Renal 11 to 20
Discuss how and where H+ is secreted in the kidney?
Prompt: How is Bicarbonate involved?
- Active secretion H+ ( H+/Na+ co transport- 2ary active secretion), allows reuptake of HCO3- from C anhydrase brush border_- H20/ CO2- Bic then into interstitium with Na via Na/K ATPase)
- Bic in cell transferred to Interstitium along gdt_
- In DCT/ Coll ducts- Principle cells/ Aldo- have H+ ATPAse channels + H/K ATPAse linked to Bic/ Cl- exchanger in BM
- 2 different mechanisms PLUS Bicarbonate
What is the limiting pH of urine and how is this limitation dealt with?
- pH 4.5 maximal acidity urine
- much > acidity required excreted
- 3 major BUFFER systems
- H2CO3 (proximal)
- HPO4 (distal)
Describe how sodium is handled in the glomerulus and the PCT.
- Most Filtered out with solutes/ AAs (90%)
- Most (60%) Na-H counter-transport,
- Bicarbonate is main anion reabsorbed with Na
- Absolutely depends on Na K ATP ase ( Basement M)/
- C Anhydrase-tub cell to generate H+/ Bic
- Small co-transport with nutrients /anions/ Cl latter part
- Approx 60%
- Good candidates will volunteer Na resorbtion through out except TALH, 60/30/7/3 % – all Na excretion last 3%
List the mechanisms that effect Na reabsorption.
- Tubulo-glom – Macula Densa, increased Na increased adenos/ Ca, aff vasocon
- Glomer/tub balance- > filtered = > resorbed (good capacity)- mainly oncotic p in eff capillaries
- Aldosterone- distal CT / ENaC, K+/H+
- PGE2 – pron Na K ATP ase block/ Ca ++ >
- Ouabain endog- ATP ase block effect
- Endothelin and IL-1 cause natriuresis (prob > PGE2)
- ANP-increased cGMP – less ENaC
- Angio 2- renal ACE increased circ Ang 1 + renal – increased PCT > reabs
Describe how anti-diuretic hormone/ Vasopressin acts on the kidney.
- ADH binds to G-receptor,
- V2 activates adenylate cyclase.
- Increased IC c-AMP -> migration of IC endosomes.
- H20 channels (aquaporin2) inserted into luminal membrane
- Increased water permeability, with increased water reabsorption
- Must list 3 properties
What factors influence ADH secretion?
- Table 39-1. Summary of stimuli affecting vasopressin secretion
- Vasopressin Secretion Increased
- Osmotic P of plasma increased 285mmol
- Decreased ECF
- Pain, emotion, “stress,” exercise
- Nausea and vomiting
- Clofibrate, carbamazepine
- Angiotensin II
- Vasopressin Secretion Decreased
- osmotic P of plasma decreased
- Increased ECF volume
- Must mention thick ascending limb of loop of Henle and reduced resorption of Na and Cl
Describe the physiologic process of Micturition.
Prompt: What are the nerves and muscles involved?
- A spinal reflex inhibited and facilitated by higher centres
- Intravesical pressure rises only after 400mls urine in bladder
- Anatomy: Detrusor m, int and ext urethral sphincters
- During micturition Detrusor contracts, and perineal muscles and EUS relax
- Nerve Supply: Parasympathetic (S 2,3,4,)
- via pelvic nn (afferent and efferents) to/from detrusor (efferent contraction) and pudendal nn to EUS (relaxation)
- Nerve Supply: Sympathetic (L1,2,3)
- Hypogastric nn via Inf Mesenteric Ganglion play no role in active micturition per se but role in prevention. (cause contraction of bladder muscle to prevent reflux of semen into bladder during ejaculation)
- Initiation – remains unsettled, pelvic floor muscle relaxation initiates. Perineal muscles and EUS can be contracted voluntarily for prolonged periods. Bladder SM has intrinsic contractile activity Post urination, female urethra empties by gravity.
- Male expels by contraction of bulbocavernosus m
List other factors that stimulate and inhibit micturition.
Prompt: What is the effect of autonomic agents on micturition?
- Stretch/pressure (intravesical volume > 400mls)
- Higher centre input
- Parasympathetics (eg organophosphates)
- Sympathetic inhibiting drug( eg a-blockers)
- Voluntary abdominal muscle contraction augments stream but does not initiate micturition per se
- Parasympathetic inhibitors (atropine)
- Higher centres
Describe how the nephron handles potassium.
- K+ is freely filtered at the glomerulus (~600 mEq/day).
- Most is reabsorbed by active transport in the proximal tubule (~560 mEq/day).
- K+ is then secreted by passive diffusion into the tubular fluid in the distal tubule.
- K+ is also generally passively secreted into the tubular fluid in the collecting ducts.
- The total K+ excretion is approximately equal to K+ intake (~90 mEq/day) and K+ balance is maintained.
- There is no direct exchange of K+ for Na+ in the tubular fluid of the distal nephron. However reabsorption of Na+ into the tubular cell tends to promote secretion of K+ (or H+) to maintain the potential difference across the apical membrane
- Bolded PLUS 1 iother
What factors influence this?
- The rate of secretion of K+ is proportional to the rate of flow of tubular fluid through the distal nephron. With rapid flow the concentration of K+ in the fluid remains lower and secretion continues.
- Increased delivery of Na+ to the collecting ducts promotes increased secretion of K+ (e.g. thiazide diuretics).
- Conversely decreased delivery of Na+ to the collecting ducts promotes decreased secretion of K+.
- Inhibition of K+ absorption in the proximal nephron (e.g. osmotic or loop diuretics) promotes excretion of K+.
- In the distal nephron K+ and H+ compete for secretion in association with reabsorption of Na+. Therefore in acidosis when H+ excretion is increased, K+ secretion is decreased.
- Aldosterone increases reabsorption of Na+ in the collecting ducts and thereby promotes K+ secretion.
- 2 of the 3 bolded
What is normal renal blood flow and how can it be measured?
- Fick principle (amount of a substance taken up per unit time divided by arterio-venous concentration difference)
- PAH (excreted, not metabolised or stored, doesn’t affect flow) is used to measure effective renal plasma flow (90% cleared)
ERPF = Clearance of PAH = UV/P = 630 mL/min
- Actual renal plasma flow = ERPF/0.9 = 700 mL/min
- Renal blood flow = RPF x 1/1-Hct (Hct = 0.45)
- Renal blood flow = approx 1250 mL/min
- Must list 3 properties
How do blood flow and oxygen extraction vary in different parts of the kidney?
- Cortical flow is high (5 mL/gm of tissue) and oxygen extraction is low
- Medullary blood flow is low (2.5 mL/gm in outer cortex, 0.6 mL/gm in inner cortex) and oxygen extraction is higher (more metabolic work done)
- Medulla is vulnerable to hypoxic damage if flow is reduced (low flow, high oxygen usage)
- 2 out of 3 bold
Describe the cell types in the glomerulus and their functions.
Prompt: What types of cells lie between blood and the capillary and filtrate in Bowman’s capsule?
Prompt: What are their functions?
- Capillary endothelial cells
- Afferent arteriole becomes a tuft of capillaries invaginated into Bowman’s capsule. Endothelium fenestrated with 70-90 nm pores. Separated from capsule epithelium by basal lamina
- Epithelial cells of Bowman’s capsule
- Podocytes possess pseudopodia that interdigitate to form 25 nm wide filtration slits over capillary endothelium. Each slit is closed by a thin membrane
- Mesangial cells are stellate and lie between capillary endothelium and basal lamina. Involved in regulation of filtration, secretion of various substances and absorption of immune complexes
- Need fenestrated capillary membrane
- Need podocytes with pseudopodia forming filtration slits
What properties of substances in the blood prevent free passage across the glomerular membrane?
- Larger diameter > 8 nm
- Lack of neutrality (charged)
- Need both points
What factors influence clearance of substances by the kidney?
- Amount of substance excreted = amount filtered + net amount transferred
- Changes in RBF and systemic
- Active transport (primary and secondary)
- Hormonal (aldosterone, angiotensin, endothelin)
- At least 3
Explain the mechanism of tubuloglomerular feedback.
- Increased rate of flow in LoH and DCT increases GFR and local Na+
- Macula densa adenosine A1 receptors activated by increased Na+/K+ activity, causing increased Ca2+, vasoconstriction and decreased GFR
- Percentage solute reabsorbed remains constant (glomerulotubular balance)
What are the buffer systems in blood?
Prompt: What binds to H+ in blood.
- Especially carbonic acid / bicarbonate system
- Plasma proteins (free carboxyl and amino groups)
- Hb (imidazole groups of histidine residues)
- Bold PLUS 1 other
Explain how carbonic acid / bicarbonate system works.
- Draw equations
- Highlight importance of carbonic anhydrase (increases speed of reaction) and where carbonic anhydrase is (intracellular)
- Outline control by respiratory and renal systems.
How is the secretion of renin regulated?
- Increased sympathetic nervous activity
- Increased circulating catecholamines;
- Increased Na+ and cr reabsorption across the macula densa;
- Increased afferent arteriolar pressure;
- Angiotensin II;
- Three of the above
- At least ONE from each
Describe the juxtaglomerular apparatus.
- Afferent and efferent arterioles and tubule touch at one point
- Macula dens a and juxtaglomerular cells.