GFR

(Glomerular Filtration Rate)

125ml/min, determined by:

1. filtration pressure in glomerulus

2.permeability of glomerular membrane

Main force for filtration pressure: hydrostatic pressure in glomerular capillaries... Also, plasma oncotic pressure.

GFR Regulated by:

1. SNS

2. Autoregulation:

• afferent arteriole stretch
• tubuloglomerular feedback: macula densa sense ↑GFR, send signal to glomerulus to  ↓GFR.  Vasoactive prostaglandins involved.

Juxtaglomerular cells

Secret renin→Angiotensin II

Endothelial cells in glomerular capsule have ACE capabilities

Constrict afferent or efferent arteriole.

Cystitis Risk Factors

Risk Factors:

Chemical irritants

Foreign bodies

Immobility

Bladder dysfunction→urine stasis

Bacteria, fungi, parasites

Sexual activity, spermacides

DM

Poor hygiene

Dehydration

More common in females than males

Ascending Infection

Common agents: E. coli, Proteus, Enterobacter

Bacterial colonization, bacteria enter bladder, deranged vesicoureteral junction, vesicoureteral reflux, into intrarenal reflux.

Hematogenous infection

Common agents: Staphylococcus, E.coli

Bacteremia down aorta into kidney.

Cystitis:

Defenses & Clinical Manifestations

Defenses: dilution of urine, voiding of urine. Urea, low pH. Premenopausal.

Prostatic secretions.

Clinical manifestations: (10% are asymptomatic) Frequency, dysuria, suprapubic pain, cloudy urine, hematuria.

Cystitis:

Pathogenesis & Diagnosis

Pathogenesis: Invasion of pathogen, inflammation of urinary tract.

Diagnosis:

Dipstick UA: bacteria, RBCs, WBCs.

Culture may not be performed.

Cystitis:

Tx for Isolated Infx

Younger female: 3 day course of antibx

Younger male: 7-10 day course of antibx

F>65: 10 day course 

M>65: 14-28 day course

Some females have low dose prophylactic Rx. Persistent bacterial infx d/t structural prob: catheter, calculi, prostatitis, congenital structure, BPH, bowel incontinence.

All pts: avoid caffeine, ETOH, chocolate, spicy food, tomatoes, some berries. ↑fluid intake, cranberry juice.

Acute Pyelonephritis:

Defenses & Risk Factors

Defenses: same as for cystitis, plus vesicoureteral junction. 

Risk factors: same as for cystitis, vesicoureteral reflux, pregnancy, neurogenic bladder, urinary obstructions.

Acute Pyelonephritis:

Pathogenesis & Clinical Manifestations

Pathogenesis: Pathogens colonize in renal papilla, spreads to parenchyma, widespread inflammation, edema, arterial constriction, renal scarring.

Clinical manifestations: Sudden onset of fever and chills, costovertebral tenderness or pain, signs of UTI. (Infants, children, elderly have more generalized symptoms.)

Acute Pyelonephritis:

Diagnosis & Tx

Diagnosis: UA - WBCs, RBCs, WBC casts. Urine culture. CBC - ↑WBC, ↑neutrophils.

Treatment: antibiotics, hydration

Glomerulonephritis:

Definition & Etiologies

Def: Inflammation of the glomeruli

Etiologies: Immune disorders, drug exposure, toxins, vascular disease, systemic disease.

Glomerulonephritis:

Pathogenesis

Insult to body tissue → inflammatory cells in bloodstream migrate to glomerulus → antibody-antigen complex trapped in glomerular basement membrane → inflammatory damage → lysosomal enzymes released that degrade glomerular walls  → glomerulus loses selective permeability → fibrin gets deposited in Bowman's capsule →  ↓GFR → local vasocactive compounds angiotensins, leukotrienes reduce perfusion to glomerular capillaries → DCT increases Na+ and H2O reabsorption.

Glomerulonephritis:

Clinical Manifestations

Gross hematuria, red cell casts, white cell cast

Proteinuria

Azotemia and oliguria

Edema and Fluid Volume Excess (FVE)

Periorbital edema

↑ BP

Glomerulonephritis:

Diagnosis

History of recent disease

UA: hematuria, proteinuria, RBC casts, WBC casts

↑ BUN, ↑ creatinine

Antibodies to strep

Renal biopsy

Glomerulonephritis:

Tx

Treatment: 

Treat causative factor

Dialysis

Antimicrobials,antihypertensives, steroids,   diuretics

Restrict Na+ intake

Nephrotic Syndrome:

Definition & Clinical Manifestations

Def: Collection of symptoms caused by a variety of renal disorders.

Clinical manifestations: Edema, hyperlipidemia, hypercoagulability, decreased immunity, vit D deficiency, hypocalcemia

Nephrotic Syndrome:

Pathogenesis

Increased glomerular permeability

↓

Proteinuria

Stimulation of                ↓

liver synthesis     ←    Hypoalbuminemia

  ↓         ↓                 ↓

Hyper-      ↓          Decreased plasma   → Generalized 

lipidemia   ↓          oncotic pressure        edema

    Excess clotting           ↓

        factors        Decreased blood volume

                       ↓                    ↓

                  RAA activation         ADH secretion

                       ↓                    ↓

                Salt & water retention      Water retention  

Nephrotic Syndrome:

Tx

Treatment: Treat underlying disease, steroids, sodium restriction, rest, diuretics.

Diet is low sodium, low sat fat, adequate to high proteins.

Vitamin D, iron, calcium.

Dialysis.  Transplant. 

Renal Calculi:

General info

Males 4x more likely to get.

50-60% recurrence rate in 10 years.

Increased concentration of solute, abnormal urinary pH, low urine volume, lack of stone formation inhibitors - citrates and magnesium.

Renal Calculi:

Calcium Oxalate

Excess bone reabsorption of calcium

Abnormal large intake of calcium or Vit D. Impaired renal function.

Hyperabsorption of oxalate - soy products, inflammatory bowel disease

Bowel surgery

Overdose of Vit C

Genetics

Fat malabsorption

Calcium: consume adequate calcium, Vit D.

Oxalate: peanuts, rhubarb, tea, coffee, spinach, nuts, choc.

Renal Calculi:

Struvite

Usually Proteus bacteria, contains enzyme that splits urea into 2 ammonia molecules.

This raises the urinary pH, stones form that include phosphate.

Prevent/treat infection.

Renal Calculi:

Uric Acid

From increased uric acid: gout, purines, chronic diarrhea, medications that cause rapid cell destruction.

Urinary pH too low.

High purine intake.

Limit organ meats, fish, purine-rich foods.

Renal Calculi:

Cystine

Hereditary, rare.

Renal Calculi:

Pathogenesis

Renal Calculi:

Clinical Manifestations & Diagnosis

Clinical manifestations: Ureteral colic pain. Sudden onset, proceeds quickly to intense, severe and sharp. Starts in flank, migrates to ipsilateral groin.

Diagnosis: Physical findings above.

UA: hematuria, urine pH, WBC. Serum BUN and creatinine to check renal function. KUB or CT or IVP to locate stone.

Renal Calculi:

Tx

Treatment: Lithotripsy

Prevention of future stones:

Dilute urine (drink 2L or more daily)

Medications

High fluid intake, ↓ Na+, adequate K+, fruits and vegetables.

↓ calculus-forming material

Acute Renal Failure

Sudden severe decrease in renal function that is potentially reversible. Decreased GFR, oliguria (<500ml/24°)/anuria, azotemia (urea nitrogen in blood).

At least 30ml/hr is functional.

40-60% mortality if not treated.

Acute Renal Failure:

General Risk Factors

Atherosclerosis, HTN, DM, CHF, liver disease, advanced age.

Medications: ACE inhibitors, diuretics, ASA, NSAIDS

Acute Renal Failure:

Prerenal Failure Causes

Caused by diminished perfusion of kidneys.

Hypovolemia - dehydration, blood loss.

Volume shifts

Decreased cardiac output

Myocardial infarction

Increased vascular resistance

Vascular obstruction

Septic shock

Acute Renal Failure:

Intrarenal Failure Causes

Caused by Acute Tubular Necrosis - proximal, distal, loop of Henle.

Trauma (crushing)

Antibiotics - Vanco, Gento

Severe muscule exertion

Infectious disease

Metabolic disorders

Gomerulonephritis, Vascular lesions, 

Solvents, pesticides

Heavy metals (lead, copper)

Acute Renal Failure:

Postrenal Failure Causes

Caused by obstruction of urinary flow at renal pelvis or below.  (Urine can't get out, backs up into the kidney.)

Ureteral obstruction

Bladder obstruction

Urethral obstruction

Acute Renal Failure:

Prerenal Failure

MAP drops below 70 (inadequate perfusion), autoregulation fails, GFR drops sharply, ischemia.

Pathogenesis: ↓ Flow rate, ↓ GFR, ↓ filtrate, → RAA system activated → Na+ and H2O retention →↓ urine output → azotemia.

↓ GFR → renal endothelial ischemia → release of vasoconstrictors & inhibition of vasodilators → ischemia of nephron → Acute Tubular Necrosis 

Acute Renal Failure:

Intrarenal Failure

Precipitating disease process (pre/postrenal fail, transfusion rxn, nephrotoxin, inflam. disease)→ischemic renal tubules shed intra-cellular debris into lumen of tubule→lumen obstructs→filtrate backs up in tubule to form retrograde pressure→increased pressure in Bowmans capsule→GFR slows profoundly→decreased renal perfusion overall→kidney becomes hypoxic→ renal blood vessels clog w/products of inflammation→kidney ceases to function.

Acute Renal Failure:

Postrenal Failure

Pathogenesis: Obstruction of urine flow distal to kidney → increase in retrograde pressure into kidney → increased pressure in Bowman's capsule → opposition to GFR → decreased urine formation → azotemia.

Buildup of retrograde urine in nephron → ischemia of nephron → Acute Tubular Necrosis

Acute Renal Failure:

Phases

1. Oliguric Phase (1-2 weeks) Debris in tubules slowing process. UO <500 ml/24hr

2. Diuretic Phase (2 days - 2 weeks) Obstruction is cleared. Very dilute; kidney can't filter well.

3. Convalescent Phase (3-12 months) Kidneys regain normal function.

Acute Renal Failure:

Diagnostics

Serum: ↑Creatinine, ↑BUN, ↑K+, ↑PO4, ↑Mg+

↓Ca+, ↓HCO3, ↓Arterial pH, ↓H/H

Na+ stays the same.

Urinary: ↑Glucose, ↑Protein, ↑RBC, ↑WBC

 ↓Specific gravity, ↓Creatinine

Overall, creatinine clearance in urine is best measure of renal function. Also x-ray, ultrasound, CT, nuclear medicine, etc. to assess renal blood flow & kidney structure.

Chronic Renal Failure:

General Info

Progressive loss of renal function over months to years. GFR<60 for 3 months or more.

Can be slowed but is ultimately irreversible.

ESRD if not treated with dialysis or transplant.

Fatal. 

Chronic Renal Failure:

Etiologies & Pathogenesis

ATN (Acute renal failure - Acute Tubular Nec.)

Congenital kidney conditions

Polycystic kidney disease

Infections

Renal cancer, benign renal tumors

Systemic diseases: DM, HTN, lupus, others.

Pathogenesis: tubular atrophy, glomerulo-sclerosis, fibrosis, infiltrates.

Chronic Renal Failure:

Stages

Decreased renal reserve: <75% nephron loss. No signs or symptoms. BUN/Creat normal.

Renal insufficiency: 75-90% nephron loss. Slight elevation in BUN/Creat. Polyuria, nocturia. May be controlled by diet/meds.

End Stage Renal Disease (ESRD): >90% nephron loss. Azotemia, uremia. Fluid/lyte abnormalties. Renal osteodystrophy (Ca+ leached out of bones). Dialysis or transplant necessary.

Chronic Renal Failure:

Clinical Manifestations & Diagnostics

Clinical manifestations of ESRD: Na+↑, fluid↑

Anuria leads to fluid overload (JVD, rales, bounding pulse, HTN, peripheral edema, "megalies"). Renal diabetes.  Renin causes RAA, causes fluid overload. Hormone irregularities (infertility, impotence, amenorrhea, ↓libido)

Osteodystrophies.

Dx in CRF: Same as for acute.

Tx: Nutritional, meds, dialysis, transplant.