L1 Role of the kidneys in homeostasis and clinical cases

Pre-note
Post lecture note

Learning Outcomes

Understand the role of kidneys in homeostasis
Control of blood volume by kidneys
Maintenance of body pH by kidneys

Patient Case Overview

Patient: Mr. MD, 72 years old, retired chef
Medical History: Hypertension, atrial fibrillation, osteoarthritis, depression
Symptoms: Fever, nausea, weight loss, vomiting, itching, shortness of breath
Diagnosis possibilities: Kidney-related conditions

Functions of the Urinary System

Excretion: Removal of organic waste products
Elimination: Discharge of waste into the environment

Essential Renal Functions

Kidney produces urine

Ureter transports urine towards urinary bladder

Urinary bladder temporarily stores urine prior to elimination

Urethra conducts urine to exterior

Excretion of endogenous waste products and drugs with their metabolites
Homeostasis of water, electrolytes, and acid-base balance
Regulation of hormone production (e.g., erythropoietin, renin)

Renal Function & Dysfunction

Renal failure can be acute (AKI) or chronic (CKD)
90% of renal failure is CKD, 10% is AKI
Severe renal failure can be fatal if untreated
Treatment: Dialysis or kidney transplantation

How Renal Dysfunction (Failure) shows in Relation to Each Essential Function

Renal Dysfunction or Failure is when the opposite of each essential function occurs

Excretion of endogenous waste products and drugs with their metabolites

Consequence: uraemia, azotaemia
Reason: Reduced renal excretory function

Excretion of drugs and their metabolites

Consequence: drug toxicity
Reason: reduced renal excretory function

Homeostasis of water, electrolytes, and acid-base balance

Consequence: metabolic

Reason: inability to maintain salt water and acid-base balance

Regulation of hormone production e.g. erythropoietin, renin

Consequence: anaemia, hypertension
Reason: compromised hormone function

Kidney's Role in Volume Homeostasis

Fluid Balance

the amount of water gained by the body each day equals the amount lost

Electrolyte Balance

the ion gain each day equals ion loss

Kidney's Role in Acid-Base Control

Acid-Base Balance

H+ gain is offset by H+ loss

Urine Formation Process

Glomerulus: Blood filtration
Proximal Tubule: Reabsorption/secretion
Loop of Henle: Urine concentration
Distal Tubule: Urine modification
Collecting Duct: Final urine modification

Renal, Cardiovascular and Respiratory Link

Hormonal Regulation of Water (ADH)

Alternative names: vasopressin or 8-arginine-vasopressin or AVP

ADH: Regulates water reabsorption
Plasma half-life: 10-15 min
Influenced by plasma osmolality and effective circulating volume (ECV)

ADH acts on V2 receptors on basal membrane of principle cells collecting duct causing an insertion of aquaporin-2 (AP-2) into apical surface

Most important hormone for water balance

Actions of ADH

Increases water reabsorption from the collecting ducts back into circulation, resulting in concentrated urine production.
Released in response to increased plasma osmolality and decreased effective circulating volume (ECV).
Triggers thirst to promote water intake, further increasing ECV.

Sensors and Pathways in Volume Regulation

Key Sensors

Plasma Osmolality and ECV: Detected by osmoreceptors and baroreceptors.
Efferent Pathways: Include ADH, thirst response, RAAS, Atrial Natriuretic Peptide (ANP), and SNS.

Effects on Renal Function

Short-term effects on heart rate and blood vessel pressure.
Long-term effects involve kidney function and Na+ excretion.

Control of Effective Circulating Volume (ECV)

Baroreceptors

Function: Detect changes in ECV; involved in regulating blood pressure and volume.
Types:
- Low-pressure receptors located in large systemic veins, cardiac atria, and pulmonary vasculature.
- High-pressure receptors in carotid sinus, aortic arch and renal afferent arteriole (renal baroreceptor).
CNS and liver sensors aren’t as important

Control of ECV

Mediated by feedback control via baroreceptor stimulation.
Triggers four effector pathways affecting renal function:
1. RAAS.
2. Sympathetic nervous system.
3. ADH release.
4. ANP release.
Key Point: Pathway 4 is unique in reducing blood pressure/volume.

Renin-Angiotensin-Aldosterone System (RAAS)

Primary Control: Renin release from the juxtaglomerular apparatus (JGA) regulates plasma Ang II levels.
Stimulated by:
- Decreased ECV (detected by renal baroreceptors).
- Decreased Na+ concentration (detected by macula densa cells).
- Decreased systemic blood pressure affecting SNS to JGA.

Actions of Angiotensin II

Enhances tubular Na+ transport, promoting Na+ and water reabsorption.
Stimulates aldosterone release from adrenal cortex, leading to increased Na+ reabsorption from distal tubule.
Acts on hypothalamus to stimulate thirst and ADH release into circulation.
Causes vasoconstriction of renal and systemic vessels, increasing systemic BP.

Longterm Effect: AngII causes renal cell hypertrophy for more protein synthesis of sodium transporters and channels

Aldosterone

Function: Collaborates with Ang II to increase ECV.
Stimulates Na+ reabsorption and K+ excretion in distal tubule and collecting duct.
Exerts indirect negative feedback on RAAS by increasing ECV and lowering plasma K+.
Conservers sodium and water
Excretes K+ from kidney which prevents large variations of K+ in plasma