UA&BF Renal Function, Renal Dz, and Renal Dz

The Urinary Tract

Kidney, Bilateral Ureters, Bladder, Urethra

Internal Gross Anatomy of Kidney

Nephrons are composed of two parts

Renal Corpuscle and Renal Tubules

Renal Corpsucle

Where blood is filtered; consists of the glomerulus and Bowmans’s capsule

Renal Tubules

Where selective reabsorption and secretion occurs; consists of the PCT(main site for reabsorption), loop of Henle(conserves water and creates hyperosmotic gradient), DCT(solute adjustment(aldosterone)), and CD(Final solute adjustment(aldosterone) and concentration(ADH))

The two kinds of nephrons

Cortical(85%) and Juxtamedullary(15%)

Cortical nephrons

Short loops of Henle; removal of waste products and reabsorption of nutrients

Juxtamedullary nephrons

Longer loops of Henle; concentrate urine

Renal Blood Circulation

Renal Artery(afferent arteriole and efferent arteriole) → Peritubular Capillary/PCT → Vasa Recta/Loop of Henle(maintains osmotic gradient necessary for renal concentration) → Peritubular Capillary/DCT → Renal Vein

Afferent arteriole

Large arteriole carrying blood to the glomerulus

Efferent arteriole

Smaller arteriole carrying blood away from the glomerulus

Functions of the Kidney:

Excretory: Eliminates toxic substances and waste

Regulatory: Maintains body electrolyte, fluid, and acid/base balance

Endocrine: Primary: produce hormones(rennin, erythropoietin, and prostaglandins); Secondary: Activate hormones produces elsewhere(Vitamin D)

Urine Production is dependent on

Renal blood flow, glomerular filtration, tubular reabsorption, and tubular secretion

Characteristics of Glomerular Filtration

Passive & nonselective filtration of blood

Glomerular Filtration Factors

Size/Charge(Glomerular Filtration Barrier) and Pressure(Net Positive Pressure)

Glomerular Filtration Barrier

3 layers based on size and charge.


1. Capillary endothelium- contains pores called fenestrations
2. Glomerular basement membrane- shield of negativity
3. Visceral epithelium- contains podocytes

Net Positive Pressure in Glomerulus

Hydrostatic pressure; Blood colloid osmotic(oncoid) pressure; capsular hydrostatic pressure

Glomerular filtration pressures are regulated by…

Juxtaglomerular apparatus by controlling arteriole size.

Low systemic BP leads to larger afferent and smaller efferent.

High systemic BP leads to smaller afferent and larger efferent.

Glomerular Filtration Rate(GFR)

Volume of plasma filtered by glomeruli per minute; normal GFR is about 120mL/min

Low GFR indicates

loss of glomerular filtration function & diminished renal function

How can GFR be estimated

eGFR or “clearance” test to evaluate glomerular function

Glomerular filtration results in what

Ultrafiltrate comprised of water, glucose, Na, Cl, other ions, HCO3, amino acids, small MW proteins, urea, uric acid, and creatinine. It has the same SG & pH of plasma

Tubular reabsorption and secretion is…

Selective

Tubular reabsorption returns water and useful nutrients to the blood via

Passive diffusion: Simple diffusion down a concentration gradient.

Active diffusion: Requires a protein carrier and energy

Active diffusion in tubular reabsorption is dependent on

Renal threshold: The plasma concentration at or above which increased amount of urine is excreted.

E.g. Glucose=160-180mg/dL

Tubular secretion results in 3 possible out comes for hydrogen ions, describe them.

1. Secreted protons combine w/ ammonia to excrete excess protons in the urine as ammonium ions
2. Secreted protons combine w/ phosphate ions to excrete excess protons in the urine as dihydrogen phosphate ions
3. Secreted protons combine w/ filtered HCO3 to return the buffer to the blood

Renal Concentrating function depends on

Creating and maintaining a hypertonic medulla which is necessary for the reabsorption of water by the descending loop of Henle & CD

Describe the Countercurrent Multiplier Mechanism

Because in the LoH the descending limb is permeable to only water(passive) and the ascending limb is permeable to only salts(active), this helps create the hypertonicity of the medulla. This has the main function of conserving water.

The term itself refers to how the filtrate flows in opposite direction up and down the LoH

Describe the Countercurrent Exchange Mechanism

Refers to how the filtrate of the LoH flows opposite to the blood in the Vasa Recta.

Requires that the blood in the Vasa Recta flow opposite to the LoH at a very slow rate.

On the descending portion, salt is reabsorbed into the blood while water is secreted.

On the ascending portion, salt is secreted into the interstitium, while water is reabsorbed

Which part of the Loop of Henle is permeable to Urea?

Medullary collecting duct

Describe the concept of Urea Trapping.

Net effect is to trap urea in the renal medulla, raising the osmotic activity of the interstitial fluid

Know the hormones produced by the kidney, their source, stimulating factor for synthesis, and action

Know the hormones regulated by the renal system, their source, stimulating factor for synthesis, and action

Function of RAAS

Maintains body’s BP by increasing sodium reabsorption in the DCT & blood vessel constriction.

When BP is high, rennin secretion is inhibited and sodium secretion is enhanced.

Where is ADH made and what does it do?

Made in the hypothalamus and stimulates renal water reabsorption in DCT and CD

Give an in depth definition of how ADH is released and its impact

High blood osmolality and a marked decrease in BP stimulates its release.

Increased blood osmolality = Increased ADH = Blood Osmolality decrease, Urine becomes more concentrated and less urine volume.

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Decreased blood osmolality = decreased ADH = Urine volume increases and is more dilute

What is the function of the PCT?

Reabsorbs: Na, Cl, K, bicarbonate, amino acids, glucose, urea, Ca

Secretes: Protons and NH3

What is the function of the descending loop of Henle?

Only reabsorbs water

What is the function of the ascending loop of Henle?

Reabsorbs: Na and Cl

Secretes: Urea

What is the function of the DCT?

Reabsorbs: Na(exchanges for aldosterone)

Secretes: Protons, K, bicarbonate, NH4

What is the function of the collecting duct?

Reabsorbs: Na(aldosterone), water(ADH), and urea

How much reabsorption occurs in the PCT

80% of all tubular reabsorption.

100% of glucose and amino acids(up to renal threshold)

70% of salts and water

What percentage of urine composition do solutes make up?

5%, the rest is water

What are the major organic solutes in urine?

Urea > Uric acid > Creatinine

Urea and creatinine can be used to ID a fluid as urine

What are the major and minor inorganic solutes in urine?

Major: Cl > Na > K

Minor: Phosphates & NH4

Aside from the organic and inorganic solutes, what other solutes may be found in urine

Medications

What formed elements can be found in urine and what can they indicate?

Cells, casts, crystals, mucus, and bacteria

Pathogenic when increasing excessively

What is the urine composition volume?

RR: 600-2000

Average: 1200-1500

What is the RR pH of blood and urine

Blood: 7.35 - 7.45

Urine: 4.5-8

What is the SG for urine composition

RR: 1.003 - 1.035

Ultrafiltrate: 1.010

What makes the solute composition of urine vary?

Hydration, metabolism, Dz processes, medications(diuretics)

What are the two categories of Renal Diseases

Based on structure initially affected and based on the time course of the disease

What are 4 renal structures that can be effected by renal diseases

Glomerular, tubular, interstitial, and vascular

What are the two types of renal diseases based of the time course of the disease

Acute Renal Failure: Rapid, within days to weeks

Chronic Renal Failure: Gradual loss of function, within years

What can a UA diagnostics test show about Renal Disease?

Glomerular damage or inflammation: Proteins present

Tubule damage: Renal tubular epithelial cells present

Infection: Bacteria, yeast, WBC present

What can a blood test show about Renal Diseases

Impaired filtering function: Increased BUN and creatinine

Renal loss: Decreased protein(albumin)

Aside from blood and UA tests, what are the other two types of diagnostic tests used to identify renal disease

Ultrasounds and kidney biopsy

What are the 5 categorizations for glomerular disease

Primary: Directly and specifically attacks only the glomeruli

Secondary: Systemic disease

Idiopathic: unknow cause

Acute: Quick

Chronic: Gradual

Describe the two possibilities of pathogenesis of glomerular injury

1. Immunological: most common


1. Circulating Immune complexes trapped in glomeruli
2. Auto-abs
2. Non immunological


1. Diabetic nephropathy
2. Exposure to toxins/chemicals

Understand the Glomerular Disease classification chart

Nephritic syndrome is a…

Sterile glomerular inflammation that can be either acute or chronic

Nephritic syndrome is characterized by…

Hematuria w/ dysmorphic RBC casts(RBC, granular, hyaline) and proteinuria

Other signs include oliguria

Describe Acute Glomerulonephritis

Inflamed and enlarged glomeruli.

Causes are immunological, often infections like post-strep A

Characterized by: Hematuria, RBC casts, and proteinuria

Rapidly progressive glomerulonephritis is a more serious form of acute glomerulonephritis that…

Progresses to renal failure within weeks - months

Describe what occurs during rapidly progressive glomerulonephritis as well as what accompanies it.

Macrophages damage capillary walls and Fibrin causes permanent damage to capillary tufts.

It is often accompanied by microscopic glomerular crescent formations.

What does the UA of rapidly progressive glomerulonephritis show?

Typical glomerulonephritis(dysmorphic RBC, RBC casts, proteinuria), but eventually progresses to more severe hyperproteinuria & decreased GFR

Chronic glomerulonephritis results from ___ and may eventually progress to _

Progressive, irreversible damage to the glomeruli; ESRD w/ anuria

What would a UA test of chronic glomerulonephritis show and what are some other signs of it?

UA: Hematuria, RBC casts, proteinuria, and broad and waxy casts

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Other signs: Oliguria and HTN

What are the causes of chronic glomerulonephritis

1. IgA nephropathy(Berger’s Dz)


1. IgA complexes deposit on and inflame the glomerular membrane
2. Dx is based on UA & Renal biopsy(deposition of IgA & complement)
2. Lupus nephritis


1. Antibodies attack the glomeruli and leave scarring

Describe nephrotic syndrome and its characteristics

Excessive permeability to plasma proteins in the glomerulus due to GBM change.

Characterized by: Massive proteinuria and lipiduria(oval fat bodies and fatty casts), no or mild hematuria.

Other signs: edema

What are the 3 kinds of primary nephrotic syndrome?

Minimal change Dz, Membranous nephropathy, and Focal segmental glomerulosclerosis

Describe Minimal change Dz of primary nephrotic syndrome

Allergic reaction, immunization, auto-immune d/o.

Primary cause of nephrotic syndrome in children.

Little evidence of glomerular scarring in kidney biopsy.

UA shows heavy proteinuria and lipiduria

Describe Membranous nephropathy of primary nephrotic syndrome

Unusual deposits of IgG and C3 immune deposits

Describe Focal segmental glomerulosclerosis of primary nephrotic syndrome.

Scarring of some glomeruli.

Secondary to other D/O(HIV or drugs-heroin & analgesic abuse.

Deposits of IgM & complement C3

What are the two most common causes of Secondary Nephrotic Syndrome

Diabetic Nephropathy and Hypertension(HTN)

Describe diabetic nephropathy and how it relates to Secondary Nephrotic Syndrome

Most common cause of ESRD.

Thickening of the glomerular basement membrane because of increased deposition of glycosylated proteins and sclerosis of vascular structure.

Tubular D/O may:


1. Effect (One/multiple) structures
2. Manifest w/ (focalized/generalized) dysfunction
3. Be (Hereditary/acquired)
4. Be (primary/secondary) to other Dz processes

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1. Both
2. Both
3. Both
4. Both

Understand this chart of tubular D/O

Describe what Renal Glucosuria is and what a UA test would show.

Occurs in PCT

Only affects reabsorption of glucose

UA: Consistent glycosuria w/ normal blood glucose(benign)

Understand this graph of Renal Tubular Acidosis(RTA)

Describe Cystinuria

Inherited defect in the renal PCT transporter protein that reabsorbs cystine and dibasic amino acids.

Excessive cystine from crystals in urine at an early age.

Describe Cystinosis

Inherited disease resulting in intracellular deposits of cystine.

Kidney and PCT cells are damaged, losing ability to normally reabsorb filtrate components

What would a UA show of cystinuria and cystinosis

Cystine crystals and all filtered substances in urine

What is Fanconi’s syndrome and how does one get it? What would a UA of it show

Generalized PCT reabsorption failure

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May be inherited w/ another genetic disorder or acquired in patients treated w/ nephrotoxic drugs

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UA: Glucosuria w/ normal blood glucose, generalized aminoaciduria, phosphaturia, and increased urine pH

What is renal Pseudohypoaldosteronism and who is most commonly affected by it

Renal tubules are unresponsive to aldosterone.

Most commonly affect infants w/ renal salt wasting(Increased urinary Na, Cl) & a normal GFR

What is Nephrogenic Diabetes Insipidus and What Characterizes it?

Failure of tubules to respond to ADH

Characterized by: polydipsia, polyuria, and a large volume(diuresis) of very dilute urine

What is Acute Tubular Necrosis(ATN) and what would a UA test of it show?

Destruction of renal epithelial cells.

UA: Renal tubular epithelial(RTE) cells, hematuria, casts(especially RTE casts)

What causes rapid onset of ATN

Ischemic damage and nephrotoxin damage(Hgb, Mgb, nephrotoxic abx, and ethylene glycol)

What do tubulo-interstitial diseases and UTIs have in common? What conditions do they include

They affect both the tubules and the interstitium.

Include

* Acute Interstitial Nephritis(AIN)
* Urinary Tract Infection(UTI)
* Upper UTI: pyelonephritis
* Acute pyelonephritis
* Chronic pyelonephritis
* Lower UTI
* Cystitis: Bladder Infection
* Urethritis: Urethra Infection

What is Acute Interstitial Nephritis(AIN) and what would a UA test show?

Allergic reaction to medication or toxins can cause inflammation of the interstitium.

UA: Increased eosinophils w/o bacteria(called sterile pyuria)

Describe Acute Pyelonephritis; what it is, its 2 possible causes, and what a UA test of it would show.

Infection of the kidneys

Causes:

* Bacteria ascend through ureters from lower UTI
* Bacteremia w/ bacteria localizing in the kidney

UA: Leukocyte esterase(+), nitrite(+/-), pyuria, WBC casts, bacteriuria, and bacterial casts

Describe Chronic Pyelonephritis and what a UA test would show.

Chronic inflammation resulting in permanent scarring progressing to renal failure.

Most serious tubulointerstital D/O

UA:

* Early stage: Same as acute pyelonephritis
* Late stage: Casts(WBC, bacteria, granular, broad & waxy), proteinuria, hematuria, decreased SG

What are Cystitis and Urethritis; what are they caused by and what would a UA test show?

Bacterial infection of lower UT

85% are caused by gram negative enteric bacteria(E. Coli)

UA: Many WBC, leukocyte esterase(+), bacterial nitrate(+/-)

Describe vascular disease.

One of the most common kidney Dz

Damage or narrowing of renal artery or intrarenal arterioles leading to ischemia(decreased perfusion of kidney)

Serum potassium decrease, urine potassium increase

What is Acute Renal Failure? What are it’s symptoms? What would test results show?

Rapid and severe loss of renal function(reversible).

Symptoms: Oliguria

Test results: GFR decrease and azotemia(blood BUN & creatinine levels increase); isosthenuria(lack of renal concentrating ability)

Understand this acute renal failure chart.

What is chronic renal failure? What are the test results for it vs the test results for ESRD?

Progressive, chronic loss of renal function.

Test results: Gradual decrease in GFR

Test results for ESRD:

* Marked decrease in GFR
* UA: Casts(granular, broad & waxy), Isosthenuria(loss of kidney concentrating function), significant proteinuria, glycosuria

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Understand this table about the stages of chronic kidney disease

What are renal calculi(kidney stones) and what are the precipitating factors for them?

Solid mineral salts are formed in the renal calyces, pelvis, ureters, or bladder.

Precipitating factors:

* Increase in urinary concentration(dehydration)
* Urinary stasis
* Favorable pH, varies depending on type
* Presence of a foreign seed body

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What are the most common types of kidney stones and what do UA findings show?

Most renal calculi contain calcium ions(80%), a/w renal failure.

Uric acid a/w gout

phosphate a/w UTI

UA: Hematuria, crystals