Patho Disorders of Renal Function

Nephron

structural and functional unit of the kidney comprised of 3 units

What are the 3 process of the nephron?

Glomerular filtration, tubular reabsorption, tubular secretion

Glomerular filtration

movement of protein-free plasma across the glomerular membrane dirven by hydrostatic pressure 

Tubular reabsorption 

movement of fluid and solutes from tubular lumen to the peritubular capillaries 

Tubular reabsorption

transfer of substances from the peritubular capillaries to the tubular lumen

Glomerular filtration rate

total volume of fluid filtered by the glomeruli approximately 120L/minute

what is the relationship between GFR and glomerular capillaries?

GFR is directly related to the perfusion pressure in the glomerular capillaries

Autoregulation and types 

strict maintenance to provide constant GFR, there is myogenic mechanism and tubuloglomerular feedback 

Autoregulation: Myogenic mechanism

as arterial pressure declines, glomerular perfusion increases; stretch on the afferent arteriolar smooth muscle decreases and arteriole relaxes

Autoregulation: tubuloglomerular feedback

when sodium filtration increases, GFR decreases

Autoregulation: hormonal mechanism 

Angiotensin II and Atrial natriuretic peptide (ANP)

Angiotensin II

constricts afferents and efferent arterioles, decreasing GFR

Atrial natriuretic peptide (ANP)

relaxes mesangial cells, increasing capillary surface area and GFR

Autoregulation: Neural regulation

SNS; strong sympathetic stimulation the afferent arterioles are constricted urine output is reduced 

Dysuria

(painful urination) buring or painful sensation during or immediately after

Nocturia

waking up frequently at night to pee

Incontinence

involuntary or accidental leakage

Hematuria

visible (gross) or microscopic blood in the urine

Proteinuria

protein (albumin) present in the urine

Bacteriuria

presence of bacteria in the urine 

Pyuria

pus in the urine; high number of leukocytes in the urine

Urinary casts

presence usually signifies that a problem originating in the kidney nephrons

Agenesis

failure of kidneys to develop 

Unilateral renal agenesis

absence or severe underdevelopment of one kidney

Hypoplasia

failure of one or two kidneys to develop to normal size

Ectopic kidney

kidney and ureter displaced out of normal position 

Horseshoe kidney

fusion of the two kidneys forming a U shape

Cystic Diseases

group of disorders characterized by formation of fluid filled sacs

Renal cyst 

dilated nephron tubule 

What can renal cyst cause

compression of renal blood vessels, degeneration of renal tissue, obstruction of tubular flow

Simple cyst

small solitary cysts that are usually harmless and does not require treatment

What population are simple cysts most common in 

elderly patients receiving dialysis 

Medullary sponge kidney

multiple dilations of collecting ducts in medulla, benign developmental defect, predispose to renal calculi and UTIs

Adult polycystic kidney (ADPKD)

autosomal dominant disorder, abnormal gene located on chromosome 16

ADPKD

First manifestations in adulthood around 40, multiple cyst develop in both kidneys

In ADPKD what causes multiple cysts to develop

abnormality in tubular cell differentiation; enlargement of kidneys, compression and destruction of kidney tissue, chronic renal failure

ADPKD manifestations 

hypertension (one of the earliest signs), flak pain, hematuria, infected kidney 

Flank pain

chronic or intermittent pain in the back due to the enlarged kidneys

Hematuria

rupture of cyst

Obstructive disorders

cause blockage of urine flow, leading to back up, urine retention and hydronephrosis

Upper urinary tract obstruction 

urine flow is blocked in the kidneys, renal pelvis, or ureters 

Lower urinary tract obstruction

urine flow is blocked in the bladder and urethra

Hydronephrosis 

water in the kidney urine is unable to drain properly and backs up, most damaging effects of obstruction, defined by distention of renal calyces  

Urolithiasis 

stones (calculi) develop anywhere in urinary tracts 

kidney stones tend to form with…

excessive amounts of solutes in filtrate, insufficient fluid intake, urinary tract infection, mainly occur with obstruction of urine flow

Urolithiasis types of stones

Calcium stones (oxalate or phosphate), struvite, uric acid stones

Calcium stones (oxalate or phosphate)

most common type, develop with high oxalate diet, dehydration, hyperparathyroidism

Struvite 

infectious calculi that is common with UITs 

What causes struvite

the pathogen proteus release urease, urea converted to ammonia, encourage stone formation. Staghorn calculus may develop over weeks (not caused by E. Coli)

Uric acid stones 

with high purine diet, purine is metabolized to uric acid 

Urolithiasis manifestations: Signs of kidney stones

stones are often asymptomatic, frequent infection leads to investigation

Urolithiasis manifestations: renal colic 

caused by obstruction of the ureter causing intense spasms of pain in flank area, that radiates to the groin, last until the stone passes or is removed. Hematuria and possible nausea and vomiting, cool moist skin, rapid pulse 

Urolithiasis treatment

small stones are passed on their own or Lithotripsy (ESWL) where large stones are crushed to pass with urine flow. Drugs can be used or surgery

Urolithiasis prevention

treatment of underlying condition, adjustment of urine pH through diet, increased fluid intake 

UTI

infection in any part of the urinary system, but most common in the lower tract (bladder and urethra)

Where do lower urinary tract infections take place

Bladder (cystitis) and urethra (urethritis)

Where do upper urinary tract infections take place

kidney pelvis (pyelitis), and kidney tissue (pyelonephritis)

Cystitis

inflammation in bladder

Urethritis

inflammation in urethra

pyelitis 

inflammation in kidney pelvis

Pyelonephritis

inflammation in kidney tissue and pelvis

Pathogens of UTIs: uncomplicated

most common Escherichia coli (present in colon) and staphylococcus saprophyticus

uropathic pathogens: complicated

gram-negative rods and gram positive cocci 

UTI predisposing factor 

UTIs are more common in women, prostatic hypertrophy due to compressed urethra leading to urine retention, congenital abnormalities in children

Frequent urge to urinate is due to

frequent urge to urinate

cystitis and urethritis manifestations

hyperactive bladder, pain in pelvic area, dysuria, nocturia,

Neonates UTIs symptoms 

Fever, abdominal distention, vomiting 

Infants UTI symptom

fever, feeding problems, foul smelling urine

Toddlers UTI symptom

abdominal pain, abnormal voiding patterns

Children UTI symptom

classic features more common

Vesicoureteral reflux

evaluate children with recurrent UTIs abnormal vesicoureteral reflux is short and micturition forces urine into ureter

UTIs and pregnancy

hormonal and anatomic changes increase the risk of UTIs; hormonal progesterone decreases peristaltic activity of ureters and anatomical: bladder displaced compressed with uterus, asymptomatic in 10% and there is an increased risk for pyelonephritis and toxemia 

Pyelonephritis

infection of one or both kidneys that ascends from the ureter into kidney, purulent exudate filles pelvis and calyces cause recurrent or chronic infection that can lead to scar tissue formation; obstruction and collection of filtrate cause hydronephrosis and this can also lead to the loss of tubule function and eventual chronic renal failure if untreated

Pyelonephritis manifestations

dull, aching pain in lower back or flank area, high temperature, urinalysis: urinary casts are present

Nephritic syndromes

group of clinical disorders characterized by proliferative inflammation there is acute poststreptococcal glomerulonephritis and gross proteinuria; most glomerular diseases produce mixed nephritic and nephrotic syndromes

Actue Poststreptococcal glomerulonephritis (APSGN)

most common form of nephritic syndrome, immune mediated, severe inflammatory response in glomeruli

Immune response in APSGN 

presence of antistreptococcal ASO antibodies, formation of an antigen antibody complex activates complement system 

What leads to the inflammatory response in glomeruli

increased capillary permeability leads to leakage of some protein and large numbers of erythrocytes and decreased GFR causes the retention of fluid and wastes

APSGN manifestations

decreased urine output, urine becomes dark and cloudy, facial and periorbital edema followed by general edema, elevated blood pressure due to increased renin secretion and decreased GFR, back pain

APSGN lab test indicators

elevated BUN (blood urea and creatinine levels), elevation of anti-streptococcal antibodies (antistreptolysin, antistreptokinase, metabolic acidosis (impaired excretion of H+) Urinalysis (proteinuria, hematuria, erythrocyte casts)

Increased capillary permeability leads to large amounts of plasma proteins escaping and causing what

proteinuria, hypoalbuminemia, edema, hyperlipidemia/hyperlipidemia

Hypertensive glomerular disease: nephrosclerosis

vascular changes in the kidney caused by poorly controlled hypertension, arteriole walls thicken and harden blood vessels become narrow and blood supply to kidneys is reduction leading to vasoconstriction and chronic renal failure 

renal cell carcinoma

most common primary tumor arising from tubule epithelium, typically in renal cortex, often metastasize occurs more freuently in men and smokers

Treatment of renal cell carcinoma

removal of kidney; tumor is radioresistant and chemotherapy is not used in most cases

Renal cell carcinoma manifestations 

painless hematuria, dull aching flank pain, palpable mass in abdomen, weight loss, anemia, paraneoplastic syndromes (hypercalcemia cushing syndrome) 

Wilms Tumor

most common malignant kidney tumor in children 3-5, its very aggressive but most curable, mutation in tumor suppressor genes on chromosome 11 increases the risk 90% cure if it hasn’t metastasized