Urinary case Flashcards
Common causes of fluid loss: (4)
- Sweating
- diarrhoea
- Hyperventilation
- Fever
Role of kidneys in fluid/ionic balance:
- Vary water reabsorption to maintain water balance (constant osmolality) and ionic balance
Common symptoms of dehydration:
- extreme thirst
- lack of urine
- fatigue
- dizziness
The role of the kidney:
- Basic
- Nephrons
- Reabsorption
- Urine composition
- Filter blood plasma
- Each kidney composed of roughly one million nephrons that filter plasma at the glomerulus
- As the filtrate passes through the nephron it undergoes reabsorption (95-99%)
- Urine consists of non-reabsorbed fluid, salts and secreted material
Entire urinary tract composition:
- Kidney, ureters, bladder and urethra
Three layers of glomerular filtration:
- Capillary endothelium
- Basement membrane
- Podocyte (epithelial cell fo bowman capsule)
juxtaglomerular apparatus:
- Contains specialised smooth muscle cells (no actin or myosin).. Instead they detect blood speed/pressure and NaCl changes and produce the hormone renin
- Renin causes an increase in arteriole smooth muscle tone, increasing BP
Hormonal functions of kidney:n(3)
- Renin: Controls blood pressure
- Active vit.D: calcium balance
- EPO: Erythrocyte production
Glomerular filtration rate: (GFR)
GFR =
GFR = KS(Pgc - Pt) - (Ngc - Nt)
- KS = filtration co efficient
- Pgc = hydrostatic pressure (glomerular capillaries)
- Pt = Hydrostatic pressure (tubule)
- Ngc = colloid osmotic pressure (glomerular capillaries)
- Nt = colloid osmotic pressure (tubules)
Glomerular filtration facts (3):
- Volumes
- Rate
- Energy expenditure
- 180 L plasma filtered, 1.5 L of urine produced every 24 hours
- Normal rate of 90-125ml/min
- Energy comes from hydrostatic pressure of blood imparted by beating heart, so no energy expenditure required
Glomerular filtrate contains: (3)
- No cells
- Trace amounts of protein
- Ions and small organic substances
Factors effecting rate of glomerular filtration of a substance: (3)
- Molecular weight (inversely proportional)
- Shape: long, thin molecules are filtered more easily
- Electrical charge: ease of filtering = +»_space; neutral»_space; -
Renal clearance:
- Definition
- Equation
- The rate at which a substance is removed from the blood
- Clearance of substance =
(Ux X V) / Px
Ux = urine concentration of substance x V = urine flow rate (ml/min) Px = plasma conc. of substance x
Control of renal blood flow (RBF) and GFR:
- Systemic blood pressure
- Renal nervous input
- Endocrine influences
General properties of proximal tubule: (4)
- Reabsorbs 60-70% of glomerular filtrate
- Brush border of microvilli: 40X SA increase
- Reabsorption is isosmotic
- Stereotyped function (no hormonal control)
Tubular transport of Na+:
- Mechanism
- Driven by …..
- Most Na+ reabsorption via secondary active transport in exchange for H+
- Driven by ionic gradients across apical membrane and ATPase in basolateral
Tubular transport of potassium and calcium:
- Most K+ reabsorption via paracellular route, passively down gradient
- Ca2+ reabsorption via transcellular and paracellular routes down ionic gradient
Tubular transport of glucose and amino acids:
- concentration gradient/mechanism
- apical
- basolateral
- Tm
- Both occur against concentration gradient, via secondary active transport (co-transport)
- Dependant on Na+ gradient on the apical membrane
- Facilitated diffusion on basolateral
- When transport maximum (Tm) is reached, excess is secreted in urine)
tubular transport of water:
- Water reabsorption down osmotic gradient
- Transcellular reabsorption on both membranes due to aquaporins
- Reabsorption also occurs in loop of hence, distal tubule and collecting duct
Tubular transport of bicarbonate and hydrogen:
- Combination
- Breakdown
- HCO3-
- HCO3- combines with H+ for indirect reabsorption in presence of carbonic anhydrase
- Once H2CO3 is absorbed CA breaks it down again and H+ is secreted via buffers
- HCO3- reabsorbed into the blood
Loop of Henle: experimental observations
- Osmotic gradient?
- An osmotic gradient exists in renal medulla
- Loops of Henle are countercurrent multipliers
- Longer loops of henle create a larger osmotic gradient
- parent kidney excretes more concentrated urine
Countercurrent multiplication in the loop of Henle:
- Descending limb: H2O exits the loop of Henle, Increasing the osmotic gradient. Osmolality of 1200
- Ascending limb: impermeable to water. No water reentry. NaCl is pumped into medulla, diluting the tubular fluid
Urine concentrating mechanism:
- Osmotic gradient established by loop of henle is utilised by the collecting duct
- majority of water is reabsorbed into the medulla
Distal tubule and regulation of potassium:
- K+ secretion/reabsorption
- Aldosterone effects
- K+ is reabsorbed in deficiency and secreted in hyperkalaemic states
- Aldosterone produced in the adrenal cortex acts on distal nephron to promote K+ secretion and H+ secretion
(via N+ H+ ATPase)
Osmolality definition:
- Concentration of impermeable solutes per Kg of solute
- Units: osm.kg^-1 solute
Control of body fluid osmolality and water balance
- Definition
- Regulation
- Plasma osmolality regulated to prevent cells from swelling or shrinking
- Regulated by control of water influx (e.g. drinking) and efflux (e.g. urine concentration)
Plasma osmolality regulation - mechanisms 1- detection 2i) pituitary gland 2ii) thirst centre 3 4
- change in plasma osmolality, detected by osmoreceptors in hypothalamus
- Hypothalamus initiates change to:
i) pituitary gland
ii) thirst centre - i) release of ADH
ii) change of thirst response - i) altered urine conc.
ii) alter water intake
Plasma osmolality general facts:
- Normal level
- Control level?
- Normal plasma osmolality (Posm): 290mosmol.kg^-1
- Variation by only 1% activates compensation mechanisms (one of the most tightly controlled homeostatic variables)
Antidiuretic hormone (ADH) increases: (3)
- Water permeability of the collecting duct
- NaCl reabsorption in the thick ascending limb of the loop of Henle
- urea permeability in the inner medullary region of collecting duct
Control of ADH secretion:
- Secreted from posterior pituitary
- ADH is released into the blood by a rise in plasma osmolality of 1% activating hypothalamic neurones
- Release reduced when osmolality falls
Ion transport: ascending loop of henle
- Apical
- Basolaateral
- Apical: Na+/K+/2Cl- transporter
- Basolateral: Na+-pump
ADH: site of action
- Receptor
- Stimulates …., generating ….. activating ……
- Increases ….
- ADH binds to V2 receptors
- Stimulating AC, generating cAMP, activating protein kinases
- Increases insertion of water channels (aquaporins)
Diabetes insipidus: (DI)
- Description
- Symptoms
- Lack of action of ADH reduces water reabsorption from CD, quantity that leaves distal tubule will leave body as urine
- polyuria of dilute urine, excessive thirst
Causes of diabetes insipidus: Central DI - Definition - Cause - Management
- Lack of ADH produced from the posterior pituitary
- Idiopathic cause or secondarily from head injuries
- Desmopressin
Causes of diabetes insipidus:
Nephrogenic DI
- Definition
- Aquired Cause
- Kidneys do not respond to ADH
- Inherited forms: affect expression of ADH V2-receptors or aquaporin proteins
- Acquired forms resulting from: renal cysts/infection, hypercalcaemia
Hypovolaemia:
- Definition
- Decreases venous return due to:(2)
- Decrease in blood volume
- Decreases venous return due to:
- Decreased cardiac filling in diastole
- Reduces stroke work, cardiac output and arterial blood pressure
Hypervolaemia:
- Definition
- Causes
due to
- An increase in blood volume
- Increase in venous return due to:
- Increased cardiac filling in diastole (preload)
- Increases stroke work, cardiac output and arterial blood pressure
How the kidney regulates blood volume: hypovolaemia control
- Senses reduced blood pressure/renal flow
- Reducing Na+ loss in urine
- This reduces water lost in urine due to osmotic retention
High pressure sensors for blood volume (kidney): (2) - Arterial baroreceptors Hypovolaemia response - Juxtaglomerular apparatus Hypovolaemia response
- Arterial baroreceptors:
Hypovolaemia: blood pressure falls, baroreceptor reflex increases sympathetic activity to kidneys - Juxtaglomerular apparatus:
Hypovolaemia: blood pressure/renal blood flow decreases, hormonal response reduces Na+ loss in urine, increasing water retention
Renal sympathetic nerve action(pressure) (4)
- Detection
- SA
- Reducing ….
- Restores
- Decrease pressure detected
- Increased sympathetic activity increases smooth muscle tone of afferent arterioles
- Reducing GFR, causing less Na+ to be filtered
- Restores blood volume
Renin: blood volume control
- secretion
- action
- Secreted by the juxtaglomerular apparatus
- Reduced Na+ excretion at the distal tubule, increasing blood volume
Renin-angiotensin-aldosterone (RAAS) system: role
- Controls NaCl levels which effect water reabsorption by the nephron
RAAS sytem steps:
- Renin action
- ACE conversion
- Angiotensin II action/effects
- Renin acts on angiotensinogen (produced by liver) making angiotensin I
- Angiotensin I converted to angiotensin II by ACE, primarily in the lung
- Angiotensin II stimulates aldosterone release from kidney, ADH release and vasoconstriction
Aldosterone:
- Hormone type and origin
- Role
- Steroid hormone secreted from zona glomerulosa
- Increases Na+ reabsorption by the nephron
Aldosterone action: (4)
- Initiation
- Receptor complex stimulates
- Increases ….. reabsorption via
- …… uptake enhanced
- Aldosteron binds to receptor.
- Receptor complex stimulates transcription of apical Na+ channels (ENaC)
- Increases NaCl reabsorption via principle cells in distal tubule/collecting duct
- Na+ uptake from lumen is enhanced: Cl- and H2O follow
the ureters (Upper urinary tract):
- Function
- How??
- Propels urine to the bladder
- Ureters are lined with smooth muscle. A wave of peristalsis originates in the renal pelvis, passing to the uretero-vesical junction
The Uretero-vesical junction
- Ureters penetrate the bladder wall as a non-return valve, as the bladder fills the wall pressure closes the valve.
Hydronephrosis:
- Urine builds up in the ureters and renal pelvis if urine is not voided properly
The lower urinary tract (LUT): Bladder anatomy
- Bladder dome
- Trigone
- Bladder dome: most of the bladder, lined by detrusor smooth muscle
- Trigone: Small region bound by apices of ureteric orifices and the bladder neck
The LUT: outflow tract
- Urethra description
- Urethra: a smooth muscle lined tube that is also surrounded by a ring of skeletal muscle (external urethral sphincter)
The bladder: filling phase
- Volume increases by up to 500ml in the normal adult bladder, very small rise in Pdet
- No flow (leakage), outflow tract contracted
- Sensory bladder nerves signal filling but the brain suppresses voiding
Control of voiding: bladder innervation
- Pelvic n. S2-S4
Control of voiding: External Urethral Sphincter
- Pudendal nerve S2-S4
Control of voiding: Urethra
- Hypogastric nerve T10-L2
Bladder filling:
- Bladder state
- Urethra
- External sphincter (EUS)
- relaxed: pelvic nerve activity suppressed
- Urethra: Sympathetic Hypogastric nerve active
- EUS: somatic (pudenal) nerve active
Voiding phase: (4)
- Brain makes a decision to void
- Bladder wall contracts and Pdetrusor increases
- Flow starts, due to rising Pdet and relaxation of outflow muscle tract
- Sensation of bladder fullness is reduced, bladder completely empties
Bladder voiding:
- Bladder state
- Urethra state and EUS state
- Activated: bladder contracts due to pelvic nerve activation
- Urethra and EUS: relaxed. Pudendal and hypogastric nerves are supressed
Renal function tests: Urine (3)
- Observation
- Dipstick examination
- Lab tests
Renal function tests: blood (5)
- UandE’s
- osmolality
- pH
- Bone profile
- Full blood count
What is used to measure GFR?
- Creatinine
Isotonic dehydration:
- Loss
- Plasma osmolality
- Plasma Na+
- ECV
- ICV
- Causes
- Water=salt
- Normal
- Normal
- Decrease
- Normal
- Acute diarrhoea
Hypertonic dehydration:
- Loss
- Plasma osmolality
- Plasma Na+
- ECV
- ICV
- Causes
- Water > salt loss
- Increase
- Increase
- Decrease
- Decrease
- Burn/fever/infection
Hypotonic dehydration
- Loss
- Plasma osmolality
- Plasma Na+
- ECV
- ICV
- Causes
- Water < salt
- Decrease
- Decrease
- Decrease
- Increase
- Chronic vomiting/diarrhoea
pH equation
pH = - log [H+]
Importance of arterial pH regulation: (3)
- Enzyme structures may be impaired
- Acidosis can predispose to decreased cardiac contractility (arrhythmias)
- Effect on other ions (Ca2+ and K+) can lead to abnormal neuromuscular and cardiac fucntions
Strong and weak acids:
- Strong acids (HCl): almost completely dissociate when dissolved.
HCL -> (H+) + Cl- - Weak acids: only partially dissociate.
H2CO3 <=> HCO3- + H+
Endogenous acids: volatile acids
- How is it produced
- Example
- Extraction
- An end product of aerobic respiration, Carbonic acid
- Exhaled as CO2
Endogenous acids: fixed acids
- Production
- Example
- Extraction
- Produced by catabolism of phospholipids, amino acids and nucleic acids
- Sulphuric and phosphoric acids
- Excreted via the kidneys
Endogenous acids:
- Gastric cells
- Pancreatic cells
- Secrete HCl into the lumen and HCO3- into the venous blood (alkaline tide)
- Secrete HCO3- into lumen and H+ into venous blood
Buffers:
- Definition
- Effect on pH
- Buffer composition
- A substance that resists the change in pH by absorbing (or releasing) H+ ions the an acid (or base) is added
- pH still changes, but magnitude is reduced
- Consists of a weak acid and its conjugate base
Henderson Hasselbach equation:
pH proportional to
[HCO3-] / PaCO2
Henderson Hasselbach equation:
pH proportional to
[HCO3-] / PaCO2
PaCO2 equation =
Rate of CO2 production/ Rate of CO2 removal
Reabsorption of filtered bicarbonate:
- Filtered at the glomerulus, 99.9% is reabsorbed
- Pathological rise of 40mmol/L will exceed reabsorption mechanism, lost in urine
Reabsorption of Filtered bicarbonate is increased by: (3)
- ECF
- R-A-A
- PaCO2
1- ECF volume contraction directly
2- activation of R-A-A system. Angiotensin II stimulates Na-H exchanger in the PCT
3- Increased PaCO2 provides more CO2 for conversion to HCO3-
Acid-base disturbances: Acidosis
- Cause
- Effect
- Cause: pathological rise in [H+] and a fall in arterial pH+
- Effect: Acidaemia
Acid-base disturbances:
- Cause: Pathological fall in [H+]
- Effect: rise in pH (alkalaemia)
Acid-base disturbances: terminology
- Respiratory
- Metabolic
- Simple
- Mixed
- Compensation:
- Respiratory: Pathological change in PaCO2
- Metabolic: pathological change in [HCO3-]
- Simple: only one disorder
- Mixed: multiple AB disorders
- Compensation: physiological change to return pH to 7.4
Potassium balance:
1- Shift of K+ into ICF:
2- Shift of K+ out of ICF:
1- Hyperkalaemia
2-Hypokalaemia
Nitrogen balance:
- Definition
- Healthy adults
- The balance between loss and gain of nitrogen
- Have a net zero nitrogen balance
Amino acid metabolism:
- Transport
- Liver role
- Broken down inside cells then transported to the liver as alanine or glutamine
- Here they are broken down and excreted as urea
Amino acid conversion to glutamine:
- Transaminase reactions
- Glutamine synthesis
- Transport
- Conversion
- Deamination
- Transaminase reactions in muscles convert amino acids to glutamate
- Glutamine synthase converts glutamate to glutamine
- Glutamine transported in blood to the liver
- Glutamine converted to glutamate, releasing NH4+
- Glutamate is deaminated inside liver mitochondria, releasing NH4+ and regenerating alpha-ketoglutarate (reactant)
Urea cycle:
- ATP, CO2, NH4+ and fumarate are consumed
- Produces fumarate
- Committed step: CO2 and NH4+ combined via 2 ATP
Glucogenic amino acids:
- Donate carbon skeletons to form pyruvate or CAC intermediates
Ketogenic amino acids:
- Donate carbon skeletons to form acetyl CoA and thus ketone bodies (enters CAC)
Marasmus and kwashiorkor:
- Marasmus: lack of protein and energy (starvation)
- Kwashiorkor: lack of protein
PKU defect:
- Defect in the gene for Phe Hydroxylase stops the conversion of Phe to tyrosine
- [Tyr] reduced, [neurotransmitters] reduced
