Renal Lectures Flashcards
3 processes in urine production
1) Glomerular Filtration
2) Tubular Reabsorption
3) Tubular Secretion
Which 3 layers of the glomerular membrane does the filtrate have to pass through?
1) Glomerular capillary walls
2) Basement membrane
3) Podocyte filtration slits
Factors involved in glomerular filtration: Glomerular Hydrostatic pressure (GHP)
Radius of efferent arteriole is smaller, increasing pressure. This favours filtration from the glomerulus into bowman’s capsule
Factors involved in glomerular filtration: Capsular Hydrstatic Pressure (CsHP)
This refers to the pressure build up within bowman’s capsule. This opposes filtration and aims to push fluid back into capilaries in the glomerulus.
Factors involved in glomerular filtration: What is Net Filtration Pressure?
Forces favouring filtration minus forces opposing filtration
Factors involved in glomerular filtration: Blood Colloid Osmotic Pressure (BCOP)
Occurs because the osmolarity is greater inside the capillaries tahn in Bowman’s capsule. This pulls the fluid into capillaries and thus opposes filtration
What is the Glomerular Filtration Rate (GFR)?
The amount of filtrate kidneys produce each minute
Which factors can impact Glomerular Filtration Rate (GFR)?
Anything that alters Net Filtration Rate (NFR) will impact GFR. An increase in arterial BP will increase GHP which heightens NFR and thus increases GFR.
Altering GHP can increase or decrease of afferent of arteriole (e.g. higher GHP = increased radius)
Name 5 barriers that must be crossed in tubular reabsorption
1) Luminal membrane of tubular cell
2) Cytosol of tubular cell
3) Basolateral membrane of tubular cell
4) Interstitial fluid
5) Capillary wall
Reabsorption of water in the proximal tubule
The aqauporins are permanently inserted into tubular cell membrane and so as Na+ reabsorption occurs, water willl follow. The Sodium potassium pump in the basolateral membrane works to pull sodium into cappillary against the concentration gradient (water follows b/c of osmosis).
Reabsorption of water in the distal tubule and collecting duct
Vasopressin release is stimulated by osmoreceptors in the hypothalamus (when osmolarity is too high) and left atrial volume receptors (when BP/ECF volume = low). Vasopresssin binds to the basolateral membrane which facilitates the insertion of aquaporins. This increases the permeability of the membrane, thus allowing for water reabsorption.
What is the purpose of the “osmotic gradient” in terms of tubular reabsorption?
Osmotic gradient increases towards the renal pelvis to allow for selective reabsorption of water in the distal and collecting duct
Role of the descending limb (loop of henle) in tubular reabsorption
Highly permeable to water (but does not reabsorb Na+)
Role of the ascending limb (loop of henle) in tubular reabsorption
Actively reabsorbs NaCl but does not contain aquaprorins (impermeable to water)
Water reabsorption in the loop of henle
Water comes in from cortex at 300mOsm. As it descends, water is drawn out at the loop of henle, the filtrate is very concentrated (1200 mOsm). The ascending limb pumps out lots of NaCl and the filtrate leaves very diluted at 100 mOsm.
What occurs in overhydration?
No vasopressin is released and thus no aquaporins are inserted into the distal tubule/collecting duct. More water is excreted and urine is dilute.
What occurs in dehydration?
Vasopressin is released, stimulating the insertion of aquaporins on the collecting duct and distal tubule membranes. This allows water to go back into blood supply and less water is excreted. This increases urine concentration.
The role of Na+ reabsorption in the proximal tubule
67% occurs here and helps with the reabsorption of glucose, AA, Cl-, urea and water.
The role of Na+ reabsorption in the distal tubule and collecting duct
This involves the hormonal control of Na+ reabsorption via the Renin-Angiotensin-Aldosterone System (RAAS)
What triggers activation of the Renin-Angiotensin-Aldosterone System (RAAS)?
Low NaCL, ECF volume and arterial blood pressure
Which 3 processes occuring in the juxtaglomerular apparatis can stimulate the release of renin? (RAAS)
1) Granular cells (baroreceptors in afferent arteriole) detect drop in BP
2) Macula densa detect fall in NaCl in distal tubule
3) Sympathetic Activation of granular cells
Describe what occurs following activation of the Renin-Angiotensin-Aldosterone System (RAAS)?
Renin is secreted (kidney), activating angiotensin I. This stimulates release of Angiotensin-Converting-(lungs). This converts Angiotensin I into Angiotensin II. This triggers Aldosterone release (adrenal cortex), driving an increase in Na+ reabsorption (Cl- reabsorption follows passively; water follows due to osmosis)
3 secondary impacts of Angiotensin II (other than the release of aldosterone)
1) Vasopressin release
2) Thirst
3) Arteriolar vasoconstriction
Tubular Secretion and increased plasma H+
Secretion of H+ is paired with HCO3- reabsorption.
H+ secretion leads to excretion and drop in plasma H+. This simultaneously causes the conservation and decreased excretion of HCO3-.
Which factors predispose the elderly to dehydration?
1) decrease in total body water
2) Altered sense of thirst (less thirsty when dehydrated; less sensitive to changes in blood volume)
3) Decreased ability to concentrate urine (urine has lower osmolarity when dehydrated)
4) Decreased vasopressin effectiveness (diurnal variations and decreased sensitivity of vasopressin receptors)
Other factors that can cause dehydration
Swallowing malfunction Reduced appetite Acute pathology (e.g. vomitting) Cognitive or communication problems Problems with drink access (e.g. mobility) Medication Lack of attention from carers/isolation
Ageing and kidneys
Decrease in kidney mass, nephron number, kidney blood flow & GFR
Elderly people have…
Reduced thirst & fluid intake
Less ability to sense blood volume deficit
Decreased renal function
Up-regulated saitey signals from the hypothalamus
What is CKD? What is required for diagnosis?
The progressive loss of renal function due to renal damage. GFR under 60 for at least 3 months OR evidence of kidney damage (e.g. structural (kidney imaging) or pathological (renal biopsy) abnormalities).
Staging of CKD
Determines treatment
5 stages
GFR and then looking at protein (albumin) in urine. More protein in the urine indicates it is more serious
Stage 1-2 need at least some albumin. As disease progresses through the stages, glomerular filtration rate gets lower and lower.
Symptoms of CKD: early stages
Often no symptoms
Increased risk heart disease
Symptoms of CKD: middle stages
Anaemia (fatigue)
Early signs - bone disease
Increased BP
Generally feel unwell
Symptoms of CKD: later stages
High BP
Inability to filter waste products/maintain homeostasis (e.g. uremic toxicity; metabolic acidosis)
Hypertension and CKD
Both a cause and complication of CKD. Increases the disease progression & predisposes patients to CVS disease. Caused by ECF fluid exansion (higher volume causes higher pressure and water, sodium etc. are retained and stay in blood). Less common cause is overactive RAAS.
Treatement of hypertension in CKD
Removing excess fluid during dialysis (reduce blood volume & pressure) AND restricting Na+ intake AND anti-hypertensive drugs
Causes of Hyperkalaemia (excessive sodium levels) in CKD
Decreased K+ excretion (in urine)
Acidosis
Medications (ACE inhibitors; Ang II receptor antagonists)
Consequences of Hyperkalaemia
Medical emergency!
Depolarises cardiac myocytes (from -90 mV to -80 mV) SO Membrane potential is closer to threshold
Severe hyperkalaemia causes cardiac arrhythmias & can cause ventricular fibrillation & death
Bone disorders and CKD
Can cause lower serum Ca2+ & activated vitamin D (which decreases the absorption of Calcium in the intestine). This causes lots of PTH release which stimulates the breakdown of bone in order to increase the levels of calcium in the blood (weakness and pain)
3 Treatments for early/middle stages of CKD:
1) Diet modifications (avoid excess protien, salt, potassium & calories in obese patients)
2) Lifestyle modifcation (excercise, smoking cessation & reduced coke intake)
3) Pharmacological intervention (hypertension, bone disease and hyperkalamia)
Key principles of dialysis
Blood is cleansed by exchanging solutes and fluid between the blood (“dirty’) and dialysis (‘clean”). Diffusion occurs across a semipermeable membrane to “clean” the blood & increase plasma calcium levels.
Artificial (e.g. haemodialysis)
Biological (peritoneal dialysis)
Haemodialysis
Blood is cleansed in the dialysis chamber and then returned to the body
Requires successful vascular access & occurs a few times a week
May get a fistula (artery and vein are joined together) the vein gets harder so it is easier to inject multiple times
Or maybe a graft between the two to be injected multiple times
Peritoneal dialysis
The peritoneal membrane acts as the filtration membrane between the blood and dialysate. Does not require blood BUT does requires the placement of an abdominal catheter to get the fluid in the body. DRAIN, FILL, DWELL (repeat)
Bladder and urethra are supported by pelvic floor muscles… What factors that can weaken pelvic floor muscles
Inactivity/overworking Pregnancy/childbirth History of back pain Ongoing consitpation & straining to empty bowels Being overweight, obese (or BMI over 25) Heavy lifting Chronic cough/sneeze Previous injury to pelvic region Aging
What is micturition?
Involves contraction of the bladder and the relaxation of two sphincters
Internal urethral sphincter
- smooth muscle
* involuntary
External urethral sphincter
- skeletal muscle
* voluntary
Muscle type and function of the Detrusor muscle
Smooth (involuntary)
Contraction during emptying and relaxation during filling
Muscle type and function of the internal sphincter
Smooth (involuntary)
Contraction to maintain continence during filling
Muscle type and function of the External sphincter
Skeletal muscle (voluntary) Contraction to maintain continence
Micturition Reflex
The micturition reflex = involuntary & controlled @ the spinal cord. The filling of the bladder stimulates stretch receptors. This triggers parasympathetic stimulation = contraction of the internal sphincter muscle. This inhibits motor neurons from innervating the ext. sphincter BUT voluntary signals can override inhibition of motor neurons SO we go to the bathroom at the right time.
Stress incontinence
Leaking of small amounts of urine due to pressure on the bladder (b/c of weak pelvic floor muscles) during certain activities (coughing, laughing, lifting).
(loss of
oestrogen decreases thickness of urethra)
Can occur in men following prostate surgery
Urge incontinence
Involuntary urination is proceeded by feelings of urgency & muscle becomes “overactive”. This can be caused by neurological disorders, irritation or enlarged prostate.
Overflow incontinence
Bladder does not completely empty and becomes distended. The Increased pressure overcomes sphincter control
Causes: obstruction (enlarged prostate, pelvic organ prolapse) OR Underactive detrusor muscle (damage to muscle or nerves e.g. diabetes)
Functional incontinence
Lack of recognition of need to urinate or inability to get to the toilet
Causes: Dementia, Mobility problems, Poor eyesight or Poor dexterity
