Renal Development Disorders

Renal Disorders: Disorders of Kidney Development

• 10% of people are born with potentially significant kidney malformations.
• These malformations can arise from hereditary influences or acquired defects during development.
• Renal agenesis: complete failure of kidney development.
  • Bilateral renal agenesis: incompatible with life, leading to stillbirth or early death.
  • Unilateral renal agenesis: more common, typically results in compensatory hypertrophy of the remaining kidney.
• Renal hypoplasia: The kidneys are small in size. Unilateral hypoplasia is usually discovered incidentally.
  • Renal hypoplasia can cause hypertension (HTN)
  • Bilateral hypoplasia can cause progressive renal failure.

Renal Dysplasia

• Renal dysplasia: can affect all or part of the kidney.
  • It can result in multicystic dysplastic kidney disorder.
  • There is the risk of hypertension and Wilms tumors.
  • Annual follow-up, including blood pressure monitoring and sonograms is recommended.

Cystic Diseases of the Kidney

• Cysts can be single or multiple.
• Cysts vary in size.
• Cysts can be symptomatic or asymptomatic.
• Cystic kidney diseases are acquired or usually hereditary.
• Examples: autosomal dominant polycystic kidney disease, autosomal recessive polycystic kidney disease, nephronophthisis, and medullary cystic disease.

Autosomal Dominant Polycystic Kidney Disease

• The most common inherited kidney disease.
• Multiple expanding cysts destroy kidney structure and cause renal failure.
  • Manifestations: pain, hematuria, urinary tract infections (UTIs), and hypertension.
• Diagnosis: ultrasound and CT scans
• Supportive care: pain management, UTI treatment, and blood pressure control.

Autosomal Recessive Polycystic Kidney Disease

• A childhood kidney disease.
• Manifestations present at birth quickly progressing to renal failure.
  • Symptoms: bilateral flank masses
  • Symptoms: severe renal failure
  • Symptoms: impaired lung development
  • Symptoms: hypertension.
• 75% of affected infants die during the perinatal period.

Nephronophthisis and Medullary Cystic Kidney Disease

• Nephronophthisis
  • Small kidneys with multiple cysts
  • Usually juvenile onset
  • Progresses to chronic kidney disease (CKD).
  • Symptoms: polyuria(excessive urination), polydipsia (excessive thirst), and enuresis (bed wetting).
• Medullary Cystic Kidney Disease:
  • Small kidneys
  • Adult onset
  • Leads to CKD
  • Symptoms: polyuria, polydipsia, and enuresis (bed wetting).

Simple and Acquired Renal Cysts

• May cause flank pain, hematuria, infection, and hypertension.
• Relatively common in people over 50.
• Diagnosis: ultrasound and CT scan.

Acute Nephrotic Syndrome

• An acute inflammatory process.
• Possible causes: post-infectious conditions or secondary to systemic diseases such as systemic lupus erythematosus (SLE).
• Signs and symptoms: sudden onset of hematuria, proteinuria, decreased glomerular filtration rate (GFR), oliguria, edema, and hypertension (HTN).

Acute Post Infectious Glomerulonephritis

• Occurs after infections with certain strains of group A β-hemolytic streptococci 7-10 days post-infection.
• Rare in industrialized nations, but common in underprivileged populations.
• Signs and symptoms: oliguria, hematuria, edema (especially face and hands), and hypertension.
• Treatment: antibiotics and supportive care, usually resolves.

Acute Pyelonephritis

• Etiology: usually from a bacterial infection typically Escherichia coli (E. coli).
• Uncomplicated: no structural abnormality.
• Complicated: structural abnormalities.
• Acute Onset: shaking, chills, moderate to high fevers, constant ache in the loin and back area usually unilateral. Dysuria, urinary frequency, and urgency.
• Treatment: antibiotics for 10-14 days.

Renal Failure

• The kidneys fail to remove metabolic end products from the blood. They also regulate fluid, electrolyte, and pH balance of the extracellular fluid.
• The underlying cause could be renal disease, systemic disease, or urologic defects from non-renal origin.
• Acute Kidney Injury (AKI): abrupt onset and reversible if recognized early.
• Chronic Kidney Disease (CKD): develops over years with irreparable damage, can lead to dialysis.

Acute Kidney Injury (AKI)

• Abrupt decline (within 48 hours) in kidney function, fluid, and electrolyte balance.
• Mortality rates range from 25%-80% depending on cause.
• Increased creatinine and reduction in urine production
• Can be caused by decreased blood flow w/o ischemic injury, ischemic, toxic, or obstructive issues.
• Types: prerenal, intrarenal, or postrenal
• Prerenal and intrarenal account for 80-95% of AKI cases.

Acute Kidney Injury (AKI): Prerenal Injury

• Most common type of injury. Characterized by marked decrease in renal blood flow.
• Reversible if the cause of decreased blood flow is identified and corrected before kidney damage occurs.
• Causes: profound depletion of vascular volume (hemorrhage), decreased perfusion due to heart failure, cardiogenic shock, anaphylaxis, or sepsis; IV contrast, ACE inhibitors, ARBs, and NSAIDs.
• Elderly patients are at increased risk.

Acute Kidney Injury (AKI): Post Renal Injury

• Results from obstruction of urine outflow from the kidneys.
• Causes: calculi, strictures, bladder tumors, benign prostatic hyperplasia (BPH, most common).
• Treatment: address the underlying cause of obstruction.

Acute Kidney Injury (AKI): Intrarenal Kidney Injury

• Damage to the kidney itself.
• Examples: infections, glomerulonephritis, diabetes mellitus (DM), and nephrotoxic substances.

Acute Kidney Injury (AKI): Diagnostic Tests

• BUN/Creatinine Ratio: BUN 8-20, creatinine level <1.2.
• Urine Analysis.
• Renal Ultrasound.
• Kidney Biopsy.

Acute Kidney Injury (AKI): Signs and Symptoms

• Decreased urine output.
• Fluid retention- edema, including pulmonary congestion.
• Hypertension
• If untreated: neuromuscular irritability, somnolence, coma, and death.

Chronic Kidney Disease

• Decline in renal function for greater than 3 months.
• Causes: hypertension, diabetes mellitus, and systemic lupus erythematosus (SLE)
• Staged according to glomerular filtration rate (GFR).
• Signs and Symptoms: Early stages are usually asymptomatic, but as it progresses fluid, electrolyte, and acid-base disturbances, hyperkalemia, hypertension, and anemia develop.

Acute Renal Failure

• Signs and Symptoms
  • Neuro: Confusion, irritability, lethargy are indications of toxins.
  • Cardiovascular: Hypertension, weight gain, edema, and arrhythmias result from electrolyte imbalance.
  • Serum electrolytes: Sodium dilution, increased potassium, magnesium, phosphate, and calcium are indicative of electrolyte imbalance.
  • GI: Halitosis, anorexia, nausea, vomiting, and constipation.
  • Skin: Pruritus and uremic frost.
  • Acute: Oliguria or anuria are followed by extreme diuresis.
  • CKD: Concentrated urine, casts, red blood cells (RBCs), and proteinuria.
• Increased risk of drug toxicity.

Immunity

• Immunity: protection from infectious disease.
• Immune Response: collective coordinated response of cells and molecules of the immune system.
• Innate Immunity: natural immunity, early rapid response.
• Adaptive Immunity: specific or acquired immunity; a less rapid but more effective response focused on a specific foreign agent.

Immunity: Cells of the Immune System

• Macrophages: mature form of monocytes, located in most tissues, engulf and kill invading organisms. Dispose of pathogens and infected cells, act as antigen-presenting cells for adaptive immunity (long lived).
• Granulocytes: (short lived), neutrophils (phagocytosis), basophils, and eosinophils.
• Lymphocytes:
  • B-lymphocytes produce antibodies and mediate humoral immunity.
  • T-lymphocytes mediate cell-mediated immunity.
  • T-helper cells help B lymphocytes produce antibodies.

Immunity: Organs of the Immune System

• Central and Peripheral Lymphoid organs
• Central Lymphoid Tissue: bone marrow, thymus. Cell production and maturation
• Peripheral Lymphoid Tissue: Lymph nodes remove protein-rich fluid (lymph), filter foreign material before it reenters the blood. They also center for proliferation and response of immune cells.
• Spleen: located in the left abdominal cavity. It filters antigens from the blood and is important in response to systemic infections.

Innate Immunity

• The innate immune system consists of:
  • Epithelial barriers.
  • Phagocytic neutrophils.
  • Macrophages.
  • Dendritic cells.

The Epithelial Barrier

• Includes physical and chemical barriers between the internal environment and pathogens of external world.
  • Epidermis (skin): Provides a protective barrier with keratin and a salty acidic environment. It contains antibacterial proteins.
• Lining of Respiratory, Gastrointestinal (GI), and Urogenital tracts: Mucus traps and washes away microorganisms. Cilia move microbes trapped in mucus to the throat for removal by sneezing and coughing.

Innate Immunity: Cells of Innate Immunity

• Phagocytic leukocytes:
  • Neutrophils respond early to infection followed by macrophages which engulf and digest microbes.
• Dendrites:
  • Derived from bone marrow and link innate and adaptive immunity responses.
• Natural killer (NK) cells:
  • A Class of lymphocytes recognize infected and stressed cells and then respond by killing these cells.

Innate Immunity: Development of Innate Immunity

• Depends on secretion of soluble mediators
  • Opsonins bind to and tag microorganisms for more efficient recognition.
  • Cytokines are released from activated leukocytes that regulate the activity of other cells, amplify inflammation, stimulate the production of acute-phase proteins. These aid with the initiation of the adaptive immune response.

Innate Immunity: Complement System

• The primary effector system for innate and adaptive immune systems.
• Consists of a group of proteins activated by microbes which promote inflammation and destruction of microbes.
• Recognition of microbes occurs in 3 ways
  • Classical pathway: Adaptive immune pathway that recognizes antibody bound to the surface of a microbe or structure.
  • Lectin pathway: Innate pathway that uses plasma protein (mannose-binding lectin) that binds to residue.
  • Alternative pathway: Innate pathway that recognizes certain microbial molecules.

Adaptive Immunity

• Distinguishes between microbes and molecules to remember pathogens quickly It produces a heightened immune response on subsequent encounters with the same agent.
• Composed of lymphocytes and their products.
• Two types:
  • Humoral immunity
  • Cell-mediated immunity

Adaptive Immunity: Antigens

• Also called is immunogens.
  • Examples: bacteria, fungi, virus, protozoa, and parasites
  • Also: Non-microbial antigens: pollen, poison ivy, inset venom, and transplanted organs.
• Stimulate an immune response.
• Are recognized by receptors on immune cells, and antibodies are formed.

###Adaptive Immunity: Cells of Adaptive Immunity

• T-lymphocytes: Differentiate into helper T cells, regulatory T cells, and cytotoxic T cells and provide cell-mediated immunity.
• CD4+ helper T cells: Trigger immune response. They are essential for the differentiation of B cells into antibody producing cells as well as differentiation of T lymphocytes into CD8+ cytotoxic T cells.
  • Antigen presenting cells: Macrophages and dendritic cells process and present antigen peptides to CD4+ helper T cells.

Adaptive Immunity: Cell Surface Major Histocompatibility Complex Molecules (MHC)

• Key recognition molecules act as the immune system and help distinguish self from non-self.
  • Class I MHC: Present in all nucleated cells. Interact with CD8+ T cells during the destruction of cells affected by intracellular pathogens, or cancer.
  • Class II MHC: Found on antigen presenting cells and B lymphocytes. Aids in cell communication between different cells of the immune system.

Adaptive Immunity: Humoral Immunity

• Protection provided by B lymphocytes. Eliminates extracellular microbes and microbial toxins.
• Primary Immune Response: When an antigen is first introduced into the body.
  • Has a latent period before antibody detection.
  • Activation takes 1-2 weeks, but it can be several weeks before a detectable antibody is present. For example, HIV.
• Secondary (memory) response: Occurs on second or subsequent exposure to an antigen.
  • A rise in antibodies occurs quicker and reaches a higher level as a response to memory cells.
  • Ex: tetanus booster

Immunoglobulins

• IgG
• IgA
• IgM
• IgD
• IgE- allergies

Adaptive Immunity: Active Immunity

 - Acquired through immunization or actually having the disease
 - Depends on response to an antigen by individuals with immune system.
 - Long lasting.
 - Requires a few days to a few weeks after first exposure for a sufficient immune response.
 - Responds within a few hours in subsequent exposures.
 - Can improve on subsequent exposures.

Adaptive Immunity: Passive Immunity

• Immunity transferred from another source.
• Passed from an infant to a mother through in utero or breast milk.
• Maternal IgG crosses the placenta and protects the baby for 3-6 months (maternal antibodies).
• Can be given by transfer of antibodies from other people or animals.
  • Immune serum and gamma globulin provides short-term protection against infectious agents.

Self Regulation of Immune Response

• Inadequate immune response can lead to immunodeficiency.
• Excessive or inappropriate immune response can lead to allergic reactions or autoimmune diseases.
• Tolerance is an inhibition of immune response; non-reactive response to antigens while still producing foreign agents. This can lead to an inability to respond to infectious agents.

Newborns

• Newborns are protected against antigens early in life by passive transfer of maternal antibodies through the placenta (IgG) and breast milk (IgA).
• The largest amount of IgG crosses the placenta in the last weeks of pregnancy.
• Stored in fetal tissue (premature infants may be deficient).
• -Transferred IgG antibodies means that an infant born to a mother with HIV will have (+) HIV, but the baby may not be infected with the virus.

Aging

• Elderly have changes in immune responses.
• They are more susceptible to infections.
• Have more autoimmune and immune complex disorders.
• There is a higher incidence of cancer.
• The elderly often have a lesser response to vaccines.