Patho exam 3

Renal disorder development

%10 of people born with significant malformation

• hereditary influence; most often acquired defect during development

• Renal agenesis

• Renal hypoplasia

Renal agenesis

Complete failure of kidney development

bilateral- incompatible with life (still born, early death after birth)

unilateral; more common, typically compensatory hypertrophy

Renal hypoplasia

Kidneys are small in size, unilateral usually discovered incidentally

• hypertension, B/L (bilateral)- progressive renal failure

Renal dysplasia

Can affect all or part of the kidney

• multicystic dysplastic kidney disorder

• risk of hypertension and wills tumors

annual follow up with blood pressure and sonograms

Cystic disease of the kidney

• can be single or multiple

• vary in size

• symptomatic or asymptomatic

• acquired, usually hereditary

ex. autosomal dominant polycystic kidney disease, autosomal recessive polycystic kidney disease, nepronophthisis, medullary cystic disease

Autosomal dominant polycystic kidney disease

• most common inherited kidney disease

• multiple expanding cysts destroy kidney structure and cause renal failure

manifestations: pain, hematuria, UTIs, HTN

US and Ct scans to diagnose

supportive care: control pain, UTIs, and BP

Autosomal recessive polycystic kidney disease

CHILDHOOD KIDNEY DISEASE

manifestations present usually at birth with infant progressing rapidly to renal failure

• bilateral flank madses

• severe renal failure

• impaired lung development

• hypertension

• 75% die during perinatal period

Nephronophthisis

• small kidneys

• multiple cysts

• usually juvenile

• progress to CKD

• polyuria, polydipsia, enuresis (bed wetting)

Medullary cystic kidney disease

• small kidneys

• Adult onset

• CKD

• polyuria, polydipsia, enuresis (bedwetting)

Renal disorders are

Simple and acquired renal cysts

• may cause flank pain, hematuria, infection

• common in people over 50

• US and CT scan

Acute nephrotic syndrome

• acute inflammatory process

• can be post infectious or secondary to acute systemic disease such as SLE

Acute nephrotic syndrome signs and symptoms

sudden onset of hematuria, proteinuria, decreased GFR, oliguria, edema, HTN

Acute Post Infectious Glomerulonephritis

occurs after certain infections with certain strains of group A- hemolytic streptococci, 7-10 post infection

• rare in industrialized nations but common is underprivileged populations

Acute Post Infectious Glomerulonephritis signs and symptoms

oliguria, hematuria, edema (especially face and hands), HTN

Treatment: ABX, supportive care, usually resolves

acute pyelonephritis

Etiology: bacterial infection usually e.coli

Uncomplicated: no structural abnormality

Complicated: structural abnormalities

Acute onset: shaking, chills, moderate high fevers, constant ache in loin and back area usually unilateral. dysuria, frequency and urgency

treatment: antibiotics for 10-14 days

renal failure

the kidney fails to remove metabolic end products from blood and regulate the fluid, electrolyte and pH balance of the extracellular fluid

• underlying causes: renal disease, systemic disease, or urologic defects from non renal origin

Acute kidney injury (AKI)

abrupt onset, often reversible if recognized early

Chronic kidney disease (CKD)

develops over the course of years, irreparable damage, can lead to need of dialysis

About Abrupt kidney injury

abrupt decline (within 48hr) in kidney function

• fluid and electrolyte balance is disturbed

• mortality rates 25-80%

• increased creatine and decrease in urine production

• can be caused by decreased blood flow w/o is ischemic injury, ischemic, toxic or obstructive

• classified as prerenal, intrarenal, or post renal

• prerenal and intrarenal account for 80-95%

AKI Prerenal injury

MOST COMMON; characterized by marked decrease in renal blood flow

• can be reversed if cause of decrease blood flow can be identified before kidney damage occurs

Causes: Hemorrhage (profound depletion of vascular volume), decreased perfusion due to heart failure, cardiogenic shock, anaphylaxis or sepsis, IV contrast , ACEi, ARBS, NSAIDS

• increased risk in elderly patients

AKI post renal

Cause: obstruction of urine outflow from kidney

• calculi, strictures, bladder tumors, BPH (most common)

treat the cause of the obstruction

AKI Intrarenal kidney injury

Damage to the kidney itself

ex: infection, glomerulonephritis, Diabetes, nephrotoxic substances

AKI diagnostic tests

BUN 8-20, cr <1.2

Urine analysis

renal ultrasound

kidney biopsy

AKI signs and symptoms

Decreased urine output

• fluid retention; edema pulmonary congestion

• HTN

• IF UNTREATED: neuromuscular irritability, somnolence, coma and death

Chronic kidney disease

Decline in kidney function for more than 3 months

CAUSES: HTN, DM, SLE

staged according to; GFR (glomerular filtration rate)

Signs and symptoms: early stages asymptomatic, as it progresses fluid, electrolytes, and acid base disturbances, hyperkalemia, HTN, anemia

Acute renal failure signs and symptoms

Neuro: confusion, irritability, lethargy (toxins)

cardiovascular: HTN, weight gain, edema, arrhythmias (electrolyte imbalance)

serum: Na+ dilution, increased K+, Mg+, phosphate, Ca+

GI: Halitosis A/N/V/c

Skin: Pruititis, uremic frost

Acute: oliguria or anuria, followed by extreme diuresis

CKD: concentrated urine, casts RBC, protein in urine

INCREASED RISK OF DRIG TOXICITY

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, less rapid but more effective response focused on specific foreign agent

Cells of the immune system

Macrophages

Granulocytes

Lymphocytes

macrophages

mature form of monocytes , located in most tissues, engulf and kill invading organisms, dispose of pathogens and infected cells, antigen presenting cells for adaptive immunity (long lived)

Granulocytes (short lived)

consists of neutrophils (phagocytosis), basophils, and eosinophils

lymphocytes

B-lymphocytes produce antibodies, mediate humoral immunity

T-lymphocytes cell mediated immunity

T helper cells help B-lymphocytes produce antibodies

Organs of the immune system

Central and Peripheral Lymphoid organs

•Central Lymphoid Tissue: bone marrow, thymus- immune cell production and maturation

•Peripheral Lymphoid tissue: Lymph nodes: remove protein rich fluid (lymph), filter foreign material before it goes back to the blood, and center for proliferation and response of immune cells

•Spleen: left abdominal cavity, filters antigens from the blood, and is important in response to systemic infections

innate immunity system consists of

•Epithelial barrier

•Phagocytic neutrophils

•Macrophages

•Dendritic cells

epithelial barrier

Physical and chemical barriers between internal environment and pathogens of external world

•Includes epidermis (skin): protective barrier, keratin, chemical create salty acidic environment, antibacterial proteins

lining of respiratory, GI, and urogenital tracts

mucus traps and washes away microorganisms, cilia: move microbes trapped in mucus to throat then sneezing and coughing removes them

Phagocytic leukocytes

Neutrophils early responding respond first followed by Macrophages that engulf and digest microbes

dendrites

derived from bone marrow, link innate and adaptive immunity responses

NK cells

Class of lymphocytes recognize infected and stressed cells respond by killing these cells

development of innate immunity

Depends on secretion of soluble mediators

•Opsonins: bind to and tag microorganisms for more efficient recognition

•Cytokinine: released from activated leukocytes, regulate activity of other cells, amplify inflammation and stimulate the production of acute phase protein, aid in the initiation of the adaptive immune response

complement system

Primary effector system for innate and adaptive immune systems

•Consists of a group of protein activated by microbes and promote inflammation and destruction of microbes

•Recognition of microbes occurs by 3 ways

Classical

Lecitin

Alternative

Classical pathway

adaptive immune pathway that recognizes antibody bound to surface of microbe or structure

Lecitin pathway

innate pathway uses plasma protein (mannose binding ligand) binds to residue

alternative pathway

innate pathway recognizes certain microbial molecules

adaptive immunity

Distinguishes between microbes and molecules to remember pathogens quickly and produces a heightened immune response on subsequent encounters with the same agent

•Composed of lymphocytes and their products

•Two types of adaptive immunity

•Humoral immunity

•Cell-mediated immunity

Antigens

Also called immunogens

•Ex: bacteria, fungi, virus, protozoa and parasites

•Non-microbial antigens: pollen, poison ivy, inset venom and transplanted organs

•Stimulate an immune response

•Are recognized by receptors on immune cells , antibodies are formed

cells of adaptive immunity

T-lymphocytes

CD4 + T helper cells

Antigen presenting cells

T-lymphocyte (adaptive immunity)

differentiate into helper T cells, regulatory T cells and cytotoxic T cells and provide cell-mediated Immunity

CD4 + T helper cells

trigger immune response and are essential for differentiation of B cells into antibody producing cells and Differentiation o T lymphocytes into CD8+ cytotoxic T cells

antigen presenting cells

macrophages and dendritic cells that process and present antigen peptides to CD4+ helper T cells

 

Cell Surface Major Histocompatibility Complex Molecules (MHC)

Key recognition molecules the immune system uses to distinguish self from nonself

Class 1 MCH

present in all nucleated cells other than those of the immune system, interact with CD8+ T cells in the destruction of cells affected by intracellular pathogens, or cancer

Class 2 MCH

found on antigen presenting cells and B lymphocytes, aid in cell communication between different cells of the immune system

humoral immunity

Protection provided by B lymphocytes- eliminates extracellular microbes and microbial toxins

primary immune response

antigen first introduced into the body

•Latent period before detection of antibody

•Activation takes 1-2 weeks, but can be several weeks before there is a detectable antibody. Ex- HIV

secondary immune response

occurs on second or subsequent exposure to an antigen

•Rise in antibodies occurs quicker and reaches higher level because of memory cells

•Booster shots ex: tetanus utilizes memory cells

 

immunoglobulins

•IgG

•IgA

•IgM

•IgD

•IgE- allergies

 

active immunity

•Acquired through immunization or actually having the disease

•Depends on response to antigen by persons immune system

•Long lasting

•Requires a few days to a few weeks to after first exposure for sufficient immune response

•Responds within a few hours in subsequent exposures

•Can improve on subsequent exposures

passive immunity

•Immunity transferred from another source

•Infant from mom in utero or breast milk

•Maternal IgG crosses placenta and protects baby for 3-6 months (moms antibodies)

•Can also be given by transfer of antibodies from other people or animals

•Immune serum, gamma globulin short term protection against infectious agents

self regulation of immune response

Inadequate response can lead to immunodeficiency

•Excessive or inappropriate response can lead to allergic reactions or autoimmune diseases

•Tolerance- inhibition of immune response, non reactive to self antigens while producing immunity to foreign agents, can lead to inability to respond to infectious agents

newborns

Newborns are protected against antigens early in life by passive transfer of maternal antibodies through placenta (IgG) and breast milk (IgA)

•Largest amount of IgG crosses placenta in the last weeks of pregnancy

•Stored in fetal tissue (premature infants may be deficient)

•Transfer of IgG antibodies to infect  born to mom with HIV will have + HIV but may not be infected with virus

aging

Elderly have changes in immune responses

•Are more susceptible to infections

•More autoimmune and immune complex disorders

•Higher incidence of cancer

•Less response to vaccines

Inflammatory response results from cellular injury that ruptures cells

Trauma

•Environmental irritants

•Micro-organisms

•Free radical damage

•Hypoxia

•Surgery

Inflammation prepares

injured area for healing

Leukocytes (neutrophils and macrophages)

remove debris and provide growth factors

Nutrients (proteins, glucose, vitamins)

provide building blocks for cells

Clotting factors and platelets

limit drainage

Cellular Injury activates___plasma protein systems

3

clotting cascade

kinin cascade

complement cascade

clotting cascade

to prevent further bleeding

kinin cascade

produces bradykinin which causes pain, vasodilation and vascular permeability

complement cascade

stimulates opsonins, chemotactic factors and anaphylatoxins which degrade Mast cells to releases histamine (a potent vasodilator)

The vascular response

Histamine and Bradykinin stimulate vasodilation

Increased blood flow to the area causes redness (rubor) and heat (calor)

•Leakage of protein rich plasma into the interstitial spaces cause swelling

•Bradykinin also causes pain (dolor)

•Cells unable to function

cellular response

Chemotactic factors attract neutrophils to

•Marginate: move to the capillary walls

•Emigrate: squeeze through capillary pores

•Migrate: through chemotaxis to the injury

•Phagocytosis: facilitated by opsonization (acts to facilitate adherence of WBC to bacteria)

The 5 Cardinal signs of Inflammation

• Redness

•Heat

•Pain

•Swelling

•Loss of function

 

Exudate (drainage)

Serous

•Fibrinous

•Serosanguinous

•Sanguinous

•Purulent (suppurative)

serous

watery, like plasma

fibrinous

clotted

serosenguinous

clear, pink, blood tinged

sanguinous

bloody

purulent (suppurative)

pus

The 3 systemic signs of inflammation

Fever: caused by specific cytokines (endogenous pyrogens)

•Leukocytosis: increased WBC >11,000 and in infection a “left shift ratio”

• Elevated ESR (erythrocyte sedimentation rate): Increased plasma proteins

•Elevated CRP

fever

One of the most prominent manifestations of acute phase response, especially those caused by infection

•Produced in response to pyrogens that act by prompting the release of prostaglandin E2 or fever producing cytokines

•4 stages of fever

•Prodromal: nonspecific complaints, mild HA, fatigue

•Chill: during which temp rises

•Flush: skin warm and red

•Defervescence stage: initiation of sweating

 

chronic inflammation

May occur due to:

•Chronic infection or contamination

•Continuous exposure to irritants

•Immune System abnormalities

May result in:

•Granuloma formation

•Giant cell formation

•Cancers in genetically susceptible individuals

The stages of wound healing include

Inflammation: usually lasts 1-2 days

•Proliferation and new tissue formation: 2-8 weeks for maximum strength to be achieved, may involve regeneration and resolution, or repair with scar tissue but loss of function

•Remodeling and maturation: up to 2 years

 

factors effecting wound healing

• oxygenation

• circulation

• hydration

• age

• immunity

• medications

oxygenation

reduced in COPD, atherosclerosis

circulation

reduced in elderly, CHF, DM, MI

hydration

reduced in illness, hydration and age

age

accelerated in young and reduced in elderly

immunity

reduced in HIV, stress, infection

medications

cortisone, chemotherapy, immunomodulators

Wound Healing Process

Healing processes occur simultaneously

•Collagen lattice forms

•Granulation tissue fills in wound

•Hypertrophic scar tissue overfills wound

•Cicatrization (maturation) of wound may take 1-2 years. Collagen contracts and the scar becomes lighter and smoother

Dysfunctional Healing

Wounds may fail to close or may re-open due to poor wound healing conditions

•Non-union: failure of adherence

•Dehiscence: wound edges separate, expose underlying tissues

•Evisceration: underlying viscera are exposed

Wounds may become infected and more tissue damage may result

•Abcess: a walled pocket of infection

•Sinus tract: a narrow tunnel forms

•Cellulitis

•Necrosis and gangrene may occur

Dysfunctional healing (extra)

Excess Fibrin or dysfunctional Collagen synthesis may result in abnormalities such as:

•Fistula formation

•Adhesions

•Contractures

•Strictures

•keloids

systemic markers of vascular inflammation

Homocysteine level: elevated in reduced folate levels, B vitamins, and riboflavin <15 mcmol/L

•Inhibits AC cascade and increased endothelial damage in arteries

•C-Reactive Protein- increases to neutralize inflammatory chemicals

•Low risk for CV events <1.0mg/L

•Average 1-3

•Increased risk >3.0 mg/L

•Infectious agents: often found in plaques

•Endothelial dysfunctions: lack of Nitrous Oxide

hypersensitivity disorders

Disorders caused by immune response

•Type I-immediate hypersensitivity disorders

•Type II- antibody mediated disorders

•Type II- immune complex mediated disorders

•Type IV- cell-mediated disorders

type 1 immediate hypersensitivity disorder

IgE mediated

•Begin rapidly – usually within minutes of an antigen challenge

•Typically referred to as allergic reactions, antigens are typically referred to as allergens

•Typical allergens- pollen, house dust, mites, animal dander, foods and chemicals such as PCN and antibiotics

•Cytokinines secreted differentiate B cells into IgE which act as growth factors for mast cells and activate eosinophils

Type I hypersensitivity reactions have 2 well defined phases

•Primary or immediate phase response (5-30mins last 60mins

•Vasodilation (histamine/bradykinin)

•Vascular leakage (histamine)

•Smooth muscle contraction (histamine/bradykinin)

•Secondary or late phase (2-8hr later, can last days)

•Intense infiltration of tissue with eosinophils and other acute or inflammatory cells

•Epithelial cell damage

•Leukotrienes and prostaglandins produce response