Clinical Chemistry 2

Respiratory/Metabolic Acidosis vs. Alkalosis (CHEM1) (miro)

R acidosis: hypoventilation → hypercapnia (increased pCO2 - low pH) → 20/2 → low BE → compensated by increased HCO3- (if N → uncomp/if increase but pH is low → partial comp) vs. R alkalosis: hyperventilation (decreased pCO2 → increase pH) → 20/0.5 → high BE → compensated by lower HCO3- vs. M acidosis: diabetic ketoacidosis → low HCO3-/low pH (normal pCO2) → 10/1 → low BE → hyperventilation compensates/kidneys excretion increases (lower pCO2), increased anion gap: MUDPILES (Diabetic ketoacidosis) vs. normal anion gap: distal renal tubular acidosis (low acid excretion)/proximal renal tubular (low reabsorption of HCO3-)/general distal nephron dysfunction (low aldosterone → hyperkalemia → low NH4+ excretion → low H+ excretion) vs. M alkalosis: electrolyte disturbance → increased HCO3- or increased pH (normal pCO2) → 40/1 → high BE → compensated by hypoventilation/kidney excretion decrease (elevate pCO2)

Cancer Overview, Types 8, Causes 3, and Staging (TNM)

Autonomous out of control cell growth → tumors/neoplasms (abnormal mass) - except leukemia ]→ Benign (local/slow growing) vs. Malignant (invasive spread → angiogenesis → metastases,

Types: carcinoma (epithelial cells)/Sarcomas (bone/soft tissues)/Leukemia (blood-forming tissue in BM)/Lymphoma (lymphocytes)/Multiple myeloma (plasma cells)/Germ cell tumors (give rise to sperm/eggs)/Neuroendocrine tumor/Carcinoid tumor (neuroendocrine → slow and gastrointestinal),

Caused by proto-oncogenes (normal growth → oncogenes → abnormal growth)/tumor suppressors (division abnormal when mutated)/DNA repairing gene (mutations will add more gene mutations)

T - Primary Tumor (1-4 or X) vs. N - Lymph node presence (0-3) vs. M - Metastases (0-1) ]→ Stage 1-4 (local → spread → lymph → metastases)

Tumor Grading scheme

Abnormality and differentiation (normalized to normal tissue): 1 - slight/well vs. 2 - more/moderate vs. 3 - very/poor vs. 4 - immature/not

Tumor Markers Clinical Applications and Properties

Markers are produced by the tumour or the host in response ]→ Screenings (w/o symptoms) - marker elevates early and localized such as PSA and FOBT vs. Diagnosis (suspected of cancer) - 100% diagnostic specific vs. Prognosis (strength of disease) - increases with progression and highest in metastasis vs. Monitoring (already has cancer) - effective treatment → decrease/disapperance

Ideally: specific for a single type/high sensitivity (lowers false negative)/high specificity (lowers false positives)/correlates to size and progression/absent in healthy individuals/short half-life in circulation (for treatment) ]- all available markers DO NOT fit

Tumor Marker Assay Method - Immunoassay Limitations

Immunoassay → linearity (extend above AMR → hook effect → false lower → dilute) vs. Heterophile Abs (interference of human Ab binding reagents → bridge or block capture AB - HAMA → flag patient) vs. Biotin Interference (water-soluble B7 supplements) ]→ Delta Checks

Protein Tumour Markers (3)

B2-microglobulin: surface of all nucleated cells → non-specific → prognostic marker for lymphoproliferative disorders

vs. Immunoglobulins: monoclonal Igs → specific plasma cell production → gammopathies (multiple myeloma)

vs. Thyroglobulin: precursor for thyroid hormone → differentiated thyroid cancers → increased TG

Enzyme Tumour Markers: ALP and PSA

ALP: liver/bone/placenta → elevated in primary/secondary liver cancer - metastatic quantification (also elevated in other malinancies - leukemia/sarcoma/lymphoma/Paget’s disease - bone) vs. placental ALP elevates abnormally in ovarian/lung/trophoblastic cancers

PSA: protease enzyme → seminal fluid viscosity and dissolve cervical mucus cap - chain glycoprotien → complex ACT or AMG or free PSA ]- immunoassays measure total PSA with free and ACT (AMG is sterically inhibited) → early detection of prostate cancer (specific to prostate tissue not cancer → increased in other prostate related diseases) → age cut off RI - include digital rectal examination/transrectal ultrasonography → PSA monitors treatment

Hormones Tumour Markers: BHCG

BHCG: glycoprotein → produced in pregnancy → elevated in gestational trophoblastic disease/germ cell tumors of ovary (prognostic)/testis (diagnosis classification + AFP) ]- correlate with mass and disease prognosis ]→ immunometric sandwich

Oncofetal Ag Tumour Markers: AFP and CEA

Proteins during fetal development →

AFP: glycoprotein related to albumin - transport protein → oncotic pressure in fetus ]- elevates in hepatocellular carcinoma and germ cell carcinoma → HCC - correlate to size → early stages (also elevates with hepatitis/cirrhosis) vs. Germ cell carcinoma: measure AFP and BHCG → classify and stage → Seminomas (grows quicker AFP/BHCG-) vs. Non-Seminomas (Yolk sac - AFP+ vs. Choriocarcinoma - aggressive testicular BHCG+ vs. Embryonal - resembling embryos AFP/BHCG+ vs. Teratoma - different tissue types AFP/BHCG-)

CEA: biomarker colorectal cancer (+ pancreatic/gastrointestinal/lung/breast/uterine/ovarian carcinomas) → NOT a screening test → staging/metastasis/monitoring → before surgery (baseline) and after (serial 2-3 months) ]→ Colorectal cancer screen - FOBT - stool samples → Pos = colorectal cancer/polyps (adenomas) in colon or anus → gFOBT (lab - blue = POS) vs. iFIT (specific Ab for human blood in stool - more sensitive)

Carbohydrate Tumour Markers: CA-15-3, CA 125, CA-19-9

15-3: staging Breast cancer → mammogram screen first (elevated in benign conditions → monitor/metastasis progression vs.

125: monitoring ovarian carcinomas → increased in benign conditions (endometriosis/menstruation/pregnancy/PIC) → elevated in stages 2-4

19-9: colorectal carcinomas and pancreatic carcinomas → Lewis a Ag+ blood type → increased in benign biliary obstruction/inflammation → quantitate malignant pancreatic disease → prognosis/recurrence

Genetic + Molecular Tumour Markers

chromosomal changes → risk/screen → oncogens (activate) and tumour suppressor genes (repair DNA) → cancer development

Hemoglobin Oxygen Saturation → %SO2 vs. FO2Hgb → Shift L vs. R

amount O2 bound to Hgb → respiration effectiveness → co-oximeter

%SO2 = O2 content/capacity = O2Hgb / (HHgb + O2Hgb) * 100%

FO2Hgb = O2Hgb/tHgb * 100%, tHgb = O2Hgb + HHgb + CO-Hgb + Met-Hgb + S-Hgb

Left: low CO2/2,3-DPB (decrease Hgb affinity for O2 → low = holds O2)/Temperature/increase pH/HgbF increased O2 affinity/increase modified Hgb (CO and Met)

Right: increase pCO2/2,3-DPG/Temperature/decrease pH

Modified Hgb: CO-Hgb, Met-Hgb, S-Hgb ]→ Co-oximeter

CO-Hgb: reversible carbon monoxide removed → O2 bind (CO readily combines Hgb - higher affinity → 4-5hr half-life vs. Met-Hgb: iron oxidized → Fe3+ - non-reversible binding with O2 ]- acquired (drugs/toxins) vs. inherited (globin chain/RBC enzyme defect) → hypoxia/cyanosis/brown blood/urine vs. S-Hgb: irreversible chemical alteration → anoxia (no O2 in tissues)/cyanosis ]→

Co-oximeter: spectro → Hgb and derivatives measured + differentiated - whole blood (Pulse Oximeter: POCT with red and infrared light → O2 sat only)

Folate Overview + Deficiencies

Greens → DNA/RNA synthesis/RBC production → fasting collection → Deficiency: increased need/low dietary intake/increased loss (dialysis)/decreased absorption (alcoholism/IBD)/anti-folic drugs ]→ Megaloblastic anemia/Atherosclerosis (decreased homocysteine → methionine → cardiovascular risk)

B12 Overview and Deficiencies

Corrin ring with central cobalt atom → myelin sheath synthesis/DNA synthesis/hematopoiesis coenzyme/fatty acid metabolism → Deficiency: diet and malabsorption (inable to form IF complex/Ab produced so no absorption/bacterial overgrowth) ]→ no mature cells complete nuclear division → Pernicious anemia/Macrocytic anemia (auto-Abs)/CNS disorders/Atherosclerosis (homocysteine)

Iron Analytical Evaluation: Iron Concentration, TIBC, Saturation, Ferritin and Transferrin

• Iron concentration: circulating transferrin bound iron ]→ Fe3+ released → Fe2+ → chromogen - decreased with IDA/Inflammation/trauma vs. increased in hepatitis

• TIBC: concentration of iron + unsaturated iron binding capacity (measured)

• Iron Saturation: concentration of iron / TIBC * 100%

• Ferritin: primary storage → low in serum - acute phase reactant (increase in inflammation/infection/liver disease/malignancy) and decreases with depleted stores (IDA - decreases before iron/saturation) ]- immunoassay

• Transferrin: liver protein that transports iron to tissues (BM) - each molecule has 2 Fe3+ binding sites - increases in iron deficiency (more made) and decreased in iron overload/liver disease/protein lost/inflammation/malignancy → TIBC / 25.1

Clinical Conditions related to Iron: IDA, ACD, Thalassemia, Hemochromatosis

• IDA: increased demand/impaired absorption/blood loss - stores deplete first (low ferritin) → low serum iron/saturation/high TIBC/transferrin → low Hgb

• Anemia of Chronic Disease: chronic infection/inflammation/autoimmune/malignancy → hepcidin production increases → inhibits iron release and decrease absorption (ferritin increases as an acute-phase reactant)

• Thalassemia Trait: inherited → decreased synthesis of globin chains → low Hgb (micro/hypo) but increased RBC count (compensate) → precipitation of excess chains/RBC damage - generally normal iron studies

• Hemochromatosis: overload - hereditary/acquired → increased stores/excess deposited → tissue injury - increased serum iron/saturation/ferritin/Low transferrin and TIBC ]- regular phlebotomy → mild anemia (hyperpigmentation/Cirrhosis/DM)

Heme Degradation: EVH vs. IVH

EVH: outside circulation → spleen → phagocyte → iron release → transferrin and protoporhyrin ring → biliveridin → unconjugated (+albumin) → conjugated → urobilinogen → excreted or smally reabsorbed ]- no free Hgb in circulation vs.

IVH: within circulation - Hgb released and binds haptoglobin (decreases) → liver ]- but if low haptoglobin → reabsorb by kidneys → hemosiderin (>5g/day break down or haptoglobin at capacity→ urine

Kidney Anatomy

Renal Cortex: outer region (glomeruli/PCT/DCT) vs. Renal Medulla: papilla (apex and duct → urine) and calices (communicate with papilla) and pelvis (funnel to ureters)

Nephrons: renal corpuscle (glomerulus and bowman’s capsule) → PCT → Loop of Henle → DCT → Collecting duct ]- Juxtamedullary (extended loop of henle) vs. Cortical (cortex mainly)

Renal Circulation

Recieves 25% of cardiac output - 2 capillary beds ]- renal artery → arcuale arteries → afferent arteries → glomerulus → efferent arterials → peritubular capillaries → vasa recta → arcuale veins → renal vein

Urine Formation: Glomerular Filtration (3 factors) → Tubular Reabsorption → Tubular Secretion

GF: filter from blood, 3 layers - Capillary endothelium (fenestrated pores with negative charge), Basement membrane (barrier allowing water and small molecules to pass), Epithelium of Bowman’s (Podocyte - filtration silts) ]- selective permeable (size and charge) ]→ Factors Affecting GFR: Glomerular Hydrostatic - high pressure → resistance of outflow maintains → water and small dissolved can filter into bowman vs. Bowman Hyrostatic: oppose filtration - obstruction in UT increases pressure → decreases GFR vs. Plasma Oncotic: albumin remain in capillaries - opposes filtration ]- Net: favors filtration

TR: water and solutes back into blood (peritubular capillaries) - 99% water and Na reabsorbed - Active (Na/K ATPase pump → gradient to drive solutes reabsorption - secondary active) and Passive (Cl-/K+/Urea - water = osmosis) ]- PCT - Na+ → Cl- passively (electic neutrality)/glucose and AA → H2O osmosis → isosmotic → urea - Renal Threshold - plasma concentration exceeds capacity → urine vs. Loop - Descend → water highly permeable → increases hyperosmotic → increase concentration and highest osmolality → Ascending → impermeable H2O → Na+/Cl- reabsorbed → more dilute ]- Countercurrent mechanism - opposite streams exchanges → amplify osmotic gradient in medulla (increasing osmolality with depth) → DCT - fine adjustments in selective reabsorption and secretion - controlled by aldosterone (angiotensin II and increased K+ in plasma → Na+ reabsorption) and ADH (water control reabsorption) → CD - final urine concentration and volume same influences in DCT

TS: eliminate waste, regulate acid-base and regulate K+ concentration ]→ PCT - secrete H+ (exchange Na+ → HCO3- reabsorption)/NH4+ (HCO3- follows)/acids and bases/drugs → DCT/CD - Aldosterone → K+ secretion, H+ secretion and NH3 and H+ forms NH4+ → net acid excretion

Kidney Regulatory Functions: ECF Concentration, Electrolytes, Acid-Base

ECF: ADH - CD reabsorb H2O → decrease concentration vs. Aldosterone - Na+ retention → H2O → K+ excreted vs. Renin - response to decreased ECF volume (hypovolemia) → angiotensin II → vasoconstriction → increase BP

Electrolytes: Na+/K+/Cl-/PO4 (PTH → PCT → excretion PO4- and Ca+ reabsorption)Ca2+/Mg2+ (reabsorbed)

A-B: waste product disposal → no cellular damage and altered blood pH → H+ + HCO3- <→ H2O + CO2 → Bicarbonate Reabsorbed (carbonic anhydrase → blood/reabsorbed) vs. Titrable Acids (PO4 + H+ + Na+ in filtrate → NaHPO4 + H+ → NaH2PO4 - excreted) vs. NH4 (secrete NH3 and HCO3- reabsorbed → NH4+ poor permeable)

BUN (Azotemia) Overview and Analysis (4 - direct vs. indirect)

BUN: urea nitrogen metabolic product of amino acid catabolism by hepatic enzymes (amount determined by dietary proteins - falsely low in undernourished) (glomerular filtration and large reabsorption passively in tubules) - Impaired kidney → no blood urea removal → increased BUN concentration in serum (inverse relation to kidney function) → Azotemia: increased nonprotein nitrogenous blood due to decreased filtration - Pre-renal (low renal perfusion/low GFR/increased tubular reabsorption/increased BUN) vs. Renal (low glomerular filtration/GFR/less BUN excreted - glomerulonephritis) vs. Post-renal (obstructions) vs. Decreased Urea: low protein/liver disease ]- Analysis: Direct - Diacetyl monoxime → diazine vs. Indirect - hydrolyse urea (Berhelot) → NH3 → colour or urea (glutamate dehydrogenase) → NH4 → NAD+ or Conductometric urea → NH4

Creatinine Overview and Analysis (2)

Produces creatine in Liver → muscles/brain → phosphocreatine → ADP muscle contraction ]- waste product of dehydration of creatine and hydrolysis → constant day to day muscle mass ]→ Affected by muscle mass/creatine turnover/renal function ]- increases due to any obstruction to excretion/filtration → Analysis: Jaffe reaction → Kinetic change in absorption overtime vs. Enzymatic - creatinine → creatine → Urea and Sarcosine

Uric Acid Overview and Analysis (2)

End product purine metabolism - endogenous mostly → 70% excreted and 30% degraded by GI tract bugs ]→ Increases from increased production (purine increases/high cell turnover or destruction), decreased renal excretion (kidney disease/lead exposure), alcohol consumption ]→ gout (monosodium urate crystals in joints/tissues) vs. Decreases in severe hepatocellular disease or defective tubular reabsorption (Fanconi) ]- Analysis: Carraway - UA + PTA→ Allantoin (prone to interference) vs. Enzymatic uricase: UA + H2O → Allantoin + H2O2 → Chromogen

Urine Protein Overview and Analysis (3)

normally very little protein in urine → Increases due to Glomerular Proteinuria (increased glomerular permeability due to damage), Overload Proteinuria (overflow filtered passes barrier → urine - septicemia), Tubular Proteinuria (Defective reabsorption due to altered/impaired function), Post-renal Proteinuria (inflammation of lower UT or proteins leak) ]- Slight proteinuria (<0.5g/day lower UTIs) vs. Moderate (0.5-4g/day glomerulonephritis) vs. Heavy (>4g/day nephrotic syndrome) ]→ Analysis: Reagent dipstick (protein w/ indicator dye) vs. Sulfosaliculic Acid Precipitation test (turbidity) vs. Microalbumin (Diabetes mellitus → renal nephropathy predictor - spot measurement on AU480)

GFR Overview → Calculate

Volume plasma filtered by glomerulus per unit of time (mL/min/1.73m²) ]- functional capacity of kidneys → numbers of functioning nephrons (renal sensitive and specific) - Decreased GFR = chronic kidney failure (declines with age) → Indirect (only): eGFR = 32788 x (serum creatinine)^-1.154 x age^-0.203 × (0.742 if female)

Creatinine Clearance Overview and Calculation

volume serum cleared of creatinine → measure GFR and early renal failure - creatinine is produced at a steady rate (GFR indicator) → constant concentration and renal excretion rate ]→ Decreased CrCl indicates decreases GFR → acute/chronic glomeruli damage/renal impairment

CrCl = Urine creatinine/serum creatinine x urine flow rate (mL/sec) x 1.73m2/BSA

24 × 60 × 60 = 86400 sec, BSA = sqrt(height x weight / 3600)

Overview: Cystatin C, Inulin Clearance, Urine osmolality and Urinalysis

Cystatin C: low molecular weight protein → constant → renal filtration freely → PCT reabsorbs → levels rise quickly in acute renal failure (compared to creatinine) ]- however, can also be related to inflammation - not specific enough - GFR inversely proportional - measured by turbidity/particle enhanced nephelometry (both are rapid/precise)

Inulin Clearance: fructose polymer (plants) - constant infusion → GFR gold standard - nonmetabolized and excreted only by kidneys, freely filtered by glomerulus and not reabsorbed/secreted ]- however, requires IV administration (injected and measured)

Urine Osmolality: dissolved particles per kg water → urine concentration - unchanged until descending loop of henle → hyperosmotic → hypo in ascending → CD hypertonic interstitium determines water reabsorption for urine osmolality → 1-3x serum osmolality → ability of kidney concentration of urine ]- increased in dehydration vs. decreases in diabetes insipidus

Urinalysis: physical/chemical/microscopic assessment of urine

Renal Infections: Pyelonephritis vs. Cystitis

UTIs: Bladder (cystitis) vs. Kidneys (pyelonephritis) → pyuria (increased WBCs), bacteriuria, positive leukocyte esterase, nitrites

Pyelonephritis: (not usually glomeruli) → multiply interstitium → necrotic tubules → abscesses (neutrophils accumulate) - may have began as a lower UTI and ascend - increased risk with structural abnormalities or obstructions or urine reflux - Vesicoureteral reflux (congenital inherited or anatomic change to junction of ureter and bladder → backflow) → Acute - rapid/responds to Abx w/o damage vs. Chronic - permanent scarring of tubules → renal calyces and pelvis/renal failure - caused by reflux/obstruction

Cystitis: inflammation of bladder (infection or cancer) - more common in females → untreated causes pyelonephritis → increased urination and painful → urine protein positive/urine blood positive/urine culture and sensitivity IDs agent

Glomerular Diseases: Glomerulonephritis, Nephrotic Syndrome and Diabetic Kidney Disease

Glomeruli damage → immunologic/metabolic/hereditary → Primary (affecting kidneys) vs. Secondary (other organs → consequential progression - Diabetes mellitus)

Glomerulonephritis: inflammed glomerulus → Acute (rapid/Group A beta-strep → immune response to basement membrane → damage/Drug exposure/Acute kidney infections/systemic immune diseases) vs. Chronic (end stage with irreversible renal tissue function loss - often undetected) ]→ edema (low osmotic pressure - Na+ and H2O retained/hypertension (low renin secretion/low GFR)/anemia/oliguria (decreased urine output) → high BUN/high creatinine/low GFR/proteinuria/hematuria

Nephrotic Syndrome: underlying conditions → increased glomerular membrane permeability - Diabetic kidney disease/lupus/carcinomas/allergic toxic reactions (penicllamine/bee venom) → excessive protein loss to urine (albumin/immunoglobins/anticoag proteins) → hypoalbuminemia → low plasma oncotic pressure → interstitial space movement → edema/weight gain (fluid retention)/increased infection susceptibility/increased thrombotic complications risks ]→ heavy proteinuria/low serum albumin/norm or low GFR/high serum lipids/lipiduria

Diabetic Kidney Disease: diabetic mellitus complication → chronic kidney disease → hyperglycemia → metabolic and hemodynamic kidney changes → hyperfiltration/increased intraglomerular pressure/thick basement membrane/progressive damage → increased albuminuria/progressive low GFR/chronic kidney disease → dialysis/transplant if advanced ]→ Edema/increased urination → serum glucose increased/increased urine glucose and protein (microalbumin)/low GFR

Tubular Disease: Renal Tubular Acidosis (2 - bone buffering), Fanconi Syndrome and Diabetes Insipidus

decreased function due to tubular function defects → reduced secretion and reabsorption or impaired urine concentrating/diluting mechanisms

RTA: defective renal acid → normal anion gap metabolic acidosis → low serum pH and low serum HCO3 → Type 1 (Distal) - impaired H+ secretion by distal nephron → inable to acidify urine → weak H+ pumps/leaky membrane (back diffusion)/tubular damage (low pump capacity) → urine pH>5.5 - autoimmune disorders/medications/toxins → Bone buffering - release alkaline salts (Ca2+/PO4) → bone demineralization → osteomalacia/hypercalciuria vs. Type 2 (Proximal) - impaired HCO3- reabsorption → metabolic acidosis (serum Cl- increases for electroneutrality) → alkaline urine → but H+ secretion is fine → acidify urine → increased Na+ delivery/aldosterone promotes K+ secretion (hypokalemia) ]- lead nephropathy/amyloidosis/inherited proximal tubular disorders → weakness/impaired growth/bone abnormalites/kidney stones

Fanconi: generalized PCT dysfunction → AA/glucose/PO4/bicarbonate → urine - caused by toxins/drugs/hereditary diseases → excessive water consumption/excess urination/bone or kidney damage → urine protein and glucose positive/high urine pH/low serum phosphate and uric acid

Diabetes Insipidus: no ADH effect (no urine concentration) - Pituitary central (no production/secretion) or Nephrogenic form (effect unresponsive - polyuria → excessive thirst) → chronic excretion hypoosmotic urine/polydipsia/nocturia → increased urine 24hr volume (very dilute)/low urine osmolality/increasing Na+ and serum osmolality/normal serum glucose

Renal Obstruction: Renal Calculi

block urine flow → backflow pressure → renal damage/failure

Renal Calculi (stones): renal calyces/pelvis/ureter/baldder → crystalized substances - Ca/Mg/Uric acid → Enhanced by - increased concentration of chemical salts (insoluble - metabolic gout/endocrine PT/dehydration/diet/medications increased nucleic acid breakdown or cytotoxic)/change urinary pH (no regular urine pH changes → increased solubility - like urea-splitting bacteria - urea → ammonia → alkaline → Mg stones)/Urinary stasis (decreased fluid intake - increased saturation/precipitation)/Foreign body (stimulates crystalline deposition) ]→ pass small stones/lithotripsy (sound waves)/cystoscopy (crush)/surgery → UTIs/pain/ulceration/urination urge → hematuria

Acute (3) vs. Chronic Kidney Disease

Dysfunction impairs ability to maintain fluid/electrolyte/acid-base/metabolic homeostasis → muscle cramps/arrhythmia/edema/oliguria/nocturia → metabolic acidosis/increase K+, PO4,BUN, and Creatinine/low Calcium and GFR

Acute: sudden renal function decline → treat cause to repair → azotemia/electrolyte imbalance → Pre-renal (hypoperfusion → hypovolemia low BP → increased Na+ and H2O reabsorption) vs. Renal (direct injury to renal tissue - necrosis/vascular obstruction/inflammation/glomerulonephritis → lose H2O and electrolytes) vs. Post-renal (structural abnormalities/obstructions)

Chronic: permanent/progressive reduced renal function → diabetes mellitus/glomerulonephritis/pyelonephritis/hypertension → decreased GFR/retained Na+/later hyperkalmemia/acidotic/hypocalcemic → renal osteodystrophy ]- loss endocrine function (loss EPO)/retain exogenous toxins/loss water balance function (polyuria) ]→ Classify based on decreasing GFR (1 - >90, 2 - 60-89, 3A - 45-59, 3B - 30-44, 4 - 15-29, 5 - <15 = kidney failure)

Treatment: Hemodialysis vs. Peritoneal Dialysis vs. Transplant

CKD, Uremic symptoms, Uncontrolled Hyperkalemia/Acidosis → unable to excrete waste products → Dialysis ]- semipermeable membrane dialysate bath → Replacement if no maintenance of fluid/electorlytes/acid base/metabolic homeostasis → persistent hyperkalemia/severe metabolic acidosis/fluid overload/uremic compications/kidney failure

Hemodialysis: machine substitutes kidney → remove waste → blood filter outside of body = pumped at high opposing direction rates → solute diffusion down concentration gradient (excess water is ultrafiltered) ]→ regular trips/introduces vascular infection/decreased quality of life (10-12% solute removal)

Peritoneal Dialysis: cleaned inside body - pump dialysis fluid into abdomen → absob waste → natural filter of peritoneal walls → catheter removed when empty → drain solution ]- infections/damage peritoneal cavity/hernia

Transplant: donor kidney → restore function → lifelong immunosuppressive therapy ]- donor shortage/rejection/complications/ongoing monitor