pathophys

what are the pH and [H⁺] ranges for acidosis and alkalosis

primary altercations and secondary responses to acidosis and alkalosis

respiratory acidosis causes

disturbance of neural respiratory control

disorders of thoracic cage

airway obstruction and severe pulmonary disease e.g. COPD, pneumonia asthma attack

metabolic acidosis causes

excessive HCO₃^- loss via kidneys or GI

Non ion gap

Diahhroea

RTA 2 - failure pf proximal tubule to reabsorb HCO₃^-

RTA 1 - disorder of acid excretion in tubules

RTA 4 - reduced ammonia excretion secondary to hypoaldosteronism

High anion gap

diabetic ketoacidosis

lactic acidosis

organic acid accumulation in blood

reparatory alkalosis causes

hyperventilation

• fever

• hypoxia

• panic attack/hysteria

increased metabolism

• pregnancy

• hyperthyroidism

• pheochromocytoma

metabolic alkalosis

GI loss - excessive vomiting

hypokalemia - causes movement oh H+ into cells

hypercalcemia + milk alkali syndrome

Explain the anion gap

consequences of acidemia

recued cardiac output

low blood pressure

arrythmias

hyperventilation - respiratory muscles fatigue

insulin resistance, inhibition of glycolysis

hyperkalemia

altered mental status + coma

consequences of alkalosis

arteriolar constriction

reduced coronary artery perfusion

arrythmias

hypoventilation

glycolysis

hypokalemia, hypocalcemia, hypophosphatemia

reduced cerebral blood flow = seizures

ICF meaning

fluid in the cells

main constituents = Calcium, magnesium, phosphate, potassium

ECF meaning

fluid outside the cell = interstitial fluid + blood plasma

main constituents = sodium, chloride, bicarbonate

electrolyte concentrations can only be measure from the blood plasma but its a good representative of ICF as well

normal serum sodium conc

135 - 145 mmol/L

controlled by aldosterone, insulin, angiotensin, renin, cortisone

normal serum potassium conc

3.5 - 5.5mmol/L

responsible for acid base balance and for kidneys to concentrate urine

normal serum magnesium conc

0.75 - 1.25 mmol/L

normal serum calcium conc

2.1 - 2.6 mmol/L

normal serum phosphate conc

0.8 - 1.45 mmol/L

types of hyponatremia

isotonic: occurs when there are elevated levels of other ECF constituents

hypertonic: other osmotically active substances like glucose or mannitol cause ICF to move ECF space, diluting sodium

hypotonic: higher TBW relative to sodium

types of hypotonic hyponatremia

the volemia refers to the quantity of [Na]

types of hypernatremia

the volemia refers to the quantity of [Na]

hypokalemia causes

dietary deficiency

drugs: catecholamines

acute leukemias

GI or renal losses

hypokalemia clinical manifestation

flattened T waves

ST depression

U waves

arrythmias

cramps, weakness, paralysis

hyporeflexia, hypo excitability

hypokalemia therapy

repletion of potassim

hyperkalemia causes

increased intake

drugs - beta blockers

acidemia

burns, rhabdomyolysis, hemolysis

decreased renal excretion

hyperkalemia clinical manifestation

peaked T waves, wide QRS, loss of p waves

arrythmias

hyperreflexia, hyperexcitability

increased release of aldosterone, insulin

hyperkalemia therapy

calcium to stabilize cell membrane

insulin to shift potassium into cells

role of magnesium?

essential for enzyme activity

acts antagonistically with calcium

magnesium deficiency causes and effects

magnesium excess/toxicity causes and effects

calcium function

99% in bone, most of the remaining 1% is in the ICF

absorbed from intestines under influence of vitamin D

calcium stimulated release of neurotransmitters, hormones and exocrine glands

PTH stimulates movement from bone to ICF

hypocalcemia causes and effects

hypercalcemia causes and effects

phosphate function

is not bound by plasma proteins

PTH reduces plasma phosphate

calcitriol increases plasma phosphate

hypophosphatemia causes and effects

hyperphosphatemia causes and effects

osteopenia

reduced bone mass

osteoporosis

clinical state resulting from osteopenia

causes: excess glucocorticoids, insulin deficiency, low estrogen (menopause), inactivity

osteomalacia (rickets)

mineralisation of bone matrix for growth plates

effects: stunted growth, bow legs, delayed closure of fontanelles, Larson sulcus

atelectasis

alveolar sacs or whole segments do not expand fully → lung collapse

leads to VQ mismatch = poor ventilation, normal perfusion → hypoxia

can be acute or chronic

2 types, absorption and compression

signs: dyspnea, asymmetry in respiration, abolished/diminished breath sounds, clubbing, cyanosis

absorption atelectasis

caused by intrinsic or extrinsic bronchial occlusion (often from mucus plugs)

and by impaired surfactant production

compression atelectasis

caused by extrinsic compression which drive air out -→ lung collapse

eg trauma, rib fractures, obesity - inhibits full expansion of thoracic cage or makes breathing painful

bronchiectasis

chronic abnormal dilation of the bronchioles

types: cylindrical, fusiform, saccular

bronchiectasis pathophysiology

causes: repeated damage to bronchial walls, abnormal mucou-cilliary clearance → breakdown of supporting tissue adjacent to airway

mucus stagnation leads to increased risk of infections and increased bronchial pressure which causes mucosal injury

bronchiectasis symptoms

productive cough, clubbing fingers, sputum, hemoptysis, crackles, diminished breath sounds

often seen in CF patients and Kartagener syndrome

hyperacpnia

increased CO₂ conc in arterial blood caused by hypoventilation

causes:

depression of respirator system by drugs

neurologic disorders affecting brain stem

thoracic cage abnormalities

airway obstruction like sleep apnea, tumour

increased work of breathing - emphysema

symptoms: respiratory acidosis, electrolyte imbalances, arrythmias, headaches, coma seizures, shortness of breath

cyanosis

5g of desaturated hemoglobin in blood regardless of Hg conc

not all patients will necessarily present with blue tinge

central and peripheral cyanosis

central cyanosis

low Oxygen saturation in arterial blood

observed in central parts eg buccal membranes and lips

periphrral cyanosis

slowed circulation to fingers and toes, nail beds

hypoxemia

restricitve vs obstructive lung diseases

COPD pathophysiology

chronic bronchitis and emphysema

smoking impairs ciliary action and macrophage function

inflammation increase mucus production

destruction of alveolar septa -→ peribronchiolar fibrosis

chronic bronchitis

emphysema

asthma

chronic reactive airway disorder, a massive overreaction to allergens

bronchospasm constricts airway, histamine stimulate excess mucus production

on inhalation the narrowed lumen can expand slightly

on exhalation increased intrathoracic pressure closes the lumen completely so air cannot escape

patient will become hypoxic which triggers hyperventilation → CO2 retention an alkalosis

intrinsic and extrinsic triggers of asthma

extrinsic

dust, pollen, food additives, mold, animal hair

intrinsic

cold, stress, exercise, severe respiratory tract infection, cough laugh, genetics, anxiety

symptoms of asthma

paroxysmal dyspnea,

dry cough that becomes productive at the end of attack

wheezing on ascultation

pneumothorax pathophysiology

accumulation of air in pleural cavity

types: open, closed, tension

a rupture in visceral or parietal pleura leads to air accumulation in the pleura and separation of the 2 layers

negative pressure is lost

the lung recoils up to hilus

every breath the patients takes the air passes through the rupture and into the pleural space

closed pneumothorax causes

air from inside the lung enters pleura

blunt chest trauma

air leakage from blebs (atelectasis)

rupture from barotrauma (pressure differences diving high attitude)

high intrathoracic pressure during mechanical ventilation

cancerous or tubercular lesions that erode pleura

interstitial lung disease

open pneumothorax causes

atmospheric air enters wound

penetrating chest wound

sucking chest wound

insertion of central line catheter

chest surgery

thoracentesis

transbronchial biopsy

tension pneumothorax causes

results when air in the pleural space is under higher pressure than air in the adjacent lung, Increasing air pressure pushes against the recoiled lung, causing compression atelectasis

penetrating chest wound treated with an air-tight dressing

fractured ribs

mechanical ventilation

high-level positive end-expiratory pressure that causes alveolar blebs to rupture

chest tube occlusion or malfunction

pulmonary edema

respiratory failure

when the lungs can maintain arterial oxygenation or eliminate CO₂

impaired gas exchange → resp. failure

alveolar hypoventilation → low O₂ sats and hypercapnia → resp, acidosis

V/Q mismatch → hypoxemia

untreated V/Q mismatch → right to left shunting → hypoxia → lactic acidosis

lactic acidosis causes tachycardia, increased stroke volume and increased risk of heart failure

ARDS causes

massive inflammation that injure alveolar capillary membrane

a form of pulmonary edema that can quickly lead to respiratory failure

causes:

sepsis

trauma

anaphylaxis

aspiration of gastric contents

near drowning

drug overdose

pulmonary contusions

ARDS pathophysiology

direct (aspiration of gastric juice) or indirect (inflammatory mediators) injury to pulmonary capillary endothelium

injury stimulates platelet aggregation, microthrombus formation, neutrophils and macrophages

this causes extensive damage to alveolar capillary membrane → increased permeability → pulmonary edema

reduced lung compliance and V/Q mismatch

alveolar injury: increased membrane permeability, increased susceptibility to infection, decreased surfactant production

resp. failure

acute kidney injury

a sudden decline in GFr and increase in urea and creatinine

prerenal aki

caused by reduced blood flow to the kidneys

eg shock, renal artery stenosis, heart failure

prolonged lack of blood flow causes injury to the structures inside the kidney and will begin to cause intrinsic injury

intrinsic AKI types

glomerular nephritis

tubulointerstitial nephritis

pyelonephritis

glomerular nephritis

lesions on the wall of the glomerular capillaries means it cannot filter macromolecules

so blood and proteins are not reabsorbed and pass into the urine

hematuria and proteinuria

small lesions - loss of small proteins up to albumin

extensive lesions - loss of albumin and IgGs

loss of proteins → hypoproteinemia → lower colloid osmotic pressure → edema

nephritic syndrome (glomerular capillary wall injury)

hematuria

azotemia (increased urea and creatinine) → oliguria

salt and water retention → edema

reduced GFR

unaffected area will hyper filtrate to compensate and maintain GFR but in the long run it will cause damage and sclerosis

nephrotic syndrome (podocyte injury)

proteinuria = hypoproteinemia and hypoalbuminemia

hypoproteinemia stimulates protein synthesis in the liver → increased lipoproteins → hyperlipidemia

hyperlipidemia → lipiduria

causes of nephrotic syndrome

minimal change diseases - children

focal segment glomerulosclerosis - adults

membranous nephropathy

diabetes lupus, amyloidosis, infections, drugs, cancer

RPGN

severe form of glomerular nephritis that can lead to irreversible renal failure

immunologically mediated

chronic glomerular nephritis

end stage glomerular disease → develop into chronic renal failure

signs: HTN, edema hematuria

tubulointerstitial nephritis pathophysiology

tubulointerstitial nephritis causes

Acute	chronic
drugs - most common infections diseases - lupus, sjorgen’s, sarcoidosis idiopathic	long term exposure to lithium, NSAIDs, heavy metals chronic infections obstructive uropathy metabolic diseases eg hypercalcemia

acute pyelonephritis

acute suppurative inflammation of the kidney caused by bacterial infection

uncomplicated, complicated, ascending

uncomplicated pyelonephritis

often occurs in young healthy women with no structural or urinary tract obstructions

complicated pyelonephritis

children/adults with functional urinary tract abnormalities of predisposing conditions

how is spread pyelonephritis

ascending from lower urinary tract

or

hematogenous spread

symptoms of pyelonephritis

abrupt onset

fever + chills

pyuria

dysuria

pollakiuria

lumbar pain radiating anteriorly

chronic pyelonephritis

recurring infection superimposed on urinary tract , obstruction or urine reflex

signs: polyuria, nocturia, signs of CKD, ultrasound - kidney decreased dimensions

Chronic kidney disease CKD

presence of kidney damage > 3 months

GFR < 60 for > 3 months

chronic and progressive even after initial cause is gone

uremia

accumulation of urine products that should’ve been excreted “urine in the blood”

CKD consequences

renal artery stenosis

nephrolithiasis

obstructive uropathy

structural or functions defect in urinary tract that blocks flow the flow of urine

obstructive uropathy may impair renal function = obstructive nephropathy

the blocked urine can get backed up and cause hydronephrosis

heart failure

when the heart is unable to generate adequate cardiac output

leads to inadequate perfusion of tissues/ increased diastolic pressure on left ventricle

leads to increased pulmonary pressure

SNS increases HR

PSNS deceases HR

preload

the volume of blood that stretches the ventricle at the end of diastole

afterload

the force that contracting heart muscle must generate to eject blood from the ventricles

compensatory mechanisms of the heart

frank starling forces - increase preload to help sustain cardiac performance

cardiac hypertrophy and remodelling

RAAS activation

alterations in myocyte regenerations and death

systolic left heart failure

inability to generate adequate contractility (most commonly caused by MI)

increased preload

excess plasma volume = edema, mitral valve disease,

diastolic left heart failure

right heart failure

inability to provide adequate blood flow to pulmonary circulation and normal venous pressure

often caused by left heart failure, increased LV pressure backs up into pulmonary circulation

peripheral edema and hepatosplenomegaly

high output failure

inability of the heart to supply blood and nutrients to tissues despite adequate blood volume and normal/increased contractibility

causes: anaemia, septicaemia, hyperthyroidism, beriberi

HTN

primary HTN - HTN without evidence of other diseases

primary HTN can evolve to secondary as renal function decreases

secondary HTN - HTN resulting from other diseases eg kidney disease

primary hypertension

mechanisms of primary HTN

sympathetic overactivity

acquired or inherited defect in the kidneys’ ability to excrete the excessive sodium load

Activation of the renin-angiotensin-aldosterone system (RAAS)

impaired release of endothelium-derived relaxing factors e.g. nitric oxide

mechanisms of secondary HTN

Target organ damage in HTN

atherosclerosis

subcortical white matter demyelination

left ventricular hypertrophy

nephrosclerosis

Dementia and cognitive impairment

circulatory shock

acute failure of the circulatory system to supply peripheral tissues with oxygen, cellular or cells inability to use oxygen

shock gradually progresses to multisystem organ failure, initially reversible but becomes irreversible if prolonged

shock often presents with hypotension and hypoperfusion but can also present with normal vitals (SNS compensates initially)