Renal system Flashcards
- Renal structure - Nephron
- Nephron 1 million
- Cortical area mostly.
- Nephron structure:
- renal corpuscle (glomerulus and bowmans capsule)
- juxtoglomerular apparatus
- renal tubules
- Renal struc - Glo/Bowmans cap
Made up of: parietal epithelium, urinary space, visc epi or podocytes (feet neg charged), glo basement membrane, capillaries, mesangium
- Renal struc - glom basement membrane
- Neg charged also.
- Less permeable to proteins.
- Injury to membrane and slits results in loss of neg charge and protein filters through.
- Renal struc - cap/mesangium
Capillaries - fenestrations to allow flow
Mesangium - macrophages, cells contractile
- Renal struc - juxtoglomerula- app
Jux cell- located afferent artery
- Sense stretch
- Produce and release renin
- Macula densa- located distal tubule near glo and sense Na
- Renal vessel
Receives 25% CO
Flow from cortex to medulla
More O2 needed in medulla for ATP
Susceptible to ischemic injury
- Autoregulation- tubuloglom feedback
Macula densa senses NaCl changes.
Decreased Na > renin release > afferent vasodilation, efferent vasoconstriction = Increase GFR.
Opposite with ^ Na.
Juxt cells - assess perfusion pressure. ^ MAP- afferent vasoconstriction.
Goal- ^ flow to glomerulus.
- Neural regulation of kidney blood flow
Sympathetic nerve -
renal artery/arterioles cause vasoconstriction
^ renin production
- Humoral reg of cort/med flow
Vasoconstriction: Angiotension II, ADH (vasopressin), endothelin
Vasodilation: NO, adenosin, Prostaglandins, dopamine
- Renal function test - Creatinine Clearance
Best indicator of renal func.
Overestimates GFR.
Normal - 120ml/min et 1.0 in serum.
UxV / P
- BUN
^ when GFR decreases.
Will rise only when 60% of renal function lost.
- BUN/Cr Ratio
10:1, 20:1 with prerenal failure.
Normal with RF as both are high.
- Fractional excretion of Na+
Integrity of tubular reabsorptive function.
If ^ 1% then tubular or glom damage.
- UA
Neg for rbc, wbc, protein, casts.
If rbc then blood into tubules.
If wbc then inflam process.
If epi cell then tub lumen degeneration or tub necrosis.
- Urine Formation - glomerular filtration
Fluid movement from cap to tub.
Filtrate devoid of cells or protein.
Nephron loss leads to compensatory hyperfiltration.
- Urine formation
Reabsorp- mvmt of substances, lytes from tub fluid into blood.
Secretion - secretion of sub from blood into tub fluid.
Concentration of tub fluid/urine - occurs in loop of henle and again in collecting ducts under ADH and aldosterone influence.
Renal production of rbc
Erythropoietin production stimulated by decrease in PaO2.
RF causes anemia.
Vit D
Made from cholesterol in skin by UV light.
Vit D inactive taken to liver. changed et taken to kidney to form Vit D under PTH influence.
Stimulates Ca and Phos absorp by sm intestine.
Stimulates osteoclast to reabsorp bone to increase Ca concen in extracellular fluid (subsides when Ca absorbed by sm intes).
- Renal regulation of fluid
Reabsorb in prox tubule along with Na reabsorp.
Aldosterone - controls Na absorp in dist tub and collect duct.
Vasopression (ADH) - targets water reabs in collect duct.
- Renal regulation of Na
Absorbed in proximal tubule and loop.
Cl passively follows.
Final reabsorp in dist tub and collect duct.
- Renal regulation of K
Same as Na.
Influenced by :
Serum K levels
Acid-base - H and K exchange for each other. Acidosis with ^ H = ^H into cell and K comes out. This decrease in K also decreases K secretion. Opposite with alkalosis.
Plasma osmolality - dist tub reabsorb Na from tub filtrate in exchange for K secretion.
Aldosterone - acts on collect duct to stimulate K secretion in exchange for Na reabsorp.
- Renal reg of calcium
Reabsorp in proximal tub.
In loop, tied to Na and k reabsorp.
In dist tub, influenced by PTH, calcitonin, acid base.
- Diuretics - osmotic
Acts on prox tub.
Attracts water not reabsorp.
Na and K excretion as well.
- Diuretics - loop
Decrease reabsorp of Na and K
Increase Ca and Mg elimination.
- Diuretics - thiazide
Acts at end of ascending loop.
Gentler.
Prevents Na, Cl, K reabsorp.
- Diuretics - aldosterone antagonists (K sparing)
Act on collect ducts.
Keeps K, rid of Na.
- Renal regulation of Hydrogen
Most secretion takes place in proximal tub.
Hydrogen excretion depends on:
Bicarb buffer system - tub secretion of excess H ions occurs in exchange for Na reabsorp.
When increased free H secreted into tub fluid make it acidic, then H must be buffered by:
Phos buffer system Ammonia buffer system takes 2-3 days.-
8.General defense mech of acid base distur
see
- Prerenal disorder etiology
Disorders that occur before the blood reaches the kidney.
Hypovolemia/hypotension decrease perfusion > decreased filtration pressure > decreased GFR
- Prerenal disorder etiology
Drugs like : ACE inhibitors (loss of efferent vasoconstriction = decreased GFR) NSAIDS - inhibit prostaglandin synthesis (vasodilator) et allows afferent vasoconstriction = decreases GFR. Structural lesions - hypoperfusion = decreased filtration pressure = decreased GFR.
- Intrarenal disease - Glomerular disease
Most are immune mechanisms. Antigen-antibody deposition Planted antigen in glomerulus Autoantibodies t cell mediated immunity
- Intrarenal disease - Glomerular disease- antigen antibody complex deposits
Antigen/Antibody Complex deposition may be deposited in: subepithelial (foot processes) subendothelial mesangial glom basement membrane
- Intrarenal disease - Glomerular disease - complex injury
Complexes produce injury in recruitment of neutrophils.
Complex complement system opsonins for neutrophil or are chemotactic for neutrophils.
Neutrophils and macrophages release: proteases, reactive oxygen species, fibroblasts, secrete cytokins - all causing damage to cells and gbm.
- Intrarenal disease - Glomerular disease - Tlymphocytes/NK cells
Also, T lymphocytes and NK cells
Platelet aggregation leading to fibrin deposit.
Vasodilation
Endothelial permeability alteration
GBM charge alteration letting protein and rbc to cross membrane
- Intrarenal disease - Glomerular disease - Mesangial cell activation
Mesangial cell activaton and proliferation leading to fibrosis and sclerosis of mesangium.
Basement membrane and glomerular thickening result from deposits, proteins, no negative charge.
- Intrarenal disease - Glomerular disease - podocyte inflam
Epithelial cell or podocytes are swollen, inflammatory mediator secretion, feet stretch, abnormal protein filtration.
Can lead to GBM denuding.
Irreversible podocyte not replaced.
Eventual decreased GFR due to mesangium fibrosis/sclerosis with less filtration occuring and leads nephron loss.
- Intrarenal disease - Glomerular disease - nephron loss
Nephron loss causes compensatory hypertrophy of glomerulus.
Blood flow designated to that nephron shuttled to other nephrons causing transcap HTN.
This initiates inflamm process causing fibrosis and sclerosis of glomeruli and damage tub causing intersititial fibrosis.
- Intrarenal disease Nephritic Syndrome
Hematuria Dec GFR Azotemia (Inc BUN, Cr) HTN Fluid and Na retention (edema
- Intrarenal disease Nephrotic Syndrom
Increased glomerular permeability to proteins: Proteinuria > 3.5g Hypoalbuminemia Edema, generalized Hyperlipidemia and lipiduria Prone to infections loss of IgG Thrombotic issues (antithrombin deficiency) Vit D deficiency Hyperparathyroidism
- Intrarenal disease Acute Glomerulonephritis - post infectious
Coomon in kids
Assoc with strep infection
Patho: deposition of immune complexes in glomerular cap endothelium (sub endo), mesangium, subepi, and GBM.
Leukocyte infiltration, proliferation of mesangial cells, complexes may be degraded or phagocytosed by leukocytes.
Clinical Manifestations:
Nephritic syndrome (7-10 days after infections)
hematuria
Response to Il-1 and TNFa
- Intrarenal disease Rapidly progressive glomerulonephritis
Etiology:
Infectious diseases, drugs, goodpastures sydnrome.
Patho:
Immune complex develop in situ causing glomerular injury.
Proliferation of parietal epi cells due to injury, macrophages, and fibrin formation. characterized by CRESCENTS.
Not charac by nephrotic syndrome.
- Intrarenal disease IgA Nephropathy
Common glomerulophritis
Follows URI 1-2 days after
Common in kids
IgA antibodies deposition in mesangium et CHARACTERISTIC.
IgA1 - mucous secretion, Gi Gu epi secretions.
IgA2 - found in blood.
- Intrarenal disease Ig A Nephropathy
Patho: Ros and proteases released. Mesangial cell proliferation leading to glomerulosclerosis. clinical manifestations: Nephritic syndrome. 50% progress to CRF
- Intrarenal disease Minimal Change Disease
Common cause of nephrotic syndrome in kids.
Patho:
T-cell mediated injury to podocyte.
With podocytes injury = Lose electrical and mechanical barrier to proteins.
Clinical manif:
Nephrotic syndrome
Preserved renal function
No HTN
- Intrarenal disease Membranous Nephropathy
Common cause of nephrotic syndrome in middle aged.
In response to antigen by podocytes.
Patho:
Depostion of complexes deposits of subepithelium along the GBM (CHARACTERISTIC).
Injury to foot processes, thickened GBM, glom sclerosis eventual.
Clinical manif:
Nephrotic syndrome
40% progress to endstage RF.
- Intrarenal disease Chronic Glomerulonephritis
Etio: Acute glomnephritis End stages of other glom diseases Patho: continued glomnephritis obliteration of glomerulus and intersitial fibrosis
Clinical manif:
progressive leading to RF
- Intrarenal disease Acute tubular injury
Primarily affect intersititium and tubules.
Characterized by tub epi cell destruction and ARF.
Etiology:
Ischemic ATI
Nephrotoxic ATI (mycins, nsaids, Iv dyes, poisons)
Patho:
Ischemia- decreased perf pressure, renin secretion, medullary hypoxia (leading to endothelial injury), endothelin secretion, decreased NO/PG = decreased GFR
Nephrotoxic:
causes tub cell injury (even if ischemic injury)
This injury disturbs blood flow = dec NO and PG.
Hypoxia leads to loss of cell polarity and adhesion.
Loss of adhesion leads to epi cells to slough and obstruct tubule which decreases perf pressure = decreased GFR.
Altered Na reabsorp leads to aff vasoconstriction by mac densa = dec GFR.
Interstitial pressure drops and tub collapses initiating inflamm response.
Eventual irreversible tub cell injury et necrosis/apoptosis.
Clinical manif: ARF Patchy tub epi necrosis UA - epi cell casts Fractional Na excretion < 99% Urine osmol is low.
- Intrarenal disease Cystic diseases of kidney
Characterized by dilation of tub structures and cyst formation.
- Intrarenal disease Polycystic disease
Common, manifests itself after 40 yrs.
Etiology: Polycystin 1 or 2 mutation.
Patho: genetic mutation leads to defect in cilia which sensing mechanism tells epi cells which way to grow.
Clinical manif: enlarged kidneys cysts interpersed pain hematuria HTN RF Simple cyts (no genetic alteration and located in cortical section)
- Intrarenal disease Pyelonephritis
Main cx: infection and inflamm of tub, interstitium, and renal pelvis.
Etiol:
Ascending infection from lower UTI
Seeding by bacteria in septicemia or endocarditis
Incompetent valves
obstruction
Neurogenic bladder
Patho:
Acute - interstitial inflamm, intratubular neurotphil aggregate, pus/abcesses in inters tissue and tubules, necrosis
Chronic - ongoing inflamm, progressive scarring and fibrosis, atrophy, calices and pelvis sclerosis. Can lead to end stage renal disease.
Clinic manif. Acute - fever chills, flank pain/CV Dysuria, polyuria UA (leukocyte casts, bacterial casts, WBC) Chronic - recurrent infection tub function defect RF
- Intrarenal disease Arterionephrosclerosis
Hyaline thickening of arteriole walls. Etiology: HTN Renal dysfunction Susceptible genes
Patho:
Vasoconstriction from HTn (Juxtaglom sensitive to MAP. with htn increased map - Mac densa causes aff vasoconstriction) cause decreased renal blood flow = ischemia of glomerulus.
Ongoing HTN - thickens arterial wall (remodeling) decreasing blood flow
HTN injures endothelium producing inflamm response
Renal hypoperfusion stimulates renin release
Proteins enter vessel walls thickening arterial walls which decreases flow.
Glom ischemia - mesangial cell prolif, accum ECM, prolif fibroblasts leading to glomsclerosis = reduction in GFr.
Malignant HTN
necrosis, hyperplastic arteriosclerosis, hemorrhages
Clinic manif:
proteinura
Hematuria
Renal insuff and failure
- Intrarenal disease Diabetic Nephropathy
Common cause of end stage failure.
Etiology:
Impairment of autoregulation of glom microcirculation.
Patho:
Loss of aff vasoconstriction leads to increased MAP.
Leads to glom HTN and hyperferfusion = glom injury
GBN thickens
Mesangial expansion and sclerosis (fibroblasts and increase matrix prolif).
Glomsclerosis from fibroblasts.
Proteins cause tub interstitial injury and fibrosis.
Clinic Manif:
Microalbinuria
Increasing proteinuria
Eventual renal insuff and failure
- Post Renal Disease - Obstructions
Blockage of urine flow causing retention
Etiol:
Mechanical - calculi, clots, prostate enlargement, scarring, neoplasms
Functional - neuropathic bladder, pg, spinal cord disease.
Patho:
dilation of renal pelvis and calyces
Compression of renal vasulature (already low flow to medulla = ischemia_
Back up in tub (diffuses into interstitium)
Altered tub func, impaired urine concentration ability, diminished GFR.
Decreased tub flow stimulates renin = HTN = injury
Obstruction = inflamm = intersitial fibrosis and atrophy
- Post Renal disease - calculi
Types:
Calcium oxalate/Ca phosphate stones
Uric acid stones
Struvite stones (mg)
Cystine stones
Clinical manif: Obstructive uropathy pain hematuria recurrent stone formation
Post renal disease - Acute cystitis
CX: symptomatic infection of urinary bladder
Etio: infection (ecoli, proteus,klebsiella Chemotherapuetic drugs radiation stones trauma
Clinic Manif: Urinary freq Low abd pain dysuria Increased wbc, fever, malaise UA >100k bacteria In elderly may be asymptomatic. Infections can lead to chronic cystitis, pyelonephritis
- Acute Renal Failure or injury
CX: rapid deterioration of renal function
Etio:
prerenal, intrarenal, or postrenal, esp if obstruction is sudden.
Clinic Manif:
Recent onset of azotemia (Hallmark sign), anuria, oliguria.
Three phases -
a. initiating event
b. maintenance phase - 1-2weeks, azotemia, sustained oliguria/anuria
c. recovery phase - months - dissipation of azotemia, improve ability to filter/conserve ions/fluid,
polyuria.
- Chronic Renal Failure
Progressive and irreversible loss of nephrons.
Etio:
pre,intra, postrenal diseases
Patho: Lossof nephrons due to htn = increased glom filtration pressure = hyperfiltration = subsequent fibrosis and scarring. Proteins filter through GBM, increase nephron destruction and loss.
4 Stages:
- Renal reserve - GRF 50% of normal (60ml.min)
- Renal insuff GRF 20-50% (24-60ml.min) azotemia, HTN from renin from MD, anemia.
- Renal failure - GRF less 20% of normal
- Endstage renal disease - GFR less than 5% of normal
Clinic manif:
Uremia
a. metabolic acidosis - nephron cannot secrete enough H or generate buffers. Kussmauls to blow off CO2.
b. Impaired acid base balance - oluguria, increase blood volume (pulm and periph edema, htn)
c. Renin-angiotensin-aldosterone stimulation - more htn and edema
d. ^ plasma K - arrhythmias
e. Decreased vit d activation - decreased serum calcium et is reabsorbed from bone = bone weakness, fibrosis
f. GI abnormalities - N/V, peptic ulcer
g. Inadquate extraction of Cr, uric acid, urea,other wastes - widespread cell inury, met encephalopathy, perip neuropathy, increased uric acid
h. Bone marrow suppression from poisons - plt suppression, leukocyte suppresion.
i. Inadequate elim of insulin and drugs - increaased blood sugar, dose adjustments
j. Erythropoietin production inadequate (normochromic, normocytic anemia)
k. frosty perspiration, ammonia breath, anorexia, nausea
