- Stimulates thirst mchanism
- Interventions that inhibit overactivity of RAAS are renoprotective and may slow or even halt CKD progression
What lifestlye modifications can be made to help manage CKD?
- Address lipid profile
- BP regulation
- Stop smoking
- Glycaemic control
What are the side effects of ACEi and ARB?
- Inhibit formation of circulating Ang II or block Ang II binding to adrenal receptor
- ACEi or ARB, respectively, interfere with stimulatory effect of Ang II on aldosterone secretion in adrenal gland, and consequently impair kidney excretion of potassium
List the 4 indications of renal replacement therapy
- Refractory hyperkalaemia
- Metabolic acidosis
- Uraemia
- Refractory pulmonary oedema
Where is renin released from?
Juxtaglomerular cells
Where is ACE normally found?
ACE is predominantly produced by vascular endothelial cells in the lungs
