Proteinuria

Question 1

What are the types of proteinuria?

Answer 1

“normal” proteinuria

intermittent proteinuria

postural porteinuria

persistent proteinuria

Question 2

“norma” proteinuria

Answer 2

upper limit is 60 mg/M² or 100 mg/day

assuming 1.5 L of urine a day, the concentration should be around 7 mg/dL

50-60% plasma proteins - 40% albumin, 9% alpha1 globulins, 2% alpha2 globulins

hormones, enzymes, glycoproteins

40-50% protein of tissue origin - uromucoid, glycoproteins, etc.

Question 3

intermitten proteinuria

Answer 3

incidence of 20% in screenings

rarely indicates significant renal pathology

normally increased by exercise, stress, norepinephrine, renin, and other stimuli

Question 4

postural proteinuria

Answer 4

observed only when the subject assumes an upright or lordotic position

may be associated with mild glomerular histological abnormalities, but there is no evidence lnking this finding with significant renal disease

Question 5

persistent proteinuria

Answer 5

present when several urine collections obtained with the subject supine at rest contain detectable protein

Question 6

What are the two components to filtration?

Answer 6

permissive - facilitating filtration of small molecules

restrictive - retarding or preventing hte passage of larger molecules and solid elements of the blood

Question 7

Describe the structure of the glomerular tuft.

Answer 7

Question 8

Describe the structure of the glomerular filtration barrier.

Answer 8

inner fenestrated endothelial layer

glomerular basement membrane

visceral epithelial cells

Question 9

nephrin

Answer 9

a transmembrane protein of the immunoglobulin gene family that interacts in a homotypic fashion with nephrin molecules from an adjacent podocyte

Question 10

WHat is the size cutoff for glomerular filtration?

Answer 10

18-56 A

size-selective function is called steric hindrance

Question 11

What are the roles of a podocyte?

Answer 11

post-mitotic cell with highly specialized structure and function specific to the glomerulus

regulates permselectivity

structural support for capillary

remodeling of GBM

endocytosis of filtered proteins

Question 12

What are the selectivity criteria for filtration?

Answer 12

size (steric hindrance)

shape and deformability

hemodynamics (convection and diffusion)

charge

Question 13

diffusion vs convection across the glomerular filter

Answer 13

diffusion - moving down a concentration gradient, more likely in a patient who is more dehydrated

convection - being dragged across by increased filtration, more likely in a patient who has strong perfusion of fluid through the glomerular filter

Question 14

streaming potential

Answer 14

a model of glomerular filtration where negatively charged molcules get into the space between the podocytes and concentrate there to a certain extent

this prevents excessive filtration of negatively charged molecules and also prevents filtration of positive molecules

Question 15

How are filtered proteins reabsorbed into the plasma?

Answer 15

mostly reabsorbed in the proximal tubule

bindd to tubular transport proteins such as megalin, cubulin, and anmionless in clathrin-coated pits

some of this protein is pinocytosed into endocytic vesicles and degraded to constituent amino acids

other, particularly albumin, is reabsorbed intact through a poorly understood “salvage” pathway

Question 16

What proteins are secreted into the urine?

Answer 16

uromucoid (Tamm-Horsfall protein) is added in the distal tubule

other proteins are added in the bladder and lower urinary tract, some from accessory sex glands such as the prostate in males

Question 17

factors mediating autoregulation

Answer 17

vessel distension from tissue pressure

metabolic (buildup of vasoactive metabolites)

diversion of flow into shunt vessels

neural control

vascular remodeling (long-term)

renin-angiotensin system

Question 18

What are some clinical modulators of glomerular macromolecule handling? What are their mechanisms?

Answer 18

hypertension - excessive filtration pressure, unless protected by autoregulation

fluid overload - filtration equilibrium no reached, convection “drags” protein across filtration barrier

fever, obesity - increases metabolic activity

dehydration - hemoconcentration, increased diffusion of protein

sepsis - podocyte dysfunction alters slit diaphragm structure and function

Question 19

What tubular dysfunctions can lead to proteinuria?

Answer 19

proximal tubular dysfunction

Dent disease - proximal tubule x-linked condition, a cause of Fanconi syndrome

Fanconi syndrome

tubulointerstitial nephritis

nephrotoxins

Question 20

Fanconi syndrome (nephropathic cystinosis)

Answer 20

amino aciduria

glycosuria

phosphaturia

proximal renal tubular acidosis

Question 21

classification sof conditions that cause proteinuria

Answer 21

persistent proteinuria

postural proteinura

intermittent proteinuria

Question 22

causes of persistent proteinuria

Answer 22

increased glomerular permeability to plasma proteins due glomerulonephritis, primary nephrotic syndrome, and other factors such as hemodynamic factors, increased filtration fraction, and increased perfusion

decreased tubular reabsorption of filtered protein from Fanconi syndrome, Dent disease, tubulointerstitial nephritis, drugs, and toxins

overflow proteinuria from repeated albumin infusions or blood transfusions, myeloma, or leukemia as well as chronic kidney disease with decreased neprhon mass

secretory proteinuria from Tamm-Horsfall proteinuria, pyelonephritis, heavy metal poisoning, or prostate disease

histuria from urothelial carcinoma or diseases causing damage to the basement membranes

Question 23

causes of intermittent proteinuria

Answer 23

random finding

non-renal abnormalities such as fever, stress, exercise, exposure to cold

contamination of urine - vaginal secretions

false positive test

Question 24

What is the underlying pathophysiology of nephrotic syndrome?

Answer 24

significant loss of plasma protein in the urine leads to decreased levels of plasma proteins, peripheral edema and multiple metabolic abnormalities

these manifestations of nephrosis may represent an appropriate physiological response by the kidney to the initial changes in plasma proteins

Question 25

What are the four main findings in nephrotic syndrome?

Answer 25

proteinuria - usually considered to be at least 3 gm/day, children 50mg/kg/day, urine protein:creatinine > 2

hypoproteinemia (hypoalbuminemia) - with a serum albumin of less than 2 gm/dL

edema

hypercholesterolemia

Question 26

What is the difference between nephrosis and nephritis?

Answer 26

nephritis has a pathologic diagnosis denoting renal inflammation - low serum albumin, peripheral edema, decreased intravascular volume, significant edema, sometimes comes with hypertension, and CXR showing normal heart with pleural fluid

nephrosis characterizes the symptom complex without any particular disease process - renal inflammation, decreased GFR, increased intravascular volume, mild edema, hypertension usually, and CXR showing cardiomegaly and pulmonary edema

Question 27

What is the initiating event in the establishment of nephrosis?

Answer 27

urinary loss of albumin

some have decreased fractional excretion of many macromolecules

others have increased macromolecular clearance

Question 28

What are the two classes of nephrotic patients?

Answer 28

those with mainly albuminuria

those with so much generalized proteinuria that they become hypoalbuminemic

Question 29

What is the characteristic of nephrotic syndrome caused by chronic glomerulonephritis?

Answer 29

hyprid clearance curve - decreased clearance of smaller macromolecules and enhaced clearance of larger ones

Question 30

What are the causes decreased clearance of some molecules in nephrotic syndrome?

Answer 30

foot process effacement - less space between the podocyte foot processes

Question 31

What are the different theories why albumin levels are decreased when glomerular filtration is decreased?

Answer 31

effacement and loss of negative charge in the basement membrane allows albumin to be filtered

also believe that albumin being filtered can lead to loss of charge in the basement membrane

could be due to the fact that the glomerular filter is “heteroporous” where there are large pores that are more open due to disease and hemodynamics

Question 32

How does renal handling of beta2-microglobulin differ between glomerular and tubular dysfunction?

Answer 32

protein is freely filtered by glomerulus

normally low in the plasma

glomerular dysfunction - high serum levels, low urine levels

tubular dysfunction - low serum levels, high urine levels