Kidney Disorders

Nephron Function

1. Filtration: glomerular filtrate is the same as plasma minus proteins and blood cells

2. Reabsorption: recover most of the filtrate in the tubules

3. Secretion: substances from blood and products by tubule cells

4. Excretion: urine output

Major Kidney Function: Glomerular Filtration

Modulation of afferent and efferent arteriolar tone by:

1. Autonomous vasoreactive reflex in afferent arteriole (AA)

2. Tubuloglomerular feedback in the macula densa (sodium)

3. Angiotensin II-mediated vascoconstriction of the efferent artierole (EA)

What does Renin Angiotensin System (RAS) respond to?

↓ blood pressure or volume

Overall, what does the Renin Angiotensin System (RAS) do?

↑ aldosterone secretion from the adrenal glands leading to ↑ Na+ (and H2O) reabsorption in the distal tubule (indirect mechanism to increase blood volume)

↑ Na+ (and H2O) reabsorption in the proximal tubule (direct mechanism to increase blood volume)

↑ systemic arteriolar vasoconstriction (direct mechanism to increase blood pressure)

What role does AG II play?

Plays an important role in the maintenance of blood pressure & in regulating glomerular filtration and kidney blood flow

-Starts with renin activation in response to low kidney blood flow

-Arteriolar vasoconstriction and increased volume by sodium and water reabsorption (directly and indirectly)

What is the Pathophysiology of CKD?

RAS activation and systemic hypertension (HTN) -> Hemodynamic/Nonhemodynamic Factors -> Albuminuria in

glomerular filtration -> Progression GFR reduction

How is CKD defined?

Presence of kidney damage/function at or after 3 months

What does ACR measure?

Structural Kidney damage (present of albuminuria)

What does GFR measure in terms of CKD?

measures abnormal kidney function,

G stage (G1-G5) cannot be reversed = drugs can only slow down GFR damage progression

How is Acute Kidney Injury (AKI) defined?

Clinical syndrome of rapid (days to weeks) deterioration of kidney function, reversible

↑ serum creatinine (SCr) and/or ↓ urine output (UOP)

AKI Pathophysiology, Prerenal (before the kidney)

↓ blood flow to the kidney

↓ cardiac output, SNS activation, RAS activation

AKI Pathophysiology, Intrarenal (within the kidney)

Damage to the glomerulus, tubule, or interstitium (tissue in between the tubules)

↓ renal blood flow, RAS activation

AKI Pathophysiology, Postrenal (after the kidney)

Obstructed urine flow

AKI Staging, Cr criteria

Stage 1: Increased Cr x1.5 from baseline or >-0.3 mg/dl

Kidney Dysfunction Assessment Rules

Signs and symptoms a patient presents with depend on the cause of the kidney dysfunction,

some may present with some or all of the typical signs and symptoms or present with NO symptoms and only have signs that are detected from blood and urine testing

Symptoms of Kidney Dysfunction

Change in urine output (common but could also have no change or increased output), Change in weight (volume stats), Change in blood pressure from patient's normal/baseline,

Leg swelling, muscle cramping, nausea, vomiting, shortness of breath, confusion, flank pain, itchy skin, fatigue

Major Indices/sign of Kidney Damage?

Proteinuria/Albuminuria

Signs of Kidney Dysfunction, Blood Markers

↑ Scr, ↑ cys C

↓ eGFR

↑ BUN (uremia)

↑ K+ (hyperkalemia)

↑ Ph- (hyperphosphatemia)

↓ Bicarbonate (acidosis)

Signs of Kidney Dysfunction, Urine Markers

Albuminuria, Hematuria, Glucosuria

Maintaining Osmotic Equilibrium

Antidiuretic hormone (ADH):

Activated by: ↓plasma volume detected by baroreceptors

Inhibited by: ↑plasma volume detected by baroreceptors

Opens up a channel that allows electrolyte-free water to flow from the tubule into the blood:

-Puts water back into body to normalize osmolality

Volume Disorders, Hypovolemia

State of combined salt and water loss

-Results in decrease in effective circulating volume (ECV); interstitial space may also be low or may be normal

Signs: Dehydration/ increased thirst, diarrhea, low bp, decreased weight, decreased urine, poor skin turgor, muscle cramping, dry mucus membrane

Volume Disorders, Euvolemia

ECV appears normal on clinical exam

Volume Disorders, Hypervolemia

State of salt retention and/or decreased water excretion, most easily seen in the interstitial space; ECV may appear normal or elevated on exam

Signs: any bp type, increased urine, swelling (leg edema, ascites, pulmonary edema), increased weight, SOB, decreased exercise capacity

Hyponatremia Causes

due to a relative excess of total body water, not a lack of sodium, serum [Na+] <135 mEq/L

Hypovolemia: ↓↓Na+/↓H2O, Euvolemia: Na+/↑H2O, Hypervolemia: ↑Na+/↑↑H2O

Hyponatremia Pathophysiology

Situations where water IN >>> water OUT:

1. Ingestion of too much water which overwhelms normal kidneys

2. Ingestion of normal amounts of water in kidney failure

3. Ingestion of normal amounts of water in the presence of AVP (more common)

Hypernatremia

Due to a gain of sodium or (more often) a loss of water which is not corrected by thirst or AVP, serum [Na+] >145 mEq/L

Hypernatremia Pathophysiology

1. Generation: factors which predispose to hypernatremia

-gain of sodium or loss of water

2. Maintenance: factors which interfere with thrist

-failure to sense thirst or unable to ingest water

Hypokalemia causes

Can be caused by diarrhea, diuretics, or vomiting

Hyperkalemia

Can be caused by Kidney dysfunction (AKI or CKD), Aldosterone antagonists, Angiotensin-converting enzyme inhibitors (ACE-I), Angiotensin receptor blockers (ARB)