Renal

urea

major end product of protein catabolism

creatinine

waste material produced by skeletal muscles

uric acid

nucleic acid breakdown product

kineys

the __ regulate:

• total body water/osmolality

• pH

• electrolytes

• mineral

• waste product excretion

endocrine

____ functions of the kidney

• erythropoietin

• 1-hydroxylase (necessary for vitamin D absorption)

• renin

paracrine

____ functions of the kidney

• bradykinin

• prostaglandins

• endothelial factors (NO, endothelin)

renal cortex

outer region of the kidney

renal medulla

inner portion of the kidney

renal pelvis

funnel-shaped reservoir that collects the urine and passes it to the ureter

Bowman's capsule

cup-shaped structure of the nephron that encloses the glomerulus, where filtration takes place.

proximal convoluted tubule (PCT)

segment of the nephron between the Bowman's capsule and the nephron loop

Loop of Henle (nephron loop)

part of the nephron composed of a descending limb and an ascending limb

distal convoluted tubule (DCT)

segment of the nephron between the nephron loop and the collecting duct

granular cells

cells in the wall of the afferent arteriole that contract when stimulated by stretch or the sympathetic nervous system. They synthesize, store, and release renin

macula densa cells

cells that monitor the NaCl content of the filtrate within the DCT

afferent arteriole

The small artery that carries blood toward the capillaries of the glomerulus.

efferent arteriole

The small artery that carries blood away from the capillaries of the glomerulus.

peritubular capillaries

The network of tiny blood vessels that surrounds the proximal and distal tubules in the kidney

vasa recta

capillary branches that supply loops of Henle in the medulla region of the kidney

glomerular filtration

The first step in urine formation in which substances in blood pass through the filtration membrane and the filtrate enters the proximal convoluted tubule of the nephron.

renal autoregulation (intrinsic controls)

myogenic mechanism and tubuloglomerular feedback

sympathetic stimulation and hormonal regulation (?)

What are the extrinsic controls of the urinary system?

myogenic regulation

smooth muscle in wall of afferent arteriole contracts in response to an increase in systemic blood pressure. Maintains glomerular blood pressure and GFR

tubuloglomerular feedback

"Back-up" mechanism by which glomerulus receives feedback on the status of the downstream tubular fluid and adjusts filtration to regulate the composition of the fluid, stabilize its own performance, and compensate for fluctuation in systemic blood pressure

increase in glomerular blood pressure and NaCl (?)

What is the stimulus for the tubuloglomerular feedback mechanism?

causes vasoconstriction and decreases GFR (?)

How does the sympathetic nervous system control glomerular filtration?

afferent arteriole and mesangial cells (?)

What are two areas that respond to the sympathetic nervous system in the renal corpuscle?

mesangial cells

contractile cells that help regulate glomerular filtration

mesangial cells (?)

what cells are stimulated by angiotensin II to contract and decrease the surface area of the filtration membrane?

afferent arteriole (?)

what vasoconstricts to decrease glomerular blood pressure and GFR when systemic blood pressure is increased?

decreases it (?)

Overall, what does the sympathetic nervous system do to glomerular filtration?

sodium reabsorption

65% is reabsorbed from the PCT

the PCT (?)

Where is the majority of bicarbonate reabsorbed?

the DCT (?)

Where would pH be regulated in the nephron?

concentration gradient in the interstitial fluid (?)

What does urea establish in the medulla of the kidney?

countercurrent multiplier

A positive feedback mechanism that is partially responsible for establishing the salt concentration gradient within the interstitial fluid

water (descending ?)

What is the descending limb of the loop of Henle permeable to

salts (descending ?)

What is the descending limb of the loop of Henle impermeable to?

result of the descending limb

water is moved from the tubular fluid into the interstitial fluid

salts (ascending ?)

What is the ascending limb of the loop of Henle permeable to?

water (ascending ?)

What is the ascending limb of the loop of Henle impermeable to?

the medulla (?)

Which gets saltier, the renal medulla or the renal cortex?

multiplied aspect of the countercurrent effect

As more water moves out of the descending limb the salt concentration in the tubular fluid increases which allows even more salts to be pumped out of the ascending limb

opposite to the loop of Henle (?)

Which direction does the vasa recta flow in comparison to the loop of Henle?

countercurrent exchange system

a system for exchanging materials or heat when the two different components flow in opposite directions past each other. The process by which the vasa recta help maintain the concentration gradient

recycled urea (?)

what makes up half of the medullary gradient?

the collecting duct, ascending limb, and the dct (_)

Urea is "cycled" between _________, ________, and _________.

the PCT (general reabsorption)

What part of the nephron will always reabsorb certain substances (sometimes 100%) because you will always need to keep them in your blood?

The nephron loop and surrounding vasa recta (?)

What structures are involved in establishing the medullary gradient?

the collecting duct (?)

where is the main site for regulating water and sodium reabsorption?

the distal convoluted tubule (?)

where is the other site for regulating water and sodium reabsorption?

renal clearance

How much of a substance can be cleared from the blood by the kidneys per given unit of time

Ex. GFR, creatinine clearance

GFR

Formula: C = UV/P

•Normal is 115–125 mL/min (corrected for body surface area)

•C is clearance rate (mL/min)

•U is the urine concentration (mg/dL)

•V is the urine volume excreted (mL/min or 24 hours)

•P is plasma concentration (mg/dL)

extrinsic regulation

SNS and vasoactive hormones (Ang II)

compensation in hypovolemia

Na+ concentration (high) sensed by the juxtaglomerular apparatus

• ADH release

• RAAS activation

compensation in hypotension

Juxtaglomerular apparatus senses low perfusion pressure

• RAAS activation

compensation in hypervolemia

• Natriuretic peptides are released in response to increased stretch

• they inhibit Na and H2O reabsorption

• vasodilate afferent arterioles

• vasoconstrict the efferent arterioles

• results in increased urine formation

compensation in hypertension

Nephrons increase their rates of filtration, reabsorption, and secretion to compensate for damaged nephrons (intact nephron theory). Leads to

• Glomerular hyperfiltration and increased glomerular capillary permeability leads to proteinuria, because proteins can now come through the membrane.

• Because proteins come in, they contribute to tubulointerstitial damage by accumulating and activating the inflammatory process.

K regulation

• Primarily regulated in the distal collecting duct

• Aldosterone = primary regulator

• Secreted in distal collecting ducts in response to aldosterone

Ca regulation

• PTH

• 1alpha-hydroxylation of 25-hydroxycholecalciferol (hepatic metabolite of vitamin D)

AKI

A sudden decline in kidney function with a decrease in glomerular filtration with a decrease in glomerular filtration and accumulation of nitrogenous waste products in the blood.

Acute failure = Rise in serum creatinine of 0.3 mg/dL or more within a 48-hour period or fall in urine output (UOP) to less than 0.5 mL/kg/h for at least six hours

AKI manifestations

Manifestations:

• Fatigue and malaise

• Later: dyspnea, orthopnea, rales, s3, peripheral edema, alt MS

• Oliguria (under 400 mL/day) can occur

• Nausea, vomiting with uremia

• Elevated blood urea nitrogen (BUN) to creatinine ratio

• Urinalysis

• Fractional excretion of sodium (FENa) under 1%

AKI treatment

prevention/treatment

• Correct fluid and electrolyte disturbances

• Manage blood pressure

• Prevent and treat infections

• Maintain nutrition

• Remember, certain drugs can be toxic

prerenal AKI

Most common type of AKI, results from low flow states or inadequate kidney perfusion.

• Due to hypovolemia from trauma, shock, GI losses, Dehydration, Sepsis, MI, HF, MODS, NSAIDS, Meds- contrast, renal artery stenosis, kidney edema some examples.

• The kidneys compensate initially by arteriolar vasodilation to increase GFR, and efferent vasoconstriction, mediated by Angiotensin II.

• But GFR eventually declines because of a decrease in filtration pressure, can progress to ATN or intrarenal AKI if untreated

intrarenal AKI

Glomerular, interstitial, vascular, and tubular

• Due to ischemic ATN, nephrotoxic ATN (due to radiocontrast, antibiotics like gentamycin), acute glomerulonephritis, vascular disease (DIC, malignant HTN), allograft rejection, interstitial disease (drug allergy, infection, tumors).

• MC cause is ATN

• Oliguria is common with intrarenal AKI, but anuria is rare.

• Proximal tubule is more vulnerable (brush boarder)

postrenal failure

• Due to obstruction that effects kidney bilaterally. (ie. B/L ureteral obstruction, bladder outlet obstruction- prostatic hypertrophy, tumors, neurogenic bladder, urethral obstruction)

• The obstruction causes increased pressure upstream and eventually decreased GFR.

• Symptoms of several hours of anuria with flank pain, followed by polyuria

FENa classification

Measures the tubular reabsorption of Na+.

A ___ of less than 1 means that 99% of Na is reabsorbed.

AKIN criteria

Criteria for AKI

• Abrupt within 48 hrs reduction in kidney function currently defined as

• an absolute increase in serum creatinine of 0.3 mg/dL or more (> 26.4)

• or  A percentage increase in serum creatinine of 50%

• or more (1.5 fold from baseline)

RIFLE classification

A classification for AKI

• Patients can be classified by either GFR or by UO.

• Criteria that supports the most severe classification should be used.

ATN patho

Patho:

• Severe hypoperfusion of tubular cells

• Tubular injury causes inflammation and GFR is decreased

• Cast formation leads to tubular obstruction

• Increased tubular intraluminal pressure leads to backleak

• Oliguria results

• 3 stages (oliguric, diuretic, and recovery)

CKD

Progressive loss of renal function, GFR less than 60 mL/min/1.73 m² for three months or more, irrespective of cause

• MC cause is DM (d/t nephron loss)

• Progressive damage causes surviving nephrons to sustain normal function (intact nephron theory)

• Proteinuria - Contributes to tubulointerstitial injury by promoting inflammation and progressive fibrosis

• Angiotensin II - Promotes glomerular hypertension and participates in tubulointerstitial fibrosis and scarring

• Increased workload on remaining nephrons

  • Hypertrophy

  • Increased glomerular capillary hydraulic pressure (leads to glomerular capillary HTN)

  • Increased GFR: hyperfiltration occurs

• More injury/destroys more nephrons, leads to glomerular sclerosis, leads to decreased GFR

• Azotemia (increased BUN and Cr)

• ESRD (uremia requires dialysis)

• Uremia: syndrome of multi-organ system derangement as a result of kidney failure

• Failure to synthesize/absorb/secrete renal products/accumulate nitrogenous waste

CKD manifestations

Manifestations:

• Edema

• Epistaxis

• Anemia

• Sallow pigmentation

• Pruritic excoriation

• Bruising

• Amenorrhea, impotence, infertility

• Myopathy

• Peripheral neuropathy

• HTN, HF, and pericarditis

• DOE

CKD treatment

Treatment/prevention:

• Reduce risk factors - HLD, diet

• BP control - ACEI and ARBs, slow down progression of proteinuria in patients with diabetic CKD

• Diabetes management

• Avoid nephrotoxic drugs

glomerulonephritis patho

Patho:

causes: postinfectious, primary renal dx, systemic dx

Immune

• Immune complex deposition (Type III hypersensitivity)

• Complement activation, leukocyte recruitment, and cytokine release

• Neutrophils, macrophages, and T cells damage membrane

• Glomerular enlargement d/t inflammation and swelling

Ischemic

• Hypoxic injury -> loss of membrane integrity 

Results in

• Increased membrane permeability and reduced surface area

• Glomerular capillary compression, decreased blood flow, hypoxic injury

• Normal negative charge is lost and damage to membrane alter normal filtration

acute nephritic syndrome patho

Patho:

Acute glomerular inflammation

• Due to immune complexes

• Hematuria with red cell casts

• Variable proteinuria

• Pyuria (WBC in urine)

• Diminished GFR

• Oliguria

• Patient gets HTN due to low GF

chronic glomerulonephritis

Progressive renal insufficiency leading to chronic kidney failure

Secondary causes:

• Diabetic nephropathy

  • Formation of advanced glycation end products

  • Podocyte injury, progressive thickening and fibrosis of the glomerular basement membrane, and expansion of the mesangial matrix

• Lupus nephritis

  • Inflammatory complication of the chronic autoimmune syndrome, systemic lupus erythematosus

  • Formation of autoantibodies against double-stranded deoxyribonucleic acid (DNA) and nucleosomes with glomerular deposition of the immune complexes

nephrolithiasis

Kidney stones/renal calculi

RF: Obesity, diabetes

nephrolithiasis patho

Patho:

• Mainly composed of calcium oxalate or uric acid (calcium phosphate MC in pregnancy, urine is alkaline)

• Supersaturated solution of crystal-forming molecules in the renal calyces.

• Stone may pass or may become lodged in the ureter or urethra

Prevention:

• Increase water intake

• reduce meat/poultry intake

• increase veggie intake

• avoid soda

diabetic nephropathy

definitions (microalbuminuria, proteinuria)

diagnostic criteria

diabetic nephropathy manifestations

Manifestations:

• Progressive decreases in GFR

• Progressive increases in proteinuria

diabetic nephropathy patho

Patho:

• metabolic, inflammatory, macrovascular, and microvascular complications due to chronic hyperglycemia

• Pathologic changes in DM:

  • thickening of the glomerular basement membrane
    expansion of the mesangial matrix and extracellular matrix

  • loss of basement membrane negative charges (can lead to nephrotic syndrome)

  • endothelial dysfunction

  • vascular fibrosis

• Leads to CKD & ESRD

cystitis

bladder infection, MC cause is E. Coli

pyelonephritis

Upper urinary tract infection, can be in ureters and kidneys. Due to obstruction of reflux of urine.

MC cause is E. coli

normal defense mechanisms

against UTI

• Low pH and high osmolality of urine

• Tamm-Horsefall protein

• Uroepithelium secretions

• Long urethra in men

• Mechanical defense (sphincter)

• Neutrophils and macrophages

UTI causes

MC causative agent: E. Coli

Uncommon agents: Klebsiella, Proteus, Pseudomonas, and Fungal

nephrotic syndrome

Primary

• minimal change disease (IgM in mesangium, effacement of podocyte foot vessels)

• Membranous glomerular nephritis (Mesangial expansions, capillary walls thicken, IgG and complement deposit in epithelium, glomerular BM thickens)

• Focal segmental glomerular sclerosis (Glomerular BM thickens, decreasing UOP d/t sclerosis)

Secondary

• SLE, diabetic nephropathy, amyloidosis, hep B & C, HIV

LOSS OF NEGATIVE CHARGE THAT NORMALLY REPELS PROTEINS FROM GLOMERULAR MEMBRANE

nephrotic syndrome manifestations

manifestations:

• Dyslipidemia

• Xanthomata

• Hypoalbuminemia

• Fatigue

• Leukonychia

• Edema – very significant (Periorbital, ascites, peripheral)

• Breathlessness, pleural effusion, fluid overload

• Frothy urine

PKD (polycystic kidney disease)

Genetic disease

• Autosomal dominant PKD or ADPKD

• Caused by genetic defect of:

  • The cell membrane protein polycystin-1 (PDK1) or:

  • The Ca+ permeable TRP (transient receptor potential channel polycystin-2) (PDK2)

age-related changes

• Kidney Mass: Decreases with age, particularly in the renal cortex where most nephrons reside.

• RBF and GFR: Both decline progressively after age 30; GFR decreases by approximately 1 mL/min per year.

• Nephron Number: Decreases due to sclerotic changes; remaining nephrons have reduced compensatory capacity.

• Fluid Balance: Older adults have a decreased thirst sensation and reduced ability to concentrate urine, increasing the risk of dehydration.

decreases (GFR)

Afferent arteriole ____ GFR

increases (GFR)

Efferent arteriole ___ GFR

erythropoiesis

The kidney do this in response to hypoxia; production fails when GFR drops below 30–45 mL/min.

Corticomedullary Gradient

A high solute concentration in the renal medulla maintained by the vasa recta and countercurrent exchange.

Distal Tubule & Collecting Duct

Sites of "fine-tuning" under hormonal control (Aldosterone for Na+/K+; ADH for water reabsorption).

Loop of Henle

Establishes the corticomedullary osmolarity gradient; descending limb reabsorbs water, ascending limb reabsorbs solutes (Na+, Cl-).

Proximal Tubule

Site of bulk reabsorption; recovers 2/3 of filtered water and electrolytes, plus all glucose and amino acids.

Autoregulation

The ability of the kidney to maintain constant RBF and GFR between systemic arterial pressures of 80 and 180 mmHg.

HF

Hydrostatic pressure is elevated d/t cardiac congestion, causing third spacing and low intravascular volume

cirrhosis

Low oncotic pressure (decreased albumin) and high hydrostatic pressure (hepatic congestion) leading to third spacing and intravascular volume depletion

nephrotic syndrome (volume regulation)

a fall in oncotic pressure due to a loss of protein in the urine