Week 3 Flashcards
1
Q
What is the function of Calcium and phosphorus? Three for each.
A
- Calcium
- Function: Muscle contraction, heart contraction, NT release
- Phosphorus
- Function: ATP, lipid membranes, bone
2
Q
What locations is calcium mainly stored in? How much in the ECF? What is the calcium state in the ECF (3 states)? Normal calcium?
What do you when albumin is low?
A
- Calcium
- Mainly stored in bone and teeth
- < 1 % in extracellular fluid
- Ionized calcium
- Protein bound calcium – mainly albumin
- When albumin is low, must correct for serum calcium
- Ca = 8.5 mg/dl + 0.8x(4-serum albumin)
- Alkalosis decreases ionized calcium by increasing binding to albumin
- When albumin is low, must correct for serum calcium
- Anion bound calcium
- Total Serum Calcium = 8.5-10.3 mg/dl
3
Q
What location is phosphorus stored in? Provide percentages. What is normal serum P?
A
- Phosphorus
- 85% in bone
- 15% in soft tissue
- < 1% in serum
- Serum phosphorus = 2.5-4.5 mg/dl
4
Q
What three locations is Ca+ transported in in the nephron?
A
PCT reabsorption, ALOH reabsorption, and DCT reabsorption
5
Q
- In the PCT,
- How much Ca+ is reabsorbed and by what method?
- What is the MOA?
- What occurs in volume depletion with Ca?
A
- PCT
- 60-70% reabsorbed via passive paracellular transport
- MOA: Calcium follow Na and water reabsorption
- Volume depletion: ATII and Aldo released → sodium reabsorbed → calcium reabsorbed
6
Q
In the ALOH,
- How much Ca+ is reabsorbed and by what method?
- What is the MOA?
- What occurs in loop diuretics with Ca?
A
- ALOH
- 20% reabsorbed via passive paracellular transport
- MOA: Positive lumen and negative blood generated by NKCC2 → calcium reabsorption
- High Ca activates CaSR which decreases permeability of the paracellular route
- Loop diuretic: blocks NKCC2 → destroys gradient → calcium excreted
7
Q
In DCT
- How much Ca+ is reabsorbed and by what method?
What is the MOA?
What occurs in thiazide diuretics with Ca?
A
- DCT
- 10% reabsorbed via active transport
- MOA: Calcium reabsorbed via a TRPV5 channel
- Thiazide: By blocking Na-Cl → lowering intracellular Na concentration → increased activity of basolateral Na-Ca antiporter → increased Ca reabsorption
8
Q
Where is phosphorus transported? How much is reabsorbed and by what mechanism?
A
- Phosphorus
- PCT
- 85% reabsorbed via active transport
- MOA: Phosphorus reabsorbed via luminal Na-PO4 symporter
- PCT
9
Q
For PTH:
- What is the location of where it is secreted?
- How is it regulated with low plasma Ca? High plasma Ca?
A
- PTH
- Location: latched on thyroid follicles
- Regulation:
- Low Ca plasma → CaSR is not activated → PTH is produced
- High Ca plasma → CaSR is activated → PTH is not produced
10
Q
What is the proces of synthesis and function of Vit D? How is it stimulated?
A
- Vitamin D
- Structure and Function:
- Cholecalciferol (steroid hormone produced by UV Light) → converted to 25-hydroxylase in liver → and 1alpha-hydroxylase (active Vit.D) in kidney
- Synthesis
- PTH (or low levels of Ca/PO4) increase expression of 1alpha-hydroxylase
- Inhibited by active Vit. D and high Ca (negative feedback)
- PTH (or low levels of Ca/PO4) increase expression of 1alpha-hydroxylase
- Structure and Function:
11
Q
What is the effect of FGF23? What does it result in?
A
- FGF-23
- Decreases Na-PO4 symporter (kidneys → phosphate excretion) and decrease vitamin D (intestine → decreases phosphate absorption)
- Resulting in decreased serum phosphate
- Decreases Na-PO4 symporter (kidneys → phosphate excretion) and decrease vitamin D (intestine → decreases phosphate absorption)
12
Q
What are the three effector organs for calcium and phosphorus?
A
Bones, kidney, intestine
13
Q
What does PTH do in bones in terms of Ca? Provide the full mechanism
A
- PTH binds to osteoblasts → up regulates RANKL → activates osteoclasts → release of Ca from bone
14
Q
What does PTH do in kidneys in terms of Ca? Provide the full mechanism
A
- Calcium
- PTH (also Vitamin D and alkalosis) increase expression of TRPV5 → increase Ca reabsorption
15
Q
What does PTH do to phosphorus in kidney? Provide the full mechanism.
A
- PTH decrease expression of Na-PO4 symporter at PCT → decreases phosphorus reabsorption
- PTH also increases phosphorus release from bones, counterbalancing the effect, however still resulting in overall serum phosphorus level
16
Q
What does Vit D do to phosphorus in kidney? Provide the full mechanism.
A
- Vit. D increase expression of Na-PO4 symporter → increased phosphorus reabsorption
17
Q
What does FGF23 do to phosphorus in kidney? Provide the full mechanism.
A
- FGF-23 → decreases Na-PO4 symporter → phosphate excretion
18
Q
What does Vit D do to calcium in intestine? Provide the full mechanism.
A
- Vit D increase production of calbindin, a calcium binding protein in the gut (slow acting ~ 2 days)
19
Q
What does Vit D do to phopshorus in intestine? Provide the full mechanism.
A
- Vit. D increase expression of Na-PO4 symporter → increased phosphorus reabsorption
20
Q
What does FGF23 do to phopshorus in intestine? Provide the full mechanism.
A
- FGF-23 → decreases Vit D → deceased phosphate absorption
21
Q
What diseases can cause increased PTH? 3 diseases
A
- Increased PTH
- Primary Hyperparathyroidism
- Caused by adenoma or hyperplasia of parathyroid
- Can be asymptomatic
- Tertiary Hyperparathyroidism
- Lithium
- Decreases the threshold for release of PTH at low Ca
- Primary Hyperparathyroidism
22
Q
What diseases can cause increased bone resorption? 3 diseases
A
- Malignancy
- Osteolytic metastasis to bone (most common in breast, lung, and multiple myeloma)
- Production of PTH related peptide
- Binds to PTH receptor
- Resistant to negative feedback from CSR
- Tumor production of Active Vitamin D
- Immobilization
- If bedridden, increased osteoclast activity
- Hyperthyroidism
23
Q
What disease states can cause increased GI absorption? 2 diseases
A
Milk-Alkali Syndrome and Increased Vit D
24
Q
Milk-Alkali Syndrome
- Etiology
- MOA
A
- Milk-Alkali Syndrome
- Etiology: Ingestion of base and calcium (i.e. TUMS)
- MOA
- ↑Ca → renal vasoconstriction → ↓GFR → ↓ filtered Ca
- ↑Ca → activated CaSR in Loop of Henle → ↓Na absorption via NKCC2 → volume depletion → ↓GFR → ↓ filtered Ca
- Alkalosis → activated CaSR in Loop of Henle
- Alkalosis → activated TRPV5 → increased tubular reclamation of Ca
- Alkalosis → ↓ionized calcium b/c ions bind to albumin→ ↓filtered Ca
25
What does increased Vit D do in the GI absorption of calcium and what is it common in?
* Increased Vit D
* Common in granulomatous diseases (i.e sarcoidosis) and excessive supplement use
26
What two diseases or drugs increase renal absorption of calcium and what is their mechanism?
* Increased Renal absorption
* Thiazide diuretics increase activation of the basolateral Ca-Na antiporter → increased Ca+ reabsorption through TRPV5 luminal channel
* Familial hypocalciuric hypercalcemia
* Autosomal dominant mutation in CaSR → cannot turn off NKCC2 → Ca keeps being reabsorbed along with Na
27
What are the neuro, cardio, renal, and GI are the symptoms
* Neuro: fatigue, coma, anxiety (NT release)
* Cardio: short QT intervals (bradycardia/arrhythmias), HTN
* Renal: kidney failure, kidney stones
* GI: nausea, vomiting
28
How do you diagnose hypercalcemia?
* Diagnosis
* Check PTH levels
* If high Ca with high PTH →
* +high urine calcium → primary hyperparathyroidism
* +low urine calcium → familial hypocalciuric hypercalcemia
* If high Ca with low PTH → malignancy, lithium, Vit D, thiazides, sarcoidosis, hyperthyroidism, etc.
29
What are the treatments for primary hyperparathyroidism, mild to moderate hypercalcemia, severe hypercalcemia, very severe?
* Treatment
* Primary Hyperparathyroidism – resection
* Mild to moderate hypercalcemia (Ca: 10.5 to 14 mg/dl
* Stop Vit D, thiazides, and calcium supplements
* Severe hypercalcemia (Ca \> 14 mg/dl
* Start on normal saline +/- loop diuretics
* Calcitonin
* Description: Secreted by the parafollicular cells of the thyroid gland
* MOA: decreases osteoclast activity
* Bisphosphonates
* MOA: decreases osteoclast activity
* VERY severe (Ca \> 18 mg/dl)
* Hemodialysis
30
What are the 6 disease states with hypocalcemia?
* Decreased PTH secretion or action
* Hypoparathyroidism: Surgery, Infiltrative Diseases, Congenital, Hypomagnesemia
* Hypomagnesemia → resistance to PTH and low secretion
* Pseudohypoparathyroidism
* Mutation in PTH receptor
* Presents with high PTH but with hypocalcemia
* Familial Hypercalciuric Hypocalcemia
* Gain of function mutation in CaSR
* Low PTH with hypocalcemia and hypercalciuria
* Decreased GI absorption (Vit D deficiency)
* GI malabsorption, Vit D deficiency (secondary to liver or CKD)
* Increased kidney excretion
* Loop diuretics/Bartter’s syndrome
* Blocks NKCC2, destroying electric gradient for Ca reabsorption
* Aminoglycosides
* Increases membrane permeability, destroying electric gradient for Ca reabsorption
* Increased tissue/bone uptake
* Pancreatitis
* Hyperphosphatemia
* Rhabdomyolysis: muscle is breaking down proteins, which releases phosphate that binds calcium → hypocalcemia
* Tumor lysis syndrome: release of phosphate that binds calcium → hypocalcemia
* Hungry Bone Syndrome
* Occurs after resection of parathyroid status-post chronic hyperparathyroidism → bone will reabsorb large amounts of Ca
* Bisphosphonates
* Decreases osteoclast activity
* Spurious
31
What are the symptoms of hypocalcemia?
* Symptoms
* Hyperactive reflexes (Chvostek’s sign), prolonged QT interval, arrhythmias, heart block
32
How do you diagnose hypocalcemia?
* Diagnosis
* Check PTH levels
* If PTH low → think destruction of parathyroid, hypomagnesemia, familial hypercalciuric hypocalcemia
* If PTH high → see everything above
33
What is treatment of hypocalcemia?
* Treatment
* Give back calcium
* If symptomatic: IV calcium gluconate
* If asymptomatic: Oral calcium
* If very severe: Calcitrol (active Vit D)
34
What is the pathophys of metabolic bone disease with hyperphosphatemia?
Hyperphosphatemia
* Pathophysiology
* Metabolic Bone Disease
* In CKD → phosphate retention → increases FGF23 → decreases active Vit D → increases PTH release and decreases Ca → secondary hyperparathyroidism → increased Ca, phosphate, and FGF23
* Though secondary hyperparathyroidism results in increased Ca, patients will present with low calcium levels because compensation is not sufficient
* Elevated FGF23 → decreases expression of Na-PO4 symporter → increased excretion of phosphate
35
What are the symptoms of hyperphosphatemia?
* Symptoms: Increased cardiovascular stiffness and symptoms associated with hypocalcemia (b/c Ca binds to excess phosphate)
36
What are the 4 conditions associated with hypophosphatemia?
Intracellular shift
Acute respiratory alkalosis
Decreased GI absorption
Increased renal excretion
37
Explain the pathophysiology of intracellular shift of hypophospahtemia?
* Intracellular Shift
* Cellular distribution affected in:
* Sepsis: catecholamines, which are prevalent → send phosphorus intracellularly → depletion of serum phosphorus
* Insulin: In a seriously hungry state, ingestion of food → rapidly increase circulating insulin levels → phosphorus moves intracellularly → depletion of serum phosphorus
38
Explain the pathophysiology of the acute respiratory alkalosis with hypophosphatemia.
* Acute respiratory alkalosis
* Stimulates PFK to send phosphorus intracellularly
39
Explain the patophys of decreased GI absorption with hypophosphatemia.
* Decreased GI absorption
* Malabsorption, Vit D deficiency
* Phosphate binders:
* Calcium Acetate
* MOA: Ca cation separates from acetate anion → Ca binds to phosphate in gut → excreted as poop
40
Explain the increased renal excretion of phosphate and the pathophys behind it.
* Increased renal excretion
* Osmotic diuresis: increased glucose in urine → increased urine volume → decreased sodium reabsorption → decreased phosphorus reabsorption via Na-PO4 symporter
* Hyperparathyroidism: increased PTH → decreased expression of Na-PO4 symporter at PCT → decreases phosphorus reabsorption
* Elevated FGF23 levels (secondary to X-linked hypophosphatemic rickets and tumoral hypophosphatemia)
* Decreases Na-PO4 symporter in renal tubules
* Fanconi syndrome (often due to carbonic anhydrase inhibitors)
* Decreases Na+ reabsorption
41
What symptoms are associated with hypophosphatemia?
* Symptoms
* CNS: seizures, irritability, encephalopathy
* Blood: Hemolysis
* Muscle: Myopathy & rhabdomyolysis
42
What is the diagnosis of hypophosphatemia?
* Diagnosis
* If low urinary phosphorus excretion → think poor GI absorption or intracellular shift
* If high urinary phosphorus excretion → think hyperparathyroidism, Fanconi’s syndrome, or elevated FGF23
43
What is the treatment of hypophosphatemia?
* Treatment
* If mild (2 to 2.5 mg/dl): correct vit D deficiency and increase dietary phosphorus (dairy, whole grains, preserved foods)
* If severe (\< 2 mg/dl): consider oral phosphorus or IV phosphorus
44
What is the general distribution for potassium in the body? Provide osmolalities.
* Distribution
* 98% intracellular (140 mEq/L)
* 2% extracellular (4 mEq/L)
45
How is potassiu regulated in the body? Intracellular shift (4) and extracellular shift (6)?
* Regulation in body
* Intracellular shift
* Insulin, aldosterone, beta-adrenergic stimulation, alkalosis
* Extracellular shift
* Insulin deficiency, aldosterone deficiency, beta-adrenergic blockade, acidosis, cell lysis, exercise
46
What occurs in the nephron at each part with potassium?
* Renal Handling
* Glomerulus – freely filtered
* PCT – reabsorbed 65%
* TAL - reabsorbed 27%
* Collecting duct – secreted (main control center of K+ concentration)
* Potassium excretion = Distal secretion
47
In the kidneys, what causes potassium reuptake?
* Regulation in Kidneys
* Potassium uptake
* Insulin, beta-adrenergic stimulation, low plasma potassium concentration
* Intercalated cells play a major role in potassium excretion
48
In the kidneys, what causes potassium excretion?
* Potassium excretion
* Aldosterone, distal flow of sodium and water, high plasma potassium concentration
* Principal cells play a major role in potassium excretion
* Renal K excretion is independent of changes in extracellular fluid volume
* Decreased volume increases aldosterone release which causes renal K wasting
* Increased volume causes decreased proximal Na reabsorption → increases distal Na delivery → renal K wasting
49
What are the mechanisms for hyperkalemia? Describe conditons for each.
* Mechanisms of Hyperkalemia
* Increased K intake
* High K foods (i.e. potatoes, OJ, tomatoes, bananas)
* Blood transfusion
* Reduced renal K excretion
* Low GFR – renal failure
* Low aldosterone – ACEi,
* Reduced distal flow – volume depletion, cirrhosis, CHF
* Increase K release
* See above, tissue breakdown, pseudohyperkalemia (fist clenching)
* Drugs
* Transmembrane K movement (Digoxin, Mannitol)
* RAASi (ACEi, ARBs, NSAIDS, triamterene)
* K containing drugs (Pencillin)
50
What is the lab value for hyperkalemia? Can hyperkalemia persist without impaired potassium excretion?
* Hyperkalemia (K \> 5.3 mEq/L)
* Hyperkalemia cannot persist without impaired urinary potassium excretion
51
What are some clinica manifestations of hyperkalemia?
* Clinical manifestations
* Muscle weakness/paralysis
* EKG changes – tall peaked T waves
* Hyperchloremic acidosis
* Chronic hyperkalemia → decreased NH3 production
52
What are three treatments modalities for hyperkalemia? Name drugs that would be used.
* Treatment
* Cardiac membrane stabilization
* Calcium gluconate
* Increased K entry into cells
* Insulin, glucose, NaHCO3, beta-adrenergic agonist (albuterol)
* K removal from body
* Diuretics, cation exchange resins, dialysis
53
What are the 5 mechanisms for hypokalemia (\<3.5)?
* Hypokalemia (K \< 3.5 mEq/L)
* Mechanisms
* Decreased K intake
* Increased entry into cells
* Alkalosis, adrenergic activity, insulin, hyperthyroidism
* GI K losses
* Vomiting, diarrhea, NG tube drainage
* Mineralocorticoid excess
* Anything that increases aldosterone
* Increase distal Na delivery
* Diuretics, nonreabsorbed anions, hypomagnesemia
* Bartter’s syndrome
* Defect in NaK2Cl channel at ALH
* Gitelman’s syndrome
* Defect in NaCl channel at DCT
* Liddle’s syndrome
* Autosomal dominant GoF ENaC mutation
54
What are the clinical manifestations for hypoklameia? Including ekg
* Clinical manifestations
* Muscle weakness, cardiac arrhythmias, constipation, glucose intolerance, impaired insulin secretion
* EKG changes – U wave
55
What are two treatments for hypokalemia?
Stop diuretics and provide K+
56
How are Na and total blood volume independent of each other
* Serum [Na+] reflects the relative amount of total body Na+ vs H20
* Total body Na+ is reflected in the physical exam (edema, skin turgor, etc.)
57
What is the dsitribution of water and Na intracellularly and extracellularly?
* Approximate distribution of H20
* Intracellular: 2/3 of total H20 volume
* Extracellular: 1/3 of total H20 volume
* Approximate distribution of Na
* Intracellular: 4 mEq/L
* Extracellular: 140 mEq/L
58
What occurs if hypotonic solution is injected in the body? (Hypotonic with the blood)
* Water proportionally moves from extracellular space to intracellular space resulting in an decreased osmolality of both intracellular and extracellular spaces
59
What occurs if isotonic solution is injected in the body? (isosmotic with the blood)
* Injection of isotonic solution (iso-osmotic with blood)
* NO movement of H20, but extracellular space increases in volume
* There is no resulting changes in osmolality of both spaces
* Therefore saline (an isotonic solution) increases the extracellular fluid more than free water (hypotonic)
60
What happens if hypertonic fluid is injected in the body (hyperosmotic with blood)?
* Injection of hypertonic solution (hypertonic with blood)
* Water proportionally moves from intracellular space to extracellular space resulting in an increased osmolality of both intracellular and extracellular spaces
61
What is the regulation of ECV determined by? The regulation of osmolality?
* Regulation of the ECV state is determined by the total body Na+ (excretion and retention)
* Regulation of the osmolality is determined by free H20
62
What is the affector limb and the effector limbs for volume regulation?
* Volume regulation
* Affector limb: baroreceptors (i.e. aortic arch, carotid arteries, CNS)
* Effector limb: Na+ control mechanisms
* Renal excretion of Na+, RAAS pathway, ANP, ADH
63
What is the general mechanism of ADH and how does it regulate blood volume? What does it change based on when you are euvolemic? What does it change based on if you are hypovolemic/hypervolemic?
* ADH
* General mechanism: controls water reabsorption at the medullary collecting duct
* Regulation
* If you are euvolemic (normal TBV), ADH is regulated based on your osmolality
* If you are hypovolemic or hypervolemic, ADH is regulated based on the TBV
64
How can edema occur (4 mechanisms and describe examples of each)?
* Edema
* Increased hydrostatic capillary pressure:
* Primary renal Na+ retention: renal disease, NSAIDS
* Venous obstruction: pulmonary edema
* Decreased arterial resistance: calcium channel blockers
* Decreased plasma oncotic pressure
* Protein loss: nephrotic syndrome
* Reduced protein synthesis: malnutrition, liver disease
* Increased capillary permeability
* Burns, trauma, inflammation, etc.
* Increased interstitial fluid oncotic pressure & impaired lymphatic drainage
* Lymph node enlargement
65
Provide the mechanism of heart failure from pulmonary edema.
* Increased pulmonary pressure → increased venous pressure → increased volume in capillaries → diffusion of water into interstitial space → edema
66
What are 4 mechanisms of true isotonic volume depletion?
* True volume depletion
* Mechanisms
* GI losses: vomiting, NG suction, diarrhea, bleeding
* Renal losses
* Salt and water: diuretics, adrenal insufficiency
* Water: diabetes insipidus
* Skin/respiratory losses: sweat, burns
* 3rd space sequestration: abnormal fluid in body cavities (i.e pancreatitis, ascites, intestinal obstruction)
67
How can you treat the following conditions:
* LE edema
* Pulmonary edema
* anasarca due to hypoalbuminemia
* Lymphedema
* Post-stroke syndrome
* Edema and ESRD
* Orthostatic HTN
* Shock from hemorrhage
* Distributive shock/decreased ECV
* Cholera
* Hyperaldosteronism
* Treatment
* Lower extremity edema: diuretics, elevation, compression stockings, low Na+
* Pulmonary edema: diuretics, dialysis
* Anasarca secondary to hypoalbuminemia: high protein diet, albumin, diuretic, treat underlying disease
* Lymphedema: compression stockings
* Post-stroke syndrome (vasodilation post stroke): compression sleeve, elevated arm
* Edema and ESRD: transplant, dialysis (no diuretics)
* Orthostatic HTN: saline, blood
* Shock from hemorrhage: blood, epi or norepi
* Distributive shock/decreased effective circulating volume: fluids
* Cholera: treat the cholera, rehydration fluid
* Hyperaldosteronism: synthetic mineralocorticoid
68
What is the normal response to freewater ingestion?
* Free water clearance:
* Following ingestion of free water
* Decrease in serum osmolality à decreases ADH
* Large increase in intravascular volume à decreased ADH
69
how is it free water excreted?
* Delivery of isotonic tubular fluid to diluting segment (mTAL, DCT) for reabsorption à removal of Na à hypotonic fluid à low ADH stops collecting duct from reabsorption of water à free water excreted
70
How does hypovolemia lead to hyponatremia?
* Decreased ECV → decreased renal clearance of free H20 → hyponatremia
* Decreased ECV →
* Increased ADH→ Decreased excretion of water
* Decreased renal blood flow → decreased GFR → decreased filtered Na
* Increased ATII → Increased PCT Na-K ATPase → increased reabsorption of PCT Na
* Due to the above mechanisms → decreased delivery of Na to diluting segment → decreased ability for ALH and DCT to reabsorb electrolytes → decreased medullary osmotic gradient → inability to create or absorb free water → decreased excretion of free water
* This results in a higher proportion of free water reabsorption to Na+ reabsorption → hyponatremia
71
differential and patho for iso-osmotic hyponatremia
* Pseudohyponatremia: marked elevations of substances resulting in a reduction in the fraction of plasma that is water and an artificially low [Na]
* Hyperlipidemia, hyperproteinemia
72
hyperosmotic hyponatremia
* Hyperosmotic: rise in plasma osmolality pulls water out of the cells → lowering plasma Na concentration by dilution
* Hyperglycemia, mannitol
73
give a differetial and mechs for..
* Hypo-osmotic
* **Hupervolemic Hyponatremia**
* Urine sodium \< 10
* Edematous states: nephrosis, cirrhosis, CHF
* Increased interstitial fluid → decreased effective circulating volume → decreased GFR → increased RAAS → increased reabsorption of Na at PCT → decreased Na to diluting segments → decreased osmotic medullary gradient → decreased creation of free water → decreased excretion of free water → hyponatremia
74
give a differetial and mechs for..
* Hypo-osmotic
* **Hupervolemic Hyponatremia**
* Urine sodium \> 40
* CKD & ESRD
* Above diseases combined with intake of H2O \> Na+ → dilutional hyponatremia
75
give a differetial and mechs for..
* Hypo-osmotic
* **Euvolemic Hyponatremia**
* Urine sodium \> 10
* H2O Intoxication
76
give a differetial and mechs for..
* Hypo-osmotic
* **Euvolemic Hyponatremia**
* Urine sodium \> 40
* SIADH (secretion of inappropriate ADH)
* Increases water reabsorption despite normal ECV → relative hyponatremia
* Inappropriately concentrated urine, mild hypervolemia, decreased BUN
77
give a differetial and mechs for..
* Hypo-osmotic
* **Hypovolemic Hyponatremia**
* Urine sodium \> 10
* If hypovolemic, normally, a patient will absorb Na+ due to the effects of aldosterone leaving minimal amounts in the urine → indicates that the loss is coming from elsewhere:
* GI Loss: vomiting, diarrhea
* Skin loss: sweating, burns, CF
* Pancreatitis
78
give a differetial and mechs for..
* Hypo-osmotic
* **Hypovolemic Hyponatremia**
* Urine sodium \> 40
* Diuretics
* Inhibit Na+ reabsorption in mTAL or DCT → decreased creation of free water into tubules → decreased excretion of free water
* Thiazides work better than loop diuretics because loop diuretics destroy osmotic gradient while thiazides maintain
* Bartter syndrome: acts like a loop diuretic
* Gitelmans Syndrome: acts like a thiazide
* Adrenal insufficiency
* Decreased sodium reabsorption → decreased create of free water in tubular lumen → decreased excretion of free water
* Addison’s disease: unable to produce aldosterone (hypotension, hyponatremia, hyperkalemia)
* Same mechanism as above
79
Hyponatremia Complications of Treatment
* Rapid increases in CSF osmolality due to treatment in patients with chronic hyponatremia can cause osmotic demyelination syndrome
* Locked-in syndrome (comatose essentially)
* Rapid correction is less dangerous than hypernatremia (risk factors: malnutrition, liver disease, alcoholism)
80
Hyponatremia Treatment
when do give water and when do you restricit?
* Give back salt and water to patient with
* True volume depletion
* Diuretic associated hyponatremia
* Adrenal insufficiency
* Restrict water intake for patients with:
* SIADH, edematous states, renal failure, primary polydispia
81
normal mech to increased in Osm or decreased water
* Normal: Increased osmolality sensed by osmoreceptors →
* Increased thirst → increased H2O ingestion
* Increased ADH → Increased aquaporin expression → increased H2O retention
82
explain Hypernatremia from excessive salt intake
* Hypernatremia from excessive salt intake
* Rare but can occur with large volume of sea salt ingestion or hypertonic saline
83
explain Hypernatremia with normal volume
* Hypernatremia with normal volume
* Long term saline without free water; hypertonic NaCl ingestion
84
explain Hypernatremia with volume contraction/depletion
also what the differentials, how about examples
* Decreased H2O intake
* No access H2O due to dementia, sedated, unconsciousness
* Defective central thirst mechanism (rare)
* Loss of H20 excess
* GI: vomiting, diarrhea, NG suction
* Skin: fever, sweating, burns
* Renal: obstructive diuresis
* Central diabetes insipidus
* Failure to secrete ADH from pituitary gland (usually due to damage)
* Nephrogenic diabetes insipidus
* Failure of V2 receptor to respond to ADH
* Aquaporin mutations
* Also seen with lithium abuse
85
what he got?
* History:
* On lithium
* Severe thirst, copious urination
* Labs:
* On a normal day → urine osmolality – 312 (high osmolality)
* Urine osmolality after DDAVP – 540 (higher osmolality, but not max)
* Urine osmolality after H2O depletion – 324 (same as initial)
* Diagnosis: Partial nephrogenic diabetes insipidus secondary to lithium
86
what he got? might be two things?
* History:
* Thirsty, lots of urine
* Labs:
* Low-normal urine osmolality (70), hypernatremia
* Diagnosis: Diabetes insipidus (ADH is not working) for one of two reasons
* Central DI: Pituitary gland is not producing ADH
* Nephrogenic DI: Kidney is not responding to ADH
* Can be differentiated by providing DVVP (synthetic ADH)
87
what he got?
* History:
* No thirst, no urine
* Labs:
* High urine osmolality (850), hypernatremia
Diagnosis: Loss of thirst mechanism secondary to dementia – ADH is active (represented by high osmolality) and thirst mechanism is dysfunctional
88
what he got?
* History:
* Thirsty, no urine
* Labs:
* High urine osmolality (850), Hypernatremia
Diagnosis: Dehydrated – ADH is active (represented by high osmolality) and thirst mechanism is functional
89
Treatment of Hypernatremia
and complications
* Provide fluids
* Complications: Cerebral edema
* Neurons will absorb too much water if osmolality is dropped in the CSF too quickly with ingestion of free water
* Neurons take multiple days to change their own osmolality to meet that of the CSF
90
chronic kidney disease staging and guidelines
* Staging/guidelines
* Guidelines: abnormalities of kidney structure or function for \>3 months
* Staging: based on decline in eGFR (estimated GFR) or increase in proteinuria
* CKD 1: GFR ≥ 90
* CKD 2: GFR 60-89
* CKD 3a: GFR 45-59
* CKD 3b: GFR 30-44
* CKD 4: GFR 15-29
* CKD 5: GFR \< 15
91
chronic kideny disease
epidemeiology and etiology/risk factors
* Epidemiology
* 15% of the population has the disease with a general predominance in African Americans
* High mortality, especially in CKD 4 and CKD 5
* Etiology/Risk Factors
* Diabetes
* HTN
* Glomerulonephritis
* Cystic Kidney Disease
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what does this stand for
MAD HUNGER
* Mnemonic: MAD HUNGER
* **M**etabolic **A**cidosis, **D**yslipidemia, **H**yperkalemia, **U**remia, **N**a+/H2O retention, **G**rowth retardation in children, **E**rythropoiesis failure, **R**enal osteodystrophy (CKD-MBD)
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complication of CKD
explain erythropoiesis failure, CVD
and treatment
* Erythropoiesis Failure
* Pathophysiology: Hepcidin is unable to stimulate kidney to produce EPO → anemia
* Treatment: IV iron, transfusions, EPO drugs
* Cardiovascular Disease
* Treatment: ASA, statins, beta blockers, aldosterone
* CKD patients have concurrent cardiovascular sx, complicating their treatment resulting in mortality
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explain progression to ESRD
patho, risk factors, tx
* Occurs when you require dialysis or transplant
* High mortality
* Pathophysiology of progression
* Normal: During high BP, the afferent arteriole is able to constrict in order to protect the glomerulus from high pressures
* CKD progression: During high BP, the afferent arteriole and the efferent arteriole dilate exposing the glomerulus to high pressures → increase in RBF → increased protein filtration → inflammation → capillary injury → release of TGF-beta → interstitial fibrosis
* Risk Factors
* Genetic predisposition: Congenital low nephron mass or AA patients predisposed to APOL1 mutation
* Uncontrolled HTN or diabetes
* High protein intake/low vegetable intake
* Proteinuria: increased protein filtration will inflame the GBM and therefore injury the glomerulus in the process
* Treatment
* ACEi
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complication of CKD
malnutrion/loss of appertite
mech and complications
* Mechanism: CKD patients will lose their appetite as they progress until they receive dialysis
* Complications: HTN/edema, Hyperkalemia, meaabolic bone disease, metabolic acidosis
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explian mech and tx of...
Complications: HTN/edema, Hyperkalemia, meaabolic bone disease, metabolic acidosis
* HTN/Edema
* Mechanism: Remaining nephrons cannot compensate for high Na+ diets → Edema/HTN
* Tx: Dietary Na+ restriction, Loop diuretics
* Hyperkalemia
* Mechanism: Less ROMK channel expression in CKD → less K+ secretion
* Tx: Insulin, albuterol, bicarb, dialysis, kayexlate (stimulates colon for excretion of K+), restrict K+
* Metabolic bone disease
* Mechanism: CKD → increase in phosphate → Increase in FGF23 → decreased in active Vit D → increase in PTH → secondary hyperparathyroidism
* Tx: Vit D, low phosphate, phosphorus binders
* Metabolic acidosis
* Mechanism: Proteins are broken down → production of organic acids → secretion of bicarb → metabolic acidosis
* Secondary to hyperkalemia
* Tx: Low proteins, high vegetables, NaHCO3
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CKD in Children
* Complications
* Cognitive problems, left ventricular hypertrophy
* Growth restriction: decreased renal clearance of IGF binding proteins → less free IGF-1 → Disrupted growth
* Tx: growth hormone
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CKD in Pregnant Women
* Normal: increased renal blood flow → increased GFR → decreases serum creatinine
* Consequences of CKD in pregnant mothers: Gestational HTN, pre-eclampsia
* Pregnancies result in premature or small gestational babies
* Tx: Daily dialysis may be needed and monitoring of HTN and renal function
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acute kidney disease
definition, whay do we care?, complications
* Acute kidney injury: a sudden loss of kidney function as evidenced by a decrease of urine output and/or an increase in serum creatinine
* Why do we care and Take-Home points
* It is common, costly, and deadly.
* Small changes in sCr are important
* More severe AKI = high mortality
* Complications
* Chronic Kidney Disease
* HTN (due to permanent changes in kidney vasculature → maintain more Na)
* Heart Failure (same mechanism as HTN)
* Recurrent AKI
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pre-rnal causes of AKI
* Pre-renal causes
* Pre-renal azotemia/volume depletion
* Heart failure
* Cardiorenal syndrome
* Mechanism: myocardial dysfunction causes renal dysfunction and vice versa
* Treatment: diruretics
* Cirrhosis
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explian pre-renal azotemia
epidemiology, patho, symptoms, tx
* Epidemiology: Common AF
* Pathology: no structural damage to the kidney
* Symptoms: volume depleted, hyperkalemic, severely decreased bicarb (acidotic), extremely high BUN
* Treatment: IV Fluid
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intra-renal causes of AKI
* Tubular injury (Acute tubular necrosis)
* Interstitial injury
* Glomerular injury (glomerulonephritis)
* Vascular injury
* Look for rash → vasculitis
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exampls of acute tubular necrosis
* HTN
* Hypxoemia
* Shock
* Rhabdomyolysis
* Sepsis
* Drugs:
* Contrast Induced Kidney Injury
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explain shock in ATN
mech, patho, symptoms
* Mechanism: low BP → Loss of O2 supply to PCT cells → tubular cells slough off →muddy brown casts (necrotic tubular cells)
* Symptoms: low BP, low O2 sat
* Pathology: no nuclei in PCT cells
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ATN
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Rhabdomyolysis in ATN
explain it?
* Mechanism: Muscle breakdown (usually due to exercise) → release of myoglobin → PCT cell injury → tubular cells slough off
* Dipsticks shows hematuria. However microscopy does not show RBCs, but shows pigmented granular casts (myoglobin) instead.
* Management: IV fluids
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how do drugs lead to ATN
ACEi, NSAIDS
* ACEi: Block angiotensin, which normally constricts the efferent arteriole → less blood supply to kidney
* NSAIDs: Blocks prostaglandin, which normally dilates at the afferent arteriole → less blood supply to the kidney
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Contrast Induced Kidney Injury leading to ATN
mech, risk factors, tx
* Mechanism:
* Hyperosmolar contrast causes release of adenosine → vasoconstriction at nephron vessels → hypoxia → ATN
* Contrast initiates release of endothelin disrupting the ability of the cell to autoregulate constriction
* Risk factors: CKD (especially diabetics), hypovolemia, intra-arterial administration (usually cardiac cath), dose of contrast
* Management: IV fluids before contrast
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Post-renal causes of AKI
mechs, symtoms, tx
* Obstruction
* Mechanisms: Enlarged prostate (old men), gynecological malignancy, bilateral kidney stones
* Symptoms: super hyperkalemic and acidotic
* Treatment: Foley to alleviate obstruction or nephrostomy tube
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what is FeNa
equations
what does it help with
* Fractional excretion of sodium: the percentage of sodium excreted in the urine compared to the amount filtered
* Measures sodium avidity
* (100 \* Na Excreted)/Na Filtered→ (100 \* Urine Na \* Plasma Cr)/(Plasma Na \* Urine Cr)
* In _oliguric patients_, helps to distinguish between pre-renal causes (FeNa \< 1%) and acute tubular necrosis of AKI (FeNa \> 2%)
* In ATN, PCT reabsorption is damaged → excrete more Na → higher FeNa
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when is supportive treatment indicated in AKI
what does it ential
* Only supportive care is indicated for acute tubular necrosis
* Avoid nephrotoxins, dose medications, maintain vital signs, provide diuretics, and IV fluids
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dialysis
when do you use it?
* Avoid dialysis unless imminent death from renal failure complications or if the patient is in multi-organ failure
* Indications: hyperkalemia, uremia, academia, volume overload, irreversible AKI
