Na+ balance (salt & water balance)

Renin secretion

180L/day

2L become urine

in the cortical collecting duct (CCD) which cells secrete K+ and which secrete H+?

K+ = principal cells

H+ = intercalated cells

1. endothelial cells

2. glomerular basement membrane

3. podocyte foot processes

>7000 is freely filtered

>70,000 is not filtered at all

YES.  You can spill solutes out of the blood space into the urinary space and not have a change in GFR.  There ARE diseases that change permeability and GFR

hydrostatic pressure for: capillary, bowmans space

Oncotic pressure for : capillary, bowmans space

what is the difference in GFR from afferent to efferent limb?

1.  High Cl- --> macula densa senses --> release adenosine which acts on smooth muscles of Af. Arter. constricting causing decrease in P_GC

2.  Low Cl- --> Macula densa --> prostaglandin release onto Granular cells --> release Renin for RAAS

Low dose Angiotensin II  constrict efferent > afferent arteriole        ↑PGC           ↑GFR

1. constricts efferent AND afferent arteriole

2. potent system vasoconstrictor to maintain blood pressure

3. stimulate ADH secretion

4.  stimulate Aldosterone secretion

5. lowers both P_GC and GFR

AA = 60 mmHg

EA = 58 mmHg

this change is mainly due to changes in EA constriction

Renin

sensing of low lumun Cl-

what cells sense low or high Cl-?

what does high Cl- mean?

NKCC cells on the macula densa

high arterial pressure

the release of adenosine to smooth muscles via the Macula densa

stretching due to pressure which causes Ca++ release and smooth muscle contraction (myogenic reflex)

UV/P

U = urine concentration

V = volume

P = plasma concentration

if GFR = (constant creatinine production)/serum creatine

then the higher about the standard (1.0) means a decrease in GFR

This is based on the asumption that the person is of normal muscle mass.  For an elderly person who has low muscle mass and a serum creatine of 2.0 then their GFR would be @ 25%

how well they can clear plasma and GFR

Ie:

Removal of end products

of metabolism

Urea

Creatinine

Uric acid

Urobilinogen

creatinine clearance = (140-age) x lean body weight (in Kg)

----------------------------

plasma creatinine (mg/dl) x 72

for women multiply by .85

1.  100-90% GFR: protineuria, hemauria

2.  90 - 60%: proteinuria, hemauria

3.  60-30% - complications possible

4. 30-15% - complications evident

5.  <15% - renal replacement therapy

total body sodium

sodium concentration does not reflect total body sodium

aortic and carotid bodies

cardiopulmonary circulation

afferent glomerular arterioles

activation of the SNS causing

increased cardiac output

increased systemic vascular resistance

increased renal sodium reabsorption in proximal tubule

increased renin secretion, activating angiotensin II

Atrial natruyretuc peptide - increases Na excretion by increasing GFR, and by inhibiting Na reabsorption in the CCD.  Also inhibits renin and AT II

Brain natriuretic peptide

the medullary concentration gradient

H20 is reabsorbed in the descending loop and is impermeable in the ascending loop.  Vice versa for NaCl reabsorption

50mOsm/kg  

With a typical daily solute intake of ~600mOsms, the maxiumum urine output would be 12 L!

1200mOsm/kg

the daily solute load (600mOsm) can be excreted in as little as 500mls of urine 

source of electrolyte free water

impaired excretion of dilute urine by the kidneys

acute cerebrail edema secondary to water moving into brain cells

agressive TX by increasing serum Na+ rapidly

hyperglycemia

hypertriglyceridaemia

severe paraproteinaemia

hyponatremia

decreased serum osmolality (<270mOsm/kg)

urine sodium >20mmol/L

Inappropriate urine concnetration (urine osmolality > 100mOsm/Kg)

exclusion of renal failure and endocrine dysfunction!

1-2mmol/hr over the first 3-4 hrs with a MAX increase of 8-12 mm in 24 hours.

saline must be hypertonic

Note: patients with hyponatremia secondary to volume depletion typically respond to isotonic normal saline as correction of the volume depletion will remove the stimulus fo ADH and permit renal excretion of a maximally dilute urine

1mm/L/hr with a maximum of 10-12mmol/L over a 24 hr period

strategies should include:

1.water restriction

2. increased Na+ intake with frusemide to promote renal EFW

3. Administration of drugs to antagonise the action of ADH

impaired thirst mechanism

difficulties with access to water

diabetes insipidus

osmotic diuresis

inadequately replaced non-renal EFW loss

deficiency of ADH

(central diabetes insipidus)

diminished response to ADH

(nephrogenic diabetes insipidus)

sweating

respiratory tract

GI losses

1. stop ongoing excessive loss of EFW

2.  Replace the EFW loss with hypotonic fluids ie: 5% dextrose, oral H20, half-normal saline

1. GI losses - vomiting or diarhhea

2.  excess sweating

3.  Renal Na losses - diuretics

increased capillary wall permeability

increased capillary hydrostatic pressure

decreased intravascular oncotic pressure

lymphatic obstruction

decreased cardiac output which lowers EABV.

By activating the RAAS and SNS this causes edema

Hyper - makes the cell less negative and thus more excitable

hypo - make sthe cell more negative and renders the cell 

insulin -> takes into the cell

aldosterone -> excreted out in urine

catecholamines ->

muscle weakness, cramps, myalgia

if severe:

muscle necrosis and rhabdomyolysis

remember that this is a disorder of the cell becoming too hyperpolarized and thus making it more difficult to invoke an action potential.

depressed ST segment and low T wave.  also prominent "u" wave

cardiac arrhytmias

increased bicarbonate reabsorption in the proximal tubule and increased hydrogen ion secretion in the cortical collecting duct cause:

METABOLIC ALKALOSIS

can cause nausea, vomiting, constipation or paralytic ileus where it;s movements are lost

can cause increase in renal ammonia leading to hepatic encephalopathy in those with liver disease.

losses causing K+ to move out of cells to maintain Em reflecting a loss in total body K+

losses through GI or diuretics

alkalosis

Beta-2-agonists

excess insulin

catechol release

people in these situations are volume depleted and thus activate aldosterone stimulating potassium secretion.

Also loss of H+ stimulates an increase in plasma bicarbonate concentration which promotes K+ secretion

metabolic acidosis

thus this underlying disorder must be treated as well to restore K+ concentration to normal

Plasma [K+]

plasma aldosterone level

distal Delivery of Na+ to distal nephron

is the hyperkalemia real?

is the hyperkalemia due to a shift of k+ from the ICF into the ECF?

Is the hyperkalemia due to inability to excrete potassium?

hemolysis due to mechanical trauma during the venipuncture

thrombocytosis or leukocytosis where K+ moves out of the platelets or white blood cells after blood is drawn.

a normal ECG in the setting of very high [K+] is suggestive of pseudohyperkalemia

acidosis

insulin deficiency

hyperosmolality

(H20 leaving the cell causes an increase in ICF [K+] causing it to leave the cell with H20)

B-adrenergic blockers who ingest large amounts of K+

ACE inhibitors

(reduce aldosterone release)

hypoaldosteronism

 (hyporenemic hypoaldosteronism or certain drugs)

K+ sparing diuretics

(can competitively inhibit the aldosterone receptor)

antagonize the membrane effects of K+

drive the extra cellular potassium into cells

remove excess potassium from the body

Ca++

this is a short lived effect and is used only for patients with severe symptomatic hyperkalemia

Insulin

(this enhances the effect of the Na/K pump)

dextrose is given with it to minimize the effects of hypoglycemia

Sodium Bicarbonate

(results in hydrogen shift out of cells and K+ movement into them)

B-adrenertic agents

Loop diuretics

or cation exchange resins

if none of the above mentioned processes work in anyway to reduce the hyperkalemia, dialysis is a necessary option

what are the 3 ways that the body deals with daily acid load? 

(50-100mm H+)

buffering free H+ ions

alveolar ventilation (removing C02)

renal H+ excretion

The kidneys regenerate bicarbonate.

This is achieved by:

A. reclaimation of all filtered HCO3 (90% at the proximal)

B.  excretion of H+ ions with resultant generation of HCO3 ions

NaH2PO4

NH4Cl

(the amount of NaH2PO4 is fixed and to excrete greater H+, extra NH4+ can be generated)

22-30

<22 implies metabolic acidosis

> 30 implies metabolic alkalosis

35-45mmHg

>40mm implies respiratory acidosis

< 40mmHg implies respiratory alkalosis

it is the calculated difference between cations and anions in the blood

the typical equation is:

Na+ - (Cl- + HCO3) = 12

1. hypoalbuminaemia

(the normal value for the anion gap is dependent on the serum protein concentration)

2. Positively charged paraproteinaemia (myeloma)

3.  rarely addition of halides to the serum

determine the etiology of a metabolic acidosis

determine if a complex metabolic disorder is present.

what are reasons for assesing the 

serum anion gap/change in bicarbonate?

as H+ load increases H+ can be buffered by things other than HCO3.  The change in the anion gap is usually greater than the change in HCO3.

if the anion gap is greater than the change in HCO3, what does this mean?

what if it is lower than the bicarb?

This suggests that there is a simultaneous presence of an underlying metabolic alkalosis (high HCO3) and anion-gap metabolic acidosis (vomiting).

presence of a non-anion gap acidossis in addition to the anion metabolic acidosis

(lactic acidosis with simultaneous renal tubular acidosis)

loss of bicarb

gain of H+

1. lactic acidosis

2.  ketoacidosis

3.  renal failure

4.  Poisoning

1. gastrointestinal HCO3 loss

2.  renal tubular acidosis

Anerobic metabolism due to tissue hypoxia

(hypotension due to sepsis, hypovolemia, or cardiogenic shock, hemoglobin problem, increased O2 requirements)

abnormal lactate metabolism in the setting of adequate tissue oxygen delivery ie. no hypoxia

(medications, mitochondrial dysfunction)

ketoacids to produce energy (primarily brain & kidneys)  

Ketoacids generates an anion gap metabolic acidosis

this is the difference between the measured plasma osmolality and the calculated osmolality.

Normal value <10 mOsm and a a high osmolal gap implies the presnce of unmeasured osmoles (alcohol, methanol, ethylene glycol)

respiratory alkalosis

(direct stimulation)

mild anion gap metabolic acidosis

(this is due to an accumulation of organic acids, lactic acids and ketoacids)

in metabolic acidosis, the UAG becomes progressively more negative (-75 to -100) reflecting an increase in NH4Cl excretion (increased NH4+ cation)

when in rental tubular acidosis there is a failure of ammonium excretion the UAG has a possitive value

1. inability to reabsorb filtered bicarbonate (proximal RTA)

2.  Impaired excretion of ammonium chloride (distal RTA)

a non anion gap metabolic acidosis

if the serum HCO3 reaches it's maximum, no further HCO3 is able to be reabsorbed because it leads to an even greater filtering of HCO3 and thus wasting of bicarbonate in the urine

1. a source of alkali is high (this most often occurs in the presence of loss of H+

2. factors that prevent the kidney from excreting the excess alkali 

(anything that causes an excretion of H+ or ECV depletion which raises NaHCO3 reabsorption)

vomiting

diuretics

primary hyperaldosteronism