1. Chronic kidney disease
1.1. Caused by
1.1.1. Diabetes - diabetic nephropathy 30-40%
1.1.1.1. .
1.1.1.1.1. Definition
1.1.1.1.2. Risk factors
1.1.1.1.3. Diagnosis
1.1.1.1.4. Pathophysiology
1.1.2. Hypertension- hypertensive nephropathy 20%
1.1.3. Glomerulonephritis (15%)
1.1.3.1. Non-inflammatory injury
1.1.3.1.1. Minimal change nephrotic syndrome/focal segmental glomerulosclerosis (MCNS/FSGS)
1.1.3.1.2. Membranous nephropathy(MN)
1.1.3.2. Inflammatory injury
1.1.3.2.1. post-streptococcal glomerulonephritis (GN)
1.1.3.2.2. Membranoproliferative GN
1.1.3.2.3. Systemic lupus erythematosus (SLE)
1.1.3.2.4. IgA nephropathy
1.1.4. Inherited diseases, such as polycystic kidney disease
1.1.5. Lupus
1.1.6. Obstructions
1.2. Symptoms
1.2.1. Beginning
1.2.1.1. Tiredness, loss of appetite, and headaches
1.2.1.2. Polyuria, newly emerging or worsening hypertension, or peripheral edemas
1.2.1.3. Oliguria or anuria and uremic encephalopathy
1.2.2. Progression
1.2.2.1. Increased tiredness, paleness, headaches, visual disturbances, and a severe loss of renal capacity
1.2.2.2. Uremic gastroenteropathy leads to a loss of appetite and nausea
1.2.3. Final stages
1.2.3.1. Dyspnea, vomiting, and increased susceptibility to bleeding
1.3. Diagnosis
1.3.1. based on
1.3.1.1. Structural or functional abnormality in kidney for >3 months
1.3.1.1.1. Can be
1.3.2. by
1.3.2.1. Blood Test
1.3.2.1.1. includes
1.3.2.2. Urine Analysis
1.3.2.2.1. inclludes
1.3.2.3. Doppler Ultrasound scan
1.3.2.3.1. shows
2. Acid and base balance
2.1. Definitions
2.1.1. ACID: Any compound which forms H + ions in solution (proton acceptor)
2.1.1.1. ACIDOSIS is a condition in which there is too much acid in the body fluids.
2.1.2. BASE: Any compound which combines with H + ions in solution (proton donor)
2.1.2.1. ALKALOSIS is a condition in which there is too much base in the body fluids.
2.2. Three lines of defense
2.2.1. First line of defense
2.2.1.1. Chemical buffers
2.2.2. Second line of defense
2.2.2.1. Respiratory system
2.2.3. Third line of defense
2.2.3.1. Renal system
2.2.3.1.1. H+ excretion
2.2.3.1.2. HCO₃ - reabsorption
2.2.3.1.3. NH₃ excretion
2.2.3.1.4. HO4P-2 reabsorption
2.3. Compensations
2.3.1. Acidosis
2.3.1.1. Decreased ratio of HCO₃ -to H+
2.3.1.2. Causing excess H+ ions
2.3.1.3. Causing complete reabsorption of HCO₃ -along with the phosphate and ammonia
2.3.2. Alkalosis
2.3.2.1. Increased ratio of HCO₃ -to H+
2.3.2.2. Causing excess HCO₃- ions
2.3.2.3. Compensated by decreasing ventilation rate
2.4. Symptoms
2.4.1. Acidosis
2.4.1.1. Headache
2.4.1.2. Shortness of death
2.4.2. Alkalosis
2.4.2.1. Confusion
2.4.2.2. Hand tremor
2.5. Causes
2.5.1. Acidosis
2.5.1.1. Tissue hypoxia
2.5.1.2. Constipation
2.5.2. Alkalosis
2.5.2.1. Diuretics
2.5.2.2. Severe vomiting
3. hydrocortisone
4. immunosuppressive drugs
4.1. Glucocorticoids
4.1.1. MOA
4.1.1.1. inhibition of intracellular NF-κB
4.1.2. Prednisolone
4.1.3. dexamethasone
4.2. Pimecrolimus
4.3. Calcineurin inhibitors
4.3.1. MOA
4.3.1.1. binding of cyclophilin → inhibition of calcineurin → inhibition of NFAT activation → ↓ IL-2 transcription → ↓ activation of T cells
4.3.2. Cyclosporine A
4.3.3. Tacrolimus
4.3.4. adverse effects
4.3.4.1. Nephrotoxic
4.3.4.2. neurotoxic Diabetogenic effects
4.4. mTOR inhibitors
4.4.1. MOA
4.4.1.1. Binding to FKBP → inhibition of mTOR kinase → inhibition of the IL-2-mediated cell cycle → ↓ response to IL-2 → ↓ T-cell activation and B-cell differentiation → ↓ IgM, IgG, and IgA production
4.4.2. Sirolimus
4.4.3. Everolimus
4.4.4. adverse effects
4.4.4.1. Insulin resistance
4.4.4.2. Hyperlipidemia
4.5. Purine analog
4.5.1. MOA
4.5.1.1. inhibition of lymphocyte proliferation
4.5.2. Azathioprine
4.5.3. adverse effects
4.5.3.1. Hepatotoxicity
4.5.3.2. Malignancies
4.5.3.3. Pancytopenia
4.6. IMDH\IMPDH inhibitors
4.6.1. MOA
4.6.1.1. Reversible inhibition of inosine monophosphate dehydrogenase → blockade of purine synthesis → selective inhibition of lymphocyte proliferation
4.6.2. Mycophenolate mofetil
4.6.3. adverse effects
4.6.3.1. Pancytopenia
4.6.3.2. Infection (especially with CMV)
4.6.3.3. Vomiting and diarrhea
4.6.3.4. Hyperglycemia
4.6.3.5. Hypertension
4.7. cytostatic and anti proliferative agents
4.7.1. Methotrexate
4.7.1.1. MOA
4.7.1.1.1. Folic acid antagonis
4.7.1.2. adverse effects
4.7.1.2.1. Mucositis
4.7.1.2.2. Hepatotoxicit, nephrotoxicity
4.7.1.2.3. Gastrointestinal side effects
4.7.2. Cyclophosphamide
4.7.2.1. MOA
4.7.2.1.1. Alkylating agent
4.7.2.2. adverse effects
4.7.2.2.1. Hemorrhagic cystitis
5. Organ transplantation
5.1. Types of graft
5.1.1. Allograft
5.1.1.1. donor is another human
5.1.2. Isograft
5.1.2.1. donor is an identical twin
5.1.3. Xenograft
5.1.3.1. donor is an animal
5.1.4. autograft
5.1.4.1. donor is also the recipient
5.2. Requirement for donor and recipient
5.2.1. Same Blood Type (ABO)
5.2.2. Same (or close) MHCI and II
5.2.2.1. made up of HLA genes
5.2.2.1.1. highly pleomorphic
5.2.2.2. Most important HLA genes for solid organ transplants: HLA-A, HLA-B, HLA-DR
5.2.3. Negative cross-matching screen
5.2.3.1. Safety measure done before transplantation to ensure safe matching between donor and recipient
5.2.3.2. Test of donor cells against recipient plasma to screen for antibodies
5.3. Complications of organ transplantation
5.3.1. Organ rejection
5.3.1.1. hyper acute
5.3.1.1.1. complement mediated reaction
5.3.1.1.2. occurs within minutes
5.3.1.1.3. preexisting alloantibodies
5.3.1.1.4. thrombosis and occlusion
5.3.1.2. acute
5.3.1.2.1. weeks to months
5.3.1.2.2. preexisting alloantibodies
5.3.1.2.3. t-cell mediated immune response
5.3.1.2.4. inflammation and leukocyte infiltration of graft vessels
5.3.1.3. chronic
5.3.1.3.1. months to years
5.3.1.3.2. results in intimal thickening and fibrosis of graft vessels and graft atrophy
5.3.1.4. graft vs host disease
5.3.1.4.1. varies
5.3.1.4.2. Donor t-cells in the graft proliferate and attack the recipient's tissue
5.3.2. Bleeding
5.3.3. Pain, wound complications
5.3.4. Infection
5.3.5. Death
5.3.5.1. .
5.3.5.1.1. defined as
5.3.5.1.2. divided into stages
5.3.5.1.3. categorized by
5.3.5.1.4. Notification of death