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The Renal System
David Carroll
[email protected]
https://www.davidontheinter.net
Learning Objectives
What you need to pass your
exam
Anatomy
Physiology
Pharmacology
Pathophysiology
Renal Anatomy
Renal Anatomy
• Each kidney has outer cortex
and inner medulla.
• Urine is formed within
functional subunits known as
nephrons.
Renal Anatomy
• Each kidney has outer cortex
and inner medulla.
• Urine is formed within
functional subunits known as
nephrons.
• Each nephron contains a
glomerulus, consisting of a tuft
of capillaries with an afferent
and efferent arteriole.
• The glomerulus is surrounded
by epithelium of the Bowman’s
capsule.
• Glomerulus and Bowman’s
capsule form renal corpuscle.
Renal Anatomy
• This initial filtrate is then modified by
a variety of secretory and
reabsorptive processes as it passes
through:
1. Proximal convoluted tubule
2. Loop of Henle
3. Distal convoluted tubule
4. Collecting duct
• The glomeruli and convoluted tubules
lie within outer cortex and loop of
Henle and collecting duct extend into
medullary region.
• End product, urine, is delivered via
renal pelvis to ureter.
What does the kidney do?
Removal of waste products
Maintenance of fluids & electrolytes
Acid-base balance
What does the kidney do?
Endocrine functions:
1. Blood pressure – Renin-angiotensin-aldosterone system
2. Haemoglobin – Erythropoeitin
3. Calcium & phosphate– Vitamin D activation
The Nephron
Functional unit of the
kidney (1,000,000)
Made up of:
Responsible for urine
formation
- Afferent and Efferent
arterioles
- Glomerulus
- Proximal Tubule
- Loop of Henle
- Distal Tubule
- Collecting Duct
Functions of the Nephron
Filtration
Reabsorption
Secretion
Excretion
Filtration
Kidneys alone receive approximately 25% of
cardiac output (sv X hr)
Cells, proteins, and other large molecules are
filtered out of the glomerulus (driven by Starling
forces) by a process of ultrafiltration, leaving an
ultrafiltrate that resembles plasma (except that the
ultrafiltrate has negligible plasma proteins) to
enter Bowman's space.
Reabsorption
Active Transport (requires ATP)
– Na+, K+ ATP pumps
Passive Transport
– Na+ symporters (glucose, amino acids, etc)
– Na+ antiporters (H+)
– Ion channels
– Osmosis
Reabsorption
Proximal tubule - reabsorbs 65 % of filtered Na+ as well as
Cl-, Ca2+, PO4, HCO3-. 75-90% of H20. Glucose, carbohydrates,
amino acids, and small proteins are also reabsorbed here
Loop of Henle - reabsorbs 25% of filtered Na+. Descending loop
impermeable to only water.
Distal tubule - reabsorbs 10% of filtered Na+ and reabsorbs
HCO3Collecting duct - reabsorbs the remaining 2% of Na+ only if
the hormone aldosterone is present. H20 depending on hormone ADH
Secretion
Proximal tubule – uric acid, bile salts,
metabolites, some drugs, some creatinine
Distal tubule – Most active secretion takes
place here including organic acids, K+, H+
and drugs
Regulation of Fluids & Electrolytes
Fluid balance is the concept of homeostasis, that the
amount of fluid lost is equal to the amount taken in.
Euvolaemia is the state of normal body fluid volume.
The major source of fluid loss is urine.
Fluid loss is regulated in the kidney hormonally. Largely
through RAAS and ADH.
Regulation of Fluids & Electrolytes
Na+ in particular is the major driving force of fluid shifts in the
body – it maintains ECF volume. Therefore it is hugely
important to maintain an appropriate Na+ balance.
+
99% of Na filtered in the glomerulus is reabsorbed. Transport
proteins in the renal tubule mediate Na+ reabsorption.
Na+ concentration gradient along the tubule allows sodium to
+
move into tubule cells. The gradient is maintained by the Na /
K+ ATPase pump.
Renin
Secreted in response to renal hypoperfusion
from juxta-glomerular apparatus – macula densa
Converts of angiotensinogen to angiotensin I
Direct Effects
Vasodilatation of afferent arteriole
+
Direct Na loss
Aldosterone
High [K+] or low [Na+] stimulates the secretion of aldosterone from adrenal cortex
Acts on DCT causing reabsorption of Na+ & water increasing ECF and increases blood
pressure
Final [K+] controlled in collecting duct by aldosterone, when aldosterone is absent, no K+
is excreted in the urine (Only means by which K+ is secreted)
Since water is passively reabsorbed down the osmotic gradient generated by Na+
transport, water reabsorption is also affected. This means that while it affects ECF volume it
has little effect on ECF [Na+], since reabsorbed Na+ is followed by a proportionate
amount of water.
Anti - Diuretic Hormone
Secreted from posterior pituitary
Secretion is ↑ if:
1. ↑ osmolality (ECF)
2. ↓ volume
3. ↓ atrial pressure
Promotes water reabsorption in the
distal convoluted tubule and collecting
duct
Also known as vasopressin – a direct
vasoconstrictor
Acid Base Regulation
• H+ levels are regulated through two buffering systems:
– Chemical buffers – binds to H+ e.g. Bicarbonate buffering system
– Physiological buffer – controls excretion of acids or bases
(kidneys) or volatile acids (lungs)
• Bicarbonate buffering system:
– CO2 + H2O
H2CO3
H+ + HCO3-
• The kidney acts as a physiological buffer:
– When pH is low excess H+ ions are secreted in the tubules via the
Na+/H+ exchanger and more bicarbonate is reabsorbed.
– When pH is high less bicarbonate is reabsorbed.
Assessment of renal function
Measure waste products of protein metabolism
- Measurement of plasma [urea] and [creatinine]
Creatinine clearance = UV/P
• U=urinary [creatinine]
• V= urinary output in 24 hours
• P= plasma [creatinine]
Glomerular Filtration Rate
Normal values are:
90-110 ml/min
80-125ml/min
In clinical practice an estimated GFR (eGFR) is provided
based on:
-
Plasma [creatinine]
Age
Gender
Ethnicity Renal Pharmacology
Loop Diuretics
MOA: Na/K/2Cl co-transporter blocker
Indications: oedema e.g. HF, resistant
hypertension
Cautions: can worsen gout, diabetes
Contra-indications: hypok+, anuria
Side effects: postural hypotension, hypok+,
hypona+, hypomg+
Thiazide Diuretics
MOA: inhibit Na reabsorption in DCT
Indications: Hypertension, heart failure
Cautions: can worsen gout, diabetes
NOT IN PREGNANCY
Side effects: postural hypotension, hypok+
, hypona+, hypomg+, hyperca2+, gout
(hyperuricaemia)
Potassium Sparing
MOA: aldosterone receptor antagonist
Indications: oedema/ascites from liver cirrhosis,
heart failure, primary hyperaldosteronism
Cautions: look out for hyperk+
Contra-indications: hyperk+, Addison’s disease
Side effects: gynacomastia, testicular atrophy,
menstrual disorders, alopecia, hirsutism
Drugs that make kidneys sad
Should be avoided in renal failure
e.g. NSAIDs, ACE-I, ARBs, aminoglycosides, large doses of
penicillins, ciclophosphamide, ciclosporine A, gold, penicillamine
What are the general principles of prescribing in renal failure?
• Reduced dose and/or increase the dosage interval according to
renal function, especially with drugs which have a small
therapeutic index
• Base changes on measures of renal function i.e. glomerular
filtration rate, serum creatinine
• Use plasma levels if possible – digoxin, gentamicin, ciclosporin.
• Avoid drugs which are nephrotoxic
Pathophysiology
Urinary Tract Infections
Causes:
Typically E. Coli (also Proteus,
Klebsiella, Staph e.g. epidermidis)
Risk Factors:
• Gender (ascending infectionshorter urethra in females)
• Stasis of urine (eg renal calculi,
reflux, tumours)
• Medical plastic (catheters)
P/C:
Symptoms:
Lower UTI (cystitis & urtheritis)frequency, urgency, dysuria
Upper UTI (pyelonephritis)- as
above plus fever, loin pain, rigors
Ix:
• Pre-treatment MSSU for
microscopy & culture. Urine
dipstick
• May need structural /functional
imaging to rule of reflux & renal
scarring if UTIs
recurrent
Acute Kidney Injury
Acute Kidney Injury (AKI) is common, expensive to manage,
prolongs hospitalization and is associated with increased
mortality
AKI is defined by an acute reduction in kidney function as
identified by an increase in the serum creatinine and reduction
in urine output.
Symptoms:
Anorexia, nausea & vomiting
Pruritis
Confusion, reduced consciousness
Acute Kidney Injury
Pre-Renal
•
•
Volume
depletion
•
Dehydration
•
Blood loss
Hypotension
•
Sepsis
•
Medications
•
Cardiac
failure
Renal
Post-Renal
•
Acute Tubular
Injury
•
Bladder outlet
obstruction
•
Interstitial
nephritis
•
•
Glomeruloneph
ritis
Bilateral
ureteric
obstruction.
•
Obstruction of
a single
functioning
kidney
•
Vasculitis
“Hidden” causes of CKD
Hypertension
Infection
Diabetes
Drugs
Kidney damage
or reduced GFR
for more than 3
months
Exotica
Nephritides
• 70% cases caused by diabetes, hypertension and
atherosclerosis.
Chronic Kidney Disease
Reduced GFR
•Fluid retention – tissue oedema and heart failure
•Reduced metabolite excretion – uraemia, increased lipids, increased plasma urate and [creatinine]
Reduced tubular function
•Reduced fluid reabsorption causing polyuria
•Reduced K+ secretion resulting in hyperkalaemia
•Reduced acid secretion resulting in metabolic acidosis
Anaemia
•Reduced erythropoietin production – normocytic normochromic anaemia
Renal bone disease
•Reduced vitamin D activation leads to decreased Ca2+ absorption from GIT
•Plasma phosphate elevated due to reduced renal excretion and reduced calcium
•Reduced levels of vitamin D and reduced calcium stimulate parathormone secretion
hyperparathyroidism
Cardiovascular complications
hypertension
•Activation of RAAS – increases PR
•Fluid retention leading to heart failure
atherosclerosis
•Increased cholesterol
secondary
Management of CKD
Renoprotection
• Maintain normal BP and restrict proteinuria
• Reducing angiotensin II activity – ACE inhibitors
• Reducing BP – diuretics and calcium channel blockers
• Manage other pathogenic conditions e.g. smoking, diabetes
Treat complications
• Anaemia - EPO
• Hyperlipidaemia - statins
• Hyperkalaemia – restrict intake
• Acidosis – oral bicarbonate
• Hyperphosphataemia – phosphate binders
• Ostemomalacia & secondary hyperparathyroidism – activated vit D analogues
Haemodialysis
• Deals with waste products and fluid/electrolyte overload
Acknowledgements
All images available via Wikimedia
Commons.
Questions?
Slides + supplementary notes will be
online
https://www.davidontheinter.net/notes/