Arsh's Deck (Rahul can't use this) - I can do whatever I want. - You a bitch Flashcards
1
Q
What are the types of cells in the following:
- Proximal convoluted tubule
- Descending limb of loop of Henle
- Ascending limb of loop of Henle
- Distal convoluted & collecting ducts
A
- Proximal convoluted tubule
- simple cuboidal with brush border microvilli
- Descending limb of loop of Henle
- simple squamous
- Ascending limb of loop of Henle
- simple cuboidal to columnar
- forms juxtaglomerular apparatus where makes contact with afferent arteriole
- Macula densa
- Distal convoluted & collecting ducts
- simple cuboidal to columnar, principal & intercalated cells which have microvilli
3
Q
How can a baby get club foot from renal agenesis?
A
- Renal agenesis → lack of urine → reduction in amniotic fluid → compression of limbs → club foot
4
Q
What disease is shown?
A
Multicystic renal dysplasia
5
Q
What is multicystic renal dysplasia and what two things is characterized by?
A
- Multicystic renal dysplasia
- Congenital malformation characterized by cysts and abnormal tissue resulting in malformed kidney and obstruction of lower urinary tract
- Characterized by heterologous cartilage and swirling stroma around cyst
- Can be either unilateral or bilateral (b/c congenital and not genetic)
- Congenital malformation characterized by cysts and abnormal tissue resulting in malformed kidney and obstruction of lower urinary tract
7
Q
For adult polycystic kidney disease:
- What kind of hereditary trend does the mutation have?
- What is the mutation in?
- What is the general epidemiolgy?
- Is it unilateral or bilateral?
A
- Adult PCK
- Autosomal dominant
- Mutation: PKD1 or PKD2 (less often) – both encode polycystin
- Membrane proteins that sense luminal flow
- Mutations result in dysregulation in tissue growth and cyst formation
- Epidemiology: common
- Always bilateral because hereditary
8
Q
For adult polycystic kidney disease:
- What is the general prognosis?
- Complications?
- Pathology?
A
- Adult PCK
- Prognosis: progressive disease leading to significant loss of renal function in late adulthood
- Complications: asymptomatic hepatic cysts, cerebral aneurysms, common cause of death due to cardiac complication of chronic renal failure
- Pathology: increased size of kidney with flattened cuboidal epithelium lining cysts
9
Q
What disease is this?
A
- Childhood PCK
10
Q
Name the diseases, but ignore B.
A
Summary
- Multicystic dysplasia
- Ignore this one
- Autosomal dominant polycystic kidney disease
- Autosomal recessive polycystic kidney disease
- Nephronophthisis-medullary cystic disease complex
- Medullary sponge kidney
11
Q
What are the two compoennts of the metanephros and how do they work?
A
- Ureteric bud (metanephric diverticulum)
- Elongates from the nephric duct and invades the metanephrogenic blastema
- Eventually produces the full kidney
- Metanephrogenic blastema (metanephric mesenchyme)
- Once connected to uretic bud, the blastemal cells undergo rapid differentiation to form ampulla
- Ampulla development initiates uretic bud to branch and divide to start the formation of nephrons
12
Q
What is the process for the development of the nephron?
A
- Mesenchymal cells cluster around the ampulla and develop lumens → forms vesicles
- Vesicles then elongate to form and S-shaped tubule
- One end of the tubule connects to the nephric duct
- Other end of the tubule becomes Bowman’s capsule and surrounds the glomerulus
- Collecting duct is formed from the uretic bud
- Distal and proximal convoluted tubules form from mesenchymal cells
13
Q
For potter syndrome:
- What gender is usually affected?
- What are the two biggest effects and what can they cause?
- What is the appearance of the baby?
A
- Potter Syndrome
- Usually affects males
- Bilateral agenesis of kidneys – usually incompatible with life
- Oligohydraminos: insufficient amniotic fluid (made up of urine from fetus)
- Fetus is compressed (limb abnormalities; i.e. club feet)
- Pulmonary hypoplasia: cannot extract amino acids from amniotic fluid
- Stillborn of severe respiratory insufficiency after birth
- Facial appearance:
- Prominent fold and skin crease beneath each eye (Asian eyes)
- Blunted nose
- Depression between lower lip and chin
14
Q
For childhood polycystic kidney disease:
- What kind of hereditary trend does the mutation have?
- What is the mutation in?
- What is the general epidemiolgy?
- Is it unilateral or bilateral?
A
- Childhood PCK
- Autosomal recessive
- Mutations: PKHD1 – encodes fibrocystin expressed in kidney and liver
- Cell differentiation in liver/kidney ducts
- Epidemiology: children, rare
- Always bilateral because hereditary
15
Q
Explian this…
threshold, Tm, splay
A
- Normal: all glucose is reabsorbed in the PCT
- Transport maximum (Tm): maximal amount of material that can be reabsorbed per unit time
- Threshold: plasma concentration at which glucose first appears in urine
- Splay: appearance of glucose in urine before Tm is reached because some nephrons may reach their individual Tm early stopping reabsorption
16
Q
For childhood polycystic kidney disease:
- Prognosis?
- Complications?
- Pathology?
A
- Childhood PCK
- Prognosis: very unlikely to survive infancy
- Complications: portal hypotension caused by congenital hepatic fibrosis
- Pathology: cysts perpendicular to kidney surface
22
Q
How do you measure Fractional excretion?
A
- Fractional Excretion (FEx) = excreted/filtered = (Ux x V)/ (GFR x Px)
- FENA < 1%; FENA >> 1%;
23
Q
For proximal RTA, what is the general pathophysiology of what occurs?
A
- Pathophysiology: defect in proximal HCO3- reabsorption effectively lowering the HCO3- absorption threshold
24
Q
What are the possible mechanisms (4) for the pathophysiology of proximal RTA (defect in proximal HCO3- reabsorption effectively lowering the HCO3- absorption threshold)?
A
- Blocked carbonic anhydrase – blocks formation for CO2 from HCO3- not allowing HCO3- to be reabsorbed
- Blocked luminal Na-H exchanger – H+ is not secreted resulting in HCO3- to remain in the lumen
- Blocked basolateral Na-K-ATPase – cannot produce gradient that drives the Na-H pump
- Blocked basolateral Na-HCO3- cotransporter - HCO3- cannot be reabsorbed into the interstitium
25
Q
What are some conditions that can cause a proximal RTA?
A
- Etiologies
- Idiopathic
- Genetic
- Fanconi syndrome, glycogens storage disorders (Fabry’s)
- Acquired
- Carbonic anhydrase inhibitors, multiple myeloma. Amyloidosis
26
Q
What are the three possible mechanisms of distal RTA? What are some etiologies of each and how do they each work?
A
- Possible defects
- Diminished luminal H-ATPase number or activity
- Not secreting H+ at intercalated cells
- H+-K exchanger will not reabsorb K due to excess potassium → hypokalemia
- Etiology: Sjogren’s: absent H-ATPase
- Increased luminal permeability
- Permeable increases → electrochemical gradients fail → decreased H+ secretion
- Results hypokalemia
- Etiology: Amphotericin B increases permeability
- Diminished Na+ reabsorption at principal cells
- Decreased Na+ reabsorption in principal cells → decreases H+ secretion in intercalated cells
- Results in hyperkalemia
- Diminished luminal H-ATPase number or activity
27
Q
What is the general pathophysiology of distal hyperkalemic RTA?
A
- Pathophysiology: aldosterone deficiency → lack of K excretion → hyperkalemia
28
Q
What are the general etiologies of distal hyperkalemic RTA?
A
- Etiologies
- Adrenal insufficiency
- Diabetic nephropathy
- Potassium sparing diuretics
- Congenital adrenal hyperplasia
29
Q
Fill what RTAs for each one.
A
“1” Distal
“2” Proximal
“4” Distal hyperkalemic
31
Q
List chloride responsive alklalosis etiologies and what it generally has to do with.
A
- Chloride responsive alkalosis – has to do with volume depletion
- GI losses: vomiting, nasogastric aspiration – H+ loss
- Renal losses
- Diuretics
- Nonabsorbable anions (e.g. carbenicillin)
- Post hypercapnia
- Recovery from lactic and ketoacidosis (overshoot)
- K+ deficiency
32
Q
List chloride resistant alklalosis etiologies and what it generally has to do with.
A
- Chloride-resistant alkalosis – has to do with mineralocorticoid excess not volume depletion
- Primary aldosteronism
- Cushing syndrome (pituitary, adrenal adenoma, ectopic)
- Renal artery stenosis
- CKD + alkali
- Adrenal enzyme defects
- Apparent mineralocorticoid excess
- Liddle, Bartter, Gitelman syndromes
33
For Minimal change disease:
* Characteristics/Pathophys
* Epidemiology
* Labs
* Characteristics:
* Foot processes become flat and disappear → disrupted filtering
* Process of disappearing is cytokine mediated
* Epidemiology:
* Children ages 2-6 y/o – most common cause of NS
* Labs:
* Urinalysis: albumin present, lack of blood, oval fat bodies present, protein present
34
What is this disease?
Minimal change disease
35
For minimal change disease:
* Imaging/Histology
* Clinical features seen
* Treatment
* Imaging/Histology:
* Normal H&E Stain
* On electron microscopy, effacement (flattening) of podocytes can be seen
* Clinical features
* Can be triggered by recent infection/immunization
* In adults, may be associated with Hodgkins or NSAID use
* Despite massive albuminuria, renal function remains good w/o HTN and hematuria
* Treatment: Corticosterioids → rapid improvement in children
37
What disease is this?
FSGS
38
For focal segmental glomerulosclerosis:
* Characteristics
* Epidemiology
* Labs
* Clinical Features
* Characteristics
* Hyalinosis and sclerosis
* Primary/idiopathic: most likely cytokine involvement
* Secondary: HIV, heroin abuse, obesity, HTN
* Epidemiology
* Children and adolescents
* Labs
* Can have few RBCs in urine (no RBC casts), proteinuria
* Clinical features
* Higher incidence of hematuria, reduced GFR, and HTN
* Worse prognosis than minimal change disease
39
For focal segmental glomerulosclerosis:
* Imaging/histology
* Treatment
* Imaging/histology
* Histology
* Collapse of portion of tuft → not many open capillary loops → sclerosis (left arrow)
* Accumulation of eosinophilic material → form nodular pink regions → hyalinosis (right arrow)
* Immunofluorescence
* Non-specific trapping of IgM and C3 in sclerotic segments
* Electron microscopy
* Effacement of foot processes
* Treatment
* May not response to steroid therapy
* Since the disease decreases renal function/mass, increased workload at glomerulus causes damage
* Therefore, RAAS drugs can be used to decrease workload
40
What disease?
* **Membranous nephropathy**
42
For **Membranoproliferative glomerulonephritis**:
* Characteristics/pathophys
* Epidemiology
* Labs
* Characteristics
* Forms:
* Antigen-antibody mediated → activation of classic complement pathway
* See immunoglobulins and complement proteins on immunofluorescence
* Complement mediated → C3NF causes persistent activation of alternate complement pathway
* Only see complement protein on immunofluorescence
* A subtype: dense deposit disease, notable for ribbon-like transformation of GBM
* Epidemiology
* Small percentages of cases of NS in children and adults
* Labs
* Urine: proteinuria
* Elevated creatinine
* Decreasing serum C3 and C3NF
43
What disease is this?
* **Membranoproliferative glomerulonephritis**
44
What disease is this?
Membranoproliferative glomerulonephritis
45
For membranous nephropathy:
* imaging/histology
* Clinical features
* Treatment
* Imaging/histology
* Electron microscopy
* Spikes and domes (deposits) of new GBM material → thickening of GBM
* Histology
* Thickened basement membrane
* Immunofluoroscence: granular (IgG deposits)
* Clinical features
* Primary: idiopathic
* Secondary: infection, lupus, diabetes, inorganic salts, drugs (NSAIDS), malignancies
* Treatment
* Associated with spontaneous remission
* However, if gone untreated, 1/3 patients develop ESRD
46
What disease:
Glomerular nephropathy
48
For membranous nephropathy:
* Characteristics/pathophys
* Epidemiology
* Labs
* Characteristics
* Phospholipase A2 receptor (PLA2R) highly expressed on podocytes → deposit at subepithelial border → causes thickening of the GBM
* This is planted antigen-circulating antibody mediated pathophysiology
* Epidemiology
* Adults
* Labs
* Albuminuria, no RBCs in urine, proteinuria
49
For **Membranoproliferative glomerulonephritis**:
* Imaging/Histology:
* Clinical features
* Imaging/histology
* Histology:
* H&E stain: Large subendothelial deposits seen as thick pink wire loops (arrows)
* Silver stain: tram-track appearance of GBM around each capillaries
* Electron microscopy
* Deposits at the subendothelial area
* Immunofluorescence
* Granular: Circulating immune complexes that deposit in subendothlium
* Clinical features
* Systemic diseases with MPGN pattern: Lupus, Hepatitis B and C
* Some have only hematuria or only proteinuria, but some present with a combined nephrotic-nephritic picture
52
For diabetic glomerulopathy:
* Pathophys
* Clinical
* Risk factors
* Histology
* Most common cause of ESRD
* Pathophysiology: glycosylation of circulating and intrarenal proteins
* Clinical: HTN and renal hyperfiltration
* Risk Factors: FHx, Diabetes, HTN, tobacco use
* Histology: GBM thickening, Kimmelstiel-Wilson nodules (indicated by \*)
54
For renal amyloidosis:
* What is the pathophys
* Histology
* Pathophysiology: abnormal folding of proteins → deposits in renal tissues as fibrils
* Histology:
* Apple green birefringence on Congo-Red Staining
* Electron microscopy: randomly oriented fibrils
55
Rapidly progressive/crescentic Glomerulonephritis
56
IgA nephropathy
57
Acute proliferative glomerulonephritis
58
Acute post-infectious glomerulonephritis
59
Acute proliferative glomerulonephritis
labs, clinical, imaging/histology,
* Labs
* Hematuria (rare RBC casts), proteinuria, azotemia (elevated BUN)
* Clinical
* Oliguria, mild to moderate HTN
* Imaging/Histology
* Histology
* Glomerular inflammation
* Proliferation of endothelial/mesothelial cells à causes compression of capillary loops
* Global proliferation (aka involves all lobules of the glomerulus)
* Immunofluorescence
* Granular IgG and C3 deposits
60
Acute post-infectious glomerulonephritis
clinical, epidemology, imaging/histology, treatment
* Clinical
* Occurs 1-2 weeks after strep throat infection
* Epidemiology
* Common in children ages 6-10 y/o
* Imaging/Histology
* Electron microscopy: Very large (“like fucking huge” – Arsh) subepithelial deposits
* Treatment
* 95% of children recover spontaneously
* Conservative management otherwise
61
IgA nephropathy
clinical, epidemiology
* Clinical
* Very common cause of gross and microscopic hematuria
* Hematuria may occur within a day or two of respiratory, GI, or urinary infection
* Can be a result of: Henoch-Schönlein purpura (HSP), a systemic disease characterized by a purpuric skin rash, arthritis, abdominal pain and nephritis.
* Epidemiology
* Most common in adolescent or young adult males
62
IgA nephropathy
lab, imaging/histology
* Lab
* Proteinuria, RBC, No cellular casts, minor proteinuria
* Normal creatinine and BUN
* Histology/Imaging
* H&E stain: Mesangial cell proliferation
* Immunofluorescence/ Electron microscopy
* IgA in mesangial stalks
63
Rapidly progressive/crescentic Glomerulonephritis
histology/imaging, labs, clinical
* Histology/Imaging:
* Will see crescent formation of cells à
* Labs:
* Urine: Albuminuria, hematoruira, numerous RBCs/WBCs, granular casts, renal tubular epithelial cells, RBC casts noted
* Anti-GBM positive
* Clinical
* Rapid progressive decline in renal function
* Poor prognosis
64
Rapidly progressive/crescentic Glomerulonephritis
describe type 1, 2, 3
talk about immunoflourence
* Type I (anti-GBM disease, in situ IC formation)
* Associated with Good Pasture syndrome
* Can cause pulmonary hemorrhage due to antibodies to renal and alveolar basement membranes
* Immunofluorescence: Anti-GBM linear
* Type II (deposition of circulating ICs)
* Associated with Post-infectious GN and lupus
* Immunofluorescence: immune complex - granular
* Type III (pauci immune disease)
* Most are ANCA associated: granulomatosis with polyangitis
* Immunofluorescence: NONE.
65
Chronic glomerulonephritis
END RESULT OF ALL PROGRESSIVE GLOMERULAR DISEASE
Associated with scarring and sclerosis and HTN
70
acute interstitial nephritis
descritpion, etiology, pe/symptoms
* Description: acute renal failure resulting from immune-mediated tubulointersitital injury, often initiated by medications, and other causes (Sjogren’s and sarcoidosis)
* Etiology
* Drugs: penicillin, sulfa drugs
* Physical Exam/Symptoms: classical triad of rash, peripheral eosinophilia, and renal failure
71
acute interstitial nephritis
labs, epidemiology, histology, diagnosis, tx
* Labs:
* Urine: positive WBC (sterile pyuria), negative culture, eosinophils
* Epidemiology
* Commonly seen in patients
* Histology:
* Eosinophilia with interstitial edema
* Diagnosis
* Biopsy
* Treatment
* Stop drugs or start patient on high-dose steroids
72
Distinguish the pathology of acute interstitial nephritis and NSAID induced interstitial nephritis
* NSAID-related interstitial nephritis is a subset of acute interstitial nephritis
* Histology
* Will see epithelioid granulomas rather than diffuse eosinophils
73
Analgesic Nephropathy
description/ pathology
* Description: chronic kidney disease caused by excessive ingestion of certain analgesics
* Have to ingest something like 2 FUCKING KGs of Aspirin over three years
* Pathology: shrinkage of the papilla (location where collecting ducts convene)
74
tumor lysis syndrome
pathogenisis, types, complications, diagnosis/labs
* Pathogenesis: tumor lyses à release of uric acid, potassium, and phosphorus
* Types:
* Acute: due to Tumor Lysis Syndrome
* Chronic: due to gout
* Complications/Histology
* Uric acids deposits and damages tubules à interstitial inflammation and fibrosis à uric acid nephropathy
* Diagnosis/Labs
* Cairo-Bishop Criteria
* Uric Acid (\>8 mg/dL), Potassium (\>6 mEq/L), Phosphorus (\>4.5 mg/dL), Calcium (\<7 mg/dL)
75
explain RCC staging and treatment for each
* Stage I
* Small (\<7 cm) and restricted to the kidney
* Therapy: nephrectomy and active surveillance
* Stage II
* Large (\>7 cm) but still restricted to kidney
* Therapy: nephrectomy, active surveillance, +/- sunitinib
* Stage III
* Big or small, escape from local environment, but not Gerota’s fascia (fascia around the kidneys); +/- nodal involvement
* Therapy: nephrectomy, active surveillance, +/- sunitinib
* Stage IV
* Invasion of tissues beyond Gerota’s fascia; +/- nodes; +/- metastasis
* Therapy: nephrectomy + resection of metastases, active surveillance,
* Clear cell – nivolumab and cabozantinib (preferred)
* Non-Clear cells – sunitinib (preferred)
76
explaijn the use of chemo in RCC
Chemotherapy
RCC is generally resistant to chemo because of a high expression of P-glycoprotein MDR pumps – pumps chemo drugs out of tumor cells
77
* In the PCT,
* How much Ca+ is reabsorbed and by what method?
* What is the MOA?
* What occurs in volume depletion with Ca?
* 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
78
In the ALOH,
* How much Ca+ is reabsorbed and by what method?
* What is the MOA?
* What occurs in loop diuretics with Ca?
* 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
79
In DCT
* How much Ca+ is reabsorbed and by what method?
What is the MOA?
What occurs in thiazide diuretics with Ca?
* 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
80
Where is phosphorus transported? How much is reabsorbed and by what mechanism?
* Phosphorus
* PCT
* 85% reabsorbed via active transport
* MOA: Phosphorus reabsorbed via luminal Na-PO4 symporter
81
What diseases can cause increased PTH? 3 diseases
* 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
82
What diseases can cause increased bone resorption? 3 diseases
* 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
83
What disease states can cause increased GI absorption? 2 diseases
Milk-Alkali Syndrome and Increased Vit D
84
Milk-Alkali Syndrome
* Etiology
* MOA
* 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
85
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
86
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
87
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
88
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.
89
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
90
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
91
What are the symptoms of hypocalcemia?
* Symptoms
* Hyperactive reflexes (Chvostek’s sign), prolonged QT interval, arrhythmias, heart block
92
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
93
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)
94
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
95
What are the symptoms of hyperphosphatemia?
* Symptoms: Increased cardiovascular stiffness and symptoms associated with hypocalcemia (b/c Ca binds to excess phosphate)
96
What are the 4 conditions associated with hypophosphatemia?
Intracellular shift
Acute respiratory alkalosis
Decreased GI absorption
Increased renal excretion
97
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
98
Explain the pathophysiology of the acute respiratory alkalosis with hypophosphatemia.
* Acute respiratory alkalosis
* Stimulates PFK to send phosphorus intracellularly
99
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
100
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
101
What symptoms are associated with hypophosphatemia?
* Symptoms
* CNS: seizures, irritability, encephalopathy
* Blood: Hemolysis
* Muscle: Myopathy & rhabdomyolysis
102
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
103
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
104
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
105
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
106
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
107
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
108
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
109
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
110
hyperosmotic hyponatremia
* Hyperosmotic: rise in plasma osmolality pulls water out of the cells → lowering plasma Na concentration by dilution
* Hyperglycemia, mannitol
111
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
112
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
113
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
114
give a differetial and mechs for..
* Hypo-osmotic
* **Euvolemic Hyponatremia**
* Urine sodium \> 10
* H2O Intoxication
115
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
116
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
117
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
118
intra-renal causes of AKI
* Tubular injury (Acute tubular necrosis)
* Interstitial injury
* Glomerular injury (glomerulonephritis)
* Vascular injury
* Look for rash → vasculitis
119
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
120
What are the events following transplant?
122
How are T-cell activated?
**How are T-Cells activated?**
* Antigen is recognized by the MHC complex (signal 1) → CD80/86 (antigen) binds to CD28 on T-cell to start co-stimulation (signal 2) → Calcineurin is activated and acts as a transcription factor to activate IL-2 (signal 3) → IL-2 causes T-cell proliferation
* Can be regulated by apoptosis, when mTOR is activated
123
Provide the MOA, Use, and SE for corticosteroids?
* Corticosteroids
* MOA: blocks cytokine gene expression and blocks T-cell activation
* Use: Induction maintenance and anti-rejection
* SE: Cushing’s, Osteoporosis, Obesity
124
What is the type of drug, MOA, and SE of anti-thymocyte globulin?
* Anti-thymocyte globulin (rATG – Thymoglobulin): destroys T-cells
* Type: inudction/immune modulation
* MOA: polyclonal rabbit antibody for CD3 receptors → T-cell destruction
* SE: Serum sickness, anaphylaxis, cytokine release syndrome
125
What is the type of drug, MOA, and SE of anti IL-2 antibodies?
* Anti-IL-2 receptor antibodies (Basiliximab)
* Type: inudction/immune modulation
* MOA: anti CD-25 (IL-2 receptor) antibody → blocks T-cell proliferation
* SE: minimal
126
What is the type of drug, MOA, and SE of anti Anti-CD52-antibody?
* Anti-CD52-antibody (Alemtuzumab)
* * Type: inudction/immune modulation
* MOA: CD-52 antibody causing lysis of T-cells and B-cells
* SE: cytokine release syndrome, long-term depletion of lymphocytes
127
What is the type of drug, MOA, and SE of cyclosporine, tacrolimus?
* Calcineurin inhibitors (CNI) - maintenance drugs
* Cyclosporine, Tacrolimus
* MOA: inhibit calcineurin → IL-2 transcription → blocks T-cell activation and blocks apoptosis
* SE: Hyperkalemia, Hyperlipidemia (esp. cyclosporine), renal insufficiency, hypophosphatemia
128
What is the type of drug, MOA, and SE of sirolimus?
* mTOR inhibitor - maintenace drug
* Sirolimus
* MOA: Inhibits mTOR → blocking T-cell proliferation → permits apoptosis
* SE: less nephrotoxicity than CNI, dyslipidemia, thrombocytopenia
129
What is the type of drug, MOA, and SE of sirolimus?
* mTOR inhibitor - maintenace drug
* Sirolimus
* MOA: Inhibits mTOR → blocking T-cell proliferation → permits apoptosis
* SE: less nephrotoxicity than CNI, dyslipidemia, thrombocytopenia
130
What is the type of drug, MOA, and SE of azathioprine?
* Anti-proliferative agents
* Azathioprine
* MOA: purine analog that blocks purine synthesis → less DNA available for WBC synthesis
* SE: skin cancer, lymphoma, pancreatitis/hepatitis
* Drug interactions: interacts with allopurinol
131
What is the type of drug, MOA, and SE of Mycophenolate Mofetil (MMF)?
* Anti-proliferative agents
* Mycophenolate Mofetil (MMF)
* MOA: blocks inositol monophosphate dehydrogenases → blocks DNA synthesis → blocks WBC synthesis
* SE: Bone marrow suppression, diarrhea, CMV infection
132
What is the type of drug, MOA, and SE of belatacept?
* Fusion protein (CTLA-4-Ig)
* Belatacept
* MOA: CTLA-4-IgG → binds to CD80/86 → blocks co-stimulation → downregulation of T-Cells
* SE: anemia, neutropenia
133
What are three types of antirejection treatments?
* Anti-rejection treatments
* Intravenous immunoglobulin (IVIG)
* Plasmapheresis
* Rituximab
* MOA: CD20 antibody that destroys B-cells
* SE: allergic reaction
134
What are two drugs for overactive bladder?
Provide MOA and SE.
* Oxybutynin
* MOA: muscarinic antagonist approved for OAB
* SE: “Can’t see, can’t pee, can’t spit, can’t s\*it,”
* Contraindications: elderly, prostate cancer, glaucoma, K+ tablets causes GI bleeds
* Mirabegron
* MOA: beta-3 agonist → increase storage capacity during filling phase
* SE: minimal
135
For UTI, provide clinical features, lab features, risk factors, and etiology.
* Clinical feature: dysuria, frequency, urgency
* Lab features: pyuria, bacteruria
* Risk factors: sexually active, multiple partners, female, spermicides, preganacy
* Etiology: E. coli (most common), Staphylococcus saprophyticus, Enterobacteriaceae
136
What are the three abx indicated for UTI?
* Trimethoprim-Sulfamethoxazole
* Fluroquinilones
* Nitrofunatoin
137
Provide MOA, SE, contraindications, and drug interactions for Trimethoprim-Sulfamethoxazole?
* Trimethoprim-Sulfamethoxazole
* MOA:
* Sulfa drug: acts on PABA
* Trimethoprim: acts on dihydrofolate reductase
* Together these drugs blocks folate synthesis in bacteria and are together are bactericidal
* SE: G6PD, steven-johnson, photosensitivity,
* Contraindications: G6PD deficiency, renal/hepatic impairment, pregnant/nursing (displacement of bilirubin)
* Drug interactions: warfarin (bleeding), ACE/ARBs (hyperkalemia)
138
For fluoroquinilones, provide an example, MOA, SE, and contraindications?
* Fluoroquinolones
* Example: Ciprofloxacin
* MOA: DNA gyrase/topoisomerase IV inhibitors
* SE: QT prolongations, tendon rupture
* Contraindications: pregnant/nursing, seizures
139
For nitrofurantoin, provide use, MOA, SE, and contraindications
* Nitrofurantoin
* Use: only for bladder infections (because it is most bioavailable here)
* MOA: Interferes with carbohydrate metabolism and cell wall formation
* SE: minimal but possible pulmonary issues
* Contraindications: hemolytic anemia if G6PD deficient, pregnant/nursing
140
What are some non-prescription therapies for UTI (4)?
* Non-prescription therapies
* Phenazopyridine – analgesic for urinary tract
* Increase fluids
* Cranberry juice
* Avoid spermicides and multiple partners
141
For bladder cancer, provide the following:
* incidence
* presentation
Incidence:
* More common and deadly in men
* Likely recurrence
Presentation
* Painless intermittent hematuria
* Common: bladder irritability, dysuria
* Advanced: flank pain, weight loss
142
For upper tract urothelium cancer, provide the incidence, presentation, and diagnosis?
* Incidence: 10% of renal neoplasms
* Presentation: Urothelial carcinoma of the kidney/ureter
* Treatment
* Nephroureterectomy
* Can also use neoadjuvant chemo
143
What is indicated by the stages of bladder cancer (stage pTa, carcinoma in situ, stage 1-4)
144
For urethral cancer, provide the following:
* Incidence
* Presentation
* Diagnosis
* Treatment
* Incidence
* Extremely rare
* Men more than women
* Presentation
* Urothelial cell carcinoma is the most common histological type
* Diagnosis
* Risk factor: multiple UTI
* Distal cancers present earlier at lower stage
* Treatment
* Tumor resection
146
causes (2) and complications of poor bladder compliance
* Causes of poor bladder compliance:
* Fibrosis – chronic inflammation, radiation
* Myelomeningocele (spina bifida) – neurological issues leading to loss of compliance (not well understood)
* Complications: hydronephrosis, UTI (due to static urine), CKD, ESRD
147
Urge incontinence
clinical defintion and causes (3)
* Clinical definition
* Over activity of the detrusor (smooth muscle that surrounds the bladder) and inappropriate contractions during the filling phase
* Causes
* Bladder irritation/obstruction (UTI, stones, tumor)
* Cerebral cortex lesion or legion of spinal cord *above* the sacral region
* Idiopathic
148
Stress incontinence
clinical definition and causes (4)
* Clinical definition
* Leaking of urine due to increased intra-abdominal pressure
* i.e. coughing, sneezing, jumping, lifting heavy objects
* Causes
* Childbirth
* Fibrosis or urethra – due to decreased estrogen
* Neurologic lesions *at* sacral cord level
* Prostatectomy in men
149
two types of messed up detrusor muscle
and their causes
* Neurogenic – poor innervation
* Sacral spinal cord or cauda equine
* Pelvic nerves going from sacral cord to bladder
* Diabetes mellitus
* Myogenic – weak muscle
* Diabetes mellitus
* Chronic overdistention
150
two types of bladder obstruction
* Anatomic
* Urethral lumen narrowed/obstructed
* Prostate enlargement, stones
* Functional
151
functional obstruction
Detrusor-sphincter dyssynergia
pathophysiology and complications
* Detrusor-sphincter dyssynergia - sphincter does not open appropriately when bladder is contracted
* Neurological disconnect
* Complications: high-pressure voiding, incomplete bladder emptying, recurrent UTI, hydronephrosis, CKD/ESRD
152
how does the femal body prevent bacteria from colonizing vagina
* Normal flora: Lactobacillis
* Compete with and inhibit growth of other bacteria by maintaining acidic pH (lacto = lactic acid)
* Vaginal fluid inhibits bacterial adhesion because of secretory IgA
153
what are bacterial factors tht increase risk of getting bacterial cystitis
3 virulence factors
* Virulence factors causing infection:
* Adhesins: promote bacterial attachment to tissue receptors
* Type 1 pili --\> associated with cystitis
* P pili --\> associated with pyelonephrits
* Hemolysins
* Absent ability so synthesize nutrients
154
vesico-ureteral reflux
what is it? epidemiology, complications
who should be tested?
* Definition: regurgitation of bladder urine into the upper urinary tract
* Epidemiology: \< 1% in healthy children, 29-50% in children with UTI, 33% in sibling of child with reflux (lmao Rahul’s brother), rare in African American (ayooo!)
* Complications: cystitis à pyelonephritis (due to regurgitation) à renal scarring à renal failure
* Can also lead to hydronephrosis à renal failure
* Who should tested?
* All children with UTI
* All babies with hydronephrosis
155
pyelonephritis
symptoms, signs, labs, imaging, tx
* Symptoms: Flank pain, fever, chills
* Signs: CV tenderness
* Labs
* Urinalysis: pyuria, bacteriuria +/- hematuria
* Imaging
* Lobar nephronia – pyelonephritis with a lobar distribution
* Treatment
* Outpatient: fluoroquinolone
* Inpatient: blood culture, IV antibiotics
156
what are these things? tx?
Pyelonephritis plus obstruction
Renal or perinephric abscess
Emphysematous pyelonephritis
* Pyelonephritis plus obstruction
* Bacteria builds up behind obstruction can lead to sepsis
* Tx: drainage
* Renal or perinephric abscess
* Bacteria builds up in abscess --\> pressure forces bacteria to blood --\> sepsis
* Tx: drainage
* Emphysematous pyelonephritis
* Necrotizing infection with gas forming bacteria --\> sepsis
* Usually occurs in diabetics
* Tx: nephrectomy
157
stones: causes, imaging, labs
Calcium oxalate
* Causes: hypercalcemia, anatomic, commonly idiopathic
* Primary hyperparathyroidism --\> hypercalcemia
* Imaging: radiopaque on XR
* Labs: variable pH
158
stones: causes, description, labs
Calcium phosphate
* Description: powder-like --\> cloudy urine
* Causes: distal RTA (Type I)
* Labs: elevated urinary pH (basic)
159
stones: causes, tx, labs, imaging
Uric acid
* Causes: hyperuricemia (gout)
* Labs: low urine pH (acidic)
* Imaging: radiolucent on XR
* Tx: alkalinzation of urine, decreased purine intake, potassium citrate, NaHCO3
160
stones: causes, labs, imaging
Struvite
* Cause: UTI
* Labs: high urine pH (basic)
* Imaging: radiopaque on XR
161
stones: causes, labs, tx, epidemiology
Cystine
* Epidemiology: children (~12 y/o); high recurrence rate
* Pathophysiology: autosomal recessive AA transport disorder --\> cystinuria
* Labs: low urine pH (acidic)
* Tx: aggressive fluid intake, low Na diet; alkalization of urine
* Resistant to shockwave lithotripsy
