Kidney Pathology

kidney is the site of

urine formation (kidney to ureter to bladder to urethra)

functional unit of the kidney

nephron

the nephron acts to

filter the blood

the filtration membrane consists of

fenestrated endothelium, basement membrane, and podocytes

fenestrated endothelium

cell layer of glomerulus capillary surrounding kidney, with pores between

glomerulus

ball of capillaries around kidney

podocytes

unique form of epithelial cells, interdigitated foot processes to hold up the basement membrane

bowman's capsule

where we first collect filtered products from blood

filtrate

cell free, all elements of plasma except protein

the filtration membrane has two barriers

size barrier and charge barrier

size barrier

only allows what is necessary through, traps bigger elements of blood, 1st level of protection

charge barrier

negative charges are repelled by charge barrier because podocytes, fenestrated endothelium and basement membrane are all negatively charged (repels most proteins)

glomerular filtration rate

mL of blood the kidney can filter/min

normal GFR

120-130mL/min

if contents accumulate at the site of filtration

it will take longer to filter the blood, decreasing GFR

a low GFR will present with

imbalance of fluid and electrolytes and waste accumulation

minor injury of kidney

loss of negative charge at filtration membrane

without charge barrier with minor injury

small proteins can fit through the size barrier

minor injury shows

albuminuria, small proteins found in blood from fitting through size barrier, found in urine sample

with albuminuria, you will loose

oncotic pressure (albumin maintains it)

nephrotic syndrome

injury to glomerular membrane causing damage to podocytes and degradation of basement membrane

podocyte damage with nephrotic syndrome

effacement (flattening) and detachment of foot processes

with degradation of basement membrane with nephrotic syndrome a person will

lose size and charge barriers, allowing lots of protein in urine and resulting in rapid protein loss

criteria for nephrotic syndrome based on protein loss

>3.5g/day (losing lots of protein in the blood)

clinical manifestations of nephrotic syndrome

massive proteinuria (>3.5g/day), hypoproteinemia, generalized edema, hyperlipidemia/lipiduria

hypoproteineinemia (nephrotic)

decreased amount of protein in the blood

generalized edema with nephrotic

driven by low oncotic pressure (without albumin) in every capillary in the body, causing swelling everywhere

RAAS activates with nephrotic syndrome because

decreased oncotic pressure without albumin causes lots of fluid to leak out of the capillary and blood volume ends up decreasing, decreased kidney perfusion kicks on RAAS and it attempts to retain fluid in the same capillaries that are rapidly leaking - more fluid leaks

hyperlipidemia and lipiduria with nephrotic

anytime albumin increases from the liver, it will also make more lipoproteins - fats spills into the urine because there is so much in the blood

hyperlipidemia primes

platelets and increases activation and can damage vascular endothelial cells which increases thrombogenic potential

loss of transferrin (nephrotic)

can cause iron deficiency

loss of anti-thrombin III (nephrotic)

increases hypercoagulability of blood

1st place to experience lost anti-thrombin

renal vein (common clotting spot)

loss of low molecular weight complement proteins (nephrotic)

reduced ability to fight infections

nephritic syndrome

injury to glomerular membrane with inflammation

with nephritic system, the subendothelial immune complex deposition (from a cause) activates

an immune response and leukocyte recruitment

neutrophils and macrophages at the kidney act to

breakdown podocytes and basement membrane causing loss of size and charge barriers - proteins and RBCs leak out

since there is immune cell activation and plasma contents leaking out of the capillary

glomeruli is clogged with cells at the filtration barrier and decreases GFR

clinical manifestation of nephritic syndrome

reduced GFR (oliguria), hematuria, azotemia, hypertension, proteinuria

oliguria

decreased GFR leads to decreased urine production

normal urine production

800-2000mL/day

oliguria value for urine production

<400mL/day

hematuria

RBC in urine because of no size barrier

azotemia

blood has abnormally high levels of nitrogen compounds - elevated BUN and creatinine (waste products usually filtered at the kidney)

hypertension (nephritic)

low GFR means no filtering at glomerus and less flow in tubules stimulating RAAS which increases blood volume and vasoconstricts (mcula denza thinks its not getting enough BF)

proteinuria

<3.5g/day, cant stop it from crossing the membrane, but not draining from blood bc GFR is so low (only leaks a little)

acute kidney injury

rapid decline kidney function (not the same as nephrotic or nephritic syndrome)

pre-renal kidney injury

severe drop in BP and reduced bloodflow, reduced perfusion at kidney (block at afferent capillary)

intrarenal kidney injury

direct kidney damage (inflammation/infection, autoimmune disease, drugs, etc)

post renal kidney injury

obstruction of urine flow (rare because it would have to happen bilaterally)

all acute kidney injury leads to

oliguria

with prerenal injury, the kidney tries to

help the problem by increasing Na+ reabsorption and secreting creatinine

normal Bum:Cr ratio

10.1:15.1

BUN:Cr ratio pre-renal

20:1 (kidney secretes creatinine to try and help the issue)

intrarenal injury will present with

high Na+ excretion because of lost ability to reabsorb Na+ (since the damage is from within the kidney) and inability to try and compensate

BUN:Cr ratio for intrarenal injury

10.1:15.1 (normal because both levels rise proportionally)

clinical manifestation of acute kidney injury

acute reductions in GFR increasing blood levels of nitrogenous wastes (azotinia) and impaired fluid and electrolyte balance (symptoms reflect this) (metabolic acidosis because cant clear H+)

if minor injury goes without recovering it could be a cause of

nephrotic syndrome

if nephrotic syndrome, nephritic syndrome, and acute kidney injury all go without recovery, they can lead to

chronic kidney disease

chronic kidney disease

kidney damage or GFR <60mL/min/1.73m^2 for 3 months or longer

common causes for permanent loss of nephroms

diabetes, hypertension, etc.

pathogenesis of chronic kidney injury

inflammatory cells produce growth factors that stimulate fibroblasts, which lay down collagen in glomeruli causing non-reversible scarring - glomerulosclerosis

glumoerulosclerosis leads to

reduced size of renal cortices, reduced GFR from scar tissue, and tubular atrophy (no flow makes it smaller_

clinical manifestations of chronic kidney injury

uremia - accumulation of organic waste products (feel bad, poor quality of life)

other manifestations of chronic kidney injury

hypertension, edema, anemia, acidosis, hypocalcemia, osteodystrophies

hypertension from kidney injury

with low filtration you cant get rid of fluid, Na+ retention and H2O retention leading to volume overload

edema from kidney injury

hydrostatic pressure driven, peripheral edema because not peeing out fluids fast enough

anemia from kidney injury

not effective at releasing erythropoeitin, decreased stimulus to make RBCs

acidosis from kidney injury

kidney is the main buffer, low GFR means low regulation, can't get H+ filtered out fast enough

hypocalcemia from kidney injury

kidney is the last step to activate vitamin D, which is required for Ca2+ intake - kidney cant activate so its hard to get ca2+ in (can lead to hyperparathyroidism from low Ca2+ releasing parathyroid to compensate)

osteodystrophies from kidney injury

low Ca2+ so body resorbs Ca2+ from bone to use it as Ca2+ as reservoir, low BMD

stage 1 kidney disease

often no sx

stage 2 kidney disease

hypertension, proteinuria

stage 3 kidney disease

HTN, proteinuria, anemia, bone disease

stage 4 kidney disease

HTN, proteinuria, anemia, bone disease, fatigue, swelling, uremia

stage 5 kidney disease

kidney failure - dialysis (all sx)

dialysis

pumps blood out of body to filter in a machine then retunr it to patient (artificial kidney)

dialysis can be

fatiguing, long duration of treatment (may walk in hypertensive and walk out hypotensive) - can still do PT

AV fistula precaustions

surgical connection of artery and vein to do dialysis at one spot - never take BP on same side, nothing tight, right below the skin (lifeline)

continuous renal replacement therapy

24 hour dialysis for crticially ill patients, can do therapy at machine

kidney transplant

ultimate fix

PT implications with kidney failure

low to moderate exercise, long warm up and cool down

BP contraindication for exercise

>200/100

renal changes with age

reduced BF and # of nephrons, low GFR, fluid/electrolyte imbalance, increase urine volume

urological changes with age

reduced bladder capacity, frequent urination, shift in night time production of urine

urinary tract infection is most common at

bladder and urethra

types of UTI

lower - cystitis, upper - pyelonephritis

risk factors for UTI

obstruction or reflex, neurogenic disorders, sexually active females, post-menopausal females (low estrogen), men with prostate disease, catheterization, diabetes

pathogenesis of UTI

bacteria enters through urethra, bacteria adheres to urinary tract mucosa and colonizes, can travel up to the bladder or continue on to kidney

clinical manifestation of lower UTI - cystitis

increased urinary frequency, dysuria, pyruia, hematuria

clinical manifestations of upper UTI - pyelonephritis

flank pain (at kidney), high fever, malaise, confusion (and all cystitis symptoms - more serious)

prevention of UTI

drink fluids, wipe front to back, change sanitary pads, wash after sex, drink cranberry juice

UTI treatment

48 hours of antibiotic treatment