5070: CKD

about how many kidneys are donated vs how many need transplants?

27k

90k need transplants

how many nephrons are are in each kidney?

1 million

about how many kidneys are donated vs how many need transplants?

27k

90k need transplants

how many nephrons are are in each kidney?

1 million

what does tubular reabsorption mean?

transport of substances out of urine and into capillary blood

what is glomerular filtration?

the ultrafiltration of plasma in the glomerulus

what is tubular secretion?

the transport of substances into the urine by taking out of the blood

what does a healthy kidney not let leak into the urine? x3 things

blood cells

proteins

glucose

what is creatinine

a product of muscle metabolism

what is urea?

a product of amino acid metabolism

what wastes does the kidney excrete in urine? x4 things

creatinine

urea

metabolic end products of drugs/hormones

acid

what is erythropoietin ?

what stimulates its release?

red blood cell growth factor

hypoxia

where does the action of erythropoietin take place?

what does it do here?

bone marrow

binds with its receptors, stimulates the production of RBCs

what does the kidney do to vitamin D2 and D3 to make it usable?

what does this allow it to help do/carry out?

second hydroxylation of Vit D2/D3

makes the active form necessary for calcium absorption

the kidney converts vitamin D to what?

what is this crucial for broadly in the body? x 3 things

its active form

bone health, Ca absorption in gut + kidneys

what does renin do in the body?

regulates blood volume and blood pressure via renin-angiotensin-aldosterone system

regarding gluconeogenesis, what are the kidneys able to do for the body?

can supply up to 10% of the body’s needed glucose

what 2 basic molecular features does the filtration membrane (aka glomerular barrier) select for?

size and charge

if the size of a molecule increases, what is its capacity for filtration through the kidney?

decreases

if the CHARGE of the molecule gets more negative, what is the chance for filtration?

decreases

what 2 molecular characteristics do plasma proteins have that NORMALLY prevent them from crossing the glomerular barrier?

large and negatively charged

where in the nephron is the site of filtration for the blood?

glomerulus

what are the 3 layers of the glomerulus?

1. fenestrated glomerular endothelium

2. basement membrane

3. filtration slits formed by pedicels of the podocytes

what do the basement membrane and proteins in filtration slit pores of the podocytes allow to pass through them?

what are 2 examples?

small molecules

glucose, metabolized drugs

what do the basement membrane and filtration slits of podocytes prevent from passing through them?

what are 2 examples of this?

cells

RBCs, larger proteins

where are mesangial cells located in the glomerulus?

in the filtration membrane, in the basement membranew

what is the function of the mesangial cells? x 4 things

provide structural support for glomerular capillaries

secrete matrix of proteins

phagocytosis

help regulate GFR

what are mesangial cells able to alter, and how do they do this?

alter available surface area for filtration, this affects GFR

through contracting and relaxing

during filtration, what two things are retained in the bloodstream?

RBCs and proteins

what charge does the basement membrane and podocytes have ?

what does this allow them to do?

negative

repels negatively charge proteins like albumin

why is the charge of the basement membrane and podocytes important?

helps glomerulus prevent plasma proteins from leaking into urine

the rest of the tubular structures of the nephron do what generally?

process the fluid

return 99% of filtered water and substances back to circulation

if the filtration membrane is damaged, what can occur?

proteins will leak through and end up in urine

where does glomerular filtrate leave the vascular space and enter the urine space ?

glomerular capillaries

what happens in the peritubular capillaries?

water, electrolytes, glucose, etc are reabsorbed by the renal tubules and returned to circulation

what does the urine contain, generally? x 5 things

hypertonic solution of water, some electrolytes, slightly acidic, metabolized drugs and hormones

what is the gold standard for measuring kidney function

GFR (glomerular filtration rate)

what is the GFR measuring?

the volume of filtrate produced per min by kidneys

what is the GFR we expect in a young adult male ?

~125 mL/min

what are 3 reasons for glomerular capillaries having such high filtration rates?

net filtration pressure is high

high surface area/permeability/fenestration

restricted movement of proteins/cells

why is net filtration pressure high in the glomerular capillaries?

high hydrostatic pressure, pushes fluid out of capillary

glomerular capillaries are how many times more permeable than muscle capillaries?

50x

what is GFR proportional to ? x 3 things

# of nephrons

surface area for filtration

renal blood flow

what does GFR tend to do as we age

decline

during a state of shock, what could we expect to happen in the kidney?

in the long term, what could this cause?

renal afferent arterioles constrict, reducing total renal blood flow and GFR

AKI

what actions regarding the afferent and efferent arterioles is GFR influenced by?

what does this influence on the glomerular capillaries?

constriction or dilation

influences the pressure

if there was an increased pressure in glomerular capillaries, what would this lead to?

increased GFR

if there was a decreased pressure in glomerular capillaries, what would this lead to?

decreased GFR

if there is a constricted afferent arteriole, what is the expected glomerular capillary pressure AND GFR?

decreased PGC AND GFR

if there is a dilated efferent arteriole, what is the expected glomerular capillary pressure and GFR?

decreased PGC and GFR

if there is a constricted efferent arteriole, what is the result on expected glomerular capillary pressure and GFR?

increased PGC and GFR

if there is dilation of the afferent arteriole, what is the expected glomerular capillary pressure and GFR?

increased PGC AND GFR

what are some glomerular abnormalities that occur? x4

sclerosis of glomerular vasc./bsmt membrane

scarring + deposition of immune complexes

loss of bsmt membrane charge

effacement of podocytes

what is sclerosis of glomerular vasculature and basement membrane usually caused by what two diseases?

DM, HTN

What is scarring and deposition of immune complexes (glomerular abnormality) usually caused by?

infection, SLE

what is loss of basement membrane charges, which normally repel protein filtration (type of glomerular abnormality) usually caused by?

diabetes

the effacement of podocytes means what?

what is this usually caused by?

change in morphology, including obliteration

diabetes

what are 3 tubular injuries that can occur in the nephron?

ischemic insult to deep medullary interstitium

more ROS vulnerability

hyperfiltration, esp w protein leakage

what are the 2 broad categories of kidney injury?

glomerular abnormalities

tubular injuries

which types of nephrons are at higher risk for ischemic event and why?

juxtamedullary nephrons

their loop of henle is long, extends into medulla. This area has less blood flow compared to cortex.

due to the high permeability of glomerular capillaries, they are more vulnerable to what generally? x 2 things

scarring and injury

what 4 things are glomerular capillaries susceptible to because of their high permeability?

bacteria/toxins

damaging antibodies

Ab-An complexes

complement proteins

where might ab-an complexes of SLE be deposited in the kidney?

glomerular basement membrane

if someone loses nephrons during a disease, what do we expect their GFR to do?

decrease

what is the #1 cause of ESRD?

diabetes mellitus

chronic hyperglycemia found in DM is associated with what 2 things ?

early hyperfiltration (increased GFR)

increased albumin excretion

during the initial stages of CKD, hyperfiltration is initially what type of mechanism?

what does it later become as CKD progresses?

compensatory

source of injury/loss of nephrons

what does AER stand for?

albumin excretion rate

what does normal filtration phase 2 mean ?

return of filtration to the normal, non-hyperfiltration range, but nephrons are damaged and GFR declines steeply

chronic hyperglycemia modifies endothelial cell properties and proteins in the glomerular basement membrane. How does this affect the filtration barrier?

alters its structure and function

what are the changes that diabetes can make in the nephrons? x 4 things

excessive vascular leakiness in kidneys

ROS/inflammation damage endothelium

glomerular bsmt membrane becomes thick, sclerotic, loses (-) charge

podocytes lose their shape (effacement) and their interlocking characteristic

what is the #2 cause of ESRD?

hypertension

what does HTN cause in small arteries and arterioles?

arteriosclerosis

What is the process of arteriosclerosis in small arteries/arterioles?

what is an early compensatory mechanism that could increase nephron injury?

smooth muscle layer thickens, lumen gets smaller

results in reduced renal blood flow and glomerular scarring

hyperfiltration

how is creatinine normally filtered and excreted? what is the rate that this is done at, and what is it dependent on?

normally freely filtered by the glomerulus and excreted in the urine at ~constant rate that is dependent on muscle mass and GFR

when GFR is decreased, how is the excretion of creatinine affected?

decreased excretion

increased serum creatinine (not as much is filtered + excreted)

what is the relationship between GFR/serum creatinine- inverse or proportional?

inverse relationship

when a patient’s serum creatinine increases, what has their kidney function done?

what is another way we can observe this?

kidney function has decreased

can be observed as decreased GFR

what is urea?

end-product of protein metabolism

what is the BUN test?

blood, urea, nitrogen

results of the BUN test can vary with what? x 3 things.

hydration status

dietary protein intake

renal function

what is the “less specific” marker of renal function?

BUN test

what is albuminuria?

leakage of albumin through the glomerular barrier when its integrity has been lost

what does uACR stand for?

urinary albumin/creatinine ratio

what substance’s measurement is GFR usually estimated from?

serum creatine

when does GFR usually reach adult function in children?

~1 year

as people age, what does the GFR usually do?

fall slowly with age

what are some concerns regarding reporting GFR?

sex of patient influencing inacurate estimate of GFR

in situations of patients having marginal CKD determined by their eGFR, what type of interpretation should be used?

careful interpretation

what is the definition of chronic kidney disease?

abnormalities of kidney structure/function, present for >3 months with either

a marker of kidney damage, or decreased GFR

what is the rate that is considered a decreased GFR?

<60 ml/min/1.73m2

what are the two things that indicate CKD, that patients should have 1+ of?

marker of kidney damage

decreased GFR

individuals with chronic kidney disease are how many times more likely to die of other diseases than progress to kidney failure?

what diseases especially?

16-40 x

cardiovascular disease

stage one of CKD with eGFR can be described with what eGFR and what term?

>90 eGFR

normal or high eGFR

stage 2 CKD has what eGFR and description?

60-89 eGFR

mildly decreased GFR

stage 3 CKD has what eGFR and description?

3a: 45-59 eGFR, mildly to moderately decreased

3b: 30-44 eGFR, moderately to severely decreased

stage 4 CKD with eGFR and description

15-29 eGFR

severely decreased GFR

stage 5 CKD with eGFR and despcription

<15

kidney failure (aka ESRD/ESKD)

what stage of CKD is considered kidney failure?

stage 5

what are the two measurements/ways that CKD can be staged?

eGFR

uACR

stage 1 CKD with uACR and definition ?

<30 uACR

normal or mildly increased

stage 2 CKD with uACR and definition

30-300

moderately increased