Pathophysiology

Introduction to pathophysiology

Pathophysiology: “ the study of changes in the body function that results from disease or disorder

Clinical manifestations are signs and symptoms:

Signs: is what we can measure and visibly see. It is OBJECTIVE DATA

Symptoms: is what the patient reports to us as to what they are feeling. It is SUBJECTIVE DATA

Epidemiology: the study of factors of a disease on a population

Etiology: the cause of the disease

Disorder: a disturbance in body function that cant be corrected by the body (unknown cause)

Disease: signs and symptoms that impairs the body's normal function (known cause)

Syndrome: a set of signs and symptoms that occur together

Incidence: the number of cases diagnosed and confirmed in a time frame

Morbidity: Number of people with the disease vs to those who don't

Prevalence: how common the disease is

Comorbidity: the presence of other diseases and conditions present in the same patient

Mortality: the death rate from a disease

Genetics

Classification of genetic diseases (3)

Monogenic
Polygenic
Chromosomal aberrations

Mutations: change in the DNA base sequence

Causes: radiation, chemicals, virus, internal, cell division mistakes and cell repair mistakes

Outcomes of mutations:

Negative: leads to the wrong protein being made leading to disorder
No effect: “Junk DNA” doesn’t code for anything but can be turned on if exposed to the stimulus due to epigenetics
Positive effects: promotes advantageous characteristics for survival = good for evolution

Types of Mutations in DNA

Substitution
Deletion
Addition
Inversion

These mutations change the proteins that are being coded and the trait being synthesized. They are then unable to fold properly to form the protein required

Proteins make up the body and are crucial for cell processes. They systematically spread playing roles in the immune system, signaling, transportation of blood, enzymatic activity, cell membrane, structures in the body, proteins in the muscle.

Single Nucleotide Polymorphism. SNPS

Most SNPS have no effect
SNPS help in predicting the individuals response to a drug
Some directly cause disease

PKU- Phenylketonuria- Autosomal recessive

A condition where there is a deficit of tyrosine being made due to phenylalanine not being broken down.

Clinical manifestations: hypopigmentation, tremors, psychosis, cognitive dysfunction,

Cystic fibrosis- it is when there is a deletion of 3 base pairs- Autosomal recessive.

It is when there is an excessive production of mucus in ducts which can block them.

This is due to a mutation in a gene which disrupts the activity of a chloride channel

Beta- globin disorders

Sickle cell: 2 altered HBB genes, alters beta globin protein, making them to stick to one another, RBC carry oxygen but fibers make them stiff and misshapen.

Beta-thalassemia- 1 or 2 altered HBB genes: there is a problem with beta globin where there is near to none being made or the protein being altered resulting in less RBC

Oxygen transport disorder: Betaglobin can't properly bind to oxygen resulting in RBC that delivers less oxygen.

Huntington's Disease- 35 or more repeats of CAG- autosomal dominant

This leads to neurodegeneration, moodiness, fidgeting, cognitive issues, personality shifts, depression, trouble focusing and muscle twitching

Chromosomal aberrations

Numerical:

Aneuploidy: having an abnormal of chromosomes due to nondisjunction eg DOWNS

Aneuploidy increases with age

Polyploidy: possessing more than 2 sets of chromosomes

Structural:

Deletion
Duplication
Inversion
Translocation

Genetic variation in meiosis is due to:

Random assortment: chromosomes line up in the equator of the cell in different orders and not in their homologous pairings

Crossing over: after maternal and paternal homologous pairs up, they exchange parts of their DNA due to close proximity

klinefelter syndrome (XXY)

When a male has an extra X chromosome, increasing the level of female hormones in the body ie: FH and LH instead of testosterone.

Clinical manifestations:

Tall stature
Gynecomastia
Infertility
Intellectual disability

Epigenetics: changes to an individual that does not change their DNA sequence, more so the expression of DNA due to diet, environment, lifestyle, gender, sleep

The Human Microbiome: the micro bacteria in our body that fights off pathogens, control our metabolism, weight, mood

We are 43% human cells and 57% microbial cells

Atherosclerosis- the abnormal thickening and hardening of artery walls due to the buildup of plaque

Cholesterol must be carried by lipoproteins in the body, as they are not water soluble

HDL = good

IDL, LDL, VLDL, chylomicrons = bad

Atherosclerosis- 3 homeostasis are disrupted

Endothelium becomes inflamed due to the damage to it, the body increases vasoconstriction and increases clotting.
Monocytes and other inflammatory and immune cells arrive and bind to the injured endothelium
Toxic oxygen radicals oxidize LDL which is engulfed by macrophages i.e. foam cells which then penetrate into the vessel walls.
As foam cells increase in number they form fatty streaks that are visible to the eye.
Macrophages also release growth factors stimulating smooth muscle cell proliferation, smooth muscle cells and collagen migrate over the fatty streak forming plaque
The plaque can calcify which can protrude through the vessel lumen and obstruct blood flow.
May rupture and cause a thrombus= ischemia and infarction

Angina: chest pain

Stable: indicates chronic condition, comes on with increased myocardial oxygen demands resulting in lactic acid, that triggers pain receptors.

Silent ischemia: no angina pain, may have dyspnea, fatigue.

Obesity: excessive adiposity/ fat accumulation in the body.

BMI over 25 is overweight and over 30 is obese.

Limitations of BMI

BMI is not a direct measure of body fatness because it is a measure of excess weight rather than excessive body fat

Factors such as:

Age, sex, ethnicity, and muscle mass can influence the relationship between BMI and body fat

Causes of obesity:

High adiposity develops when energy intake exceeds energy expenditure, however other factors can have a significant impact on the energy and balance equation.

Risk factors for obesity

There is no single cause, unhealthy diet, physical inactivity, stress, smoking , socioeconomic factors, genetics, metabolic disorders, hormone imbalances all play a role.

Adipose cells are metabolically active

They produce hormones and cytokines that regulate food intake, lipid storage, metabolism, insulin sensitivity, and female reproduction.
They influence the immune system and vascular homeostasis
Stimulate angiogenesis

Fat cell types:

Brown fat, beige, white fat

Ghrelin- hunger hormone, increases your appetite

Produced from GI cells

Leptin- full hormone, decreases appetite

Produced by adipose cells

Obesity and chronic inflammation

Excess adiposity results in increased production of free fatty acids and pro-inflammatory cytokine.
Chronic inflammation has been linked to many chronic diseases, including atherosclerosis, cancer and depression.
As FFA increases, insulin is less effective causing muscles and cells to be insulin resistant= no uptake in cells.

Complications: hyperglycemia, HDL decreases, metabolic syndrome= prediabetes, T2DM, gallbladder and liver diseases, mortality of death increases, cardiovascular diseases, respiratory disorders- sleep apnoea, osteoarthritis.

Assessment of Obesity:

Health history, Physical examination, bloods, BMI, waist circumference, body fat distribution,

Management of Obesity:

Non Pharmacological lifestyle changes

Healthier diet
Regular exercise
Sleep and relation
Lifestyle programs

Strong emphasis should be on improving activity levels as fitness can significantly improve overall health

Pharmacological: supplements

Bariatric surgery

Childhood obesity:

Around 10-12% of NZ kids are obese

Risk factors:

Sedentary lifestyle
Low socioeconomic status
Family factors, if parents are obese then the kid is more likely to be
Psychological factors
High calorie

Complications:

Social and psychological issues
Changes in bone shape
Darkened skin areas
Onset of puberty altered
Gynecomastia in boys

Smoking causes cancer

Smoking increases risk for non communicable diseases→ heart disease, ling, diabetes, COPD, tuberculosis, eye disease, rheumatoid arthritis

Tobacco smoke:

Nicotine is addictive. 60 other substances are carcinogenic
End up in your bloodstream. Increases heart rate and blood pressure, and narrows the capillaries
Carbon monoxide robs muscles, brain and body of oxygen, prevents oxygen binding.
It slows blood flow, reducing oxygen

Long term effects:

Skin: smokers tend to get wrinkles sooner, reduced blood flow damages tissues such as elastin and collagen

Mouth: causes gum diseases, cancers, loss of taste and teeth.

Brain: thinner cerebral cortex, destroys gray matter. It is crucial for thinking, learning skills, including memory. Neuron degeneration.

Respiratory system affects:

Mucus and cilia is impaired, down regulated. Cilia are no longer functional.
Down regulation of immune response
Alteration and expression of genes, increased cytokines, mucus
Alveoli, tar, impaired exchanges of gas, damage to walls
Reduction in airway diameter due to plugged up airways ie mucus
Chronic inflammation
Pre cancerous changes to cells

Smoking chemicals can cause switching on and off of genes, increasing the rate of errors in cell division. Modifies the cell cycle inducing uncontrolled cell proliferation.

Second hand smoke→ commonly in children

No safe level of smoking

Causes in children:

Middle ear disease
SID- sudden infant death

Nicotine is addictive, moves easily through the blood brain barrier.

Acetylcholine is an ANS transmitter
Acetylcholine to the nicotinic receptors, the effect is stimulatory on the body- stimulates Dopamine
Stimulates limbic system - emotions and memory. Positive reward feedback feels nice.
If receptors are constantly exposed to nicotine they become desensitized over time, causing addiction needing more nicotine.
Positive feedback.

Vaping: smoking cessation

Used to help people quit smoking, vaping substances are heated and become aerosol- gas and aqueous particles, vaping products are humectants.

These particles penetrate deeply into lung tissues

Long term effect of hygroscopic substances is not fully known.

Dehydration of epithelium
Inflammation in lungs
Disruption of alveoli ie: gas exchange, mucous concentrations, surfactant concentrations (keeps alveoli inflated), surface tension.

Hypertension: high blood pressure → Silent killer

High blood pressure can damage the vessel walls, leading to strokes, damages valves in the heart

→ 140/90 mmhg

primary - causes family history, obesity, sedentary, age, gender, high salt, diabetes

Secondary- kidney disease, endocrine imbalances, drugs,

Neural response: vasoconstriction/dilation

Hormonal: RAAS system: determines how much water is retained or let go for blood volume.

Heart wall pathology- myocardial due to prolonged hypertension

Dilated cardiomyopathy- shrinks
Hypertrophic cardiomyopathy- left ventricle is thicker as compensation
Restrictive, not able to pump out a lot of blood out of ventricles

Management of hypertension

Lifestyle changes
Physical activity
Diet changes
Medications:

ACE and ARBS
Beta blockers
Calcium channel blockers
Diuretics

Theories of mental health:

Natural development of the mind and mental well being:

Neurological development
Emotional and social development
Macro determinants of mental health
Mental wellbeing through the lifespan

Neurological development:

Cerebral cortex: cognition, intellect and sensation
Limbic system: emotions and memory

Brain and functions:

Cerebral cortex: high order functions
Basal ganglia: motor, planning, and movement, reward
Thalamus: sensory gateway, seeing, hearing
Hippocampus: formation of memory
Amygdala: associated emotions with experiences
Hypothalamus: regulates body functions and motivates behaviours

Limbic system:

Basal ganglia: movement, learning, habits, cognition and emotions
Thalamus: sleep, consciousness and alertness
Hippocampus: memory and navigation
Amygdala: memory, decision making, and emotional responses
Hypothalamus: controls body temperature, hunger, fatigue and sleep

Emotional and social development:

Maternal and infant bonding and attachment is most significant factor influencing development
Emotional regulation, stress

Macro Determinants of mental ill health

Economic stability
Housing
Employment
Education
Purpose, participation in community

Socioeconomic determinants of mental health

Poverty
Stress, exclusion
Marginlisation
Stigma
Loss of self esteem

Mental wellbeing through the lifespan:

Infancy
Childhood
Adolescence
Adulthood
Old age

Mental illness:

Bio- psyscho-social model

Neurochemical factors

Neurotransmitters: acetylcholine, dopamine, serotonin, glutamate, adrenaline/noradrenaline, GABA

Addiction and substance abuse:

What is addiction?

A complex condition of where the user does not have control over their actions towards the substances even after knowing the consequences of using it.

How it works:

Basal ganglia: which play an important role in positive forms of motivation, including the pleasurable effects of health activities like eating, socializing. These areas form a key node of what is called the brain's reward circuit. Drugs over activate this circuit, producing the euphoria of the drug high, with repeated exposure, the circuit adapts to the presence of the drug, diminishing its sensitivity and making it hard to feel pleasure from anything besides the drug/

The extended amygdala: plays a role in stressful feelings like anxiety, irritability and unease, which characterize withdrawal after the drug high fades, and thus motivates the person to seek the drug again. This circuit becomes increasingly sensitive with increased drug use. Over time a person with substance use disorder uses drugs to get temporary relief from this discomfort rather than to get high.

The prefrontal cortex: powers the ability to think, plan, solve problems and make decisions and exert self control over impulses. This is also the last part of the brain to mature. Shifting balance between this circuit and the circuits of the basal ganglia and extended amygdala make a person with a substance use disorder seek the drug compulsively with reduced impulse control.

Risks for addiction

Adverse childhood experiences
Genetic susceptibility
Culture
Loss + trauma
Poverty
Abuse, neglect, household dysfunction

Alcohol misuse

Clinical manifestations

Cerebral cortex: loss of emotional control, reduced ability to learn new information, affected senses.

Hippocampus: blackouts, impaired memory, reduced reception to learn new info

Hypothalamus: slowed heart rate

Medulla: slow breathing, lower body temperature, coma

CNS: slurred speech, poor muscle control, slower reaction

Cerebellum: affected coordination and balance, slowed reflexes, shaking and tremor

Amphetamine like substances

How it affects the brain:

Dopamine in the reward centers is released into the gaps between neurons, crosses to the next neuron and binds to receptors, providing a jolt of pleasure
Methamphetamine, stimulates the release of excessive dopamine heightening the feeling of pleasure.

Opioids- a substance with morphine like effect on the CNS

Synthetic: methadone, fentanyl

Semi synthetic: heroin

Opiate: naturally occurring opioid made from poppy juice, morphine

Cannabis- psychoactive ingredient- impairing memory and difficulty focusing

AUD

Is chronic relapsing brain disorder characterized by an impaired ability to stop or control alcohol use despite adverse social, occupational or health consequences.

Addiction

craving
Wanting to cut down or stop but not managing to
Taking the substance in high amounts and longer
Neglecting other parts of life because of substance abuse
Continuing to use it when it causes problems in relationships
Using substances even when they put you in danger

Alcohol in the body:

20% of Alcohol is absorbed through the stomach, and 80% in the small intestine and is then carried in the bloodstream everywhere. Passing through the blood brain barrier.
Alcohol stays in the body until it's processed or peed out

Pharmacokinetics of alcohol

The alcohol molecule is highly water soluble and small therefore easily and rapidly distributed throughout the body
The key alcohol metabolism pathway is via ADH at the rate of ~7.5g/hour
3 enzymes play a role in alcohol metabolism, CYP2E1, ADH, and ALDH

Pharmacodynamics of alcohol:

Low alcohol levels can cause mild euphoria and sometimes alter behavior from sociability towards aggression.
Increased opiate levels help explain the euphoric effect of alcohol white its effects on GABA can cause anxiolytic and sedative effects
Impaired performance in relation to complex tasks is also noted

Tolerance and withdrawal

GABA and Glutamate are key neurotransmitters for alcohol tolerance
Long term heavy alcohol use is linked to decreased GABA inhibitory function and increased NMDA glutamate activity
This imbalance only becomes an issue when alcohol intake is stopped and these neurotransmitter systems become overactive and withdrawal symptoms occurs

Long term effect:

Physical: diseases, stroke, cancers, heart issues
Fetal Alcohol spectrum disorder- alcohol also passes through the placenta and is consequently a teratogenic substance

Anxiety

Is a psychological, physiological , and behavioral state induced by a threat to wellbeing or survival, either actyal or potential.

Risk factors:

Being female
Socially disadvantaged
Exposure to traumatic events
Comorbidity, substance abuse
Family history
Age 16-24 and 25-44

Aetiology

Anxiety disorders appear to be caused by an interaction of biopsychosocial factors, genetic vulnerability interacts with situations that are stressful or traumatic to produce clinically significant syndromes

Meds
Herbal meds
Substance abuse
Trauma
Childhood experiences
Panic disorders

The Anxious brain:

The amygdala is responsible for initiating the fight or flight response, two circuits feed into it, one that enhances its activity and one that dampens it. In people with anxiety disorders the normal workings of these circuits are disturbed and the amygdala is hyperactive.

Centers in the brain that control anxiety

Prefrontal cortex: center for rational, logical thought, it is involved in laying down new memories and tempering learned fear responses

Prefrontal and anterior cingulate cortex: amplifies negative information in your surroundings and makes you pay attention to it

Amygdala: emotional memories and our learned reactions to them are stored here. When active, it triggered the release of hormones responsible for the fight or flight response.

Pathophysiology:

Anxiety can cause your brain to release stress hormones on a regular basis, when you feel anxious or stressed your brain floods your nervous system with hormones and chemicals designed to help you respond to a threat.

Adrenaline and cortisol are two examples

Long term exposure to stress hormones can be harmful, overactive SNS stimulation causes cortisol imbalance.

Symptoms:

Nausea
Feeling dizzy or faint
Excessive use of the toilet
Sleep disturbances
Muscle tension and tiredness
Increased heart rate

Types of extreme anxiety:

General anxiety disorder: feelings of excessive worry about events, activities and situations

Obsessive compulsive: unwanted recurring thoughts and compulsive repetitive behaviors.

Post traumatic stress disorder: extreme anxiety and distress symptoms due to being exposed to a traumatic event

Panic disorder: intense and recurrent panic attacks that occur unexpectedly

Social anxiety disorderL feelings of extreme anxiety in social situations.

How stress and anxiety affects the body:

Difficulty concentrating, irritability, mood, mind fog
Higher cholesterol, high blood pressure,
Hair loss, dull brittle hair, dry skin, acne,
Increased inflammation tension, aches and pains, muscle tightness,
Diarrhea, constipation, bloating, pain
Decreased immune system
Decreased hormone production
Decreased libido

Assessment of anxiety:

Persistent for at least 6 months
History of specific anxiety disorders
Screening questions
Onset, severity and duration

Diabetes:

Insulin increases in response to, increase in blood glucose, amino acids and gastrointestinal hormones, parasympathetic stimulation during rest and digest restoration process

Insulin decreases in response to low blood glucose, but high insulin levels

Insulin is an anabolic hormone, it works in synergy with glucagon.

Insulin is required for the uptake of glucose by many cells, particularly those of the liver, muscle and adipose cells.
Insulin promotes protein synthesis, and formation and storage of lipids
Insulin facilitates transport across the cell membrane

Amylin is a beta cell hormone that is co-secreted with insulin

Amylin suppresses the release of glucagon from alpha cells

C- peptide is secreted by beta cells

Co- secreted with insulin (bi-product)
Measures the endogenous blood insulin levels.

Glucagon: catabolic hormone

Increases in response to low BSL
Causes glycogenolysis: conversion of glycogen stores into glucose
May stimulate gluconeogenesis: conversion of non carbohydrate sources into glucose
Promotes lipolysis: release of fatty acids from adipose cells
Sympathetic nervous systems may prompt glucagon release in response to stress.

Types of diabetes

T1DM

T2DM

Gestations

Cystic fibrosis related diabetes

Neonatal

MODY- maturity onset diabetes of the young.

Type 1 DM

Absolute or significant deficit of insulin, cell mediated immune destruction of beta cells in the pancreas
10% of the population has this
Alpha cell function abnormal, glucagon still released in the presence of hyperglycemia as not suppressed by amylin.
Individuals may be genetically susceptible
Clinical manifestations: ketonuria, ketonaemia, reduced or undetectable c peptide, glycosylated hemoglobin, positive tests for autoantibodies
Polydipisa, polyuria, polyphagia, weight loss, nocturia

Gestational diabetes

Glucose intolerance with onset during pregnancy

Pre diabetes:

Impaired fasting glucose
Impaired glucose tolerance

Metabolic syndrome:

Central visceral obesity
Persistent hyperglycemia
Dyslipidemia
Hypertension, atherosclerosis

T2DM

Often asymptomatic, manifestations can be vague,non specific, or related to a number of chronic conditions and complications.

Recurrent infections, struggles in wound healing
Polyphagia, polydipsia, polyuria
Neuropathy, nephropathy, retinopathy

What Is Neonatal Diabetes?

Neonatal diabetes mellitus is a rare form of diabetes that occurs within the first 6 months of life. Our bodies need insulin to help our cells make energy. Infants with this condition do not produce enough insulin, which increases blood glucose levels.

Neonatal diabetes is often mistaken as type 1 diabetes, which is much more common. But type 1 diabetes usually occurs in children older than 6 months.

Half of babies diagnosed with neonatal diabetes have a lifelong condition. This is called permanent neonatal diabetes mellitus. It occurs in 1 in 260,000 babies in some areas of the world.
For the other half, the condition disappears within the first twelve weeks of life: but it can reoccur later. This is called transient neonatal diabetes mellitus.

Fetuses with neonatal diabetes do not grow as well in the womb, and these newborns may be small for their gestational age. This is called intrauterine growth restriction.

MODY is genetic- MODY is the name given to a collection of different types of inherited forms of diabetes that usually develop in adolescence or early adulthood. MODY stands for “Maturity-onset diabetes of the young” and was given that name in the past because it acted more like adult type of diabetes (Type 2 Diabetes) but was found in young people.

MODY limits the body’s ability to produce insulin, but is different than the juvenile type of diabetes (Type 1 Diabetes). When our bodies don’t produce enough insulin, it can increase blood glucose levels. High blood glucose levels lead to diabetes.

Neoplasia

Neoplastic cells ignore genetic controls resulting in

Excessive cellular proliferation
Loss of cellular differentiation
Most cancers start from one altered cell

Benign: Malignant

Differentiated - dedifferentiated cells
Slow -variable growth
Encapsulated -irregular borders
Localized - invades surroundings and spreads
No metastasis - spreads and forms metases

Altered genes leading to cancer:

Mutator gene: normal function: repair DNA mutations

Oncogene: code for proteins that regulate cell growth, their normal counterparts are proto-oncogenes that switch on cell growth processes/ when proto-oncogenes mutate into oncogenes they disrupt cell growth

Tumor suppressor genes normally prevent excessive cell division and promote apoptosis.

3 stages:

Initiation
Promotion
Progression

Normal → dysplasia → localized neoplasm → invasive neoplasm

The hallmarks of cancer

cancer cells have specific properties which allow them to avoid the body’s normal removal mechanisms and hence they are capable of persisting

self sufficiency in growth signals
insensitivity to antigrowth signals
tumor invasion and metastasis
lack of immune rejection
evading apoptosis
angiogenesis
limitless replication

cancer growth, spread and metastasis

autonomy and anaplasia
Angiogenesis must occur in order for a tumor to enlarge
primary tumor
local and regional invasion
metastasis

cancer and the immune system

role of immune surveillanced

Defects of the immune system substantially increase the incidence of some cancers

Chronic inflammation is an important factor in the development of cancer
Cytokine and growth factor release from inflammatory cells
Mutation promotion

Risk factors for cancer

Smoking, diet, obesity, alcohol consumption, UV exposure, diabetes

Clinical manifestations of cancer

Pain: caused by tumor causing pressure, obstruction, stretching, tissue destruction and inflammation, influenced by fear, anxiety, sleep loss, fatigue and overall physical deterioration
Infection: caused by leukopenia due to direct tumor invasion of the bone marrow, risk increased when the absolute neutrophil and lymphocyte count falls
Anemia: a decrease of hemoglobin in the blood: caused by chronic bleeding resulting from iron deficiency
Fatigue: can be debilitating and difficult to measure: may be caused by sleep disturbance, psychosocial factors, anemia, and environmental factors.
Cachexia: most severe form of malnutrition, can lose 80% of adipose and skeletal muscle mass → manifestations include: anorexia, early satiety, weight loss, taste alterations and altered metabolism

Diagnosis and tests:

Tumor cell markers, are substances produced by cancer cells or that are found on plasma cell membranes in the blood, CSF, urine eg: hormones, enzymes, genes, antigens
Tumor markers are used to: screen and identify individuals at high risk for cancer, diagnose specific types of tumors, observe clinical course of cancer

Treatment of cancer:

Chemotherapy
Immunotherapy
Ionizing radiation
Surgery
Complementary and alternative treatments

Renal

The nephron is the functional unit of the kidney, 1 million in one kidney

Composed of the glomerulus, proximal tube, loop of henle, distal tubule, collecting duct

Functions of the kidney

Regulations of body volume
Supports maintenance of body ph and electrolyte balance
Elimination of metabolic wastes and toxins
Production of erythropoietin which stimulates red bone marrow to produce red blood cells
Production of renin
Regulation of blood pressure
Activation of vitamin D

Urine characteristics

Yellow color from pigment of blood cells and bilirubin breakdown
Cloudy urine may indicate bacteria, cells, high solute concentration
Food, vitamins, medications can change urine color
Ph 4.6-8 usually acidic

What SHOULDN'T be in urine:

Bilirubin
Ketones
Glucose
Protein
Bacteria
White blood cells
Red blood cells
Crystals
Fat

Chronic pyelonephritis:

Pathophysiology:

Persistent or recurrent infection causing scarring of the kidney
Usually in conjunction with obstructive condition
Progressive inflammation, destruction of tubules, diffuse scarring, decreased ability to concentrate urine
Fibrosis and inflammation in interstitial space

Clinical manifestations

Hypertension, flank pain, frequency, dysuria

Diagnosis: urinalysis, ultrasound, intravenous pyelography

Treatment: removal of, relief from obstruction, antibiotics

Hypertension and kidney disease:

When BP is high blood flows through the blood vessels with more force. Damaged arterioles are not able to deliver blood to the kidney tissue. Damage occurs to the glomerulus and the capillaries.

Upper urinary tract obstruction

Stricture narrowing of the tube
Compression from blood vessel, tumor, scarring, abdominal inflammation
Congenital compression
Calculi, kidney stones
Cancer

Sites of obstruction

Multiple sites where urinary obstruction can occur

The severity of the obstructive uropathy is determined by:

Site of the obstruction
Whether it is bilateral or single sided
The completeness of the obstruction
The duration
Nature of the lesion

How obstruction occurs:

Backflow of urine from the site of obstruction, causing dilatuon of the urinary system, as urine continues to be produced it is unable to drain. Increasing risk of infection and comprimised renal function.
Hydro ureter: accumulation of urine in the ureters
Hydro nephrosis: accumulation of urine in the nephron

Damage to glomeruli increases the longer the obstruction remains

→ dehydration, metaboic acidosis

Hydronephrosis: prolonged obstruction of the ureter causes pressure to build up resulting in hydroureter and hydronephrosis

Obstructive renal calculi

Development of kidney stones in the renal system: solid masses (crystals) precipitated from filtrate

Cause: urinary stasis, dehydration concentrates the solutes in urine, elevated urinary levels of salts proteins, most stones contain calcium

Clinical manifestations: renal colic: moderate to severe pain, flank radiating to groin, nausea, vomiting, haematuria, urgency, frequent voiding

Obstructive benign prostatic hypertrophy:

Pathophysiology: abnormal increase of cells in the prostate gland, tissue surrounding urethra compresses urethra.

Clinical manifestations: enlargement of the prostate gland, frequency, urgency, full bladder feeling after urination, poor force of stream, straining to pass urine, intermittent flow

Prostate cancer:

Often symptomless, until advanced, frequent low volume urination, weak stream, pain on urination, blood in urine, rectal obstruction may occur, bowel obstruction, difficulty with defecation, late signs include bone pain, bone fractures, liver enlargement, mental confusion

CKD:

Pathophysiology

Various causes
Complication of systemic disease: hypertension, diabetes
Complication of renal disease eg chronic obstruction, chronic pyelonephrititis
Damage to tubules, decreases GFR
Glomerulosclerosis
Inflammation and fibrossi in interstitial space between tubules
Proteinuira

Clinical manifestations:

Azotaemia: increased levels of serum urea and nitrogenous waste due to decreased kidney function
Uraemia: a pro-inflmmatory state, systemic symptoms caused be accumulation of toxins and nitrogenous waster
Decreased GFR
Anemia: interrupted production of erythropoietin
Disruption to fluid and electrolyte imbalance
Sodum and water retained leading to hypertension and edema
Potassium increases
Metabolic acidosis
Hypocalcaemia

Peritoneal dialysis:

In peritoneal dialysis a substance, usually glucose is placed into the peritoneal cavity to draw water out in a process called osmosis

The peritoneal cavity of most adults can comfortably hold two to three liters of fluid

Peritoneal dialysis solution containing a higher concentration of glucose will draw more fluid than a weaker concentration

During the dwell phase, excess water and waste products from the blood are drawn across the peritoneal membrane into the dialysate

Respiratory

Impaired ventilation

A problem of blocking airflow in and out of the lungs

Two major mechanisms implicated:

Compression or narrowing of the airways
Disruption of the neuronal transmissions needed to stimulate the mechanics of the airways

Impaired ventilation perfusion matching

Two possible scenarios:

Lungs are ventilated but not perfused
Lungs are perfused, but not ventilated

Ventilation perfusion mismatching

Inadequate ventilation (air) in well perfused areas of the lungs
Inadequate perfusion (blood) in well ventilated areas of the lungs

The effects of impaired ventilation and diffusion

Hypoxaemia: decreased arterial oxygen
Hypoxia: cells deficient in oxygen
Hypercapnia: elevated blood levels of carbon dioxide

COPD- emphysema and bronchitis

Pathophysiology:

Diagnosis is based on the presentation of a persistent productive coughs lasting three months or greater for two or more consecutive years

It is a result of:

Chronic inflammation and edema in the airways
Hyperplasia of the bronchial mucous glands and smooth muscles
Destruction of cilia
Squamous cell metaplasia
Bronchial wall thickening and development of fibrosis

Chronic bronchitis affects the airways causing and loss of cilia and hyperplasia of the bronchial glands, the increased mucous plugs up the bronchioles allowing pathogens to flourish and cause repeated infections

Chronic bronchitis clinical manifestations:

Cough
Purulent sputum
Dyspnoea
Adventitious lung sounds
Cyanosis
Normal weight, clubbing of fingers

Clubbing of fingers: clubbing of the fingers occurs most often in people who have heart or lung disorders that decrease the amount of oxygen in the blood, this causes the fingertips and fingernails to spread out and become rounder.

Emphysema: irreversible enlargement of the air spaces beyond terminal bronchioles

Destruction of the alveolar walls
Obstruction of airflow
Air trapping
Eventually weight loss due to increased work of breathing

Chronic smoking often most implicated, small percentage have genetic deficiency

Clinical manifestations: persistent cough, dyspnea, wheezing, barrel chest, pursed lip breathing

Cardiac:

Hardening of the arteries, the formation of plaques, obstructs blood flow through the artery leading to hypoxia and tissue death

Results in coronary heart disease, heart attack, cerebral ischemia, and stroke and peripheral artery disease

Damage heart muscle due to a heart attack is replaced by scar tissue: if damage is severe the heart may be unable to pump enough blood through the body a condition called heart failure
Life threatening irregular known as arrhythmias can occur

Coronary artery disease: a class of diseases that involves the coronary arteries, happens when the major blood vessels in the heart get narrow and stiff due to atherosclerosis

The arteries of the heart cannot deliver enough oxygen rich blood to the myocardium

Risk factors:

Non modifiable: advancing age, male or female after menopause, family history

Modifiable: dyslipidemia, atherosclerosis promoting diet, hypertension, cigarette smoking, T2DM, insulin resistance, obesity and sedentary lifestyle

Angina:

Angina is chest discomfort or pain caused by reduced blood flow to the heart muscle and is a symptom of CAD
Chest pain / discomfort is usually transient, if blood flow is restored no permanent changes or damage to the heart muscle.
Pain is caused by a buildup of lactic acid and or abnormal stretching of the ischemic myocardium that irritates myocardial nerve fibers

Two types of angina:

STABLE = chronic. Caused by gradual luminal narrowing and hardening of the arterial walls, the affected vessels cannot dilate in response to increased myocardial demands associated with physical exertion
UNSTABLE = acute. Results from acute obstruction of a coronary artery without myocardial infarction, this can be more dangerous and may indicate an impending MI

Peripheral vascular disease:

A type of cardiovascular disease and usually used to refer to peripheral artery disease

Caused by narrowing, blockage or spasms in blood vessels outside of the heart or brain

Typically caused by atherosclerosis- atherosclerotic plaques harden and narrow the opening of the arteries, restricting blood flow
Less common causes include: infection/ inflammation of a blood vessel, injury to the affected limb and irregularly shaped muscles or ligaments in the limb.

Heart failure: defined as a syndrome encompassing several types of cardiac dysfunction resulting in inadequate perfusion of tissue and organs

Often characterized by underlying structural abnormality or cardiac dysfunction that impairs the ability of the left ventricle to fill or eject blood.

The right ventricle may also have dysfunction- this is most often related to pulmonary dysfunction

Definitions:

Diastole: relaxation phase where chambers fill
Systole: contraction of heart chambers pumping out blood
End diastolic volume: EDV: the volume of blood in the LV at the end of ventricular filling
End diastolic pressure: EDP: the pressure exerted due to the EDV
Preload: initial stretching of the cardiac myocytes prior to contraction
Afterload: the amount of resistance the heart must overcome to open the aortic valve and push blood into the systemic circulation
Frank starling law of the heart: the stroke volume of the left ventricle will increase as the LV increases due to the myocyte stretch causing a more forceful systolic contraction
Stroke volume: the volume of blood ejected from the LV during systole. Influenced by contractility, preload and afterload

Ejection fraction: measures as a percentage how much blood is ejeected from the left ventrocle with each cardiac oontraction

Normal: 52-74%

EF below 40% = HF with reduced EF contraction issue

Heart failure pathophysiology:

Reflects an inadequacy of heart pumping so that the heart fails to maintain the circulation of blood

Result of:

Impaired cardiac functioning
Excessive workload demands
Left and right heart failure

Similiar concepts- different systems:

Ischemic heart disease:

Myocardial oxygen demand increases while coronary artery oxygen supply decreases causing angina, Mi, heart muscle damage

Heart failure: fatigue, impaired organ function, organ failure

Increase systemic oxygen demand, systemic oxygen supply decreases.

Systole: the ventricles eject blood and squeeze, systolic failure, pumping problem, inability of ventricle to contract

Diastole: the ventricles fill with blood and relax, diastolic failure, relaxing problem

Left heart failure:

Systolic reduced ejection fraction HRrRF
Inability of the heart to generate adequate cardiac output to perfuse vital tissues
Contractility reduced by diseases that disrupt myocyte activity
Aetiology: MI, CAD, cardiomyopathies, valvular issues, hypertension leading to ventricular remodeling- hypertrophy and dilation of the ventricle

Clinical manifestations:

Due to pulmonary congestion and inadequate perfusion of the systemic circulation
Dyspnea
Orthopnoea
Cough with frothy sputum
Fatigue
Decreased urine output
Odema

Left heart failure

Diastolic preserved ejection fraction HFpEF
Can occur by itself or along with systolic heart failure
Definition: pulmonary congestion despite a normal EF
Results from decreased compliance of the left ventricle and abnormal diastolic relaxation= increased pressure in the left ventricle
Pressure backflows to the lungs= pulmonary odema
Causes hypertension and myocardial ischemia

Clinical manifestations:

Similar to HFrEJ due to pulmonary congestion/ odema
Dyspnea
Orthopnea
Cough with frothy sputum
Fatigue
Odema

Right heart failure

Right sided heart failure refers to the disease state of muscle weakness

Results from the left heart failure due to increased pulmonary pressure or thr hypoxic pulmonary diseases
Pressure backflows into the systemic venous circulation
Hepatosplenomegaly
Ascites
GI symptoms and nausea
Increased jugular pressure

Clinical manifestations

Decreased appetite
Abdo discomfort
Engorged abdo organs
Hepatosplenomegaly
Fatigue
Peripheral edema

HF when stroke volume decreases:

LHF: blood dams back into the lungs, respiratory symptoms, orthopnea, low BP, weak peripheral pulses, fatigue

Etiology: IHD, hypertension, valve disease

= LEFT SIDE OF HEART NOT PUMPING WELL. FLUID BUILDS UP IN THE LUNGS

RHF: blood dams back into the vena cava: engorged abdo organs, GI symptoms, ascites, lack of appetite, and dependant edema

Etiology: pulmonary hypertension from COPD, lung injuries

= RIGHT SIDE OF HEART NOT PUMPING WELL. PAIN AND SWELLING IN ABDO and FLUID build up in LEGS.

Compensatory measures to increase cardiac output:

Recall CO= HR x SV

As cardiac output drops

Sympathetic activity increases heart rate and contractility/ vasoconstriction
Myocardium hypertrophies
Chambers dilates to increase S
RAAS is activated to increase vascular volume

Compensatory mechanisms:

Baroreceptors in the aortic and carotid arteries sense a drop in the BP
The SNS releases adrenaline and noradrenaline
Low CO and vasoconstriction results in decreased renal perfusion → Renin is released by the kidneys
This initiates RAAS;

In short =

SNS activation results in increased heart rate, and increased contractility which increases blood pressure
Neurohormonal activation results in: increased blood volume, which increases preload angiotensin 2, decreases vascular capacity which increases afterload.

Improving cardiac output:

Reduce the pressure in the cardiovascular system by decreasing blood volume and direct result of this is to decrease blood pressure

Diuretics work by increasing excretion of sodium therefore water, reducing fluid overload, reducing the work of the heart (furosemide)

Am is to decrease BP by:

Decreasing total blood volume (preload)
Decrease sodium reabsorption by kidney

4 classfications of diuretics:

Loop
Thiazide
Potassium sparing
Osmotic diuretics

Intestinal disorders:

Pathophysiology of crohn's disease:

Chronic inflammation anywhere throughout the GI tract from mouth to Anus but commonly in the terminal ileum, ascending and transverse colon

Impaired mucous production
Inflammatory response involves all layers of intestinal walls
Thickened intestinal wall and deep ulcerations
Fissures between inflamed mucosa
Segments of normal tissue between diseased tissue: skip lesions → cobblestone appearance
Fistulas

Clinical manifestations:

Diarrhea
Weight loss
Vomiting fever
Lower abdo pain
Possible bleeding from bowel
Possible bleeding from bowel
Possible deficiency of vitamin b12
Strictures, obstructions, fistulas

Ulcerative colitis:

Inflammatory disease of colon and rectum
Ulcerations occur in mucosal inner most layer of bowel wall
Ulcerations do not extend through all bowel layers
Fistulas and abscesses are rare

Clinical manifestations:

Periods of remission and exacerbation
Diarrhea
Bloody stools
Cramp and pain
Weight loss
Anemia
Fever

Treatment and therapies:

Symptom management, pharmacologic treatment, dietary changes, surgical treatments
Crohns: surgical resection
Ulcerative: removal of rectum and all or part of bowel

Nursing assessment and management:

Patient education
Pain and symptom management
Diarrhea, skin care
Rest and diet
Stress management
Meds and bloods monitoring

Diverticulitis:

Diverticula are small herniations of the mucosa through the colon walls
Outward protrusion of these sac like pouches from mucosal lining of the colon is known as diverticulosis
Inflammation or infection of the diverticula is called diverticulitis

Pathophysiology of diverticulitis:

Most common site sigmoid colon
Caused by increased intraluminal pressure
May see thickening of the circular and longitudinal muscles surrounding the diverticular
Hypertrophy and contraction of these muscle occurs
Reduction of diameter of colon

Clinical manifestations:

Abdo pain
Bloatging
Flatulence
Change in bowel habit
Severe diverticulitis
Acute pain lower left quadrant, palpable mass
Symptoms of infection
Bleeding

Treatment and therapies

Increase in dietary fiber
Adequate fluid intake
Fiber supplements
Stool softeners
Weight reduction if overweight
Severe diverticulitis
Clear liquid diet and antibiotics
surgery may be required for severe cases

Bone disorders

Rheumatoid arthritis

Autoimmune disease
Genetic susceptible
Triggering event: may be an infection/ smoking/ stress
Over time autoantibodies develop that attack host tissue, especially the synovial membrane causing inflammation
Lymphocytes infiltrate the joint: immune complexes form: complement activation attracts more WBC that release enzymes that further damage synovium

Clinical manifestations:

Initially systemic symptoms fever fatugue anorexia