Module 8 Flashcards
- balance and constancy
- keeping the internal environment compatible with life (pH 6.8-8.0)
Homeostasis
Body Fluid Compartments
60% Body weight is Water
40% Body weight is Intracellular Fluid
20% Body weight is Extracellular Fluid
15% Body weight (75% ICF) Interstitial Fluid
5% Body weight Plasma
Babies are made up of __ water
75%
- fluid inside the normal body cavities
- includes intraocular fluid, synovial fluid, water in gallbladder and water in urinary bladder
Transcellular Fluid
Extracellular Fluid is divided into
- Transcellular Fluid
- Insterstitial Fluid
- Plasma
Constituents of ECF and ICF
• Made up of Ions and Proteins
– CATIONS: Positively-charged molecules
– ANIONS: Negatively-charged molecules
- Number 1 Cation in the ECF
- main determinant of plasma osmolarity (where sodium goes, water follows)
Sodium
- Number 1 Cation in the Intracellular Fluid (ICF)
Potassium
Number 1 Anion in the ECF
Chloride
Number 1 Anion in the ICF
Phosphate and organic Anions
• Flow of water from a solution of low solute concentration to a solution of high solute concentration across a semi-permeable membrane
Osmosis
Transport of Water
- Movement of water is via OSMOSIS (utilize water channels)
- It is based on concentration gradient
Movement of Solute and Solvent
Solute - move from high concentration to low concentration
Solvent - move from low concentration to high; hypertonic to hypotonic
– Number of osmotically active particles in a solution
– One osmole = 6.02 x 10^23 of solute particles
OSMOLE (Osm)
Normal value of Osmolarity
300
– Osmoles per kilogram of water (according to weight of water)
– more accurate because it doesn’t vary according to temperature
OSMOLALITY
– Osmoles per liter of water (according to volume)
– “Pogi Points”
– Equal to molar solute concentration x number of particles that the solute dissociates into once dissolved
– Approximately 300mOsm/L in the body compartments
– PLASMA OSMOLARITY: Mainly determined by Sodium
concentration
OSMOLARITY
The higher the osmolarity, the __ the ability to attract water
higher
Osmolarity vary according to temperature. Water tends to expand in high temperature. The higher the temperature, the __ the serum osmolarity
lower
At human body temperature (37.5C), the difference between the osmolarity and osmolality is __
Less than 1%
– Not completely semi-permeable membrane
– Takes into account effect of solute permeability
Effective Osmolarity or Tonicity
TYPES OF SOLUTIONS
– Hypertonic solution
– Isotonic solution
– Hypotonic solution
What is the difference between:
Isotonic, Hypotonic, Hypertonic
Isoosmotic, Hypoosmotic, Hyperosmotic
“…TONIC”: impermeant solutes; may cause change in cell
volume.
“…OSMOTIC”: permeant solutes; may NOT cause change in
cell volume
What will happen if you have a RBC that is 300 mOsm/L when you place in hypotonic solution (209mOsm/L)?
Water will move from outside to inside. The cell will swell.
What will happen if you have a RBC that is 300 mOsm/L when you place in hypertonic solution (360mOsm/L)?
Water will move from inside of RBC to outside causing RBC to SHRINK.
Volume and Osmolarity of ECF and ICF in Abnormal States
• Water moves because of changes in TONICITY, and not VOLUME – ISOTONIC INFUSION – HYPERTONIC INFUSION – HYPOTONIC INFUSION
– Due to loss of sodium in the ECF or gain of excess water in the ECF
– E.g. diarrhea, vomiting, diuretics, Addison’s Disease, Syndrome of Inappropriate Anti-Diuretic Hormone Secretion (SIADH)
HYPONATREMIA
– Due to excess sodium in the ECF or loss of water in the ECF
– E.g. Diabetes Insipidus(Central and Nephrogenic), Dehydration secondary to exercise or fever
HYPERNATREMIA
- Contributes to homeostasis
* Composed of the kidneys, ureters, bladder, urethra
RENAL SYSTEM
Functions of the Kidneys
- Excretion of waste products and foreign chemicals
– (Urea, Uric Acid, Creatinine, Bilirubin, hormone metabolites) - Regulation of water, electrolyte balances
- BP Regulation
– Excretion of variable amounts of H2O and NaCl
– Production of Renin - Regulation of Acid-Base Balance
– Excretion of acids
– Urinary buffer systems - Produce Erythropoietin (EPO)
- Hormone Secretion
– Active form of Vit D, kinins, renin - Gluconeogenesis
Functions of the Kidneys (3)
- Homeostasis
- Secretion of certain substances like EPO
- Excretion of waste products
- T12-L3
- Right kidney lower than Left kidney
- 150g
Kidney
BASIC PARTS of the KIDNEY
– Capsule
– Cortex
– Medulla
– Papilla, Calyces, Pelvis
- pus developing underneath the renal capsule that will stretch the capsule and it will detect as pain
- positive kidney punch test
Acute Pyelonephritis
Renal Circulation
Renal Artery»_space; Segmental Artery»_space;
Interlobar artery»_space; Arcuate artery»_space;
InterLOBULAR artery(cortical radiate/radial artery)»_space; Afferent Arteriole»_space;Glomerular Capillaries»_space;
Efferent Arteriole»_space; Peritubular Capillaries/Vasa Recta
»_space; Interlobular Vein»_space; Arcuate Vein»_space;
Interlobar vein»_space; Segmental Vein»_space; Renal Vein
- part of the kidney that is more vascular because most of the glomerular capillaries are located here
Renal Cortex
- made up of loops of Henle and collecting tubule
Renal Medulla
Collection of Urine
Renal Papillae»_space; Minor calyces
» Major Calyces »_space; Renal Pelvis
»_space; Ureter»_space; Urinary bladder»_space; Urethra
- ultrafiltrate of blood
Urine
- 22% of Cardiac Output
* Has 2 Capillary Beds
Renal Circulation
- Highly-fenestrated (for filtration)
* Responsible for Glomerular Filtration Rate (GFR)
GLOMERULAR CAPILLARIES
- Supplies O2 and Glucose to the Tubular Cells
* Secretes Erythropoietin (EPO)
PERITUBULAR CAPILLARIES
CORTICAL NEPRONS
percentage: 75% OF NEPHRONS
location: RENAL CORTEX
loops of henle: SHORT
capillary network: PERITUBULAR CAPILLARIES
JUXTAMEDULLARY NEPHRONS
percentage: 25% OF NEPHRONS
location: CORTICO-MEDULLARY JUNCTION
loops of henle: LONG
capillary network: VASA RECTA
type of cell of the peritubular capillaries that produces Erythropoietin
Interstitial Cell
- hairpin loop shaped similar to loop of Henle
- act as counter current exchanger
Vasa Recta
- Functional and Structural unit of Kidney
- 1 million nephrons per kidney
- Cannot be regenerated
*kidneys undergo compensatory hypertrophy upon 75%
damage to nephrons
The Nephron
Parts of the Nephron
- Renal Corpuscle (Malphigian Corpuscle)
2. Renal Tubular System
- site for filtration
- Afferent arterioles, glomerular capillaries, efferent arteriole, podocytes, mesangial cells, JG apparatus
- Bowman’s Space
- Bowman’s Capsule
Renal Corpuscle (Malphigian Corpuscle)
- site for reabsorption and secretion
- composed of Proximal Convoluted Tubule (PCT), Loop of Henle (LH), Distal Tubule (DT), Collecting Duct (CD)
Renal Tubular System
3 Filtration Barrier (from inner most to outer most)
- Capillary Endothelium
- Basement membrane
- Podocytes - foot processes
- Highly-fenestrated; with pores 8 nanometer (80 angstrom)
in diameter - 50x more permeable than skeletal muscle capillaries
- Secrete Nitric Oxide and Endothelin-1
Capillary Endothelium
- have large spaces
- main charge barrier (most negative charge)
- with Type IV Collagen, Lainin, Agrin, Perlecan, Fibronectin
Basement Membrane
- Cells of capillary endothelium
- final filtration barrier
- Contains:
- Foot Processes
- Filtration Slits
With Filtration Slit Diaphragm (made up of Nephrin,
NEPH-1, Podocin, Alpha-actinin 4, CD2-AP)
Podocytes
Why we can’t filter albumin?
Because albumin and basement membrane is negatively charged (like charges repel) therefore albumin is not filtered
Components of Juxtaglomerular Apparatus
- Juxtamedullary Cell
- Macula Densa
- Lacis Cell
- Found in between capillaries
- Contractile, mediates filtration, take up immune complexes, involved in glomerular diseases
- modified smooth muscle that is capable of phagocytosis
- can cause traction in the lumen (makes diameter smaller) but has insignificant effect on GFR (maliit lang ang narrowing na nangyayari)
Mesangial Cells
2 Types of Mesangial Cells
- Intraglomerular Mesangial Cells - found in between glomerular capillaries
- Extraglomerular Mesangial Cells (Lacis Cells) - component of JG Apparatus; found outside the Bowman’s Capsule/glomerulus
- Aka “glomerular cells of the afferent arterioles”
- found at the walls of the Afferent Arterioles
- Secrete Renin
JG Cells
- found in the walls of the Distal Convoluted Tubule
- Monitor Sodium (Na+) concentration in the Distal Tubule (and consequently, blood pressure)
Macula Densa
JG Cell and Macula Densa
JGA, MD
JG Cell: Afferent Arteriole
Macula Densa: Distal Tubule
RENAL TUBULAR SYSTEM
- Proximal Convoluted Tubule (PCT)
- Loop of Henle (LH)
- Descending Limb of the Loop of Henle
- Thin Ascending Limb of the Loop of Henle
- Thick Ascending Limb of the Loop of Henle - Distal Tubule (DT)
- First Part/Early: Early Distal Tubule
- Second Part/Late: Late Distal Tubule/Connecting Tubule, Cortical Collecting Tubule - Collecting Duct (CD)
Medullary Collecting Tubule and Collecting Duct
Macula Densa (Low BP)
Low BP»_space; JG cell will be activated
|»_space; Renin is released (Renin-angiotensin-aldosterone System)
- filtration of the glomerular capillary is only 20-25%
- the 80% will bypass the glomerular capillary and will go directly to the efferent arteriole in the renal tubular system
Filtration Fraction
- workhorse of the nephron because it is the site for reabsorption and also site where there has a lot of transport proteins
- always reabsorb 66% of Sodium, Potassium and Water
- reabsorb 100% of the filtered GLUCOSE and AMINO ACIDS
- secretes excess ACIDS and BASES
- has microvilli (increases the surface area for REABSORPTION and increase number of transport proteins found inside)
Proximal Convoluted Tubule
- needs more ATP
- sensitive to hypoxia and most prone to ischemia
Proximal Convoluted Tubule
(Loop of Henle)
- permeable only to water and not on solutes
Descending Limb
(Loop of Henle)
- permeable only to solutes and impermeable to water
Ascending Limb (ASINding limb)
The characteristics of the wall of the Ascending and Descending Limb of the Loop of Henle is the contributor in the __
Counter-current multiplier
- you will find the Na-K-2Cl cotransport/symport pump (reabsorb Sodium, Potassium and 2 units of Chlorides from the lumen towards renal interstitium or reabsorb towards the blood) which is also involve in the counter-current multiplier
- DILUTING SEGMENT OF THE NEPHRON since you can reabsorb sodium but did not reabsorb water
Thick Ascending Limb of the Loop of Henle (TAL of LH)
- a diuretic that will inhibit the Na-K-2Cl because of this sodium will remain inside therefore increase urine output
Loop Diuretic (Furosemide/Lasix)
Distal Tubule is divided into:
- First Part/Early Distal Tubule - Macula Densa
2. Second Part/Late Distal Tubule - Principal Cells and Intercalated Cells (stimulated by Aldosterone)
- reabsorb sodium and water; secrete potassium
Principal Cells
- secrete H+
Intercalated Cells
- you will find the macula densa
- found in the renal cortex; will have a characteristic that is similar to Thick Ascending Limb of Loop of Henle
- permeable only to solutes; impermeable to water
- CORTICAL DILUTING SEGMENT
First Part/Early Distal Tubule
- where Antidiuretic Hormone is going to act to insert to Aquaporin type II water channels/ water gradients (by this you will be able to reabsorb water)
Collecting Duct
If ADH is HIGH
Increase Aquaporins»_space; increase Water reabsorption
» Decrease Urine volume
» Increase urine concentration
If ADH is LOW
Decrease Aquaporins»_space; Decrease water reabsorption
|»_space; Increase urine volume»_space; Increase urine concentration
- inhibits ADH secretion causing massive diuresis
Alcohol
When a substance in high clearance, the substance will go to __
Urine
When a substance is low clearance, the substance will go to __
Blood
Which substance has the highest clearance?
Para-amino hyppuric acid
Which substance has the lowest clearance?
Glucose and Amino Acids
- Movement from Glomerular Capillaries to Bowman’s Space
- will go to the URINE otherwise reabsorbed
- will only happen at the level of Glomerular Capillaries
(Glomerular) Filtration
- Movement from Tubules to Interstitium to Peritubular
Capillaries - movement from the lumen of the tubules towards the interstitium to the Peritubular Capillaries (Vasa Recta)
- occurs in the tubular system
(Tubular) Reabsorption
- Movement from Peritubular Capillaries to Interstitium to
Tubules - substance was not filtered; tendency is go to the URINE
- occurs in the tubular system
(Tubular) Secretion
If the substance is reabsorb it means
- they were FILTERED
2. going back to the Blood
Excretion
Excretion = (Amount Filtered) – (Amount Reabsorbed) +
Amount Secreted
Inulin and Creatinine
- filtered only (not reabsorb and not secreted)
- clearance is directly proportional to GFR since they are not absorbed and secreted
- used the clearance of inulin and creatinine to estimate the GFR and renal function
- no transporters for absorption and secretion
Most electrolytes (Sodium, Potassium, Calcium, Magnesium, Chloride) has the following characteristics
- filtered and only Partially reabsorbed
Glucose and Amino Acids
- filtered and 100% reabsorbed
- normally, not found in the urine
- transport mechanism is in the PCT using SGLT2 and sodium-amino acid cotransport pump
- will have ZERO clearance
Para-amino hippuric acids, Organic Acids and Bases
- filtered, secreted and not reabsorbed
- will have the highest clearance because all of it will eventually find its way to the urine
- clearing the blood and go to the urine
Clearance
- Amount filtered in the glomerular capillaries per unit time
- 125mL/min or 180L/day
GFR
- Fraction of renal plasma flow that is filtered
- Normal Filtration Fraction: 20%
Filtration Fraction
Filtration Fraction
GFR/Renal Plasma Flow (RPF)/Renal Blood Flow
Constriction of Afferent Arteriole
Effect on GFR: Decrease
Effect on RPF: Decrease
Effect on FIltration Fraction: No Change
Constriction of Efferent Arteriole
Effect on GFR: Increase
Effect on RPF: Decrease
Effect on FIltration Fraction: Increase
Filterability of Solutes
- will vary according to SIZE and CHARGE
- the smaller the solute, the easier to filter
- the more positive the solute, the easier to filter
Filterability of Solutes: According to SIZE
- Inversely proportional
- Water, Na, Glucose, Inulin > Myoglobin > Albumin
- 20 angstrom or less: filtered freely
- > 42 angstrom: not filtered at all
Filterability of Solutes: According to CHARGE
Positive Substances > Neutral Substances > Negative
Substances
Starling Forces
- Glomerular Capillary Hydrostatic Pressure
- Bowman’s Space Hydrostatic Pressure
- Glomerular Capillary Oncotic Pressure
- Bowman’s Space Oncotic pressure
- pressure inside the the glomerular capillaries which promotes FILTRATION
- tendency of the water is to go out of the capillaries
Glomerular Capillary Hydrostatic Pressure
- pressure outside the capillaries which OPPOSES filtration
- tendency of the water is to go out of the bowman’s space and towards the glomerulus capillaries
Bowman’s Space Hydrostatic Pressure
- protein inside the glomerulus tends to attract water thats why it will tend to attract water into the capillary
- OPPOSES FILTRATION
Glomerular Capillary Oncotic Pressure
- refers to the pressure exerted by proteins found in the Bowman’s space
- it tends to attract water towards the interstitium
- promotes FILTRATION
Bowman’s Space Oncotic Pressure
Favors Filtration/Increase GFR
- Increase in Glomerular Capillary Hydrostatic
- Decrease in Glomerular Capillary Oncotic
- Increase in Bowman’s Space Oncotic
- Decrease in Bowman’s Space Hydrostatic
- describes the capillary permeability
- measure of the product of the hydraulic conductivity and surface area of the glomerular capillaries
- hydraulic conductance or ratio coefficient
- refers to how close, how wide the clefts are in the glomerular capillaries
Kf
Effects of Histamine in Glomerular Capillaries
Burn»_space; mast cell in tissue produce Histamine
» widen the pores of the glomerular capillaries
» filtration of fluid toward the interstitium
» causing EDEMA
Bowman’s space oncotic pressure is __ because normally there will be no proteins that will be filtered
ZERO
- proteins that slough off from renal tubule (PCT, LH, DT and CD)
- present in minute concentration that they are clinically insignificant enough to raise Bowman’s Space oncotic pressure
Tamm-horsfall Proteins
what is the greatest contributor to filtration in the glomerular capillaries (GFR)?
Glomerular Capillary Hydrostatic Pressure (60 mmHg)
Least contributor to GFR
Bowman’s Space Oncotic Pressure (0 mmHg)
Glomerular Filtration Rate
GFR = Kf [(PGC-PBS) – (OGC- OBS)]
Kf = Filtration coefficient of the Glomerular Capillaries PGC= Glomerular Capillary Hydrostatic Pressure PBS = Bowman’s Space Hydrostatic Pressure OGC= Glomerular Capillary Oncotic Pressure (mmHg) OBS = Bowman’s Space Oncotic Pressure (mmHg)
(Effect on GFR)
Afferent Arteriole: Dilate
Increase
(Effect on GFR)
Afferent Arteriole: Constrict
Decrease
(Effect on GFR)
Afferent Arteriole: Dilate
Decrease
(Effect on GFR)
Efferent Arteriole: Constrict Moderately
Increase
(Effect on GFR)
Efferent Arteriole: Constrict Severely
Decrease
- albumin and other proteins cannot easily pass through»_space; concentration of albumin in glomerular capillary will increase»_space; increased glomerular capillary oncotic pressure
» GFR will decrease
- Gibbs Donnan Effect
- negatively charged albumin will attract with positively charged sodium ions (where sodium goes, water follows) so sodium and water will remain in the glomerular capillaries»_space; less of them being filtered
- massive sympathetic stimulation that results in massive vasoconstriction of the kidneys
Gibbs Donnan Effect
(Effect on GFR)
Glomerular Capillary Hydrostatic Pressure: Increased
Increase
(Effect on GFR)
Glomerular Capillary Oncotic Pressure: Increased
Decrease
(Effect on GFR)
Bowman’s Space Hydrostatic Pressure: Increased
Decrease
(Effect on GFR)
Kf: Increased
Increase
Characteristics of Renal Blood Flow
- Blood Flow in the Renal Cortex > Renal Medulla
- Exhibits Local Autoregulation at a BP between 75-160 mmHg (value of the GFR will always remain constant at 125 ml/min as long as the BP is between 75-160mmHg)
- Sympathetic NS has very little effect because of this, unless in acute, severe disturbances
- aka Macula Densa Feedback
- Maintains GFR at a constant 125ml/min (Autoregulates GFR at a BP of 75-160mmHg)
- number 1 make sure the BP is autoregulated and GFR is at 125ml/min
Tubuloglomerular Feedback
Adenosine vs Nitric Oxide in Tubuloglomerular Feedback
Adenosine: vasoconstricts afferent arteriole (usually a vasodilator in systemic arteriole but act as vasoconstrictor on Kidneys)
Nitric Oxide: vasodilates afferent arteriole
(Tubuloglomerular Feedback)
Scenario 1: if BP is low (e.g. 75mmHg)
- Low BP»_space; Low GC Hydrostatic Pressure»_space; Decreased
GFR (> Detected by Macula Densa - Macula Densa increases secretion of:
1. Angiotensin II (via RAAS stimulation)
Vasoconstricts EFFERENT Arteriole»_space; Increases GFR back
to normal (125ml/min)
- Nitric Oxide
Vasodilates AFFERENT Arteriole»_space; Increases GFR back to
normal (125ml/min)
(Tubuloglomerular Feedback)
Scenario 2: if BP is high (e.g. 160mmHg)
- High BP»_space; High GC Hydrostatic Pressure»_space; Increased
GFR (>125ml/min)»_space; Detected by Macula Densa - Macula Densa increases secretion of:
1. Adenosine - Vasoconstricts AFFERENT arteriole»_space; decreases GFR back to normal (125ml/min)
- the massive sympathetic stimulation that results in massive vasoconstriction of all the arterioles except the Brain and Heart arterioles
- occurs when BP is less than 60 mmHg and optimal when BP is equal to 20mmHg
- Implication: blood is shunted towards the Brain and Heart
- Emergency response, Last ditch effort of the brain to save the body
- activated when brain is having Ischemia which occurs when the brain has low BP
CNS Ischemic Response
- “Percentage of solute reabsorbed is held constant”
- Buffers effects of drastic GFR changes on urine output
- intrinsic ability of the tubules to increase their reabsorption rate in response to increased tubular load
- whether the GFR is increased or decreased, the percentage will not change but the absolute value will depend on GFR
Glomerulotubular Balance
Mechanism of Glomerulotubular Balance
Increased GFR»_space; increased amount of
filtered water and electrolytes in the Bowman’s Space
» peritubular capillaries has less water and electrolytes
but same amount of plasma proteins
»_space; Increased peritubular capillary oncotic pressure
» increased water and solute reabsorption
» same percentage of water and electrolytes reabsorbed
Tubuloglomerular Feedback vs Glomerulotubular Balance
TUBULOGLOMERULAR FEEDBACK
- Macula Densa Feedback; For Autoregulation of GFR
GLOMERULOTUBULAR BALANCE
- Percentage of solute reabsorbed is held constant; Buffers effect of drastic GFR changes on urine output
• Volume of plasma that is completely cleared of the
substance by the kidneys per unit of time”
• clearing the blood with something
(ilan yung matatanggal sa blood na pupunta sa urine)
Clearance
HIGH CLEARANCE vs LOW CLEARANCE
HIGH CLEARANCE - you will find the substance in the urine
LOW CLEARANCE - you will find the substance in the blood
RELATIVE CLEARANCES
Para-Amino Hippuric Acid > K+ > Creatinine > Inulin > Urea > Na+ > Glucose, Amino Acids, HCO-
- Para-Amino Hippuric Acid- Highest clearance since its filtered, secreted and not reabsorbed; you won’t detect anything in the blood
- Glucose, Amino Acids, HCO- - has the lowest clearance because they are filtered and 100% reabsorbed under normal condition
TO ESTIMATE GFR
Clearance of Inulin, Creatinine
- because its only filtered, not reabsorbed and not secreted
- clearance is directly proportional to GFR
TO ESTIMATE RENAL PLASMA FLOW, RENAL BLOOD
FLOW
Clearance of Para-Amino Hippuric Acid (PAH)
- because its filtered, secreted but not reabsorbed
- dependent on blood flow in the glomerular capillaries and peritubular capillaries
Substances that do not appear in the urine have a clearance of ___.
Zero
Substances filtered and partially reabsorbed have a clearance __ than the GFR.
Less
Substances filtered and with net secretion have a clearance __ than the GFR.
More
Clearance of inulin is ___ to that of the GFR.
Equal
Urinary Bladder (Capacity)
- Capacity: 500-600ml
- 150ml - start to feel urge
- 300-400ml - reflex contraction
- once the urinary bladder is 25% filled, you will feel the urge to urinate
- once the urinary bladder is 50% filled, you will have reflex contraction or reflex urination
- you will only see urinary bladder that is 100% filled on pathologic conditions like neurogenic bladder
Urinary Bladder (parts)
• 2 MAIN PARTS
– Body
– Neck
• 3 MUSCLE LAYERS
– spiral, longitudinal and circular
• Detrusor muscle empties the bladder
• 2 SPHINCTERS
– Internal urethral sphincter (involuntary
– External urethral sphincter
Urinary Bladder (Urine Output)
• Daily Usual Urine Output – 720ml-2400ml/day
– Minimum Urine Output: 500 mL (1200mosm/kg)
– Maximum Urine Output: 23.3L (30mosm/kg)
- a smooth muscle that reacts to stretch
- you will have calcium channels that are responsive to stretch
- the moment there is 300 ml in the bladder, it will open up these channels»_space; calcium will now enter the smooth muscle»_space; reflex contraction
Detrusor muscle
Maximum and Minimum Urine Concentration
Maximum Urine Concentration: 1200 mOsm/kg
Minimum Urine Concentration: 30 mOsm/kg
- involuntary, made up of smooth muscle
Internal urethral sphincter
- voluntary; made up of skeletal muscle
- you can consciously control
External urethral sphincter
Urinary Bladder: INNERVATION
PELVIC NERVES (both sensory and motor) • Motor is via parasympathetic fibers
PUDENDAL NERVE
• For external urethral sphincter
• 3 layers: mucosa, muscularis, fibrous • 3 muscle layers: spiral, longitudinal and circular bundles • Peristaltic contraction: 1-5x/min *Enhanced by parasympathetic stimulation • Well-supplied with pain fibers
Ureters
(ureter)
• Oblique passage to bladder wall to prevent back flow
PSEUDOSPHINCTER
Blocked ureters may lead to reflex constriction of the urter and the renal arterioles
URETERORENAL REFLEX
Micturition Center
found in the PONS
Micturition can be inhibited by the
cerebral cortex
During micturition:
- Abdominal muscle contracts»_space; Detrusor muscle contract
- External and internal urethral sphincters relaxes and prevents reflux»_space; Urinate
Why do you shiver when you urinate?
Whenever you urinate, you urinate at least 150 ml of water. That 150 ml of urine that is needed by the human body temp which is 37.5 C, when you lose the 150 ml of water, it will make your body temporarily colder than normal that’s why the reaction is to shiver
MOST Solutes actively reabsorbed or secreted exhibit
– RENAL THRESHOLD
– RENAL TRANSPORT MAXIMUM
- SOME nephrons affected
- Substance start appearing in the urine
- plasma concentration where at least one out of 1 million nephrons are saturated
RENAL THRESHOLD
- ALL nephrons affected
- All excess substance start appearing in the urine
- All 1 million nephrons are saturated
- rate of absorption will plateau
RENAL TRANSPORT MAXIMUM
Which characteristic of active transport is the basis for the renal threshold and transport maximum?
Saturation
– Does NOT have Transport Maximum and Threshold
GRADIENT-TIME TRANSPORT
GRADIENT-TIME TRANSPORT
– Exhibited by
- SOME solutes (e.g. Na+ in the PCT) actively transported
– Due to greater activity of Na-K-ATPase pump compared to net sodium reabsorption
– Also due to backleak of sodium in the tight junctions - For ALL passively transported solutes (Cl-, Urea)
GRADIENT-TIME TRANSPORT is dependent upon
- ELECTROCHEMICAL GRADIENT
- the greater the gradient, the greater the rate of transport - MEMBRANE PERMEABILITY
- the more permeable the membrane, the greater the rate of transport - TIME
• the slower the flow rate, the more time you have to transport substances therefore the greater the rate of transport
• workhorse of the nephron – Highly Metabolic – Large number of Mitochondria – Extensive Brush Border (microvilli) – Extensive Channels – Low columnar with extensive brush border
Proximal Convoluted Tubule
• Reabsorbs 100% of filtered Glucose and Amino Acids
• Involved in Active Reabsorption of 60-70% of filtered
solute (NaCl)
• Involved in Passive Reabsorption of 60-70% of filtered
H2O
• Involved in secretion of H+
• Causes active secretion of organic acids, bases (bile
salts, oxalate, urate, catecholamines) and drugs
– RAPIDLY FILTERED AND ALMOST NONE REABSORBED
Proximal Convoluted Tubule
Proximal Convoluted Tubule
- Reabsorption of 66% Sodium, Chloride, Potassium, Water
- 100% reabsorption of Glucose and Amino Acids
- Secretions of organic acids and bases
Which is more hypertonic relative to the other – the fluid
entering the PCT, or the fluid leaving the PCT?
Both are Isotonic to each other because you reabsorb the same percentage of water and sodium.
• Thin descending, thin ascending, thick ascending segments
• THIN SEGMENTS
– simple squamous with no brush border and few mitochondria
• THICK SEGMENTS
– simple cuboidal
Loop of Henle
- With graded osmolarity
- 20% of filtered H2O is reabsorbed
- 25% of filtered Na, K, Cl is reabsorbed
- Mg2+ and Ca2+ also reabsorbed (compete with each other for the same reabsorption transporter; whenever you have hypercalcemia, it is usually associated with hypomagnesemia)
- Hydrogen is secreted via Na-H countertransport
Loop of Henle
– moderately permeable/impermeable to Solutes
– Permeable to Water
DESCENDING LIMB
– impermeable to Water
– Permeable to Solutes (Na-K-2Cl cotransport)
ASCENDING LIMB
– Simple cuboidal w/o brush border
– Early Distal Tubule
– Contains JuxtaGlomerular Apparatus (JGA) specifically the Macula Densa
– Similar characteristics to thick segment of LH
FIRST PART of the Distal Tubule
– Simple cuboidal w/o brush border
– Late Distal Tubule and Cortical Collecting Tubule
– Contains PRINCIPAL CELLS and INTERCALATED CELLS
– Responsive to effects of Aldosterone, Vasopressin
SECOND PART of the Distal Tubule
- Reabsorb Na+, H2O
* Secrete K+
PRINCIPAL CELLS
- Reabsorb K+
* Secrete H+ (H+-ATPase pump; Na+-H+ Countertransport)
INTERCALATED CELLS
Functions of Aldosterone
- Sodium Reabsorption (Principal Cells)
- Potassium Secretion (Principal Cells)
- Hydrogen Secretion (Intercalated Cells)
MNEMONIC: “PRINCEPE K”
Principal Cells: secrete K+
Intercalated Cells: secrete H+
- Reabsorbs 5% of filtered H2O
* Impermeable to urea
Distal Tubule
- Cuboidal with well-defined boundaries between cells
- SITE FOR REGULATION OF FINAL URINE VOLUME AND CONCENTRATION
- Reabsorption of as much as 10% of filtered H2O
- Responsive to Vasopressin (rapid insertion of Aquaporin-2)
- Permeable to Urea
- Secretes H+ ions also
- Maximum urine osmolality – 1200mosm/kg of H2O
*number of water bridges is not constant and is dependent on the amount of ADH
Medullary Collecting Tubules and Collecting Ducts
Effect of Starling Forces: Peritubular Capillary Hydrostatic Pressure
Peritubular Capillary Hydrostatic Pressure
– INCREASED BY Increased BP
– DECREASED BY Afferent or Efferent Arteriole Vasoconstriction
Effect of Starling Forces: PERITUBULAR CAPILLARY ONCOTIC PRESSURE
PERITUBULAR CAPILLARY ONCOTIC PRESSURE
– INCREASED BY Plasma protein concentration and Filtration Fraction
Reabsorption vs Secretion
Reabsorption - movement from the lumen of the tubules towards the interstitium to the capillary then go back to the blood
Secretion - movement from the peritubular capillaries/vasa recta going to the interstitium then going to the lumen
What will happen when peritubular capillary hydrostatic pressure increases?
- reabsorption decreases because it opposes to it
- secretion increases because they are going to the same direction
What will happen when peritubular capillary oncotic pressure increases?
- reabsorption will increase because it has the same direction as the peritubular capillary oncotic pressure
- secretion will decrease because it has the opposite direction
Site of Action: Collecting Tubule Effects: - Inc Na+ reabsorption - Inc H2O reabsorption - Inc K+ secretion - Inc H+ secretion
Aldosterone
Site of Action: PCT, Thick Ascending Limb LH, Distal Tubule Effects: Inc Na+ reabsorption Inc H2O reabsorption Inc H+ secretion
Angiotensin II
Site of Action: Distal tubule, Collecting tubule and Duct
Effects: Inc H2O permeability and reabsorption
Vasopressin
Site of Action: Distal tubule, Collecting tubule and Duct
Effects: Dec Na+ reabsorption
- counter regulatory hormone of aldosterone
- secreted by the atrium of the heart
- secreted when you have volume overload
Atrial Natriuretic Peptide (ANP)
Site of Action: PCT, Thick Ascending Limb LH
Effects:
- Dec phosphate reabsorption at the PCT
- Inc Ca2+ reabsorption at the level of Distal Tubule
- stimulates 1alpha hydroxylase (for final activation of Vitamin D)
*increases active Vitamin D
PTH
- secreted by the cardiac ventricles
- marker for Left heart failure
Brain Natriuretic Peptide
SYMPATHETIC Nervous System
- Constricts Renal Arterioles»_space; decreases GFR»_space; increased reabsorption»_space; decreased excretion of sodium and water
- Increases Na+ reabsorption
- Increases Renin and Angiotensin II formation
How do we concentrate urine?
- > 87% of our water is reabsorbed before the collecting duct automatically
- Water reabsorption in the collecting duct is variable
- The Collecting Duct is where our final urine output and urine concentration is determined
- Levels of ADH and its effect on the Collecting duct dictates final urine output and urine concentration
(ADH and Collecting Duct)
If ADH Levels are high, what happens to water reabsorption at the Collecting Duct, Urine Volume and Urine Concentration?
- Water Reabsorption: High (more aquaporins inserted)
- Urine Volume: Low (Min: 500mL/day)
- Urine Concentration: High (Max: 1200 mOsm/L)
(ADH and Collecting Duct)
If ADH Levels are low, what happens to water reabsorption at the Collecting Duct, Urine Volume and Urine Concentration?
- Water Reabsorption: Low (less aquaporins inserted)
- Urine Volume: High (Max: 20L/day)
- Urine Concentration: Low (Min: 50mOsm/L)
How do we concentrate urine?
- Aside from ADH LEVELS, the countercurrent current
mechanism is also needed to concentrate urine - COUNTERCURRENT MECHANISM provides the stimulus for water reabsorption (ADH provides the opportunity)
(Countercurrent Mechanism)
- Loops of Henle
- Creates the Corticopapillary Osmotic Gradient in the renal
interstitium
Countercurrent Multipliers
(Countercurrent Mechanism)
- Vasa Recta
- Maintains the Corticopapillary Osmotic Gradient in the
renal interstitium (prevents dissipation of gradient)
Countercurrent Exchangers
Why is the Loop of Henle able to act as a countercurrent
multiplier?
- Countercurrent Flow (hairpin-loop shape)
- Difference in Permeability to water and electrolytes in the Ascending and Descending Wall
- Na-K-2Cl pump in the TAL LH
- Slow Flow in the LH
Creation of the Gradient
- Na-K-2Cl pump in the thick ascending limb
- Characteristics of the Wall of the descending and ascending limb
- Slow flow of fluid from the PCT to LH
What is the end-result due to the countercurrent mechanism?
Corticopapillary Osmotic Gradient: 300mOsm as you
enter the PCT, 1200mOsm/L at the tip of the Loop of Henle
Why do you need a countercurrent exchanger?
- Gradient would dissipate quickly if Na+ and Urea+
are removed quickly - Vasa Recta (countercurrent exchanger) preserves
this gradient basically by “MOVING AROUND IN CIRCLES” Na+, Urea and water
- Contributes to the hyperosmolarity of the renal medulla
up to 50% of renal medullary interstitial osmolarity - ADH stimulates Urea Receptors (UT-1)
More urea reabsorbed»_space; the more concentrated the renal
interstitium becomes»_space; more concentrated the final urine - Determines osmolarity at tip of LH: from 600-
1200mOsm - role: increases the osmolarity near the tip of the Loop of Henle/ increases the concentration
Urea Recycling
What happen if increased ADH on urea?
increased ADH»_space; increased Urea receptors
|»_space; more urea reabsorbed»_space; more concentrated the renal interstitium»_space; more concentrated the final urine
– (Water excretion rate or Urine Flow Rate) – (Osmolar Clearance)
– Rate of solute-free water being excreted by the
kidneys
FREE WATER CLEARANCE
FREE WATER CLEARANCE
• If positive, EXCESS WATER IS EXCRETED
• If negative, EXCESS SOLUTES IS EXCRETED, WATER IS CONSERVED
*Happens whenever Urine Osmolarity > Plasma Osmolarity
- Head injuries, infection, congenital diseases
- Lack ADH/unable to produce ADH from the posterior pituitary gland
- Absent or Little ADH
- Tx: Desmopressin
CENTRAL DIABETES INSIPIDUS
- Drugs such as Lithium, Tetracyclines
- High ADH/ Normal ADH
- Problem with ADH receptors(Unresponsive ADH Receptors)
- Tx: Thiazide Diuretics, correct cause
NEPHROGENIC DIABETES INSIPIDUS
Regulation of Water
- 180L of fluid/day passes thru the kidneys
- Vasopressin or ADH plays a major role in water reabsorption
- 87%-98.7% of filtered water is reabsorbed
Regulation of Glucose
- Na+-Glucose Cotransport in proximal tubule (GLUT-1)
- Threshold is 200mg/100ml
- Maximum of 375mg/100ml
- Splay is the region between threshold and maximum
Regulation of Sodium
• Major role in electrolyte balance
• Coupled to movement of H+, phosphate, amino acids,
lactate, etc
• Actively transported in all parts of the renal tubule EXCEPT the descending limb of the Loop of Henle
Regulation of Choride, Urea
• Passively absorbed with water
Regulation of Creatinine
- Waste product of metabolism
- Large and impermeant
- Almost all is excreted
Thirst Center
ANTEROVENTRAL WALL OF 3rd VENTRICLE and PREOPTIC NUCLEI
Thirst
• 30-60 minutes for absorption and distribution to the
body
• Work in tandem with ADH to maintain normal ECF Osmolarity
Increase Thirst
- Increase Osmolarity
- Decrease Blood Volume
- Decrease Blood Pressure
- Increase Angiotensin
- Dryness of mouth
Decrease Thirst
- Decrease Osmolarity
- Increase Blood Volume
- Increase Blood Pressure
- Decrease Angiotensin II
- Gastric Distention
(Angiotensin II and Aldosterone’s Effect of Renal Handling of Sodium)
AT II and ALDOSTERONE
– Increases BOTH sodium and water reabsorption
• Increases ECF Volume
• Little effect on ECF Concentration
(Angiotensin II and Aldosterone’s Effect of Renal Handling of Sodium)
HIGH SALT INTAKE AND LOW ALDOSTERONE
– Little increase in ECF Sodium Concentration
• overshadowed by ADH-Thirst System
Regulation of Potassium
Plasma K+ = 4.2 mEq/L
HYPERKALEMIA: Arrhythmias (Ventricular Fibrillation)
HYPOKALEMIA: Weakness (muscle)
How to regulate Potassium?
1st LINE OF DEFENSE: Movement among ECF and ICF
High Potassium in ECF
- move potassium from ECF to ICF
Low Potassium in ECF (Plasma)
- move potassium from ICF to ECF
Factors that shift K+ into Cells (ECF to ICF)
- Insulin
- Aldosterone
- B-adrenergic stimulation
- Alkalosis
Factors that Shift K+ Out of Cells (ICF to ECF)
- Insulin deficiency
- Addison’s Disease
- B-adrenergic Blockade
- Acidosis
- Cell Lysis
- Strenuous Exercise
- Inc ECF osmolarity
- also acts like insulin
- has effects on the sweat glands, salivary gland and colon
- cause potassium to move from ECF to ICF
Aldosterone
- used as treatment in hyperkalemia along with dextrose
Insulin
Why aldosterone is not used as treatment in Hyperkalemia?
Because of its adverse effect in the Kidneys.
Sodium reabsorption»_space; Hypertension
Hydrogen secretion»_space; Metabolic alkalosis
Potassium secretion»_space; hypokalemia
Regulation of Potassium (Renal Regulation)
- Day-to-day Renal Regulation occurs in the Late Distal Tubule and Cortical Collecting Tubules (NOT before)
- Potassium reabsorbed (Intercalated Cell) or secreted (Principal Cell) depending upon the body’s needs
- Hyperkalemia - stimulates Principal Cells
- Hypokalemia - stimulates Intercalated Cells
Stimulation and Inhibition of the Principal Cells
STIMULATES PRINCIPAL CELLS
- Inc ECF K+
- Inc Aldosterone
- Inc Tubular Flow Rate
- Chronic Acidosis
INHIBITS PRINCIPAL CELLS
- Acute Acidosis
(Regulation of Potassium)
INC ECF K+ STIMULATES PRINCIPAL CELLS
- Inc ECF K+»_space; Inc Na-K-ATPase pump action»_space; Inc intracellular K+»_space; inc K+ diffusion to the lumen
- Inc ECF K+»_space; prevents backleak of K+ from the inside of the cells to the basolateral membrane
- Inc ECF K+»_space; stimulates Aldosterone»_space; inc secretion of K+
(Regulation of Potassium)
INC ALDOSTERONE STIMULATES PRINCIPAL CELLS
- Increases Na-K pump (NOT the Na-K-ATPase pump)
- Increases permeability of the luminal membrane to potassium
(Regulation of Potassium)
INC TUBULAR FLOW RATE STIMULATES PRINCIPAL CELLS
- Prevents K+ from accumulating in the lumen»_space; increases driving force for diffusion of K+ from the cells to the lumen
- Increased tubular flow rate occurs in
- Volume Expansion
- High Sodium Intake
- Use of diuretics
- Helps preserve normal K+ excretion during high sodium intake
(Regulation of Potassium)
ACIDOSIS
ACUTE ACIDOSIS
- Inhibits K+ secretion
- MOA: Inhibition of Na-K-ATPase Pump»_space; dec intracellular K+»_space; dec diffusion of K+ into the lumen
CHRONIC ACIDOSIS
- Stimulates K+ secretion
- MOA: Dec H2O and Na reabsorption in the PCT»_space; inc tubular flow rate»_space; inc K+ secretion
Regulation of Calcium (Plasma Ca)
Plasma Ca2+ = 2.4mEq/L
*referring to free plasma calcium
HypoCa: Tetany/ Spasm of Skeletal muscle
HyperCa: Arrhythmias
Regulation of Calcium
- 90% of calcium in the GI tract goes directly to the feces; only 10% is absorbed
- 99% of body calcium found in the bones
- 1% of body calcium in plasma – half bound to proteins, half in free ionized form
*ONLY THE FREE IONIZED FORM IS ACTIVE
¥ Calcium reabsorption in the kidneys controlled by Vitamin D and PTH and parallels that of Sodium and Water
Regulation of Calcium (Acidosis vs Alkalosis)
ACIDOSIS
- less calcium bound to plasma proteins»_space; Hypercalcemia
- pinapalitan ni H+ ang Calcium na nakabound sa protein para tumaas ang pH
- Acidosis always associated with hypercalcemia
ALKALOSIS
- more calcium bound to plasma proteins»_space; Hypocalcemia
Factors that Alter Renal Calcium Excretion (Decrease Calcium Excretion)
- Increase Parathyroid Hormone
- Decrease Extracellular fluid Volume
- Decrease Blood Pressure
- Increase Plasma Phosphate
- Metabolic Acidosis
- Vitamin D3
Factors that Alter Renal Calcium Excretion (Increase Calcium Excretion)
- Decrease Parathyroid Hormone
- Increase Extracellular fluid Volume
- Increase Blood Pressure
- Decrease Plasma Phosphate
- Metabolic Alkalosis
Regulation of Phosphate
Transport Maximum of Phosphate = 0.1mM/min
- Often exceeded in diets with milk and meat
- Counteracted by PTH
Regulation of Magnesium
- Plasma Mg2+ = 1.8mEq/L
- 50% stored in the bones
- Only 10% of plasma Mg excreted daily
- PCT -25% reabsorption
- LH – 65% reabsorption
- Antagonistic to Calcium levels
Where is Magnesium mainly reabsorbed?
Loop of Henle - 65%
ACIDS
- Proton donors
- Strong Acids: dissociates rapidly (e.g. HCl)
- Weak Acids: does NOT dissociate rapidly (e.g. H2CO3)
BASES/ALKALI
- Proton acceptors
- Also has strong bases (OH-) and weak bases (HCO3-)
- Substance that can reversibly bind H
BUFFER
Basic Acid-Base Physiology
- Almost all enzyme systems are influenced by H+ levels and must be regulated
- Normal Plasma H+ = 0.00004 mEq/L
- Reason for using pH system
- Normal Plasma pH = -log [H+] = 7.4
- pH = 6.8 – 8.0 (Compatible with life)
pH and H Concentration of Body Fluids (Extracellular Fluid)
Arterial Blood: 4.0x10^-5 pH - 7.40
Venous Blood: 4.5x10^-5 pH - 7.35
Interstitial Fluid: 4.5x10^-5 pH - 7.35
pH and H Concentration of Body Fluids (Intracellula Fluid)
1x10^-3 to 4x10^-5 pH - 6.0 to 7.4
pH and H Concentration of Body Fluids (Urine)
3x10^-2 to 1x10^-5 pH - 4.5 to 8.0
pH and H Concentration of Body Fluids (Gastric HCl)
160 pH - 0.8
Systems that regulate H+ Concentrations
- Body Fluid Buffer Systems
- Respiratory Center
- Kidneys
Controls HCO3- (Metabolic Acidosis/Alkalosis)
Body Fluid Buffer Systems
- Bicabonate Buffer System (number 1 buffer system in the extracellular fluid compartment)
- CO2 + H2O = H2CO3 = H+ + HCO3- - Phosphate Buffer System (H2PO4- and HPO4-)
- Intracellular Proteins
- Controls PCO2/Partial Pressure of Carbon Dioxide (Respiratory Acidosis/Alkalosis)
- Metabolic Acidosis - Increase Respiratory Rate (less CO2 in the blood, less carbonic acid in the blood)
Respiratory Center
- Controls HCO3- (Metabolic Acidosis/Alkalosis)
- In respiratory Acidosis, it will try to excrete the excess acid and reabsorb the base to counteract the acidosis
Kidneys
used to calculate the concentration of a weak acid (HA) and its conjugate base (A-)
Henderson – Hasselbalch Equation
Henderson – Hasselbalch Equation: what is it used for?
- titration and charge of amino acids
- predicting shifts in the bicarbonate buffer system
CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3- - predicting distribution and excretion of drugs
If actual > pKa; substance is DEPROTONATED
acid-COOH>acid-COO- + H+ ACID IS CHARGED
base-NH3+>base-NH2 + H+ BASE IS UNCHARGED
If actual
acid-COOH>acid-COO- + H+ ACID IS UNCHARGED
base-NH3+>base-NH2 + H+ BASE IS CHARGED
An increase in bicarbonate ion causes the pH to rise
Regulated by the kidneys
An increase in carbon dioxide causes the pH to fall
Regulated by the rate of respiration
Respiratory Control of Acid-Base Balance: Responds to H+ levels
Increased H+ : increased RR»_space; dec PCO2
Decreased H+ : decreased RR»_space; inc PCO2
Respiratory Control of Acid-Base Balance
- Effectiveness of 50-75% in returning pH back to normal within 3-12 minutes
- Abnormality which increases RR will cause: RESPIRATORY ALKALOSIS
- Abnormality which decreases RR will cause: RESPIRATORY ACIDOSIS
Renal Control of Acid-Base Balance: MECHANISMS
- Secretion of H+
- Na+-H+ Countertransport in the PCT , LH, DT
- H+ATPase pump in the Distal Tubules and CD - Reabsorption of HCO3-
- Coupled to H+ Secretion - Production of New HCO3-
- Use of Ammonia (NH3) and Phosphate(NaHPO4-) buffers
Renal Control of Acid-Base Balance
H+ is titrated to HCO3-
- Excess HCO3- will NOT be reabsorbed»_space; Excreted into the urine
- Excess H+ will cause all filtered HCO3- to be reabsorbed and urinary buffers for H+ to be activated»_space; H+ excreted into the urine
Factors that Increase H+ secretion and HCO3 reabsorption
- Increase PCO2
- Increase H+, Decrease HCO3-
- Decrease Extracellular fluid volume
- Increase Angiotensin II
- Increase Aldosterone
- Hypokalemia
Factors that Decrease H+ secretion and HCO3 reabsorption
- Decrease PCO2
- Decrease H+, Increase HCO3-
- Increase Extracellular fluid volume
- Decrease Angiotensin II
- Decrease Aldosterone
- Hyperkalemia
pH: ↓
H+: ↑
PCO2: ↑↑
HCO3-: ↑
Respiratory Acidosis
Respiratory Acidosis: Compensation
Inc H+ excretion,
Inc HCO3- reabsorption
pH: ↑
H+: ↓
PCO2: ↓↓
HCO3-: ↓
Respiratory Alkalosis
Respiratory Alkalosis: Compensation
Dec H+ excretion
Dec HCO3- reabsorption
pH: ↓ H+: ↑ PCO2: ↓ HCO3-: ↓↓ Compensation: Hyperventilation
Metabolic Acidosis
pH: ↑ H+: ↓ PCO2: ↑ HCO3-: ↑↑ Compensation: Hypoventilation
Metabolic Alkalosis
- Due to DECREASED VENTILATION (RR)
- E.g. Opiates, Sedatives, Anesthetics, Guillan-Barre Sydrome, Polio, Amyotrophic Lateral Sclerosis, Multiple Sclerosis, Airway Obstruction, ARDS, COPD
Respiratory Acidosis
- Due to INCREASED VENTILATION (RR)
- E.g. Pneumonia, Pulmonary embolus, High Altitude, Psychogenic, Salicylate Intoxication
Respiratory Alkalosis
- Due to EXCESS ACID or LOSS OF BASE
- E.g. Severe diarrhea, Renal Tubular Acidosis, Diabetic Ketoacidosis, Ingestion of acids like ASA and methanol (forms formic acid), Vomiting of Intestinal Contents, Chronic Renal Failure
Metabolic Acidosis
Metabolic Acidosis
- Anion Gap (AG) used to help diagnose cause of metabolic acidosis
- Serum Anion Gap = [Na+] – [Cl-] + [HCO3-]
- Normal AG = 12mEq/L + or – 4
- gain of acid
- (MUDPILES mnemonic)
Methanol, Uremia, DKA, paraldehyde, Iron Isoniazid, Lactic Acidosis, Ethylene Glycol, Salicylic Acid
High Anion Gap Metabolic Acidosis
- loss of bases
- also called as Hyperchloremic metabolic acidosis
- HARD-UP mnemonic: Hyperalimentation, Acetazolamide, RTA, Diarrhea, Uerteroenteric fistula, Pacreaticoduodenal Fistula
Normal Anion Gap Metabolic Acidosis
- Due to LOSS OF ACID or GAIN OF BASE
- E.g. Administration of Diuretics (Except Carbonic Anhydrase Inhibitors), Vomiting of Gastric Contents, Hyperaldosteronism, Ingestion of Alkaline Drugs (Sodium Bicarbonate)
Metabolic Alkalosis
Treatment of Acidosis and Alkalosis
- Correct the underlying cause first
- SODIUM BICARBONATE (oral)
- Neutralizes excess acids
- Sodium lactate and sodium gluconate maybe given IV
- AMMONIUM CHLORIDE (oral)
- For alkalosis