phrm 825 renal pathophysiology

Bowman's capsule

100% filtrate produced

Proximal tubule

80% filtrate reabsorbed

Active and passive transport

loop of henle

8% filtrate reabsorbed

H2O and salt conservation

Distal tubule

9% filtrate reabsorbed

Variable reabsorption, active reabsorption

collecting tubule

4% filtrate reabsorbed

Variable salt and H2O reabsorption

Normal frequency of urination?

1mL/min

How does this change with a diuretic?

inc the flow

How might this impact medication adherence?

may have to go to bathroom more often because of the drug

measure kidney function

1. serum creatinine

2. BUN

3. Creatinine Clearance

4. GFR

Markers of Damage

1. Urinary abnormalities (protein, RBCs suggestive of membrane malfunctions)

2. Imaging abnormalities (MRI/CT scans)

kidney function declines with age due to...

1. decline in kidney mass

2. DEC in Nephron number

3. GFR DEC

compensatory response to renal injury

renal injury leads to a dec in nephrons that is compensated by HYPERTROPHY of remaining nephrons

BUT as time passes Lesions develop that prevent compensation

which leads to DEC GFR--> Azotemia--> uremic syndrome--> death

Intact Nephron Hypothesis

Loss of nephrons leads to remaining nephrons hypertrophying to compensate filtration, secretion an reabsorption

Hyperfiltration Hypothesis

intact nephrons after kidney insult are eventually damaged by inc plasma flow and GFR leading to maladaptation

Sources of kidney Injury/failure

HTN and Diabetes account for >60% of renal failure cases in US

pathophysiology of acute kidney failure

An increase in SCr ≥0.3 mg/dL (≥26.5 μmol/L) within 48 h; or

An increase in SCr >50% (≥1.5 times baseline), which is known or presumed to have occurred within the prior 7 days; or

A reduction in urine output (oliguria of

prerenal acute kidney injury

happens before the kidneys

intrinsic acute renal injury

happens in the kidneys

postrenal acute renal injury

happens after the kidneys

perfusion pressure

maintained by afferent vasodilation and efferent vasoconstriction

Affected (dec perfusion pressure):

-NSAIDs

-ACE-I and ARB

Major causes of intrinsic acute kidney injury

1. Sepsis

2. Ischemia

3. Nephrotoxins

post renal AKI (anatomic sites/causes of obstruction)

-ureter, bladder, sphincter, urethra

-stones, blood clots, tumor, strictures, etc.

common key elements of progressive

1. Increased glomerular capillary pressure

2. proteinuria

3. Glomerulosclerosis

Key abnormalities that give rise to CKD-MBD

1. Impaired phosphate excretion

2. Decreased production of 1,25-dihydroxyvitamin D3

Uremia

due largely to the accumulation of organic waste products, not all identified as yet, that are normally cleared by the kidneys

Nephrotic

Proteinuria ++++

Hematuria may occur

RBC casts: absent

Serum albumin: low

glomerulonephritis

1. inflammation of glomeruli

2. acute and chronic forms

3. presents w/ proteinuria and/or hematuria

4. Primary causes include inheritable trait (alport syndrome)

5. secondary causes include infections, drugs, and autoimmune disorders (vasculitis, Lupus)

6. IMMUNE RXN (Ab assoc injury, cell-mediated immune, etc)

KEY: renal cell death provokes the activation of numerous innate immune cells which cause inflammatory damage

pyelonephritis

Inflammation of kidney tissue

Acute and chronic forms

Presents flank pain with painful urination

Causes are bacteria from blood or urinary tract

White cells in urine

May lead to sepsis

interstitial nephritis

1. primary injury to renal tubules and interstitium

2. Undetected until causes significant decrese in renal function

Causes:

1. Drugs (70-75%), mostly antibiotics

2. Infection (4-10%)

3. Autoimmune (10-20%), SLE, sarcoidosis

Drugs assoc w/ interstitial Nephritis

Antibiotics

Anticonvulsants

Diuretics

Analgesics

Penicillins

most common cause of interstitial nephritis

-has a lot of break down roducts

Autosomal Dominant (adult) polycystic Kidney disease (APKD)

multiple expanding cysts of both kidneys that ultimately destroy the intervening parenchyma

pathogenesis of Autosomal Dominant APKD

Inherited mutation of PKD1 (Polycystic kidney disease-1) or PKD2 gene in renal tubular cells

Abnormal Cysts formation in both kidneys

Ultimately destroy the intervening parenchyma

Intermittent gross hematuria (blood in urine)

Hypertension and Urinary infection

Ultimately fatal → Renal transplantation is necessary

Autosomal Recessive Polycystic Kidney Disease Pathogenesis

autosomal recessive inheritance

mutation in PKHD1-fibrocystin (polyductin)

Autosomal Recessive Polycystic Kidney Disease Clinical features

Serious manifestations are usually present at birth

Young infants may die quickly from pulmonary or renal failure

Patients who survive infancy develop liver cirrhosis (congenital hepatic fibrosis)

Nephrolithiasis

aka kidney stones

lifetime prevalence: 10% men, 5% women

arises from a supersaturation of solutes (e.g. calcium)

Contrast-induced Nephropathy

25% increase in SCr within 72 of contrast media administration

CIN causes 1/3 of hospital-acquired AKI

Affects 1-2% US population

Hydration for prevention

Avoid concurrent nephrotoxins

Serum Creatinine is ____

– Predominantly removed by filtration

  – Increase = bad

Blood Urea Nitrogen (BUN) is a ____

– Measure of waste from liver breakdown of AAs

  – Increase = bad

Creatinine Clearance is____

Useful for predicting secretion and drug clearance

Nephritic

Proteinuria ++

Hematuria +++

RBC casts: present

Serum albumin: normal/slightly reduced

Nephritic Syndrome definition

Inflammation disrupting glomerular basement membrane

Nephrotic Syndrome definition

Podocyte damage leading to glomerular charge-barrier disruption