wk 11, lec 2 Flashcards by Claire Jamieson

therapeutics for hypertesnion

ARBs, ACE - reduce RAAS

diuretic- lose water and salt in urine

calcium channel blocker- vasodilate

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hypertension and arteriole tone

increased arteriole wall responsiveness to vasoactive stimuli –> vasoconstriction

increase resistance via lumen narrowing (arteriosclerosis)

hyaline deposite; brain, heart, renal

less vasodilation (i.e NO)

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arteriosclerosis in HTN

deposit ECM, hypertrophy and hyperplasia of smooth muscle cells

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hypertension and intravascular volume

Na+ and cant excrete; increase blood volume and mean arterial pressure

if not hypertensive then would down regulate Na/H and Na/Cl transporters if eat too much salt; but not in HTN

increased pressure causes atrophy and ischemic damage , glomerulosclerosis

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hypertesnion and autonomic nervous system

increase SNS and reset baroreceptor

Vasoconstriction of systemic arterioles (alpha-1 receptors)
Increased ADH release (increased water retention)
Increased release of renin and AT2

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renal denervation in hypertesnion

a procedure to ablate/ destroy SNS outflow to kidneys

to lower blood pressure and resistance

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hypertesnion and RAAS

both after ATII

AT2 receptors: vasodilation, sodium loss (natriuresis), NO proaction

AT1 receptors: vasoconstriction, increase BP, hypertesnion

activated via glomerular hypo perfusion or increase SNS

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hypertesnion and infalmmation

leukocytes

-activated by increase extraecullar sodium
-ILC3 and Th17 c ells for vascular remodelling esp in kidneys

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insulin resistance and obesity in hypertension

impair vasodilation

SGLT2 (sodium glucose) impacted

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antihypertesnives ACE and ARBs

ACE inhibitors: block angiotensin into ATII –> no vasoconstriction and Na+ retention

ARB (ATII receptor blockers): block AT1 receptors –> leads to dilation and block aldosterone secretion

both are potassium sparing diuretics

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loop and thiazide diuretics in hypertesnion

loop diretics: thick ascending limb block NKCC transporter, can cause hypokalmeia

thiazide diuretics: act on Na/Cl transport in DCT, less severe hypokalemia

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tubulointerstitial nephritis

causes

characteristics

cause acute kidney injury

Inflammation of the renal intersitium with variable
damage to the epithelial cells of the tubules - quick
Fibrosis of the renal interstitium as a consequence
of inflammation - slow
Atrophy/death of cells in tubular compartment –
can be quick, but slower than inflammation

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major causes of acute kidney injury

ATN, acute tubular necrosis;

DIC, disseminated intravascular
coagulation;

HTN, hypertension;

PCN, penicillin; PPI, proton pump inhibitors;

TTP/HUS, thrombotic
thrombocytopenic

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causes of acute tubulointerstitial nephritis

**vancomycine, iodinated IV contrast agents

medications (NSADIS, IV contrast, beta lactam, diuretics)

pyelonephritis

autoimmune

crystal nephroblathy

myoglobin from rhabdomylosos

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allergic interstitial nephritis (acute tubulointerstitial nephritis)

triad sx

allergy mediated
i.e. drug allergies (beta lactic, sulfonamid)

triad: eosinophilia, fever, skin rash

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lupus nephritis and sjogre syndrome causing tubulointerstitial nephritis

sjogren: lymphocytic invasion and chronic
fibrotic destruction of a variety of exocrine glands (especially eyes/ lacrimal, salivary glands) (infiltrate interstitiation and fibrous of tubules

lupus: Immune complex formation and tubulointerstitial
inflammation

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tubulointersitial nephritis clinical findings

cant concentrate urine (polyuria, nocturia)

salt wasting

cant excrete acids (metabolic acidosis) (hyperkalemia)

defects in tubular reabsorb and secrete

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Acute Tubular Necrosis

ischemia

tubular: mitochondrial injury, lose polarity, apoptosis and necrosis, desquamation of cells

microvascular: vasoconstriction increase, smooth muscle damage, leukocyte adhesions

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acute tubular necrosis pathophysio

mitochondria dysfunction, ROS

cant absorb salt and water; increase vascular resistance, reduce blood flow, more ROS and cytoksletal rearrange

cells detach from basement membrane and die; tubular back leak; edema

pathogenesis of acute tubular necrosis

Causes of Tubular Injury:
Toxic Injury (e.g., drugs, myoglobin, hemoglobin)
Ischemia (low blood flow) → leads to vasoconstriction and worsens injury

Results of Tubular Injury:
Tubular cells die and slough off

Leads to:
Tubular back-leak (fluid leaks into tissues instead of forming urine)
Obstruction (dead cells clog the tubule)
Interstitial inflammation
Decreased glomerular filtration rate (GFR) → less blood filtered

Clinical Effects:
Decreased urine output (oliguria)
Decreased GFR → worsened kidney function

injury causing acute tubular necrosis

drugs, myoglobin, hemoglobin

findings in acute tubular injury

rupture basement mamebrnae

necrosis

lose brush borders adn polarization

casts- granular proteinaceous mass of Tamm Horsfall protein (uromodulin)

leukocytes in vasa recta

casts in acute tubular injury

casts- granular proteinaceous mass of Tamm Horsfall protein (uromodulin)

3 phases of acute tubular injury

initiation phase: decrease urine output, increase BUN
maintenance phase: oliguria, salt and water overload, hyperkalemia, metabolic acidosis
recovery phase: increase urine volume, Na K and H2o loss due to loss of tubular function

Tubulointerstitial Nephritis (TIN) - Chronic causes

Vesico-ureteric reflux Chronic exposure to medications toxins (leads, cadmium) Hyper-uricemia or hyperoxaluria (crystal-induced) ▪ Chronic glomerulonephritis ▪ Chronic UTIs/pyelonephritis ▪ Long-term ischemia ▪ Sickle-cell disease

Tubulointerstitial Nephritis (TIN) - Chronic appearance

* Over time, fibrosis and tubular atrophy leads to shrunken kidneys macroscopically and a disorganized, cell-poor appearance microscopically ▪ Tubulointerstitial fibrosis

vesicoureteric reflux causing Tubulointerstitial Nephritis (TIN) - Chronic

Retrograde flow of urine from bladder to ureter detrusor muscle no longer effective valve chronic pyelonephritis; impaired filtration and atrophy thinned cortex hypertesnion and protreinuria

sickle cell nephropathy causing chronic Tubulointerstitial Nephritis

sickling events --> necrosis and inflammation--> atrophy and scarring hypertonic medulla proteinuria, hematuria, and reduced concentrating ability

urate nephropathy causing chronic Tubulointerstitial Nephritis

high levels of uric acid crystalline deposits in kidney parenchyma

benign nephrosclerosis

thickening of arteries in kidneys --> ischemia ▪ Glomerulosclerosis and chronic tubulointerstitial injury (ischemic) result ▪ Renders nephrons less effective risks: hypertesnion and diabetes

benign nephrosclerosis patholgoy

thicken tunica media and intima hyaline deposits, increase basement membrane shrink cortex, scarred narrow lumens ischemia: atrophy, necrosis, fibrosis

impacts of benign nephrosclerosis

Despite the many morphological changes, usually does not cause renal insufficiency or uremia, by itself small decrease in GFR and tubular function,

common causes of urianry tract obsructuoon

congenital anomalies urinary calculi benign prostatic hypertrophy tumors prenngacy uterine prolapse infalmmation (ie. prostatic) functional: diabetic nephropathy, spinal cord damage sloughed papillae

consequences of urinary tract obsruction

infections, stone formation renal atrophy ( hydronephrosis or obstructive uropathy) -->Dilation of the renal pelvis + calyces due to obstructive outflow of urine

acute vs chronic urinary tract infection

acute: pain, distention, oliguria chronic: hypertension, tubulointersitial nephritis, cant concentrate urine; polyuria, salt wasting

urolithiasis (kidney stones) types and most common

Calcium stones (70%) – calcium oxalate Struvite stones (15%) – magnesium ammonium phosphate Uric acid stones (5-10%) – associated with gout Cysteine (1-2%)

calcium oxalate stones

only 5% hypercalcemia mostly hypercalcuria (in urine) but serum is normal Calcium inhibits oxalate absorption from the intestine -->Therefore low calcium diets and/or high oxalate diets tend to greatly increase the risk of stone formation

struvite stones cause

kidney stones from bacterial infection; turn urea into ammonia urine is alkaline and precipitate magnesium salts cause: proteus mirabilis largest stones; stag horn calculi

uric acid stones

hyperuricemia (high uric acid) with or without gout, leukemia, Lesch-Nyhan syndrome 1/2 have normal serum uric acid

cystine stones

worse with acidic urine cysteine not reabsorbed but also other amino acids: ornithine, lysine, arginine

features of urolithiasis (kidney stones)

colicky and constant pain, N/V Smaller stones tend to be more dangerous acutely, since they will migrate down the ureters and cause obstruction as well as renal colic Larger and smaller stones can result in hematuria

complication in urolithiasis

unilateral so usually dont cause acute renal failure predispose pt to infection

Autosomal-dominant polycystic kidney disease gene mutation in??

Mutations in polycystin-1, polycystin-2, or fibrocystin Mutation of polycystin-1, which is an integral transmembrane protein that interacts with components of ECM * Can also be caused by mutation of polycystin-2, which is a calcium channel found in renal tubules

pathophysiology in Autosomal-dominant polycystic kidney disease

Altered mechanosensation by tubular cilia (sensing fluid flow is impaired) Altered calcium signaling (flux) inside kidney cells Both changes lead to altered tubular epithelial growth and differentiation, causing: Abnormal extracellular matrix production Excessive cell proliferation Excess fluid secretion into the tubules Result: Cyst formation in the kidneys Over time, cysts cause: Glomerular and blood vessel damage Inflammation and fibrosis (scarring) in the kidney tissue

Autosomal-dominant polycystic kidney disease clinical features

massive kidneys azotemia and uremia and hematuria liver cysts real failure dialysis and transplant needed