Urinary Flashcards
Where are the kidneys located?
Retroperitoneal at T11-12
What is different about the anatomical structure of the right kidney as compared to the left and why?
Right is lower because of the liver
What organ has highest blood flow per 100g
Kidneys
400ml/min/100g
List the main functions of the kidneys
Regulation of ECF ions/volume
Excretion of waste products
Endocrine - e.g. RAA, Erithropoeitin
Metabolism - Vit D activation
Where is the glomerulus
Cortex
After reabsorption at the PCT, where do the ions go?
Peritubular capillaries
What is the major site of reabsorption in the nephron?
Pct
Where in the nephron H+ actively secreted?
Dct
Where loop of henle
Medulla
What does loop of henle do?
Set up increasing osmolarity gradient in medulla (main)
Also further reabsorption of salts
Dct function
Variable reabsorption of electrolytes and water
ALSO ACTIVELY SECRETES H+
Collecting duct function
Passes through increased osmolarity of medulla!
Na+ recovery: RAA, hence affect ecf volume
Water recovery: ADH, hence affect ecf osmolarity
Watch this video
https://youtu.be/gNwWxpWZQJ8
Talk through briefly an overview of the journey through kidney without going into specifics.
Blood in Renal corpuscle - ultrafiltrate Tubule system Medullary rays Ducts of Bellini Renal papillae
How is the renal corpuscle formed?
Primitive renal tubule envelopes growing glomerulus (capillary tuft pushes in it, and it is a blind ending tube so it envelopes it.
What is the primitive renal tubule a derivative of
Ureteric bud
Describe the structure of the filtration barrier at the renal corpuscle
Fenestrated capillaries, surrounded by the visceral layer of the bowman’s capsule
Visceral layer like meshwork. Has podocytes with foot processes that surround the capillaries, with gaps that act as filtration slits.
Parietal layer of bc forms funnel for ultrafiltrate
What are the two poles of the renal corpuscle?
Vascular
Urinary
I have windows but no door
I have feet but no hands
My windows and feet are separated by only a basement
What am I?
A renal corpuscle
Windows- fenestrations on capillary
Feet - podocytes
Basement - only one basement membrane shared between both
Histology of PCT
Simple cuboidal epithelium
pronounced brush border
Histology of thin descending limb of loop of Henle
(simp.squa@likeacapillary.com), no brush border
Histology of Thin ascending limb of loop of henle
Same as thin descending limb
(simp.squa@likeacapillary.com), no brush border
Histology of thick ascending limb of Loop of Henle
Best seen in the medulla – interspersed with thin limbs, vasa recta and collecting ducts • Simple cuboidal epithelium – no brush border • Active transport
DCT histology
Cortical • Makes contact with its “parent” glomerulus • Contain numerous mitochondria • Compared to PCT – No brush border – Larger lumen
What three groups of cells form the juxtaglomerular apparatus?
1) Macula densa
2) Juxtaglomerular cells (of afferent arteriole of glomerulus)
3) Extraglomerular mesangial cells (aka lacis cells)
Histology of collecting duct
Continuation of DCT via collecting tubule
• Similar appearance to the thick limbs of Henle’s loop
• But lumen is larger and tend to be more irregular rather than circular
Histology of ureter
A muscular tube • 2 layers of smooth muscle – a third appears in the lower 1/3 of the ureter • Lined by specialised epithelium – transitional epithelium, aka urinary epithelium or urothelium
Structure and histology of bladder
3 layers of muscle • Outer adventitia • Epithelium is transitional
Urothelium” • Stratified epithelium • “umbrella cells” on the surface layer which make
the epithelium impermeable
What is average resting renal blood flow. What does renal plasma flow mean?
1.1L
Plasma flow is amount of plasma in blood (taking out haematocrits which are 45% of blood)
List the blood supply to the nephron starting at the renal artery and ending at the renal vein.
Renal artery->segmental artery->interlobar artery->arcuate artery->interlobular artery->afferent arteriole->efferent arteriole->peritubular capillaries->venules->interlobular veins->arcuate veins-> interlobar veins->segmental veins->renal vein.
Why is it difficult for anions to pass through the filtration barrier at the renal corpuscle?
The basement membrane between the endothelium and visceral layer of the bowman’s capsule is an acellular, gelatinous layer which has glycoproteins.
These are negatively charged, hence repel anything else with a negative charge. Hence anions are less likely to pass through the barrier.
What three forces are involved in driving plasma into BC?
1) Hydrostatic force of glomerular capillary (forces plasma IN)
2) Hydrostatic force of Bowman’s capsule (forces plasma OUT)
3) Oncotic pressure of proteins in glom cap (sucks plasma back OUT)
How are short term changes in blood pressure dealt with to keep GFR stable?
Myogenic autoregulation: afferent arteriole responds by changing tone
Tubular-Glomerular feedback:
Macula densa cells in DCT
Sense changes in (Na)Cl concentration
Send chemical signals to vasodilate either arteriole (depending on whether GFR is increased or reduced).
Adenosine to vasodilate EA.
Prostaglandins to vasodilate AA.
What is/are the key Na transporter(s) in the PCT?
Na/H antiporter
Na/glucose symporter
What is/are the key Na transporter(s) in the Loop of Henle?
Na/K/2Cl Symporter
NKCCT
What is/are the key Na transporter(s) in the early DCT?
Na/Cl symporter
What is/are the key Na transporter(s) in the late DCT and collecting duct?
ENaC
ROMK
Renal Outer Medullary Potassium channels
In urinary, what is Tm?
Transport maximum - maximum concentration of a substance after which it will spill into urine
(Maximum reabsorption is taking place in nephron, so any more will be left in tubules and pass out)
Hence why diabetics may have glycosuria when hyperglycaemic
A patient was given morphine after surgery.
Morphine is an organic cation.
Describe the process of excretion of organic cations in the kidney at a celullar level.
Two important exchangers on apical membrane that work together with Na+/K ATPase (which is at the basolateral membrane)
- Na+/H+ exchanger
- H+/OC+ exchanger
At basolateral membrane, 3Na+/2K+ ATPase sets up favourable gradient
OC+ enters cell by carrier-mediated diffusion across bl membrane
Low Na inside cells favours Na/H exchange at apical membrane, resulting in low H+ in cell
This in turn favours H+/OC exchange at apical membrane
Examples of cations
Dopamine, adrenaline, morphine
Examples of anions
Bile salts, fatty acids, penicillin
What percentage of Na+ is reabsorbed at each part of the nephron?
67% PCT
25% Ascending LoH
5% DCT
3% CD
Effectors of Na reabsorption in kidney
Change in osmotic/hydrostatic pressure in peritubular capillaries (pressure natriuresis and diureses)
RAAS - Na reabso in PCT
Aldosterone - Priniciple cells DCT / CD
Briefly outline the segments of the PCT
S1 - glucose, aa main reabsorbed
S2 - cl- reabsorbed,
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What is glomerotubular balance?
PCT always tries to maintain 67% Na reabsorption to minimise downstream effects
If hypoxia, what part of nephron one of first affected?
LoH because TAL vv active
ADME
Absorption
Distribution
Metabolism
Excretion
What is the meaning of xenobiotic
Body sees (substance) as foreign
Define clearance
Rate of removal of drug by liver and kidney
What factors affect renal clearance?
How well the kidneys ‘see’ the drug i.e. Amount in plasma
Hence:
Lipophilicity - enters tissues, partitions to fats, ‘hidden’ vs hydrophilicity
Binding to plasma proteins - won’t pass filtration barrier
Binding to tissue proteins - again, hidden
What is apparent volume of distribution?
Assuming all tissue and fluid is one compartment for convenience, used to work out renal plasma flow
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Samuel was given penicillin for an infection. Penicillin is an anion. What effect will a drop in his urine pH have on the renal clearance of penicillin from his plasma?
The anion will become protonated
It will become electrically neutral hence more lipophilic
Can be reabsorbed in the nephron
Hence reduce clearance
What
Answer
Mineralocorticoid deficiency and excess symptoms
Deficiency: low sodium, dehydration, high potassium
Excess: high sodium, hypertension, low potassium
Glucocorticoid deficiency and excess features
Deficiency: low glucose, weight loss, nausea, hypotension, underweight
Excess: high glucose, weight gain, increased appetite, hypertension, cushingoid
Acth is released as…
Pomc -> acth and msh
Major cause of hyperthyroidism and its ttmt
Graves
Autoimmune activation of TSH receptors
Carbimazole
Major cause of hypothyroidism and its ttmt
Hashimotos
Autoimmune destruction of thyroid follicles and blocking of TSH receptors
Give oral T4 - measure TSH level, it will become normal when correct T4 dosage given
Plasma pH must be maintained within a tight range. Give values.
7.35-7.45
Why alkalaemia bad?
Alkalaemia lowers free calcium by causing Ca2+ ions to come
out of solution
Increases neuronal excitability
Parasthesia then Tetatany
Why acidaemia bad?
Increases plasma potassium ion concentration. Affects cardiac muscle - arrythmias.
Also, H+ denatures proteins
How can an change in ventilation cause a change in blood pH?
Hypervent = hypocapnia = low pCO2 - pH 👆( resp. Alkalaemia)
Hypovent = hypercap = high pCO2 - pH 👇(resp. Acidaemia)
Outline RAAS in control of bp
Low NaCl delivery to macula densa cells of DCT, low renal pressure, or sympathetic stimulation causes kidney to release renin.
Renin converts angiotensinogen into angiotensin 1
Angiotension 1 is converted to angiotensin 2 by ACE
Angiotensin 2 stimulates the adrenal glands to make aldosterone
It also vasoconstricts
AND ALSO INCREASES NA+ REABSORPTION IN PCT
Why do ACE inhibitors work?
Firstly, they stop angiotensin 1 from being converted to angiotensin 2 by inhibiting the ACE enzyme. This prevents the effects of AG2 such as Na+ reabsorption, vasoconstriction and stimulation of aldosterone production.
It also promotes vasodilation by increasing bradykinin, a local vasodilator, which is normally broken down by ACE. inhibiting ace thus results in more bradykinin, hence even less vasoconstriction.
Natriuresis = loss of Na+
Explain how the heart can be involved in promoting natriuresis
Atrial natriuretic peptide Released when cardiac myocytes stretched Increases Na loss Decreases circulating volume Eventual decrease in ANP