Chron ic k idney d isease St ruc tura l anatomy

� The kidneys are two bean shaped organs lying retroperitoneally on each side of the vertebral column slightly above the level of umblicus. � The range in length & weight, respectively, from approximately 6cm & 24gms in a full term infant to more than equal to 12cm & 150gms in an

adult

Nephron

� Each kidney contains approx.1 million nephrons. � In humans,formation of nephron is complete at 36-40 wks of gestation, but functional maturation with tubular growth & elongation continues

during the 1st decade of life � New nephrons can’t be formed after birth, so any disease that results in progressive loss of nephrons can lead to renal insufficiency. � A Nephron consist :-

o OUTER LAYER (the cortex) à Glomeruli, PCT & DCT, CD o INNER LAYER (the medulla) à Straight portion of tubules, LOH, vasa recta,terminal CD

Jux tag lomeru lar apparatus

� The cells of the distal tubule in the part that comes in contact with the afferent arterioles of the glomerulus are more dense than the cells in the rest of tubule are called MACULA DENSA

� The smooth muscle cells of afferent arterioles that approximate macula densa contain prominent secretory cytoplasmic granules which are the site of renin activity.

� JGA is composed of the afferent & efferent arterioles, the macula densa & lacis cells located in the triangular space in between these structure. � It is involved in systemic blood pressure regulation,electrolyte hemeostasis & tubuloglomerular feedback mechanism.

Loop o f hen le

� Responsible for producing a concentrated urine by forming a concentration gradient within the medulla of k idney. � When ADH is present, water is reabsorbed and urine is concentrated. � Counter-current multiplier

Rena l

vascu la ture

� The renal artery arising from aorta divides into fine Segmenta l Ar ter ies . � The latter divides into the In ter lobar Arter ies ,which branch into Arcuate Arter ies near the junction of the Cortex & medulla. � Interlobar arteries provide the afferent arterioles for the glomeruli. � The glomerular capillaries join to form the efferent arteries that leaves the glomerulus & form an extensive network of peritubular capillaries that

surround the tubules,mostly in the cortex,forming Vasa Recta .The VR along with LOH are responsible for the urine concenteration

Funct ions o f k idney

Excre tory

1 . Glomeru lar f i l t ra t ion o Renal corpuscle o Filtration membrane o Fenestrated endothelium of capillaries o Basement membrane of glomerulus o Slit membrane between pedicels of podocytes

2 . Tubu lar reabsorpt ion o Water, glucose, amino acids, urea, ions o Sodium diffuses into cell; actively pumped out – drawing water with it o In addition to reabsorption, also have tubular secretion – substances move from peritubular capillaries

into tubules – a second chance to remove substances from blood 3. Tubu lar secret ion

Homeostat ic

1 . Regu la te b lood vo lume and b lood pressure : a. by adjusting volume of water lost in urine b. releasing erythropoietin and renin

2 . Regu la te p lasma ion concentra t ions : a. sodium, potassium, and chloride ions (by controlling quantities lost in urine) b. calcium ion levels

3 . Help s tab i l i ze b lood pH à by controlling loss of hydrogen ions and bicarbonate ions in urine 4 . Conserve va luab le nutr ients à by preventing excretion while excreting organic waste products 5 . Ass is t l i ver to detox i fy po isons

Endocr ine

§ Kidneys have primary endocrine function since they produce hormones § In addition, the kidneys are site of degradation for hormones such as insulin and aldosterone. § In their primary endocrine function, the kidneys produce erythropoietin, renin and prostaglandin. § Erythropo ie t in is secreted in response to a lowered oxygen content in the blood. It acts on bone marrow, stimulating the

production of red blood cells. § Ren in - the primary stimuli for renin release include reduction of renal perfusion pressure and hyponatremia. Renin release

is also influenced by angiotension II and ADH. § It is a key stimulus of aldosterone release. The effect of aldosterone is predominantly on the distal tubular network,

effecting an increase in sodium reabsorption in exchange for potassium. § The kidneys are primarily responsible for producing vitamin D3 from d ihydroxycho leca lc i fe ro l

Metabo l ic Kidney perform gluconiogenesis during periods of starvation Ac id base

ma in ta inance

                 

 

 Chron ic k idney d isease

De f in i t ion

o CKD à Progressive and irreversible loss of renal function over times; based on a gradual decline in the GFR and creatinine cleareance, frequently leading to ESRD

o Uremia à is the clinical and lab syndrome, reflecting dysfunction of all organ systems as a result of untreated or undertreated acute or chronic renal failure

o End stage renal disease (ESRD) à a clinical state or condition in which there has been an irreversible loss of renal function and these patients usually need to accept renal replacement therapy in order to avoid life threatening uremia

Essent ia l o f d iagnos is

1. Progressive azotemia over months to years 2. Symptoms and signs of uremia when nearing end-stage disease. 3. HTN in majority 4. Isosthenuria and broad casts in urinary sediment are common 5. Bilateral small kidneys on US 6. In CKD, reduced clearance of certain solutes principally excreted by the kidney results in their retention in the body fluids. The solutes are end

products of the metabolism of substances of exogenous origin (eg, food) or endogenous origin (eg, catabolism of tissue)

E t io logy

Common causes o f CRF 1. Diabetes mellitus 2. Glomerulonephritis 3. Polycystic kidney 4. Hypertension

Symptoms

Symptoms develop slowly and are nonspecific 1. Patients may remain asymptomat ic until renal failure is far-advanced (GFR < 10-15 ml/min) 2. Manifestations can inc lude fa t igue , ma la ise , weakness , prur i t i s . 3. GI c/o anorexia, n/v, metallic taste and hiccups are common. 4. Neurologic problems include irritability, difficulty concentrating, insomnia, and forgetfulness 5. Menstrual irregularities, infertility, and loss of libido are also common as condition progresses 6. G.Exam; reveals a chronically ill-appearing patient. 7. Look for possible underlying cause (DM, lupus) 8. HTN is common 9. Skin may be yellow, with evidence of easy bruising 10. Uremic fetor (fishy breath) may be present 11. Cardiopulmonary and mental status changes are frequently noted also

Lab d iagnos is

1. Dx made by documenting elevations of BUN and serum creatinine concentrations 2. Low GFR 3. Persistent proteinuria is suggestive of CKD, regardless of GFR level 4. UA: broad, waxy casts (evidence of loss of tubular concentrating ability) 5. May see anemia, metabolic acidosis, hyperphosphatemia, hypocalcemia, and hyperkalemia…with both acute and chronic renal failure 6. Further eval needed to differentiate between acute and chronic renal failure. Evidence of previously elevated BUN and creatinine, abnormal prior

UA, and stable but abnormal serum creatinine on successive days is most consistent with a chronic process

Imag ing

1. Ultrasound à Finding of small echogenic kidneys b/l (<10 cm) by US supports dx of CKD/irrev. dz  2. Xray à Radiological evidence of renal osteodystrophy is another helpful finding. Check phalanges of hands 3. Dopler ultrasound 4. MRA 5. Static renal scan

o The Radiopharmaceutical is 99mTc- DMSA. o It is given intravenously. Image is obtained in 2 hours. o It binds sufficiently to the renal tubules and lasts for several hours. This will permit good renal cortical imaging. o The main clinical application of DMSA scan is in acute pyelonephritis in children.

Compl ica t ions

Uremia and other toxins accumulate in the blood and causing life threatening issues 1. Uremia induced platelet dysfunction à increased tendency to bleed and ecchymosis à ecchymosis and GI bleeding 2. Uremic pericarditis à chest pain, malaise à pericardial friction rub 3. Uremic encephalopathy à headache, confusion, coma

Prognos is

◦ Mortality higher for pts on dialysis than for age-matched controls ◦ Most common cause of death is cardiac dysfunction ◦ For those who require dialysis to sustain life, but decide against it, death ensues within days to weeks

 

His to logy resu l t o f rena l b iopsy

Normal g lomeru lus

Light micrograph of a normal glomerulus. o There are only 1 or 2 cells per capillary tuft, the capillary

lumens are open, o The thickness of the glomerular capillary wall (long

arrow) is similar to that of the tubular basement membranes (short arrow),

o The mesangial cells and mesangial matrix are located in the central or stalk regions of the tuft (arrows).

Acute pro l i fe ra t ive g lomeru lonephr i t i s

q Enlarged , hypercellular glomeruli. q Hypercellularity is caused by infiltration of both leucocytes and

monocytes, proliferation of endothelial and mesenchymal cells and in severe cases there crescent formation.

q Interstitial edema q Tubules often contain red cell casts

Membranopro l i fe ra t ive g lomeru lonephr i t i s

� Thickening of capillary walls, usually global and diffuse. � There is also hypercellularity. Much of this hypercellularity is

mesangial proliferation, and some of the capillary wall thickening is caused by mesangial interposition into the subendothelial zone of the capillary loops.

Foca l segmenta l g lomeru losc leros is

ü Biopsy from a patient with FSGS. ü One of the glomeruli shows segmental sclerosis while others

appear unremarkable. ü Tubular atrophy is also seen.

D iabet ic nephropathy (d i f fuse

g lomeru losc leros is)

ü Most common lesion in diabetic nephropathy. ü Diffuse increase in mesangial matrix and thickening of capillary

wall. ü Mesangial increase is typically associated with overall

thickening of GBM. ü Matrix deposition is PAS-positive. ü As the disease progresses, the expansion of mesangial areas

can extend to nodular configuration.

D iabet ic nephropathy (nodu lar

g lomeru los leros is)

ü Also known as Intercapillary glomerulosclerosis or Kimmelstiel-wilson disease.

ü Consists of largely acellular nodules that are located in the intercapillary regions.

ü Nodules vary in size and often have laminated appearance. ü They are ecsinophilic, argyrophilic, PAS-positive and stain

green with masson’s trichrome stain and blue with mallory’s stain.

ü Ultrastructurally they are composed of masses of extra cellular mesangial matrix which is the result of both increased synthesis and decreased degradation of mesangial matrix